Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Medicine　Surgery　Surgery

Affiliation (Master)

• Faculty of Medicine　Surgery　Surgery

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Profile and Settings

Affiliation

• Hokkaido University, Graduate School of Medicine

Profile and Settings

• Name (Japanese)

  Taketomi

• Name (Kana)

  Akinobu

• Name

  200901089286283070

Alternate Names

https://surg1.med.hokudai.ac.jp/

Affiliation

• Hokkaido University, Graduate School of Medicine

Achievement

Research Interests

• 肝細胞癌   C型肝炎   ジアシルグリセロールキナーゼ   肝臓外科学   無再発生存   RT-PCR   Fascin   浸潤   転移   予後   C型肝炎ウイルス   インターロイキン12   リアルタイムPCR法   免疫抑制   ラバマイシン   PDGFα受容体   PLGAナノ粒子   腫瘍血管新生   調節性T細胞   樹上細胞   生体肝移植   移植外科   遺伝子治療   ヒアルロン酸くし型共重合体   臨床   ウイルス   マイクロRNA   移植再生医療   再発   ATP   消化器外科・肝臓   molecular biology   recurrence   transplantation   liver surgery   hepatocellular carcinoma   

Research Areas

• Life sciences / General surgery, pediatric surgery
• Life sciences / Digestive surgery

Research Experience

• 2011/11 - Today 北海道大学大学院医学研究科消化器外科学分野Ⅰ 教授
• 2003 - 2011 九州大学大学院消化器・総合外科 講師
• 2003 - 2003 九州大学大学院消化器・総合外科 助手
• 2001 - 2003 中津市立中津市民病院 診療部外科医長
• 1998 - 2001 米国ユタ大学ハンツマン癌研究所 ポスドク
• 1996 - 1998 九州がんセンター消化器部外科 医員
• 1992 - 1996 Kyushu University Medical Institute of Bioregulation

Education

•        - 1995  九州大学大学院
•        - 1990  Kyushu University  School of Medicine
•        -   Kyushu University

Awards

• 2017 日本外科学会 Best Reviewer Award
   

  受賞者: 武冨 紹信
• 2011 第29回日本肝移植研究会 優秀演題賞
   

  受賞者: 武冨 紹信
• 2006 第20回大学勤務医福岡県医師会長賞
  

Published Papers

• Role of Heavy Water in Modified University of Wisconsin Solution for Extended Cold Storage of Rat Liver.

  Moto Fukai, Kengo Shibata, Sodai Sakamoto, Takahisa Ishikawa, Norio Kawamura, Masato Fujiyoshi, Sunao Fujiyoshi, Kosei Nakamura, Hiroki Bochimoto, Shingo Shimada, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 56 (8) 1890 - 1895 2024/10 

  To resolve the critical donor shortage worldwide, enlarging the potential donor pool to include expanded criteria donors is necessary. Despite numerous attempts to establish new preservation solutions, no dramatic innovation has occurred since University of Wisconsin (UW) solution displaced Euro Collins' solution; UW solution remains the global gold standard. We previously developed a heavy water (D2O)-containing organ storage solution, Dsol, which is effective for livers subjected to extended cold storage (CS), and reported its effectiveness. Dsol is a modified UW solution; however, the substances or conditions that exhibit a synergistic or additive effect with D2O are unclear. Here we made UWD solution by removing hydroxyethyl starch (HES) from and adding 30%-D2O to UW solution, and compared the effects of these solutions. After 48 hours of CS, the livers were reperfused at 37 °C on an isolated perfused rat liver apparatus, and their perfusion kinetics, functions, and injuries were compared. In the UW group, portal vein resistance significantly increased and the oxygen consumption rate and bile production decreased; in contrast, these changes were suppressed in the UWD group. Organ expansion and liver damage progressed in both groups. These results confirmed that the removal of HES from and addition of D2O to the UW solution reduced CS-induced cellular function impairments and microcirculatory disorders. However, to reduce injury during reperfusion after CS, it is necessary to provide conditions that inhibit injury progression after reperfusion.
• The anticancer effects of Aronia berry extract are mediated by Chk1 and p53 in colorectal cancer.

  Yoh Asahi, Caiming Xu, Keisuke Okuno, Akinobu Taketomi, Ajay Goel

  Phytomedicine : international journal of phytotherapy and phytopharmacology 135 156086 - 156086 2024/09/19 

  BACKGROUND: Aronia berry extracts (ABE) have recently been reported to possess significant anti-cancer effects in various malignancies, including colorectal cancer (CRC), due to their high polyphenolic content. However, the molecular mechanism(s) underlying the anti-cancer effects of ABE in CRC remain unclear, which is important to consider when considering their use as complementary medicine approaches in cancer. METHODS: We performed genome-wide transcriptomic profiling and pathway enrichment analysis to identify specific growth signaling pathways associated with ABE treatment in CRC cells. In addition, a series of systematic and comprehensive cell culture studies were performed to investigate the anti-cancer effects of ABE in SW480 and HCT116 CRC cell lines. Subsequently, these findings were validated in patient-derived 3D organoids (PDOs) models. RESULTS: Transcriptomic profiling analysis identified p53 signaling as one of the key enriched pathways mediating the anti-cancer activity of ABE. Analysis of public datasets revealed that Chk1, a key regulator of p53, was one of the critical targets of ABE in CRC. Chk1 and p53 activation was shown to be downregulated with ABE treatment, leading to the induction of cell cycle arrest (p = 0.003-0.014) and enhanced DNA damage (p = 0.015-0.026). Furthermore, these findings were validated in PDOs, where the ABE treatment resulted in significantly fewer and smaller PDOs in a concentration-dependent manner (p = 0.045 - <0.001). CONCLUSIONS: We firstly provide evidence for the role of the p53 signaling pathway as a mediator of the anti-cancer activity of ABE, which provides a rationale for its use as a safe and effective integrative medicine approach in CRC.
• Positivity of high-sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non-HBV-related HCC.

  Naohiro Yasuura, Goki Suda, Masatsugu Ohara, Akimitsu Meno, Takuya Sho, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Tomoya Saitou, Masaya Sugiyama, Takasuke Fukuhara, Masaru Baba, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Mitsuteru Natsuizaka, Koji Ogawa, Akinobu Taketomi, Naoya Sakamoto

  Alimentary pharmacology & therapeutics 2024/09/04 

  BACKGROUND AND AIMS: The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. METHODS: We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC. RESULTS: A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC. CONCLUSIONS: In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.
• Risk model for morbidity and mortality following liver surgery based on a national Japanese database.

  Tatsuya Orimo, Shinya Hirakawa, Akinobu Taketomi, Hisateru Tachimori, Taro Oshikiri, Hiroaki Miyata, Yoshihiro Kakeji, Ken Shirabe

  Annals of gastroenterological surgery 8 (5) 896 - 916 2024/09 

  AIM: We evaluated the morbidity and mortality associated with liver surgery in Japan and developed a risk model for liver resection using information from a national database. METHODS: We retrospectively reviewed 73 861 Japanese patients who underwent hepatectomy between 2014 and 2019, using information from the National Clinical Database (NCD) registrations. The primary endpoints were 30 days and in-hospital mortality, and the secondary endpoints were postoperative complications. Logistic regression risk models for postoperative morbidity and mortality after hepatectomy were constructed based on preoperative clinical parameters and types of liver resection, and validated using a bootstrapping method. RESULTS: The 30-day and in-hospital mortality rates were 0.9% and 1.7%, respectively. Trisectionectomy, hepatectomy for gallbladder cancer, hepatectomy for perihilar cholangiocarcinoma, and poor activities of daily living were statistically significant risk factors with high odds ratios for both postoperative morbidity and mortality. Internal validations indicated that the c-indices for 30-day and in-hospital mortality were 0.824 and 0.839, respectively. CONCLUSIONS: We developed a risk model for liver resection by using a national surgical database that can predict morbidity and mortality based on preoperative factors.
• Effects of the COVID-19 pandemic on short-term postoperative outcomes of emergency surgery for gastroduodenal perforation: A nationwide study in Japan based on the National Clinical Database.

  Shimpei Ogawa, Hideki Endo, Masahiro Yoshida, Tomomitsu Tsuru, Michio Itabashi, Hiroyuki Yamamoto, Yoshihiro Kakeji, Hideki Ueno, Yuko Kitagawa, Taizo Hibi, Akinobu Taketomi, Norihiko Ikeda, Masaki Mori

  Annals of gastroenterological surgery 8 (5) 795 - 806 2024/09 

  AIM: To examine the potential negative effects of the COVID-19 pandemic on short-term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. METHODS: A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30-d mortality, surgical mortality, and complications (Clavien-Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. RESULTS: Nationally, data from 2019 vs 2020 and 2021 showed 30-d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001-1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30-d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. CONCLUSION: The COVID-19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic.
• Appendiceal goblet cell adenocarcinoma with perineural invasion extending into the ileocecal lesion.

  Yuka Hosokawa, Sunao Fujiyoshi, Ken Imaizumi, Kengo Shibata, Nobuki Ichikawa, Tadashi Yoshida, Shigenori Homma, Takeaki Kudo, Nanase Okazaki, Utano Tomaru, Akinobu Taketomi

  Surgical case reports 10 (1) 183 - 183 2024/08/07 

  BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is a rare subtype of primary appendiceal adenocarcinoma with an incidence of 1-5 per 10,000,000 people per year. Appendiceal tumors are often diagnosed after appendectomy for acute appendicitis. Notably, however, there is currently no standard treatment strategy for GCA, including additional resection. We report a case of appendiceal GCA with perineural extension into the cecum, in which ileal resection was considered effective. CASE PRESENTATION: A 41-year-old man was diagnosed with acute appendicitis and underwent appendectomy. Histopathological findings revealed GCA (T3, Pn1). He was referred to our hospital for additional resection. Preoperative examination indicated a diagnosis of GCA cT3N0M0. Laparoscopic ileocecal resection and D3 lymph node dissection were performed 2 months after initial appendectomy. The patient had a good postoperative course and was discharged 8 days after surgery. Histopathological findings showed a GCA invading the cecum, despite an intact appendiceal stump, no lymph node metastasis, no vascular invasion, and no horizontal extension into the submucosa. Direct invasion of the tumor through the serosa was not observed, but perineural extension was conspicuous in the cecum, suggesting that the GCA extended into the cecum via perineural invasion. The resection margins were negative. The patient has survived free of recurrence for a year after ileocecal resection. CONCLUSIONS: The current patient was diagnosed with appendiceal GCA following appendectomy for acute appendicitis. Despite intact of appendiceal stump and no evidence of lymph node or distant metastasis, he underwent laparoscopic ileocecal resection and D3 lymph node dissection 2 months after initial appendectomy, with a favorable outcome. Despite the detection of perineural invasion, the patient declined adjuvant therapy. This case suggests that extensive resection may be required in patients with appendiceal GCA, but the role of adjuvant therapy remains unclear.
• Unusual rapid development of portopulmonary hypertension after shunt closure for congenital portosystemic shunt.

  Shohei Honda, Issei Kawakita, Kazuyoshi Okumura, Momoko Ara, Ryoichi Goto, Atsuhito Takeda, Tsuyoshi Shimamura, Insu Kawahara, Akinobu Taketomi

  Journal of paediatrics and child health 2024/08/06
• Early graft-infiltrating lymphocytes are not associated with graft rejection in a mouse model of skin transplantation.

  Ryo Kanazawa, Ryoichi Goto, Takuya Harada, Takuji Ota, Nozomi Kobayashi, Kazuaki Shibuya, Yoshikazu Ganchiku, Masaaki Watanabe, Masaaki Zaitsu, Norio Kawamura, Tsuyoshi Shimamura, Akinobu Taketomi

  Scandinavian journal of immunology e13397  2024/07/30 

  Graft-infiltrating lymphocytes (GILs) play an important role in promoting rejection after organ transplantation. We recently reported that GILs that accumulated up to 3 days post-transplantation did not promote rejection, whereas GILs present 3-5 days post-transplantation promoted rejection in a mouse heart transplantation model. However, the immunological behaviour of GILs in murine skin transplantation remains unclear. GILs were isolated on days 3, 5 or 7 post-transplantation from C57BL/6 (B6) allogeneic skin grafts transplanted onto BALB/c mice. BALB/c Rag2-/- γc-/- mice (BRGs) underwent B6 skin graft transplantation 10 weeks after adoptive transfer of day 3, 5, or 7 GILs. BRGs reconstituted with day 5 or 7 GILs completely rejected B6 grafts. However, when B6 grafts harvested from recipient BALB/c mice on day 5 or 7 were re-transplanted into BRGs, half of the re-transplanted day 5 grafts established long-term survival, although all re-transplanted day 7 grafts were rejected. BRGs reconstituted with day 3 GILs did not reject B6 grafts. Consistently, re-transplantation using day 3 skin grafts resulted in no rejection. Administration of anti-CD25 antibodies did not prevent the phenomenon observed for the day 3 skin grafts. Furthermore, BRGs reconstituted with splenocytes from naïve BALB/c mice immediately rejected the naïve B6 skin grafts and the re-transplanted day 3 B6 grafts, suggesting that day 3 GILs were unable to induce allograft rejection during the rejection process. In conclusion, the immunological role of GILs depends on the time since transplantation. Day 3 GILs had neither protective nor alloreactive effects in the skin transplant model.
• Improved survival outcome of curative liver resection for Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma in the era of tyrosine kinase inhibitors.

  Yoh Asahi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Takeshi Aiyama, Yuzuru Sakamoto, Kazuki Wakizaka, Shunsuke Shichi, Hirofumi Kamachi, Akinobu Taketomi

  Hepatology research : the official journal of the Japan Society of Hepatology 2024/07/26 

  AIM: This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions. METHODS: Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n = 24) or after (n = 43) TKI approval ("beforeTKI" and "afterTKI" group, respectively). RESULTS: There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1 months, respectively; p = 0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9 months, respectively; p = 0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p < 0.001). CONCLUSION: These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.
• 人工肛門閉鎖術における単回使用創傷治療システムを用いて遷延性縫合閉鎖を行う皮膚閉鎖方法

  今泉 健, 本間 重則, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 下國 達志, 笠島 浩行, 中西 一彰, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 79回 743 - 743 2024/07
• Robot-assisted distal gastrectomy and local resection for gastric cancer and gastrointestinal stromal tumor.

  Chihiro Ishizuka, Takahisa Ishikawa, Hayato Yagi, Yoichi Yamamoto, Daisuke Koro, Takahiro Nishikoshi, Yasuyuki Koshizuka, Naoyuki Yanagida, Taiichiro Shibaki, Hiromitsu Akabane, Shunsuke Yasuda, Kei Ishibashi, Akinobu Taketomi

  Asian journal of endoscopic surgery 17 (3) e13310  2024/07 

  Gastrointestinal stromal tumors surrounding the esophagogastric junction are often challenging to resect, with no consensus regarding the optimal surgical technique. Here in, we present a case of concurrent gastric cancer in the antrum and gastrointestinal stromal tumors adjacent to the esophagogastric junction. The patient underwent simultaneous distal gastrectomy and local resection assisted by a surgical robot, avoiding the need for total gastrectomy. The utilization of robot-assisted surgery has become an increasingly popular technique, holding promise for simplifying complex surgical procedures across diverse medical settings.
• Quantitative measurements of M2BPGi depend on liver fibrosis and inflammation.

  Haruki Uojima, Kazumi Yamasaki, Masaya Sugiyama, Masayoshi Kage, Norihiro Ishii, Ken Shirabe, Hisashi Hidaka, Chika Kusano, Miyako Murakawa, Yasuhiro Asahina, Takashi Nishimura, Hiroko Iijima, Kazumasa Sakamoto, Kiyoaki Ito, Keisuke Amano, Takumi Kawaguchi, Nobuharu Tamaki, Masayuki Kurosaki, Takanori Suzuki, Kentaro Matsuura, Akinobu Taketomi, Satoru Joshita, Takeji Umemura, Sohji Nishina, Keisuke Hino, Hidenori Toyoda, Hiroshi Yatsuhashi, Masashi Mizokami

  Journal of gastroenterology 59 (7) 598 - 608 2024/07 

  BACKGROUND: The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology. METHODS: We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation. RESULTS: In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001). CONCLUSIONS: The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage.
• Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

  Yusuke Takemura, Hideki Endo, Taizo Hibi, Yutaka Nakano, Ryo Seishima, Masashi Takeuchi, Hiroyuki Yamamoto, Hiromichi Maeda, Kazuhiro Hanazaki, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Hideki Ueno, Masaki Mori, Yuko Kitagawa

  Hepatology research : the official journal of the Japan Society of Hepatology 54 (7) 685 - 694 2024/07 

  AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.
• Impact of the coronavirus disease 2019 pandemic on 20 representative surgical procedures in Japan based on the National Clinical Database: annual surveillance of 2021 by the Japan Surgical Society.

  Taizo Hibi, Hiroyuki Yamamoto, Takahiro Miyoshi, Norihiko Ikeda, Akinobu Taketomi, Minoru Ono, Masakazu Toi, Hisato Hara, Hiroaki Nagano, Yuko Kitagawa, Masaki Mori

  Surgery today 54 (7) 751 - 762 2024/07 

  PURPOSE: The volume of surgical services has significantly reduced globally due to the coronavirus disease 2019 (COVID-19) pandemic. This study evaluated the level of recovery in terms of the number of operations performed in Japan in 2021, based on nationwide periodic surveillance. METHODS: Information on the weekly and annual volumes of 20 representative procedures in 6 surgical subspecialties in 2021 was extracted from the National Clinical Database. Statistical data for 2018 and 2019 (pre-pandemic era) were compared with those for 2020. Data on waves of infection, peak period, and high-prevalence areas (13 of 47 prefectures) were analyzed individually. RESULTS: The volumes of the 10 procedures, including gastrectomy, hepatectomy, valve replacement and valve plasty, coronary artery bypass grafting, infrarenal abdominal aorta replacement, ventricular septal defect closure, lung lobectomy, inguinal hernia repair (age < 16 years old), and appendectomy (age < 16 years old), did not reach 95% of that in the pre-pandemic era. The most striking decline in the surgical volume of these 10 procedures was observed during the peak period of wave 5 in high-prevalence areas. CONCLUSION: This near-complete enumeration survey identified the polarization of 20 representative procedures in terms of resumption of surgical service after the pandemic.
• 脾彎曲結腸癌に対する郭清成績と長期予後に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 柴田 賢吾, 今泉 健, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 77 (6) 382 - 382 0047-1801 2024/06
• Impact of Portal Flow on the Prognosis of Children With Congenital Portosystemic Shunt: A Multicentric Observation Study in Japan.

  Hajime Uchida, Masato Shinkai, Hiroomi Okuyama, Takehisa Ueno, Mikihiro Inoue, Toshihiro Yasui, Eiso Hiyama, Sho Kurihara, Yasunaru Sakuma, Yukihiro Sanada, Akinobu Taketomi, Shohei Honda, Motoshi Wada, Ryo Ando, Jun Fujishiro, Mariko Yoshida, Yohei Yamada, Hiroo Uchida, Takahisa Tainaka, Mureo Kasahara

  Journal of pediatric surgery 2024/05/17 

  BACKGROUND: Although congenital portosystemic shunts (CPSSs) are increasingly being recognized, the optimal treatment strategies and natural prognosis remain unclear, as individual CPSSs show different phenotypes. METHODS: The medical records of 122 patients who were diagnosed with CPSSs at 15 participating hospitals in Japan between 2000 and 2019 were collected for a retrospective analysis based on the state of portal vein (PV) visualization on imaging. RESULTS: Among the 122 patients, 75 (61.5%) showed PV on imaging. The median age at the diagnosis was 5 months. The main complications related to CPSS were hyperammonemia (85.2%), liver masses (25.4%), hepatopulmonary shunts (13.9%), and pulmonary hypertension (11.5%). The prevalence of complications was significantly higher in patients without PV visualization than in those with PV visualization (P < 0.001). Overall, 91 patients (74.6%) received treatment, including shunt closure by surgery or interventional radiology (n = 82) and liver transplantation (LT) or liver resection (n = 9). Over the past 20 years, there has been a decrease in the number of patients undergoing LT. Although most patients showed improvement or reduced progression of symptoms, liver masses and pulmonary hypertension were less likely to improve after shunt closure. Complications related to shunt closure were more likely to occur in patients without PV visualization (P = 0.001). In 25 patients (20.5%) without treatment, those without PV visualization were significantly more likely to develop complications related to CPSS than those with PV visualization (P = 0.011). CONCLUSION: Patients without PV visualization develop CPSS-related complications and, early treatment using prophylactic approaches should be considered, even if they are asymptomatic. LEVEL OF EVIDENCE: Level III.
• 救命率向上のための急性肝不全に対するチーム医療 急性肝不全に対するチーム医療肝癌治療における複数診療科での対応を参考に

  後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 柏浦 愛美, 山本 真由美, 神山 俊哉, 松居 剛志, 姜 貞憲, 嶋村 剛, 武冨 紹信

  肝臓 (一社)日本肝臓学会 65 (5) 245 - 245 0451-4203 2024/05
• 急性肝不全に対する移植スコアリングシステム High-flow hemodiafiltration時代の急性肝不全診療

  川村 典生, 嶋村 剛, 後藤 了一, 巖築 慶一, 渡辺 正明, 中井 正人, 荘 拓也, 森川 賢一, 小川 浩司, 武冨 紹信

  肝臓 (一社)日本肝臓学会 65 (5) 249 - 249 0451-4203 2024/05
• E型肝炎ウイルス感染による急性肝不全5例の検討

  市村 健太郎, 川村 典生, 渡辺 正明, 後藤 了一, 巖築 慶一, 嶋村 剛, 武冨 紹信

  肝臓 (一社)日本肝臓学会 65 (5) 254 - 255 0451-4203 2024/05
• 侵襲性アスペルギルス症を発症し,脳出血にて死亡した急性肝不全2例の検討

  巖築 慶一, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  肝臓 (一社)日本肝臓学会 65 (5) 257 - 257 0451-4203 2024/05
• Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

  Koki Goto, Jun Watanabe, Toshiya Nagasaki, Mamoru Uemura, Heita Ozawa, Yohei Kurose, Tomonori Akagi, Nobuki Ichikawa, Hiroaki Iijima, Masafumi Inomata, Akinobu Taketomi, Takeshi Naitoh

  Surgical endoscopy 38 (5) 2454 - 2464 2024/05 

  BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.
• Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis.

  Shunsuke Shichi, Ko Sugiyama, Yoh Asahi, Chisato Shirakawa, Hiroki Nakamoto, Saori Kimura, Kazuki Wakizaka, Takeshi Aiyama, Akihisa Nagatsu, Tatsuya Orimo, Tatsuhiko Kakisaka, Akinobu Taketomi

  Cancer medicine 13 (9) e7238  2024/05 

  BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported. METHODS: Immunohistochemistry (IHC) with anti-DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (-, 1+, 2+, 3+) and divided into two groups (DGKα- and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki-67 expression was evaluated as a cell proliferation marker. The number of Ki-67-positive cells was counted, and the relationship with DGKα expression was examined. RESULTS: DGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα- group (-: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence-free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki-67-positive cells increased in association with the staining levels of DGKα. CONCLUSION: Pathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.
• Impact of SARS‐CoV‐2 infection on short‐term postoperative outcomes after gastroenterological cancer surgery using data from a nationwide database in Japan

  Masashi Takeuchi, Taizo Hibi, Ryo Seishima, Yusuke Takemura, Hiromichi Maeda, Genta Toshima, Noriyuki Ishida, Naoki Miyazaki, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Hideki Ueno, Masaki Mori, Ken Shirabe, Yuko Kitagawa

  Annals of Gastroenterological Surgery 2475-0328 2024/05 

  Abstract Background Due to the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening, diagnosis, and treatment have changed. This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection prior to gastroenterological cancer surgeries on postoperative complications using data from a nationwide database in Japan. Methods Data on patients who underwent surgery for cancer including esophageal, gastric, colon, rectal, liver, and pancreatic cancer between July 1, 2019, and September 300, 2022, from real‐world sources in Japan were analyzed. The association between preoperative SARS‐CoV‐2 infection and short‐term postoperative outcomes was evaluated. A similar analysis stratified according to the interval from SARS‐CoV‐2 infection to surgery (<4 vs. >4 weeks) was conducted. Results In total, 60 604 patients were analyzed, and 227 (0.4%) patients were diagnosed with SARS‐CoV‐2 infection preoperatively. The median interval from SARS‐CoV‐2 infection to surgery was 25 days. Patients diagnosed with SARS‐CoV‐2 infection preoperatively had a significantly higher incidence of pneumonia (odds ratio: 2.05; 95% confidence interval: 1.05–3.74; p = 0.036) than those not diagnosed with SARS‐CoV‐2 infection based on the exact logistic regression analysis adjusted for the characteristics of the patients. A similar finding was observed in patients who had SARS‐CoV‐2 infection <4 weeks before surgery. Conclusions Patients with a history of SARS‐CoV‐2 infection had a significantly higher incidence of pneumonia. This finding can be particularly valuable for countries that have implemented strict regulations in response to the COVID‐19 pandemic and have lower SARS‐CoV‐2 infection‐related mortality rates.
• Effects of the COVID‐19 pandemic on short‐term postoperative outcomes of emergency surgery for gastroduodenal perforation: A nationwide study in Japan based on the National Clinical Database

  Shimpei Ogawa, Hideki Endo, Masahiro Yoshida, Tomomitsu Tsuru, Michio Itabashi, Hiroyuki Yamamoto, Yoshihiro Kakeji, Hideki Ueno, Yuko Kitagawa, Taizo Hibi, Akinobu Taketomi, Norihiko Ikeda, Masaki Mori

  Annals of Gastroenterological Surgery 8 (3) 450 - 463 2024/04/15 

  AIM: Possible negative effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation in Japan were examined in this study. METHODS: The National Clinical Database (NCD) is a large-scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30-day mortality, surgical mortality, and postoperative complications (Clavien-Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. RESULTS: In the NCD, postoperative 30-day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30-day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04-1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10-1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08-1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01-1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. CONCLUSIONS: The COVID-19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.
• 当科におけるロボット支援下直腸癌切除の中期成績

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 柴田 賢吾, 今泉 健, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 77 (4) 240 - 240 0047-1801 2024/04
• 鏡視下手術に対する最適な静脈血栓塞栓症予防 腹腔鏡下胃癌大腸癌周術期における静脈血栓塞栓症発症リスク因子の検討

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 柴田 賢吾, 今泉 健, 蒲池 浩文, 川村 秀樹, 横田 良一, 大野 陽介, 舩越 徹, 前田 好章, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 WS - 1 2024/04
• 鏡視下手術に対する最適な静脈血栓塞栓症予防 潰瘍性大腸炎に対する腹腔鏡下大腸切除後の門脈血栓症のリスク因子の解明および周術期予防法についての後方視的検討

  今泉 健, 本間 重紀, 柴田 賢吾, 藤好 直, 市川 伸樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 WS - 2 2024/04
• 大腸がんの再発・転移におけるメトホルミンの抗腫瘍効果およびT細胞誘導メカニズムの解明

  木村 沙織, 本間 重紀, 白川 智沙斗, 中本 裕紀, 志智 俊介, 松井 博紀, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 北村 秀光, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 SF - 3 2024/04
• ラット肝温阻血再灌流障害におけるUDPNアセチルヘキソサミンの動態

  柴田 賢吾, 深井 原, 今泉 健, 藤好 直, 坂本 聡大, 市川 伸樹, 吉田 雅, 川村 典夫, 藤好 真人, 本間 重紀, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 SF - 4 2024/04
• 切除不能転移性大腸癌原発巣切除例のリンパ球/単球比と予後の検討

  和久井 洋佑, 市川 伸樹, 今泉 健, 柴田 賢吾, 藤好 直, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 SF - 4 2024/04
• 結腸がん切除手術における手縫い吻合と器械吻合の実施状況と臨床的アウトカムに関するDPCデータを用いた研究

  海老沼 翔太, 國澤 進, 愼 重虎, 伏見 清秀, 市川 伸樹, 吉田 雅, 柿坂 達彦, 本間 重紀, 武冨 紹信, 今中 雄一

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 SF - 5 2024/04
• E-PASSを用いた高齢者の腹腔鏡下右側結腸切除術における術後合併症リスク因子の検討

  南波 宏征, 今泉 健, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 PS - 6 2024/04
• 潰瘍性大腸炎関連腫瘍に対するロボット支援下大腸全摘術

  本間 重紀, 今泉 健, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 PS - 4 2024/04
• 神経周囲浸潤により回盲部へ進展を認めた虫垂goblet cell adenocarcinomaの一例

  細川 侑香, 藤好 直, 今泉 健, 柴田 賢吾, 岡崎 ななせ, 中里 信一, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 RS - 1 2024/04
• von Willebrand病に併存した小腸間膜裂孔ヘルニアによる絞扼性イレウスの一例

  田中 奨真, 柴田 賢吾, 今泉 健, 藤好 直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 RS - 4 2024/04
• 新型コロナウイルス感染を契機に増悪し大腸亜全摘を施行した潰瘍性大腸炎の1例

  長安 健, 藤好 直, 本間 重紀, 市川 伸樹, 吉田 雅, 柴田 賢吾, 松井 博紀, 桂田 武彦, 中久保 祥, 畑中 佳奈子, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 57 (4) 204 - 211 0386-9768 2024/04 

  新型コロナウイルス感染症(Coronavirus Disease 2019;以下,COVID-19と略記)のパンデミック発生から4年が経ったが,潰瘍性大腸炎(ulcerative colitis;以下,UCと略記)との関連につき一定の見解は得られていない.今回,COVID-19罹患後増悪し手術となったUCを経験した.症例は62歳の男性で,UCに対し内科加療中であった.COVID-19発症後に血便や腹痛などの症状が増悪し,免疫抑制剤を増量したが症状の改善が見られず,腎機能も悪化したため内科的治療の限界と判断し,発症後29日目に腹腔鏡下大腸亜全摘術+回腸単孔式人工肛門造設術を施行した.切除検体の病理で急性期UC所見を認めた.COVID-19による各種臓器障害ではウイルスによる直接的障害や免疫応答を介した間接的障害の機序が提唱され,治療困難となった際は早期手術を考慮すべきである.(著者抄録)
• COVID-19感染拡大が及ぼした腹腔鏡下手術への影響

  白下 英史, 遠藤 英樹, 猪股 雅史, 赤木 智徳, 山本 博之, 坂井 義治, 掛地 吉弘, 北川 雄光, 武冨 紹信, 森 正樹

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 124回 SF - 2 2024/04
• SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma.

  Sunao Fujiyoshi, Shohei Honda, Momoko Ara, Takafumi Kondo, Nozomi Kobayashi, Akinobu Taketomi

  Journal of hepato-biliary-pancreatic sciences 31 (4) 223 - 233 2024/04 

  BACKGROUND: Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based chemotherapy; however, 22.3% of patients develop cisplatin resistance and thus face a poor prognosis. We hypothesized that glucose transporters are associated with acquiring cisplatin resistance with increasing sugar intake inhibiting glucose transporters could reduce cisplatin resistance in hepatoblastoma patients. METHODS: We established cisplatin-resistant HepG2 and HuH6 cells by continuous treatment with cisplatin. We evaluated the relationship between cisplatin resistance and glucose uptake. We used an expression array to select cisplatin-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo. RESULTS: We found a strong relationship between cisplatin resistance and glucose uptake. Additionally, SGLT2 was upregulated in resistant cells after cisplatin treatment. After dapagliflozin treatment, glucose uptake and cisplatin resistance decreased in resistant cells. CONCLUSIONS: Cisplatin-resistant hepatoblastoma cells exhibited upregulated SGLT2 expression and activated glucose uptake to survive under cisplatin stress. SGLT2 inhibition decreased cellular resistance to cisplatin. SGLT2 inhibition with cisplatin therapy could be a novel therapeutic strategy for cisplatin-resistant hepatoblastoma patients.
• TCF1highPD-1+Ly108+CD8+ T Cells Are Associated with Graft Preservation in Sensitized Mice Treated with Non-Fc Receptor-Binding CD3 Antibodies.

  Takuji Ota, Ryoichi Goto, Takuya Harada, Agustina Forgioni, Ryo Kanazawa, Yoshikazu Ganchiku, Norio Kawamura, Masaaki Watanabe, Moto Fukai, Tsuyoshi Shimamura, Akinobu Taketomi

  ImmunoHorizons 8 (4) 295 - 306 2024/04/01 

  The non-Fc-binding anti-CD3 Ab [anti-CD3F(ab')2] can induce graft acceptance depending on the therapeutic window in a rodent heart transplant model. The delayed protocol allows for early graft infiltration of lymphocytes, which may behave in an inhibitory manner. We investigated the most effective protocol for anti-CD3F(ab')2 in sensitized conditions to confirm the evidence for clinical application. C57BL/6 mice were sensitized with BALB/c tail skin grafts and transplanted with BALB/c heart grafts at 8-12 wk after sensitization. Fifty micrograms of anti-CD3F(ab')2 was administered daily for 5 consecutive days on days 1-5 (day 1 protocol) or days 3-7 (delayed protocol). In nonsensitized mice, the delayed protocol significantly prolonged graft survival after transplantation from BALB/c to naive B6 (median survival time [MST], >100 d). In contrast, the delayed protocol was unable to prevent graft rejection in sensitized mice (MST, 5 d). A significantly increased percentage of granzyme B+ CD8+ T cells was observed in the graft on day 3 posttransplantation in sensitized conditions. Further, the day 1 protocol significantly prolonged graft survival (MST, 18 d), even in sensitized conditions. Day 1 treatment significantly increased the percentage of Foxp3+CD25+CD4+ T cells and phenotypically changed CD8+ T cells in the graft (i.e., caused a significant increase in the proportion of Ly108+TCF1highPD-1+CD8+ T cells). In conclusion, different timings of delayed anti-CD3F(ab')2 treatment promoted allograft preservation in association with phenotypic changes in CD4+ and CD8+ T cells in the graft under sensitized conditions.
• Treatment of delayed pancreatic fistula associated with anastomosis breakdown after pancreaticoduodenectomy using percutaneous interventions.

  Reimi Suzuki, Yuji Konishi, Kai Makino, Yosuke Wakui, Kazuhiro Mino, Hideki Kawamura, Ryo Morita, Tatsuhiko Kakisaka, Daisuke Abo, Akinobu Taketomi

  Clinical journal of gastroenterology 17 (2) 356 - 362 2024/04 

  We here present a rare case of development of a postoperative pancreatic fistula and breakdown of the pancreaticojejunal anastomosis 8 months after pancreaticoduodenectomy. A 70-year-old man underwent pancreaticoduodenectomy for distal cholangiocarcinoma and initially recovered well. However, 8 months later, he developed abdominal pain and distention and was admitted to our institution with suspected pancreatitis. On the 17th day of hospitalization, he suddenly bled from the jejunal loop and a fluid collection was detected near the pancreaticojejunal anastomosis site. The fluid collection was drained percutaneously. Subsequent fistulography confirmed breakdown of the pancreaticojejunal anastomosis. Considering the patient's overall condition and the presence of postoperative adhesions, we decided to manage him conservatively. An additional drain tube was placed percutaneously from the site of the anastomotic breakdown into the lumen of the jejunum, along with the tube draining the fluid collection, creating a completely new fistula. This facilitated the flow of pancreatic fluid into the jejunum and was removed 192 days after placement. During a 6-month follow-up, there were no recurrences of pancreatitis or a pancreatic fistula. This case highlights the efficacy of percutaneous drainage and creation of an internal fistula as a management strategy for delayed pancreatic fistula and anastomotic breakdown following pancreaticoduodenectomy.
• Impact of the COVID‐19 pandemic on short‐term outcomes after pancreaticoduodenectomy for pancreatic cancer: A retrospective study from the Japanese National Clinical Database, 2018–2021

  Yusuke Takemura, Hideki Endo, Taizo Hibi, YUTAKA NAKANO, Ryo Seishima, Masashi Takeuchi, Hiroyuki Yamamoto, Hiromichi Maeda, Kazuhiro Hanazaki, Akinobu Taketomi, Yoshihiro Kakeji, yasuyuki seto, Hideki Ueno, Masaki Mori, Yuko Kitagawa

  Annals of Gastroenterological Surgery 2475-0328 2024/03/23 

  AbstractAimThe coronavirus disease 2019 (COVID‐19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan.MethodsData on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD.ResultsThis study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID‐19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien–Dindo grade ≥4 complications, and the 30‐day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID‐19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID‐19 pandemic.ConclusionThe increasing trend in the number of pancreaticoduodenectomies and favorable short‐term outcomes even in the COVID‐19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.
• Expression Analysis of Early Metastatic Seeding of Colorectal Cancer.

  Akifumi Sawada, Masafumi Ohira, Kanako C Hatanaka, Hiroki Matsui, Nobuki Ichikawa, Tadashi Yoshida, Moto Fukai, Yoshihiro Matsuno, Shigenori Homma, Yutaka Hatanaka, Akinobu Taketomi

  Annals of surgical oncology 31 (3) 2101 - 2113 2024/03 

  BACKGROUND: Distant metastasis is the leading cause of death in patients with colorectal cancer (CRC). Tumor dissemination for metastasis formation occurs in advanced cancers and also during early stages of tumorigenesis. Here, we investigated the genes involved in early metastatic seeding of CRC using gene expression analysis. PATIENTS AND METHODS: We performed a cDNA microarray using specimens resected from stages I-II CRC with and without metachronous metastatic recurrence. For the candidate genes, we immunohistochemically validated protein expression using a tissue microarray of stages I-III CRC. RESULTS: The expression of TROP2, VWCE, and BMP7 was upregulated in the recurrence group rather than in the non-recurrence group. Protein expression analysis revealed significant association of these genes with distant metastatic recurrence. The specimens with high expression of BMP7 showed worse recurrence-free survival (RFS; p = 0.02). Those with high expression of TROP2 and VWCE showed worse overall survival (OS) and RFS (TROP2: p = 0.01 and p = 0.03; VWCE: p < 0.05 and p < 0.001, respectively). In the multivariate analysis, high expression of VWCE and BMP7 was an independent predictor of recurrence [VWCE: hazard ratio (HR) 3.41, p < 0.001; BMP7: HR 2.93, p = 0.005]. In contrast, TROP2 was an independent prognostic factor for OS (HR 4.58, p = 0.03). CONCLUSIONS: Gene expression analysis revealed that TROP2, VWCE, and BMP7 were involved in early metastatic seeding. The high expression of these genes may warrant careful surveillance or adjuvant therapy, even in stages I-II CRC cases.
• Questionnaire survey of Japanese board-certified expert hepatobiliary and pancreatic surgeons and instructors on the surgical indications for hepatocellular carcinoma.

  Keiichi Akahoshi, Junichi Shindoh, Minoru Tanabe, Shuichi Watanabe, Hayato Takamizawa, Susumu Eguchi, Itaru Endo, Shoji Kubo, Akinobu Taketomi, Hiroaki Nagano, Masafumi Nakamura, Kiyoshi Hasegawa, Etsuro Hatano, Tomoharu Yoshizumi, Norihiro Kokudo

  Journal of hepato-biliary-pancreatic sciences 31 (3) 143 - 151 2024/03 

  BACKGROUND: Recent advancements in systemic therapy for hepatocellular carcinoma (HCC) necessitate the establishment of resectability criteria for advanced HCC. METHODS: A questionnaire survey sought to clarify the perspectives of Japanese expert hepatobiliary surgeons regarding surgical indications for HCC. Thirty-one questions were used to determine when surgery is strongly recommended (resectable: R) or not recommended (unresectable: UR). RESULTS: A total of 351 responses were obtained. While 64.7% of the respondents considered solitary tumors as being R, irrespective of size, opinions diverged on the upper limit of the number of tumors/tumor size for R: (1) up to three nodules with no size limit (27.9%), (2) up to three nodules ≤5 cm in diameter each (21.4%) and (3) up to three nodules ≤3 cm in diameter each (19.4%). Vp1, Vp2, Vp3, and Vp4 were considered as being R by 90.9%, 70.7%, 39.0%, and 8.0% of respondents, respectively. Half of the respondents indicated they would consider resection even for cases with extrahepatic spread under limited conditions. CONCLUSIONS: The current views of Japanese expert surgeons on the resectability criteria for HCC were clarified for the first time. The findings could serve as a basis for preparing expert consensus statements on the resectability criteria for HCC.
• 腸管切除後出血のリスク因子の検討

  坂村 颯真, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 85 (2) 297 - 297 1345-2843 2024/02
• 高齢潰瘍性大腸炎に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 85 (2) 298 - 298 1345-2843 2024/02
• ハイリスク症例の大腸憩室穿孔に対する人工肛門造設術の検討

  細川 侑香, 柴田 賢吾, 今泉 健, 藤 好直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本腹部救急医学会雑誌 (一社)日本腹部救急医学会 44 (2) 451 - 451 1340-2242 2024/02
• von Willebrand病に併存した小腸間膜裂孔ヘルニアによる絞扼性イレウスの一例

  森越 健之介, 柴田 賢吾, 今泉 健, 藤 好直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本腹部救急医学会雑誌 (一社)日本腹部救急医学会 44 (2) 455 - 455 1340-2242 2024/02
• 非外傷性S状結腸間膜血種に対し,左半結腸切除術を施行した1例

  津坂 隼也, 柴田 賢吾, 今泉 健, 藤好 直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本腹部救急医学会雑誌 (一社)日本腹部救急医学会 44 (2) 456 - 456 1340-2242 2024/02
• 進行胃癌に対する腹腔鏡下胃切除の短期成績

  川村 秀樹, 三野 和宏, 小丹枝 裕二, 津坂 翔一, 石黒 友唯, 今 裕史, 横田 良一, 吉田 雅, 本間 重紀, 武冨 紹信

  日本胃癌学会総会記事 96回 463 - 463 2024/02
• Investigation of the impact of COVID‐19 on postoperative outcomes using a nationwide Japanese database of patients undergoing laparoscopic distal gastrectomy and low anterior resection for gastric cancer and rectal cancer

  Tomonori Akagi, Hideki Endo, Masafumi Inomata, Hidefumi Shiroshita, Shigeki Yamaguchi, Susumu Eguchi, Norihito Wada, Yukinori Kurokawa, Yosuke Seki, Yoshiharu Sakai, Hiroyuki Yamamoto, Yoshihiro Kakeji, Yuko Kitagawa, Akinobu Taketomi, Masaki Mori

  Annals of Gastroenterological Surgery 8 (3) 521 - 529 2475-0328 2024/01/28 

  Abstract Background The COVID‐19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID‐19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID‐19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID‐19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web‐based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity‐leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot‐assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre‐pandemic period. Conclusions Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID‐19 pandemic.
• Immunoglobulin-like transcript 2 as an impaired anti-tumor cytotoxicity marker of natural killer cells in patients with hepatocellular carcinoma.

  Toshihiro Sakata, Sachiyo Yoshio, Taiji Yamazoe, Taizo Mori, Eiji Kakazu, Yoshihiko Aoki, Nobuyoshi Aoyanagi, Toru Okamoto, Takanori Ito, Hidenori Toyoda, Takumi Kawaguchi, Yoshihiro Ono, Yu Takahashi, Akinobu Taketomi, Tatsuya Kanto

  Frontiers in immunology 15 1389411 - 1389411 2024 

  INTRODUCTION: Natural killer (NK) cells play a pivotal role in immune surveillance in the liver. We aimed to identify potential targets for NK cell-mediated immune intervention by revealing the functional molecules on NK cells in HCC patients. METHODS: To evaluate the impact of aging on NK cell phenotypes, we examined NK cells from healthy volunteers (HVs) of various ages. Because ILT2 expression on CD56dim NK cells increased with increasing age, we enrolled age-matched HCC patients and HVs. We determined the NK cell phenotypes in blood mononuclear cells (PBMCs) and intrahepatic lymphocytes (IHLs) from cancerous and non-cancerous tissues. We evaluated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) of NK cells in vitro. RESULTS: ILT2-positive CD56dim NK cells in PBMCs were increased in HCC patients compared with HVs. In HCC patients, ILT2-positive CD56dim NK cells were increased in cancerous IHLs compared with non-cancerous IHLs and PBMCs. We examined the impact of macrophage migration inhibitory factor (MIF) on ILT2 expression in co-cultures of HCC cells and NK cells. The enhanced expression of ILT2 on CD56dim NK cells from HCC patients was inhibited by masking antibodies against MIF and CXCR4. ILT2-positive CD56dim NK cells exhibited lower capacities for cytotoxicity and ADCC than ILT2-negative cells, which were partially restored by ILT2 blockade. CONCLUSIONS: In HCC patients, ILT2 is a signature molecule for cancerous CD56dim NK cells with impaired cytolytic capacity. The MIF-CXCR4 interaction is associated with ILT2 induction on CD56dim NK cells and ILT2 serves as a target for functional NK cell restoration.
• Expression of Wnt5a and ROR2, Components of the Noncanonical Wnt-Signaling Pathway, is Associated with Tumor Differentiation in Hepatocellular Carcinoma.

  Kazuki Wakizaka, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Takeshi Aiyama, Shunsuke Shichi, Akinobu Taketomi

  Annals of surgical oncology 31 (1) 262 - 271 2024/01 

  BACKGROUND: Wnt5a is the key ligand of the noncanonical Wnt pathway, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a receptor associated with Wnt5a. The association between the noncanonical Wnt-signaling pathway and carcinogenesis in hepatocellular carcinoma (HCC) is unclear. This study investigated the significance of ROR2 expression in HCC. METHODS: The study examined ROR2 expression in liver cancer cell lines. Immunohistochemical staining of ROR2 was performed on 243 resected HCC specimens. The study investigated ROR2 expression and its association with clinicopathologic factors and prognosis. RESULTS: Findings showed that ROR2 was expressed in well-differentiated Huh7 and HepG2 cells, but not in poorly differentiated HLE and HLF cells. Expression of ROR2 was positive in 147 (60.5%) and negative in 96 (39.5%) HCC specimens. A significant association was shown between ROR2 negativity and high alpha-fetoprotein (AFP) level (P = 0.006), poor differentiation (P = 0.015), and Wnt5a negativity (P = 0.024). The 5-year overall survival (OS) rate for the ROR2-negative group (64.2 %) tended to be worse than for the ROR2-positive group (73.8%), but the difference was not significant (P = 0.312). The 5-year OS rate was 78.7% for the ROR2+Wnt5a+ group, 71.3 % for the ROR2+Wnt5a- group, 80.8% for the ROR2-Wnt5a+ group, and 60.5 % for the ROR2-Wnt5a- group. The OS in the ROR2-Wnt5a- group was significantly poorer than in the ROR2+Wnt5a+ group (P = 0.030). The multivariate analysis showed that Wnt5a-ROR2- was an independent prognostic factor (hazard ratio, 2.058; 95% confidence interval, 1.013-4.180; P = 0.045). CONCLUSIONS: The combination of ROR2 and Wnt5a may be a prognostic indicator for HCC. The Wnt5a/ROR2 signal pathway may be involved in the differentiation of HCC. This pathway may be a new therapeutic target for HCC.
• Important Constituents of Heavy Water-containing Solution for Cold Storage and Subsequent Reperfusion on an Isolated Perfused Rat Liver.

  Moto Fukai, Sodai Sakamoto, Kengo Shibata, Takahisa Ishikawa, Norio Kawamura, Masato Fujiyoshi, Sunao Fujiyoshi, Kosei Nakamura, Hiroki Bochimoto, Shingo Shimada, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 56 (1) 223 - 227 2024/01/09 

  The University of Wisconsin (UW) solution is the most effective preservation solution currently used; however, to safely use expanded-criteria donor grafts, a new cold storage solution that alleviates graft injury more effectively is required. We prepared a heavy water (D2O)-containing buffer, Dsol, and observed strong protective effects during extended cold storage of rat hearts and livers. In the current study, we modified Dsol (mDsol) and tested its efficacy. The aim of the present study was to determine whether mDsol could protect the rat liver more effectively than the UW solution and to clarify the roles of D2O and deferoxamine (DFX). Rat livers were subjected to cold storage for 48 hours in test solutions: UW, mDsol, mDsol without D2O or DFX (mDsol-D2O[-], mDsol-DFX[-]), and subsequently reperfused on an isolated perfused rat liver for 90 minutes at 37°C. In the UW group, the liver was dehydrated during cold storage and rapidly expanded during reperfusion. Accordingly, the cumulative weight change was the highest in the UW group, together with augmented portal veinous resistance and ALT leakage and decreased oxygen consumption rate and bile production. These changes were significantly suppressed in the mDsol-treated group. In the mDsol-D2O(-) and mDsol-DFX(-) groups offered partial protection. In conclusion, mDsol appeared to be superior to the UW solution for simple cold storage of the rat liver, presumably due to improved microcirculation in the early phase of reperfusion. Both heavy water and deferoxamine are essential for alleviating seamless organ swelling that occurs during cold storage and subsequent reperfusion.
• A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.

  Caiming Xu, Eunsung Jun, Yoshinaga Okugawa, Yuji Toiyama, Erkut Borazanci, John Bolton, Akinobu Taketomi, Song Cheol Kim, Dong Shang, Daniel Von Hoff, Guixin Zhang, Ajay Goel

  Gastroenterology 166 (1) 178 - 190 2024/01 

  BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.
• Impact of COVID-19 pandemic on short-term outcomes after low anterior resection in patients with rectal cancer: Analysis of data from the Japanese National Clinical Database.

  Ryo Seishima, Hideki Endo, Taizo Hibi, Masashi Takeuchi, Yutaka Nakano, Hiroyuki Yamamoto, Hiroaki Miyata, Hiromichi Maeda, Kazuhiro Hanazaki, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Hideki Ueno, Masaki Mori, Yuko Kitagawa

  Annals of gastroenterological surgery 8 (1) 107 - 113 2024/01 

  AIM: The Coronavirus Disease 2019 (COVID-19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short-term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. METHODS: Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID-19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). RESULTS: This study included 74 181 patients, including 43 663 (58.9%) from COVID-19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30-day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. CONCLUSION: Although the pandemic temporarily decreased the ICU admission rate, its impact on short-term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.
• Phospholipase A2 Group IIA Is Associated with Inflammatory Hepatocellular Adenoma.

  Sadahiro Iwabuchi, Kenta Takahashi, Kazunori Kawaguchi, Akihisa Nagatsu, Tadashi Imafuku, Shigeyuki Shichino, Kouji Matsushima, Akinobu Taketomi, Masao Honda, Shinichi Hashimoto

  Cancers 16 (1) 2023/12/28 

  Although benign hepatocellular adenomas (HCA) are very rare, recent observations have shown their occurrence in patients with diabetes mellitus. Consequently, most of these cases are treated by resection due to concerns regarding their potential progression to hepatocarcinoma (HCC). This decision is largely driven by the limited number of studies on HCC subtyping and the lack of molecular and biological insights into the carcinogenic potential of benign tumors. This study aimed to comprehensively investigate the subtype classification of HCA and to compare and analyze gene expression profiling between HCA and HCC tissues. One fresh inflammatory HCA (I-HCA), three non-B non-C HCCs, two hepatitis B virus-HCCs, and one normal liver tissue sample were subjected to single-cell RNA sequencing (scRNA-seq). Comparative analysis of scRNA-seq among different tissues showed that phospholipase A2 group IIA (PLA2G2A) mRNA was specifically expressed in I-HCA, following RNA-seq analysis in formalin-fixed paraffin-embedded tissues from other HCAs. Immunohistochemistry using the PLA2G2A antibody in these tissues indicated that the positive reaction was mainly observed in hepatocytes of I-HCAs and stromal cells surrounding the tumor tissue in HCC were also stained. According to a clinical database, PLA2G2A expression in HCC does not correlate with poor prognosis. This finding may potentially help develop a new definition for I-HCA, resulting in a significant clinical contribution, but it requires validation with other fresh HCA samples.
• Evaluation of the advantage of surgeons certified by the endoscopic surgical skill qualification system participating in laparoscopic low anterior rectal resection

  Naruhiko Sawada, Tomonori Akagi, Manabu Shimomura, Yukitoshi Todate, Kunihiko Nagakari, Hiroaki Takeshita, Satoshi Maruyama, Manabu Takata, Nobuki Ichikawa, Koya Hida, Hiroaki Iijima, Shigeki Yamaguchi, Akinobu Taketomi, Takeshi Naitoh

  Annals of Gastroenterological Surgery 8 (3) 464 - 470 2475-0328 2023/12/14 

  Abstract Background A technical qualification system was developed in 2004 by the Japan Society for Endoscopic Surgery. An analysis of the EnSSURE study on 3188 stage II–III rectal cancer patients, which was performed by including the participation of qualified surgeons as assistants and advisers without restricting their participation as operators, revealed that the participation of technically qualified surgeons in surgery improved the technical and oncological safety of laparoscopic rectal resection. Aim This secondary retrospective analysis of the EnSSURE study examined the advantage of qualified surgeons participating in laparoscopic low anterior resection (LAR). Methods The outcomes of low anterior resection were compared between groups with and without the participation of surgeons qualified by the Endoscopic Surgical Skill Qualification System (Q and non‐Q groups, respectively). We used propensity score matching to generate paired cohorts at a one‐to‐one ratio. The postoperative complication rate, short‐term results (hemorrhage volume, operative time, number of dissected lymph nodes, open conversion rate, intraoperative complication rate, and R0 resection rate), and long‐term results (disease‐free survival rate, local recurrence rate, and overall survival rate) were evaluated. Results The frequencies of postoperative complications, anastomotic bleeding, and intraperitoneal abscess were significantly lower, the operative time was significantly shorter, the postoperative hospital stay was significantly shorter, and the number of dissected lymph nodes was higher in the Q group. No significant differences were observed in disease‐free survival, local recurrence, or overall survival rate rates between the groups. Conclusion The participation of qualified surgeons in LAR is technically advantageous.
• 新型コロナウイルス感染蔓延下での長期待機後に脳死肝腎同時移植を実施した末期原発性硬化性胆管炎の1例

  坂村 颯真, 後藤 了一, 山口 将功, 植林 毅行, 伊藤 啓一郎, 津坂 翔一, 原田 拓弥, 太田 拓児, 川村 典生, 渡辺 正明, 田邉 起, 堀田 記世彦, 篠原 信雄, 嶋村 剛, 武冨 紹信

  北海道外科雑誌 北海道外科学会 68 (2) 106 - 110 0288-7509 2023/12 

  新型コロナウイルス感染蔓延による本邦の脳死下臓器提供の減少から現病の進行の管理に苦慮しつつ待機する症例が増加した。今回,新型コロナウイルス感染蔓延下での長期待機後に脳死肝腎同時移植を実施した症例を経験したので報告する。症例は37歳男性。2018年に黒色便を主訴に前医受診,原発性硬化性胆管炎・肝硬変と診断され,2020年2月脳死肝移植待機リストに登録した。待機中に肝腎症候群による腎不全が増悪,透析導入となり肝腎同時移植登録となった。MELD30以上で上位待機するも臓器提供は無く,コロナ禍の面会制限などから抑鬱状態となった。さらに消化管出血や血圧低下から治療継続に難渋した。登録後8ヵ月を綿密な治療介入で乗り切り脳死下肝腎同時移植を実施した。術後複数回の透析治療を要したが,徐々に腎機能改善し25PODで透析離脱,経過良好につき50PODで退院となった。(著者抄録)
• 膵移植後の抗体関連型拒絶反応治療に免疫グロブリン静注療法(intravenous immunoglobulin:IVIG)を使用した症例の調査研究 本邦膵移植後IVIG4症例の報告

  伊藤 泰平, 剣持 敬, 後藤 了一, 渡辺 正明, 武冨 紹信, 嶋村 剛, 平光 高久, 鳴海 俊治, 富丸 慶人, 小林 省吾, 江口 英利, 大島 稔, 岡野 圭一, 中川 健, 江川 裕人

  移植 (一社)日本移植学会 58 (3) 273 - 280 0578-7947 2023/12 

  2001～2121年度の膵臓移植474例のうち膵移植後の抗体関連型拒絶反応(ABMR)に対し免疫グロブリン静注療法(IVIG)を用いた4例(男性2例、女性2例、移植時年齢40代3例、50代1例)について調査した。原疾患は4例全てI型糖尿病で、糖尿病性腎症の合併による血液透析中2例、腎移植後2例であった。観察期間中、全例で抗ドナー特異抗体(DSA)陽性を認めた。転帰は、ABMRを制御できず膵・腎グラフトを摘出しインスリン、透析再導入1例、膵グラフト生着3例のうち1例はABMR発症後にインスリン再導入となった。IVIG治療による有害事象は無く、治療後1年時点で全例生存しており生命予後は良好であった。
• New chemiluminescent enzyme immunoassay for quantitative measurement of Mac-2 binding protein glycosylation isomer in chronic liver disease.

  Haruki Uojima, Kadzuki Nakabayashi, Kazumi Yamasaki, Masaya Sugiyama, Norihiro Ishii, Ken Shirabe, Takuya Kyoutou, Koji Ueda, Yoichi Takahama, Nobuharu Tamaki, Masayuki Kurosaki, Hisashi Hidaka, Chika Kusano, Keisuke Amano, Takumi Kawaguchi, Akinobu Taketomi, Satoru Joshita, Takeji Umemura, Miyako Murakawa, Yasuhiro Asahina, Takanori Suzuki, Kentaro Matsuura, Takashi Nishimura, Hiroko Iijima, Kazumasa Sakamoto, Kiyoaki Ito, Sohji Nishina, Keisuke Hino, Hidenori Toyoda, Hiroshi Yatsuhashi, Masayoshi Kage, Masashi Mizokami

  Journal of gastroenterology 58 (12) 1252 - 1260 0944-1174 2023/12 

  BACKGROUND: This study aimed to evaluate the quantitative measurement of Mac-2 binding protein glycosylation isomer (M2BPGi) levels using the new chemiluminescent enzyme immunoassay. METHODS: The data of a total of 347 patients with hepatitis C virus (HCV) infection and 150 health volunteers from 13 locations in Japan were evaluated. The quantitative system for measuring M2BPGi-Qt levels was based on a new chemiluminescent enzyme immunoassay. We evaluated the reproducibility and quantitation range in quantitative M2BPGi-Qt measurement. We also investigated the confidence ratio of M2BPGi-Qt levels measured by the new quantitative system to M2BPGi levels measured by the current semi-quantitative system for validating the clinical utility of the new method. RESULTS: The reproducibility of M2BPGi-Qt in HCV samples with negative, positive 1+, and positive 2+ was 0.77 ± 0.02 AU/mL, 2.25 ± 0.03 AU/mL, and 6.55 ± 0.21 AU/mL, respectively, and the corresponding coefficient of variation (CV)s were 2.1%, 1.3%, and 3.2%, respectively. The range of quantification assessment resulted that all CVs showed less than 5% in investigated range. Sample stability testing found that the mean percentage difference between the pre- and post-storage values of 6 samples ranged between 96.2 and 103.9%. The correlation coefficient between M2BPGi and M2BPGi-Qt in patients with HCV and the healthy volunteers was 0.986 and 0.991, respectively. M2BPGi-Qt could be quantitatively assessed in a patient with over 20 C.O.I. CONCLUSION: Compared with qualitative methods, the M2BPGi quantitative measurement system could provide a numerical value unaffected by interpretation bias, and measurements are more precise at high M2BPGi levels.
• Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer.

  Shuhei Sano, Takashi Akiyoshi, Noriko Yamamoto, Yukiharu Hiyoshi, Toshiki Mukai, Tomohiro Yamaguchi, Toshiya Nagasaki, Akinobu Taketomi, Yosuke Fukunaga, Hiroshi Kawachi

  Clinical colorectal cancer 22 (4) 411 - 420 2023/12 

  BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression. MATERIALS AND METHODS: The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing. RESULTS: High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB. CONCLUSION: ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.
• Endoscopic Surgical Skill Qualification System: propensity-score matched cohort analysis of accredited supervisors in laparoscopic rectal cancer surgery.

  Yuki Kiyozumi, Tomohiro Yamaguchi, Nobuki Ichikawa, Shigenori Homma, Koji Ikeda, Ryo Inada, Koki Otsuka, Akinobu Furutani, Hiroaki Iijima, Masahiko Watanabe, Akinobu Taketomi, Takeshi Naitoh

  The British journal of surgery 110 (12) 1834 - 1839 2023/11/09 

  BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) in Japan evaluates the surgical skills required for laparoscopic surgery as an operator as well as a supervisor. This study aimed to demonstrate the benefits of an ESSQS-certified surgeon's participation in laparoscopic rectal resections as a supervisor (assistant or advisor). METHODS: We retrospectively reviewed laparoscopic resection results for cStage II and III rectal cancer performed at 56 Japanese hospitals between 2014 and 2016. We used propensity score matching to generate paired cohorts with or without an ESSQS-certified supervisor at a one-to-one ratio. The impact of ESSQS-certified supervisors' participation on short-term outcomes was assessed. In the matched cohort, multivariable logistic regression analysis and multivariable regression analysis of postoperative complication rate and intraoperative blood loss were performed to further mitigate the impact of pathological factors. RESULTS: Two groups (n = 399 each) with or without an ESSQS-certified supervisor were well matched by clinical factors. The group with an ESSQS-certified supervisor had lower blood loss (68 mL vs. 98 mL, P = 0.036) and a lower incidence of severe morbidities of Clavien-Dindo grade ≥IIIa (8.0% vs. 13.3%, P = 0.016). Multivariable logistic regression analysis and multivariable regression analysis confirmed that the attendance of ESSQS-certified supervisors reduced postoperative complication occurrence (adjusted odds ratio: 2.28, 95% confidence interval: 1.38 - 3.80, P = 0.001) and intraoperative blood loss (estimated difference: -15.7 mL, P = 0.016). CONCLUSION: This study demonstrated the educational benefits of ESSQS-certified supervisors, including assistants and advisors, evidenced by their superior short-term outcomes.
• Feasibility of Laparoscopic and Robotic Total Proctocolectomy for Ulcerative Colitis-related Colorectal Cancer.

  Tadashi Yoshida, Shigenori Homma, Nobuki Ichikawa, Sunao Fujiyoshi, Kengo Shibata, Ken Imaizumi, Akinobu Taketomi

  Anticancer research 43 (11) 5245 - 5252 2023/11 

  BACKGROUND/AIM: To evaluate the feasibility of laparoscopic and robotic total proctocolectomy (TPC) for ulcerative colitis-associated colorectal cancer (UC-CRC). PATIENTS AND METHODS: We retrospectively analyzed the postoperative outcomes of TPC in 13 patients with UC-CRC between January 2011 and December 2021. Laparoscopic TPC was performed in 10 patients. TPC consisted of two procedures: ileal pouch-anal anastomosis (IAA) and TPC with end ileostomy. Using the da Vinci Xi platform with six ports, robotic TPC and abdominal perineal resection (APR) were performed in two and one patients, respectively. Transanal total mesorectal excision (TaTME) was performed using the perineal approach in five patients. RESULTS: UC-CRC was located in the transverse colon, sigmoid colon, rectum, and anal canal in 1, 1, 10, and 1 patients, respectively. IAA, TPC with end ileostomy, and APR were performed in nine, three, and one patients, respectively. Postoperative complications included colitis, portal vein thrombosis, and liver dysfunction, without mortality. The pathological stages were 0, I, IIa, IIIb, and IIIc in five, four, one, two, and one patients, respectively. The tumors were completely resected in all cases. Eleven patients with pStages 0, I, and II survived without recurrence; however, two patients with pStage III died of cancer recurrence. CONCLUSION: This study demonstrated the feasibility of laparoscopic and robotic TPC in patients with UC-CRC. However, long-term outcomes in terms of oncology and patient quality of life must be investigated in future large-scale studies.
• A Study of risk factors of postoperative ileus after laparoscopic colorectal resection.

  Sunao Fujiyoshi, Shigenori Homma, Tadashi Yoshida, Nobuki Ichikawa, Kengo Shibata, Hiroki Matsui, Akinobu Taketomi

  Annals of gastroenterological surgery 7 (6) 949 - 954 2023/11 

  AIM: Postoperative ileus (POI) is a common complication after abdominal surgery. However, the risk factors for POI after laparoscopic colorectal resection are unclear. We therefore investigated the risk factors for POI after laparoscopic colorectal surgery. METHODS: This retrospective study involved 484 patients who underwent laparoscopic surgery for primary colorectal cancer at Hokkaido University Hospital. We categorized the patients into a POI group (n = 19) and non-POI group (n = 465). We compared sex, age, smoking, chronic obstructive pulmonary disease (COPD), diabetes mellitus, body mass index (BMI), cardiac disorder, serum albumin, American Society of Anesthesiologists-physical status, tumor location, tumor stage, operative duration, stoma formation, lymph node dissection, operator, and bleeding as potential risk factors for POI between the POI group and non-POI group by univariate and multivariate analyses. RESULTS: The univariate analysis results showed that the POI group had a higher incidence of male sex (P = 0.036), COPD (P = 0.029), and a BMI of <20 kg/m2 (P = 0.0487) as well as a higher bleeding volume (P = 0.014). The multivariate analysis results showed that male sex (odds ratio [OR], 0.2799; 95% confidence interval [CI], 0.089-0.993; P = 0.0298), COPD (0.2866; 0.095-0.862; P = 0.0262), and a BMI of <20 kg/m2 (0.2985; 0.112-0.794; P = 0.0154) were independent risk factors for POI after laparoscopic colorectal resection. CONCLUSION: Our findings suggest that male sex, COPD, and a BMI of <20 kg/m2 are independent risk factors for POI after laparoscopic colorectal surgery for treatment of colorectal cancer.
• The impact of COVID-19 for postoperative outcomes using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer.

  Masashi Takeuchi, Hideki Endo, Taizo Hibi, Ryo Seishima, Yutaka Nakano, Hiroyuki Yamamoto, Hiroaki Miyata, Hiromichi Maeda, Kazuhiro Hanazaki, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Hideki Ueno, Masaki Mori, Yuko Kitagawa

  Annals of gastroenterological surgery 7 (6) 887 - 895 2023/11 [Refereed]
   

  BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had resulted in either failure to provide required medical resources or delayed treatment for gastric cancer patients. This study aimed to investigate the impact of COVID-19 on the incidence of postoperative complications using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer. METHODS: We collected the data of patients who underwent distal gastrectomy from January 2018 to December 2021 from the National Clinical Database (NCD), a web-based surgical registration system in Japan. The number of surgical cases, the use of intensive care units, and the incidence of morbidity per month were analyzed. We also calculated the standardized mortality ratio (SMR), defined as the ratio of the number of observed patients to the expected number of patients calculated using the risk calculator established in the NCD, for several morbidities, including pneumonia, sepsis, 30-day mortality, and surgical mortality. RESULTS: A decrease of 568 gastrectomies was observed from April 2020 to May 2020. Although the absolute number of patients admitted to intensive care units had declined since 2020, the proportion of patients admitted to the ICU did not change before and after the pandemic. Mortality and critical morbidity (such as pneumonia and sepsis) rates were not worse during the pandemic compared to pre-pandemic periods per the SMR. CONCLUSIONS: Surgical management was conducted adequately through the organized efforts of the entire surgery department in our country even in a pandemic during which medical resources and staff may have been limited.
• NCD/JCVSDの利活用推進のためのワークショップ(食道・心外) COVID-19パンデミックが日本の消化器領域癌手術に与えた影響 食道癌手術において

  竹内 優志, 遠藤 英樹, 日比 泰造, 清島 亮, 中野 容, 山本 博之, 宮田 裕章, 前田 広道, 花崎 和弘, 武冨 紹信, 掛地 吉弘, 瀬戸 泰之, 上野 秀樹, 森 正樹, 北川 雄光

  日本胸部外科学会定期学術集会 (一社)日本胸部外科学会 76回 NCD2 - 3 2023/10
• 【COVID-19のみならず!肝胆膵と感染症】肝胆膵診療での感染症各論 日常臨床における肝エキノコックス症

  相山 健, 柿坂 達彦, 折茂 達也, 長津 明久, 脇坂 和貴, 志智 俊介, 岡田 宏美, 武冨 紹信

  肝胆膵 (株)アークメディア 87 (3) 287 - 294 0389-4991 2023/09
• コロナが大腸肛門診療にもたらした影響-病院に及んだ影響,クリニックに及んだ影響- COVID-19感染拡大が及ぼした腹腔鏡下直腸癌手術への影響

  白下 英史, 遠藤 英樹, 猪股 雅史, 赤木 智徳, 山本 博之, 坂井 義治, 掛地 吉弘, 北川 雄光, 武冨 紹信, 森 正樹

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (9) A93 - A93 0047-1801 2023/09
• コロナが大腸肛門診療にもたらした影響-病院に及んだ影響,クリニックに及んだ影響- COVID-19感染拡大が及ぼした腹腔鏡下直腸癌手術への影響

  白下 英史, 遠藤 英樹, 猪股 雅史, 赤木 智徳, 山本 博之, 坂井 義治, 掛地 吉弘, 北川 雄光, 武冨 紹信, 森 正樹

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (9) A93 - A93 0047-1801 2023/09
• Lymphaticovenous anastomosis for treatment of refractory chylous ascites: A case report.

  Shoichi Tsuzaka, Takeshi Aiyama, Hirofumi Kamachi, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Taku Maeda, Toshiya Kamiyama, Akinobu Taketomi

  Microsurgery 43 (6) 606 - 610 2023/09 

  Chylous ascites, the leakage of lymphatic fluid into the abdominal cavity caused by lymphatic fluid stasis or lymphatic vessel damage, can be treated by lymphaticovenous anastomosis (LVA). We report rarely performed abdominal LVA to treat a case of refractory ascites possibly caused by ligation of the thoracic duct and pleurodesis in a man aged 60 years requiring weekly ascites drainage. Ligation was abandoned because the leakage site was not determined. The greater omentum (GO) was generally edematous and showed lymphatic effusion by gross appearance, and was considered suitable for LVA. We performed once LVA in the lymphatic vessels and veins of the GO using common microsurgical instrumentation and lateral anastomosis. Lymphatic vessels in the omentum were dilated to 2-3 mm, and LVA was simple. After LVA, GO edema improved. Postoperatively, the patient developed paralytic ileus, which improved within a few days, and the patient was discharged without any increase in ascites after starting to diet. One year post-surgery, there was no recurrence of ascites. LVA at the GO may be effective for the treatment of refractory chylous ascites because of its absorptive lymphatic draining capabilities and large transverse vessels.
• Preoperative mechanical bowel preparation using conventional versus hyperosmolar polyethylene glycol-electrolyte lavage solution before laparoscopic resection for colorectal cancer (TLUMP test): a phase III, multicenter randomized controlled non-inferiority trial.

  Tadashi Yoshida, Shigenori Homma, Nobuki Ichikawa, Yosuke Ohno, Yoichi Miyaoka, Hiroki Matsui, Ken Imaizumi, Hiroyuki Ishizu, Tohru Funakoshi, Masahiko Koike, Hirofumi Kon, Yo Kamiizumi, Yasuhiro Tani, Yoichi Minagawa Ito, Kazufumi Okada, Akinobu Taketomi

  Journal of gastroenterology 58 (9) 883 - 893 2023/09 

  BACKGROUND: A hyperosmolar ascorbic acid-enriched polyethylene glycol-electrolyte (ASC-PEG) lavage solution ensures excellent bowel preparation before colonoscopy; however, no study has demonstrated the efficacy of this lavage solution before surgery. This study aimed to establish the non-inferiority of ASC-PEG to the standard polyethylene glycol-electrolyte solution (PEG-ELS) in patients undergoing laparoscopic resection for colorectal cancer. METHODS: This was a prospective, single-blind, multicenter, randomized, controlled, non-inferiority clinical trial. Overall, 188 patients scheduled for laparoscopic colorectal resection for single colorectal adenocarcinomas were randomly assigned to undergo preparation with different PEG solutions between August 2017 and April 2020 at four hospitals in Japan. Participants received ASC-PEG (Group A) or PEG-ELS (Group B) preoperatively. The primary endpoint was the ratio of successful bowel preparations using the modified Aronchick scale, defined as "excellent" or "good." RESULTS: After exclusion, 86 and 87 patients in Groups A and B, respectively, completed the study, and their data were analyzed. ASC-PEG was not inferior to PEG-ELS in terms of effective bowel preparation prior to laparoscopic colorectal resection (0.93 vs. 0.92; 95% confidence interval, - 0.078 to 0.099, p = 0.007). The total volume of cleansing solution intake was lower in Group A than in Group B (1757.0 vs. 1970.1 mL). Two and three severe postoperative adverse events occurred in Groups A and B, respectively. Patient tolerance of the two solutions was almost equal. CONCLUSIONS: ASC-PEG is effective for preoperative bowel preparation in patients undergoing laparoscopic resection for colorectal cancer and is non-inferior to PEG-ELS.
• Early-stage sigmoid colon cancer resection followed by liver metastasis recurrence 1 year later and mesenteric recurrence more than 5 years later: a case report.

  Yumeto Mikuni, Michio Tani, Nobuki Ichikawa, Hiroki Matsui, Shin Emoto, Tadashi Yoshida, Takuya Otsuka, Shigenori Homma, Takahashi Norihiko, Akinobu Taketomi

  Surgical case reports 9 (1) 151 - 151 2023/08/31 

  BACKGROUND: Early-stage colorectal cancer (CRC) is often treated endoscopically, but additional surgical resection may be considered depending on pathological findings. CASE PRESENTATION: A 73-year-old man was found to have early-stage sigmoid colon cancer by colonoscopy during a medical examination, and endoscopic mucosal resection (EMR) was performed. The lesion was a 7-mm-sized sessile polyp, and the pathological diagnosis was well-differentiated tubular adenocarcinoma, pT1 (submucosal invasion of 400 μm), with no lymphovascular invasion, low budding grade, and negative horizontal and vertical margins. Therefore, the patient was observed without postoperative treatment. One year later, a computed tomography (CT) scan showed multiple liver metastases. After five courses of preoperative chemotherapy with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and panitumumab, liver metastases were reduced. The patient underwent extended right hepatic lobectomy. The pathological finding was well-to-moderately differentiated tubular adenocarcinoma, and immunohistochemistry findings were consistent with liver metastases from sigmoid colon cancer. Postoperatively, the patient received five courses adjuvant chemotherapy with FOLFOX. Although the patient had been recurrence-free for 5 years after liver resection, a CT scan revealed a nodular lesion in the sigmoid mesentery. Positron emission tomography (PET) showed abnormal accumulation in the same lesion. Therefore, the mesenteric nodules diagnosed as lymph metastasis and recurrence of sigmoid colon cancer and performed laparoscopic sigmoid colon resection with lymph node dissection. The pathological findings showed that the recurrent lesion in the mesentery formed a nodular infiltrate with venous, lymphatic, and neural invasion, but lymph node structures were not found, and it was assumed to be metastasis or recurrence due to lymphovascular invasion. The pathologic specimen of the sigmoid colon had no neoplastic lesions, which are considered to be a local recurrence on the mucosal surface. After sigmoid colectomy, adjuvant chemotherapy with CapeOX was conducted, and the patient has been recurrence-free for 13 months at present. CONCLUSION: Even early-stage CRCs that have no pathological indications for additional resection have risks of metastases and recurrences, and we may need to consider that the criteria for additional resection should not be limited to pathological findings alone.
• NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases.

  Shin Kobayashi, Hideaki Bando, Akinobu Taketomi, Takeshi Takamoto, Eiji Shinozaki, Manabu Shiozawa, Hiroki Hara, Kentaro Yamazaki, Koji Komori, Nobuhisa Matsuhashi, Takeshi Kato, Yoshinori Kagawa, Mitsuru Yokota, Eiji Oki, Keigo Komine, Shinichiro Takahashi, Masashi Wakabayashi, Takayuki Yoshino

  BMC cancer 23 (1) 779 - 779 2023/08/21 

  BACKGROUND: The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. METHODS: The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. DISCUSSION: The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. TRIAL REGISTRATION: jRCT2031220025, April. 16, 2022.
• Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-Cirrhotic Patients. A Multicentric Study of 44 International Expert Centers.

  Richard X Sousa Da Silva, Eva Breuer, Sadhana Shankar, Shoji Kawakatsu, Wacław Hołówko, João Santos Coelho, Heithem Jeddou, Teiichi Sugiura, Mohammed Ghallab, Doris Da Silva, Genki Watanabe, Florin Botea, Nozomu Sakai, Pietro F Addeo, Stylianos Tzedakis, Fabian Bartsch, Kaja Balcer, Chetana Lim, Fabien Werey, Victor López, Luciana Peralta Montero, Rodrigo Sanchez Claria, Jennifer Leiting, Neeta Vachharajani, Eve Hopping, Orlando J M Torres, Satoshi Hirano, Daan Andel, Jeroen Hagendoorn, Alicja Psica, Matteo Ravaioli, Keun S Ahn, Tim Reese, Leonardo Agustin Montes, Ganesh Gunasekaran, Cándido Alcázar, Jin H Lim, Muhammad Haroon, Qian Lu, Antonio Castaldi, Tatsuya Orimo, Beat Moeckli, Teresa Abadía, Luis Ruffolo, Josefina Dib Hasan, Francesca Ratti, Emmanuele F Kaufmann, Roeland de Wilde, Wojciech G Polak, Ugo Boggi, Luca Aldrighetti, Lucas McCormack, Roberto Hernandez-Alejandro, Alejandro Serrablo, Christian Toso, Akinobu Taketomi, Jean Gugenheim, Jiahong Dong, Faisal Hanif, Joon S Park, José M Ramia, Myron Schwartz, Diego Ramisch, Michelle De Oliveira, Karl J Oldhafer, Koo J Kang, Matteo Cescon, Peter Lodge, Inne H M Borel Rinkes, Takehiro Noji, John-Edwin Thomson, Su K Goh, William C Chapman, Sean P Cleary, Juan Pekolj, Jean-Marc Regimbeau, Olivier Scatton, Stéphanie Truant, Hauke Lang, David Fuks, Philippe Bachellier, Masayuki Otsuka, Irinel Popescu, Kiyoshi Hasegawa, Mickaël Lesurtel, René Adam, Daniel Cherqui, Katsuhiko Uesaka, Karim Boudjema, Hugo Pinto Marques, Micha Grąt, Henrik Petrowsky, Tomoki Ebata, Andreas Prachalias, Ricardo Robles-Campos, Pierre-Alain Clavien

  Annals of surgery 278 (5) 748 - 755 2023/07/19 

  OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a five-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant co-morbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1,4-8 or H4-8) disclosed higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cut-offs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation or novel chemotherapy regimens.
• 肝細胞癌におけるWntシグナル伝達経路受容体ROR2の発現についての検討

  脇坂 和貴, 志智 俊介, 相山 健, 長津 明久, 折茂 達也, 柿坂 達彦, 三橋 智子, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 78回 P100 - 6 2023/07
• 【肝胆膵外科手術における術中トラブルシューティング】肝臓 開腹肝切除における肝門操作時の門脈・肝動脈損傷への対処法

  長津 明久, 柿坂 達彦, 折茂 達也, 相山 健, 脇坂 和貴, 志智 俊介, 武冨 紹信

  外科 (株)南江堂 85 (8) 868 - 873 0016-593X 2023/07 

  ＜文献概要＞開腹肝切除における門脈・動脈損傷は肝胆膵外科医なら誰しも直面しうる場面であるが,出血性ショック・重症感染症・肝不全から時折致命的になる.損傷回避のために慎重な操作が求められるが,実際に損傷した場合,手術の進行度や視野,および損傷の形態や部位,程度により対応は異なる.出血時には早急なクランプなどによる損傷の拡大を避けて,ガーゼや用手的な圧迫止血で視野を確保した後,適切な修復を行うことが肝要である.
• Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

  Masashi Takeuchi, Hideki Endo, Taizo Hibi, Ryo Seishima, Yutaka Nakano, Hiroyuki Yamamoto, Hiroaki Miyata, Hiromichi Maeda, Kazuhiro Hanazaki, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Hideki Ueno, Masaki Mori, Yuko Kitagawa

  Esophagus : official journal of the Japan Esophageal Society 20 (4) 617 - 625 2023/06/22 

  BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.
• Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death.

  Sodai Sakamoto, Hiroki Bochimoto, Kengo Shibata, Nur Khatijah Mohd Zin, Moto Fukai, Kosei Nakamura, Takahisa Ishikawa, Masato Fujiyoshi, Tsuyoshi Shimamura, Akinobu Taketomi

  Journal of clinical medicine 12 (11) 2023/06/04 

  Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H+]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.
• 大腸がんの再発・転移におけるメトホルミンの抗腫瘍免疫に及ぼす効果

  木村 沙織, 本間 重紀, 白川 智沙斗, 中本 裕紀, 志智 俊介, 今泉 健, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 北村 秀光, 武冨 紹信

  日本がん免疫学会総会プログラム・抄録集 日本がん免疫学会 27回 105 - 105 2023/06
• Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen Gas Treatment Reduces Ischemia-Reperfusion Injury in Rat Livers.

  Moto Fukai, Sodai Sakamoto, Kengo Shibata, Masato Fujiyoshi, Sunao Fujiyoshi, Hiroki Bochimoto, Takahisa Ishikawa, Shingo Shimada, Kosei Nakamura, Norio Kawamura, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 55 (4) 1027 - 1031 2023/05 

  We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and a subsequent 90-minute reperfusion in an isolated perfused rat liver system. The experimental groups were the immediately reperfused control group (CT), the CS with University of Wisconsin solution (UW) group, the CS with Dsol group, the CS with UW and post-reperfusion H2 treatment group (UW-H2), and the CS with Dsol and post-reperfusion H2 group (Dsol-H2). We first compared the Dsol-H2, UW, and CT groups to evaluate this alternative method to conventional CS. The protective potential of the Dsol-H2 group was superior to that of the UW group, as evidenced by lower portal venous resistance and lactate dehydrogenase leakage, a higher oxygen consumption rate, and increased bile production. Multiple comparison tests among the UW, Dsol, UW-H2, and Dsol-H2 groups revealed that both treatments, during CS and after reperfusion, conferred a similar extent of protection and showed additive effects in combination therapy. Furthermore, the variance in all treatment groups appeared smaller than that in the no-treatment or no-stress groups, with excellent reproducibility. In conclusion, combination therapy with Dsol during CS and hydrogen gas after reperfusion additively protects against graft injury.
• 当施設における肝移植後de novo腫瘍の検討

  太田 拓児, 後藤 了一, 原田 拓弥, 川村 典生, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科系連合学会誌 日本外科系連合学会 48 (3) 424 - 424 0385-7883 2023/05
• ハイリスク症例に対する術前リスク評価の重要性 ハイリスク高齢者直腸癌症例に対する術式選択

  吉田 雅, 本間 重紀, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本外科系連合学会誌 日本外科系連合学会 48 (3) 318 - 318 0385-7883 2023/05
• 腸管切除後出血のリスク因子の検討

  藤好 直, 本間 重紀, 吉田 雅, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本外科系連合学会誌 日本外科系連合学会 48 (3) 427 - 427 0385-7883 2023/05
• 大腸憩室に対する姑息的人工肛門造設術の検討

  柴田 賢吾, 松井 博紀, 藤好 直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科系連合学会誌 日本外科系連合学会 48 (3) 436 - 436 0385-7883 2023/05
• Warm Ischemia Induces Spatiotemporal Changes in Lysophosphatidylinositol That Affect Post-Reperfusion Injury in Normal and Steatotic Rat Livers.

  Kengo Shibata, Takahiro Hayasaka, Sodai Sakamoto, Satsuki Hashimoto, Norio Kawamura, Masato Fujiyoshi, Taichi Kimura, Tsuyoshi Shimamura, Moto Fukai, Akinobu Taketomi

  Journal of clinical medicine 12 (9) 2023/04/27 

  Warm ischemia-reperfusion injury is a prognostic factor for hepatectomy and liver transplantation. However, its underlying molecular mechanisms are unknown. This study aimed to elucidate these mechanisms and identify the predictive markers of post-reperfusion injury. Rats with normal livers were subjected to 70% hepatic warm ischemia for 15, 30, or 90 min, while those with steatotic livers were subjected to 70% hepatic warm ischemia for only 30 min. The liver and blood were sampled at the end of ischemia and 1, 6, and 24 h after reperfusion. The serum alanine aminotransferase (ALT) activity, Suzuki injury scores, and lipid peroxidation (LPO) products were evaluated. The ALT activity and Suzuki scores increased with ischemic duration and peaked at 1 and 6 h after reperfusion, respectively. Steatotic livers subjected to 30 min ischemia and normal livers subjected to 90 min ischemia showed comparable injury. A similar trend was observed for LPO products. Imaging mass spectrometry of normal livers revealed an increase in lysophosphatidylinositol (LPI (18:0)) and a concomitant decrease in phosphatidylinositol (PI (18:0/20:4)) in Zone 1 (central venous region) with increasing ischemic duration; they returned to their basal values after reperfusion. Similar changes were observed in steatotic livers. Hepatic warm ischemia time-dependent acceleration of PI (18:0/20:4) to LPI (18:0) conversion occurs initially in Zone 1 and is more pronounced in fatty livers. Thus, the LPI (18:0)/PI (18:0/20:4) ratio is a potential predictor of post-reperfusion injury.
• Rapid and Reliable Steatosis Rat Model Shrsp5-Dmcr for Cold Storage Experiment.

  Moto Fukai, Hiroyuki Sugimori, Sodai Sakamoto, Kengo Shibata, Hiroyuki Kameda, Takahisa Ishikawa, Norio Kawamura, Masato Fujiyoshi, Sunao Fujiyoshi, Kohsuke Kudo, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 55 (4) 1032 - 1035 2023/04/10 

  Interventions for liver grafts with moderate macrovesicular steatosis have been important in enlarging donor pools. Here, we tested a high-fat and cholesterol (HFC) diet to create a steatosis model for cold hepatic preservation and reperfusion experiments. The aim of the present study was to assess the steatosis model's reliability and to show the resulting graft's quality for cold preservation and reperfusion experiment. Male SHRSP5-Dmcr rats were raised with an HFC diet for up to 2 weeks. The fat content was evaluated using magnetic resonance imaging (MRI) proton density fat fraction (PDFF). The nonalcoholic fatty liver disease activity score (NAS) was evaluated after excision. Steatosis created by 2 weeks of HFC diet was subjected to 24-hour cold storage in the University of Wisconsin and the original test solution (new sol.). Grafts were applied to isolated perfused rat livers for simulating reperfusion. The NAS were 2.2 (HFC 5 days), 3.3 (HFC 1 week), and 5.0 (HFC 2 weeks). Ballooning and fibrosis were not observed in any group. An MRI-PDFF showed 0.2 (HFC 0 days), 12.0 (HFC 1 week), and 18.9 (HFC 2 weeks). The NAS and MRI-PDFF values correlated. Many indices in the isolated perfused rat liver experiment tended to improve in the new sol. group but were insufficient. Although the new sol. failed to be effective, it acted at multiple sites under difficult conditions. In conclusion, the HFC diet for 2 weeks in SHRSP5-Dmcr rats, together with MRI-PDFF evaluation, is a reliable method for creating simple steatosis and provides good-quality cold preservation and reperfusion experiments.
• 肝移植をめぐる諸問題 当院における肝移植後de novo非アルコール性脂肪性肝疾患(NAFLD)の検討

  後藤 了一, 嶋村 剛, 武冨 紹信

  肝臓 (一社)日本肝臓学会 64 (Suppl.1) A189 - A189 0451-4203 2023/04
• 肝切除術後の門脈血栓症に対する治療の検討

  脇坂 和貴, 相山 健, 長津 明久, 折茂 達也, 柿坂 達彦, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 4 2023/04
• 生体肝移植後の胆管空腸吻合合併症に対するバルーン補助下消化管内視鏡を用いた治療

  渡辺 正明, 嶋村 剛, 後藤 了一, 川村 典生, 太田 拓児, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 6 2023/04
• 当施設における肝移植後de novo腫瘍の検討

  太田 拓児, 後藤 了一, 原田 拓弥, 川村 典生, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 5 2023/04
• マウス心移植モデルにおける冷阻血中インフラマソーム阻害がグラフト生存期間に与える影響

  原田 拓弥, 後藤 了一, Agustina Forgioni, 太田 拓児, 巖築 慶一, 渡辺 正明, 川村 典生, 深井 原, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 2 2023/04
• 肝移植後の急性拒絶反応によるグラフト不全から回復した移植前腎障害合併の2例

  磯川 真里奈, 後藤 了一, 太田 拓児, 川村 典生, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 RS - 12 2023/04
• 肺MAC症を併発したWilson病による非代償性肝硬変,肝細胞癌合併症例に対し,脳死肝移植を施行した1例

  谷口 広樹, 渡辺 正明, 嶋村 剛, 後藤 了一, 川村 典生, 太田 拓児, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 RS - 1 2023/04
• 大腸手術における合併症軽減・術後臓器機能温存やQOL低下防止のための工夫 腹腔鏡下大腸手術前処置における腸管洗浄剤の有効性と安全性に関する多施設ランダム化比較試験

  吉田 雅, 本間 重紀, 市川 伸樹, 石津 寛之, 舩越 徹, 小池 雅彦, 今 裕史, 上泉 洋, 谷 安弘, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 WS - 1 2023/04
• 線維性癌間質反応による大腸癌術後補助化学療法の適正化

  八木 駿, 松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 SF - 7 2023/04
• 大腸がんの再発転移におけるメトホルミンの免疫学的作用メカニズムの解明

  木村 沙織, 本間 重紀, 白川 智沙斗, 中本 裕紀, 志智 俊介, 松井 博紀, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 北村 秀光, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 SF - 3[Y] 2023/04
• Klintrup gradeに基づいた大腸癌内視鏡的切除術後の外科的追加切除

  松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 1 2023/04
• 低侵襲手術時代の開腹手術の教育

  本間 重紀, 松井 博紀, 柴田 賢吾, 藤好 直, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 4 2023/04
• 腹腔鏡下大腸癌手術において,COPD既往は術後麻痺性イレウスのリスク因子となる

  藤好 直, 本間 重紀, 吉田 雅, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 2 2023/04
• 直腸癌手術におけるICG蛍光法を用いた吻合部血流評価法について

  柴田 賢吾, 本間 重紀, 松井 博紀, 藤好 直, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 DP - 7 2023/04
• 術前に診断しえた小網裂孔ヘルニアの1例

  別所 光, 柴田 賢吾, 松井 博紀, 藤好 直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 RS - 3 2023/04
• 新型コロナウイルス感染をきっかけに増悪し大腸亜全摘に至った潰瘍性大腸炎の一例

  長安 健, 藤好 直, 本間 重紀, 市川 伸樹, 吉田 雅, 柴田 賢吾, 松井 博紀, 八木 駿, 武冨 紹信, 中久保 祥, 畑中 佳奈子

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 123回 RS - 3 2023/04
• Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers but Fails to Restore Organ Function.

  Moto Fukai, Sodai Sakamoto, Hiroki Bochimoto, Nur Khatijah Mohd Zin, Kengo Shibata, Takahisa Ishikawa, Shingo Shimada, Norio Kawamura, Masato Fujiyoshi, Sunao Fujiyoshi, Kosei Nakamura, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation proceedings 55 (4) 1016 - 1020 2023/03/20 

  BACKGROUND: We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H2 gas. METHODS: Liver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H2 gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated. RESULTS: Portal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H2 groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H2 treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H2 group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H2 group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H2 groups. CONCLUSIONS: In conclusion, HMP and H2 gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.
• 急性肝不全の病態と治療～基礎・臨床の観点から～ 当院における急性肝不全に対する肝移植

  後藤 了一, 川村 典生, 渡辺 正明, 巖築 慶一, 嶋村 剛, 武冨 紹信

  肝臓 (一社)日本肝臓学会 64 (3) 168 - 168 0451-4203 2023/03
• 高齢潰瘍性大腸炎に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 120 (臨増総会) A339 - A339 0446-6586 2023/03
• The clinical impact of COVID‐19 on endoscopic surgery in Japan: Analysis of data from the National Clinical Database

  Hidefumi Shiroshita, Hideki Endo, Masafumi Inomata, Tomonori Akagi, Hiroyuki Yamamoto, Shigeki Yamaguchi, Susumu Eguchi, Norihito Wada, Yukinori Kurokawa, Yosuke Seki, Yoshiharu Sakai, Hiroaki Miyata, Yoshihiro Kakeji, Yuko Kitagawa, Akinobu Taketomi, Masaki Mori

  Annals of Gastroenterological Surgery 7 (4) 572 - 582 2475-0328 2023/02/15 [Refereed][Not invited]
   

  AIM: This study aimed to evaluate the impact of the coronavirus disease (COVID-19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database. METHODS: We retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups. RESULTS: In 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot-assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020. CONCLUSION: The number of endoscopic surgeries decreased in 2020 as a result of the COVID-19 pandemic. However, the procedures were performed safely in Japan.
• Long‐term risk of a fatty liver in liver donors

  Ryoichi Goto, Norio Kawamura, Masaaki Watanabe, Yoshikazu Ganchiku, Akihisa Nagatsu, Kazufumi Okada, Yoichi M. Ito, Toshiya Kamiyama, Tsuyoshi Shimamura, Akinobu Taketomi

  Annals of Gastroenterological Surgery 7 (4) 645 - 653 2475-0328 2023/02/02 

  AIM: Approximately 30 years have passed since the first experience of living donor liver transplantation. The time to evaluate the long-term safety of living donors has been fulfilled. Meanwhile, nonalcoholic fatty liver disease is increasingly common and a critical problem. The aim of this study was to evaluate the safety of living donor, focusing on fatty liver postdonation hepatectomy. METHODS: Living donors (n = 212, 1997-2019) were evaluated by computed tomography (CT) at >1-year postdonation. A liver to spleen (L/S) ratio of <1.1 was defined as fatty liver. RESULTS: Among 212 living liver donors, 30 (14.2%) detected fatty liver at 5.3 ± 4.2 years postdonation. The cumulative incidence rates of fatty liver were 3.1%, 12.1%, 22.1%, and 27.7% at 2, 5, 10, and 15 years postdonation, respectively. Of 30 subjects who developed fatty liver, 18 (60%) displayed a severe steatosis (L/S ratio <0.9). Five (16.7%) had a prior history of excessive alcohol abuse. More than 30% developed metabolic syndrome including obesity, hyperlipidemia, and diabetes. Although six (20%) had a Fib-4 index of >1.3, which included a case with a Fib-4 index of >2.67, no significant increased Fib-4 index was observed in the subjects with fatty liver as compared to those without fatty liver (p = 0.66). The independent predictive risk factors for developing fatty liver were male sex, pediatric recipient, and higher body mass index (>25) at donation. CONCLUSION: Living donors with risk factors for developing fatty liver should be carefully followed-up for the prevention and management of metabolic syndrome.
• ステージII大腸癌における脈管侵襲の再発に与える影響の検討

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (2) 193 - 193 0047-1801 2023/02
• 直腸癌におけるCTによる側方リンパ節転移予測の検討

  江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (2) 204 - 204 0047-1801 2023/02
• 直腸切断術におけるTpTME導入成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (2) 208 - 208 0047-1801 2023/02
• 直腸癌術前放射線化学療法施行例における内視鏡的完全奏功所見の検討

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 松井 博紀, 柴田 賢吾, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (2) 226 - 226 0047-1801 2023/02
• 新型コロナウイルス感染を契機に増悪し大腸亜全摘を施行した潰瘍性大腸炎の1例

  藤好 直, 本間 重紀, 吉田 雅, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (2) 252 - 252 0047-1801 2023/02
• IFN‐γ‐STAT1 ‐mediated NK2R expression is involved in the induction of antitumor effector CD8 ⁺ T cells in vivo

  Weidong Shen, Xiangdong Wang, Huihui Xiang, Shunsuke Shichi, Hiroki Nakamoto, Saori Kimura, Ko Sugiyama, Akinobu Taketomi, Hidemitsu Kitamura

  Cancer Science 114 (5) 1816 - 1829 1347-9032 2023/01/30 

  The induction of antitumor effector T cells in the tumor microenvironment is a crucial event for cancer immunotherapy. Neurokinin receptor 2 (NK2R), a G protein-coupled receptor for neurokinin A (NKA), regulates diverse physiological functions. However, the precise role of NKA-NK2R signaling in antitumor immunity is unclear. Here, we found that an IFN-γ-STAT1 cascade augmented NK2R expression in CD8+ T cells, and NK2R-mediated NKA signaling was involved in inducing antitumor effector T cells in vivo. The administration of a synthetic analog of double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C), into a liver cancer mouse model induced type I and type II IFNs and significantly suppressed the tumorigenesis of Hepa1-6 liver cancer cells in a STAT1-dependent manner. The reduction in tumor growth was diminished by the depletion of CD8+ T cells. IFN-γ stimulation significantly induced NK2R and tachykinin precursor 1 (encodes NKA) gene expression in CD8+ T cells. NKA stimulation combined with anti-CD3 monoclonal antibody (mAb) treatment significantly augmented IFN-γ and granzyme B production by CD8+ T cells compared with the anti-CD3 mAb alone in vitro. ERK1/2 phosphorylation and IκBα degradation in activated CD8+ T cells were suppressed under NK2R deficiency. Finally, we confirmed that tumor growth was significantly increased in NK2R-deficient mice compared with that in wild-type mice, and the antitumor effects of poly I:C were abolished by NK2R absence. These findings suggest that IFN-γ-STAT1-mediated NK2R expression is involved in the induction of antitumor effector T cells in the tumor microenvironment, which contributes to the suppression of cancer cell tumorigenesis in vivo. In this study, we revealed that IFN-γ-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8+ T cells in the tumor microenvironment, which contributes to suppressing the tumorigenesis of liver cancer cells in vivo.
• Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells

  Xiangdong Wang, Huihui Xiang, Yujiro Toyoshima, Weidong Shen, Shunsuke Shichi, Hiroki Nakamoto, Saori Kimura, Ko Sugiyama, Shigenori Homma, Yohei Miyagi, Akinobu Taketomi, Hidemitsu Kitamura

  Cancer & Metabolism 11 (1) 1 - 1 2023/01/13 [Refereed]
   

  Abstract Background Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. Methods We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo. Living cell numbers and migration ability of CT26 cells were evaluated in the presence of ARG inhibitor in vitro. Results Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular l-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. Conclusion Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy.
• Solid pseudopapillary neoplasm of the pancreas after living-donor liver transplantation

  Shoichi Tsuzaka, Norio Kawamura, Takuya Harada, Takuji Ota, Yoshikazu Ganchiku, Masaaki Watanabe, Ryoichi Goto, Hirofumi Kamachi, Toshiya Kamiyama, Tsuyoshi Shimamura, Nanase Okazaki, Tomoko Mitsuhashi, Akinobu Taketomi

  Journal of Pediatric Surgery Case Reports 88 2023/01 

  Background: Solid pseudopapillary neoplasm of the pancreas has been classified by the World Health Organization as a low-grade malignant tumor with potential to metastasize. The standard treatment for this neoplasm is complete surgical resection. However, it is not always feasible to perform a complex procedure such as pancreaticoduodenectomy or distal pancreatectomy, especially for patients with a history of hepato-biliary-pancreatic surgery. In such cases, the treatment strategy must consider the patient's postoperative quality of life. We herein report a case of solid pseudopapillary neoplasm of the pancreas following living-donor liver transplantation. Case presentation: The patient was a 13-year-old girl who had undergone the Kasai procedure for biliary atresia at 140 days of age. She thereafter underwent living-donor liver transplantation because of recurrent cholangitis and progressive jaundice. Her repeated history of cholangitis had caused narrowing of the portal vein. Therefore, the portal vein was reconstructed using the donor's ovarian vein as an interposition graft. At 13 years of age, a mass was identified at the head of the pancreas. Biopsy was performed and the patient was diagnosed with solid pseudopapillary neoplasm of the pancreas. Surgical resection was planned, and three options were considered: pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, and enucleation. Considering the complications associated with radical surgery, tumor enucleation was performed. The patient developed a postoperative pancreatic fistula that required prolonged fasting and drainage. She began a low-fat diet on postoperative day 15. Because the pancreatic fistula was well controlled with a low-fat diet, the patient was discharged on postoperative day 51 after she and her parents had received dietary guidance. At the time of this writing, 1 year had passed since the enucleation with no evidence of recurrence. Conclusions: We have herein reported a case of solid pseudopapillary neoplasm of the pancreas after living-donor liver transplantation. Although a radical operation such as pancreaticoduodenectomy or distal pancreatectomy is preferable from an oncological perspective, enucleation should be considered for patients with high surgical risk.
• Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation.

  Ryoichi Goto, Yasutomo Fukasaku, Yoshikazu Ganchiku, Norio Kawamura, Masaaki Watanabe, Takuji Ota, Kanako C Hatanaka, Tomomi Suzuki, Tsuyoshi Shimamura, Akinobu Taketomi

  Frontiers in pediatrics 11 1172516 - 1172516 2023 

  The roles of post-transplant anti-HLA donor specific antibody (DSA) in pediatric liver transplantation (LT), including therapeutic strategies, remain controversial. This study aimed to identify the risks of post-transplant DSA for graft fibrosis progression in pediatric living donor LT (LDLT). We retrospectively evaluated 88 LDLT pediatric cases between December 1995 and November 2019. DSAs were assessed with single antigen bead test. Graft fibrosis was histopathologically scored with METAVIR and the centrilobular sinusoidal fibrosis system. Post-transplant DSAs were detected in 37 (52.9%) cases at 10.8 (1.3-26.9) years post-LDLT. The histopathological examination of 32 pediatric cases with post-transplant DSA revealed that 7 (21.9%) with a high DSA-MFI (≥9,378) showed graft fibrosis progression (≥F2). No graft fibrosis was observed in the subjects with a low DSA-MFI. The risk factors for developing graft fibrosis in pediatric cases with post-transplant DSA were an older graft age (>46.5 years old), lower platelet count (<10.7 × 104/ml) and higher Fib4 index (>0.7807, recipient age; >1.8952, donor age). Limited efficacy of additional immunosuppressants was observed in DSA positive pediatric cases. In conclusion, pediatric cases with a high DSA-MFI and risk factors should undergo a histological examination. The appropriate treatment for post-transplant DSA in pediatric LT needs to be determined.
• 局所進行直腸癌における術前FOLFOX療法の長期成績における有効性

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 宮岡 陽一, 舩越 徹, 大野 陽介, 腰塚 靖之, 赤羽 弘充, 服部 優宏, 佐藤 正法, 大森 一吉, 野村 克, 横田 良一, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (1) 59 - 59 0047-1801 2023/01
• 潰瘍性大腸炎合併colitic cancerに対する腹腔鏡下大腸全摘術の手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (1) 77 - 77 0047-1801 2023/01
• 当科におけるロボット支援下手術の初期成績

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 大野 陽介, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (1) 84 - 84 0047-1801 2023/01
• SM大腸癌の手術成績の検討

  江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (1) 94 - 94 0047-1801 2023/01
• 進行結腸癌肥満症例に対する腹腔鏡下手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 76 (1) 97 - 97 0047-1801 2023/01
• 人工甘味料の多量摂取が原因と考えられた直腸癌術後回腸ストマからのhigh output症候群の1例

  竹元 小乃美, 江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 高桑 恵美, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 56 (1) 20 - 26 0386-9768 2023/01 

  症例は57歳の男性で,1年前からの便通異常を主訴に前医を受診した.直腸癌多発肝転移肺転移と診断され,当科で腹腔鏡下低位前方切除術を施行したが,air leak test陽性のため双孔式回腸ストマを造設した.術後10日目より回腸瘻からの排便量が1日2,000ml以上となった.止痢薬は奏効しなかったが,術後20日目キシリトール含有の飴を1日12個(キシリトール15.5g)摂取していたことが判明し,摂取を中止すると回腸瘻からの排便量が1日300～500ml程度に改善した.キシリトールは人工甘味料の一つで,飴やガムなどに幅広く使用されている.キシリトールには腸管から吸収されにくい性質があり,多量摂取により下痢を誘発することが報告されている.回腸人工肛門造設状態の患者において,人工甘味料がhigh output症候群の原因なりうる可能性を念頭に置く必要がある.(著者抄録)
• Effect of Continuous Box-trainer Training on Laparoscopic Skills of Surgical Residents: A Prospective, Observational Study.

  Ken Imaizumi, Nobuki Ichikawa, Shigenori Homma, Keiichiro Yamamoto, Chihiro Ishizuka, Ryo Takahashi, Takumu Fukasawa, Takumi Hamada, Kazuya Hamada, Hiroki Matsui, Yoichi Miyaoka, Tadashi Yoshida, Akinobu Taketomi

  In vivo (Athens, Greece) 37 (1) 476 - 482 2023 

  BACKGROUND/AIM: As opportunities for hands-on surgical training during residency have decreased, off-the-job training before surgery is gaining importance. We developed a training program using a box-trainer for surgical residents. This study aimed to verify the effectiveness of the program. Using task-achievement time, we demonstrated the learning curve through continuous task training and verified the efficiency of our training tasks. In addition, we examined the circularity of the cut circle to evaluate the task accuracy and summarized the questionnaire results. PATIENTS AND METHODS: A prospective, observational study was conducted at a single center with five trainees from April 2019 to March 2020. The training consisted of four tasks based on the Fundamentals of Laparoscopic Surgery module. The trainees had to achieve expert proficiency time targets. The task-achievement time and circularity of the cut circle were used for objective assessment; subjective evaluation was done using a questionnaire. RESULTS: Although the learning curves of the task-achievement time seemed to reach a plateau between the third and the fifth skills lab, all the trainees achieved expert proficiency times for the three tasks. Circularity of the cut circle tended to be more accurate after training. All trainees perceived an improvement in their skills after the training program. The level of satisfaction of the training program was rated as 'very satisfied' or 'satisfied'. CONCLUSION: Continuous box-trainer training for 1 year may be effective for improvement in preoperative laparoscopic surgical skills of surgical residents.
• Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.

  Junko Kuramoto, Eri Arai, Mao Fujimoto, Ying Tian, Yuriko Yamada, Takuya Yotani, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Moto Fukai, Yosuke Seki, Kazunori Kasama, Nobuaki Funahashi, Haruhide Udagawa, Takao Nammo, Kazuki Yasuda, Akinobu Taketomi, Tatsuya Kanto, Yae Kanai

  Clinical epigenetics 14 (1) 168 - 168 2022/12/05 

  BACKGROUND: In recent years, non-alcoholic steatohepatitis (NASH) has become the main cause of hepatocellular carcinoma (HCC). As a means of improving the treatment of NASH-related HCCs based on early detection, this study investigated the feasibility of carcinogenic risk estimation in patients with NASH. RESULTS: Normal liver tissue (NLT), non-cancerous liver tissue showing histological findings compatible with non-alcoholic fatty liver from patients without HCC (NAFL-O), non-cancerous liver tissue showing NASH from patients without HCC (NASH-O), non-cancerous liver tissue showing non-alcoholic fatty liver from patients with HCC (NAFL-W), non-cancerous liver tissue showing NASH from patients with HCC (NASH-W) and NASH-related HCC were analyzed. An initial cohort of 171 tissue samples and a validation cohort of 55 tissue samples were used. Genome-wide DNA methylation screening using the Infinium HumanMethylation450 BeadChip and DNA methylation quantification using high-performance liquid chromatography (HPLC) with a newly developed anion-exchange column were performed. Based on the Infinium assay, 4050 CpG sites showed alterations of DNA methylation in NASH-W samples relative to NLT samples. Such alterations at the precancerous NASH stage were inherited by or strengthened in HCC samples. Receiver operating characteristic curve analysis identified 415 CpG sites discriminating NASH-W from NLT samples with area under the curve values of more than 0.95. Among them, we focused on 21 CpG sites showing more than 85% specificity, even for discrimination of NASH-W from NASH-O samples. The DNA methylation status of these 21 CpG sites was able to predict the coincidence of HCC independently from histopathological findings such as ballooning and fibrosis stage. The methylation status of 5 candidate marker CpG sites was assessed using a HPLC-based system, and for 3 of them sufficient sensitivity and specificity were successfully validated in the validation cohort. By combining these 3 CpG sites including the ZC3H3 gene, NAFL-W and NASH-W samples from which HCCs had already arisen were confirmed to show carcinogenic risk with 95% sensitivity in the validation cohort. CONCLUSIONS: After a further prospective validation study using a larger cohort, carcinogenic risk estimation in liver biopsy specimens of patients with NASH may become clinically applicable using this HPLC-based system for quantification of DNA methylation.
• ASO Author Reflections: Hepatectomy for Multiple Hepatocellular Carcinomas.

  Tatsuya Orimo, Toshiya Kamiyama, Akinobu Taketomi

  Annals of surgical oncology 29 (13) 8446 - 8447 2022/12
• 若年発症の急性肝不全型Wilson病に対し待機的に脳死肝移植を施行した1例

  和久井 洋佑, 後藤 了一, 渡辺 正明, 川村 典生, 小川 浩司, 三橋 智子, 嶋村 剛, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 119 (12) 1096 - 1102 0446-6586 2022/12 

  症例は15歳女性.黄疸を主訴に近医受診し,急性肝不全型Wilson病(T-bil9.2mg/dl,PT41.3%)と診断され,MELD25点で脳死待機リストへ登録した.当初緊急の肝移植が必要な状況であったが,急性期の集学的治療により待機中の状態を維持しえた.待機期間18ヵ月で脳死ドナー発生,脳死肝移植を施行した.脳死ドナーの発生が少ない本邦においては,特に長期待機可能な全身管理が重要である.(著者抄録)
• 肝移植後の急性拒絶反応によるグラフト不全から回復した2例

  磯川 真里奈, 後藤 了一, 太田 拓児, 武冨 紹信, 川村 典生, 渡辺 正明, 嶋村 剛

  北海道外科雑誌 北海道外科学会 67 (2) 183 - 184 0288-7509 2022/12
• 日本内視鏡外科学会技術認定取得医によるロボット支援下直腸癌切除成績の時系列変化

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 27 (7) 1341 - 1341 1344-6703 2022/12
• 腹腔鏡下大腸癌手術において、COPD既往は術後腸管麻痺症のリスク因子となる

  藤好 直, 本間 重紀, 吉田 雅, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 27 (7) 1739 - 1739 1344-6703 2022/12
• 術前化学放射線療法後直腸癌のロボット支援下手術における骨盤MRIの有用性

  松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 27 (7) 2445 - 2445 1344-6703 2022/12
• 潰瘍性大腸炎合併colitic cancerに対する鏡視下大腸全摘術

  吉田 雅, 本間 重紀, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 27 (7) 2973 - 2973 1344-6703 2022/12
• serrated polyposis syndromeを背景とした進行性大腸癌の1例

  棟方 裕貴, 藤好 直, 本間 重紀, 吉田 雅, 市川 伸樹, 柴田 賢吾, 松井 博紀, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (12) 2121 - 2121 1345-2843 2022/12
• 線維性癌間質反応による大腸癌術後補助化学療法の適正化

  八木 駿, 松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 藤好 直, 柴田 賢吾, 武富 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (12) 2122 - 2122 1345-2843 2022/12
• 術前に診断しえた小網裂孔ヘルニアの1例

  別所 光, 柴田 賢吾, 松井 博紀, 藤好 直, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  北海道外科雑誌 北海道外科学会 67 (2) 175 - 175 0288-7509 2022/12
• 新型コロナウイルス感染を契機に増悪し大腸亜全摘を施行した潰瘍性大腸炎の1例

  長安 健, 藤好 直, 本間 重紀, 市川 伸樹, 吉田 雅, 柴田 賢吾, 松井 博紀, 八木 駿, 武冨 紹信

  北海道外科雑誌 北海道外科学会 67 (2) 186 - 186 0288-7509 2022/12
• Effects of the COVID‐19 pandemic on gastroenterological surgeries in 2020: A study using the National Clinical Database of Japan

  Hiromichi Maeda, Hideki Endo, Hiroyuki Yamamoto, Hiroaki Miyata, Masaya Munekage, Akinobu Taketomi, Yoshihiro Kakeji, Yasuyuki Seto, Kazuhiro Yoshida, Hiroki Yamaue, Masakazu Yamamoto, Yuko Kitagawa, Mori Masaki, Kazuhiro Hanazaki

  Annals of Gastroenterological Surgery 7 (3) 407 - 418 2022/11/18 [Refereed]
   

  AIM: This study aimed to investigate the effect of the coronavirus disease pandemic on the number of surgeries for gastroenterological cancer cases in Japan. METHODS: The data recorded in the National Clinical Database of Japan between 2018 and 2020 were utilized for this study. Five specific surgeries for primary cancers and surgery for acute diffuse peritonitis were considered the primary endpoints. We divided the study period into the prepandemic and postpandemic (after April 2020) periods and examined the number of surgeries in relation to clinical factors. RESULTS: Overall, 228 860 surgeries were analyzed. Among the five primary cancer surgeries, the number of distal gastrectomies for gastric cancer decreased the most (to 81.0% of the monthly number in the prepandemic period), followed by that of low anterior resections for rectal cancer (91.4%). In contrast, the number of pancreaticoduodenectomies for pancreatic cancer increased by 7.1%, while that of surgeries for peritonitis remained stable. This trend was observed nationwide. We also noted a marked reduction in the number of distal gastrectomy (to 72.5%), low anterior resection (84.0%), and esophagectomy (88.8%) procedures for T1 tumors. The noncurative resection rate and mortalities were low despite the increased proportion of T4 tumors and older patients. CONCLUSION: A marked reduction in surgeries for gastric and rectal cancers with early T factors may reflect prioritization of surgeries and reduction in cancer screenings. Although the quality of the surgery was maintained in terms of reduced mortalities and morbidities, the long-term effects of this pandemic should be monitored.
• Interischial Spine Distance Is a Simple Index of the Narrow Pelvis That Can Predict Difficulty During Laparoscopic Low Anterior Resection.

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Shin Emoto, Ken Imaizumi, Hiroki Matsui, Michio Tani, Yoichi Miyaoka, Akinobu Taketomi

  Surgical laparoscopy, endoscopy & percutaneous techniques 32 (6) 666 - 672 2022/10/11 

  BACKGROUND: A narrow pelvis makes laparoscopic rectal resection difficult. This study aimed to evaluate whether a simple measurement on computed tomography can predict procedural difficulty. METHODS: A total of 62 patients with low rectal cancer underwent conventional laparoscopic low anterior resection. The interischial spine (IS) distance (ie, the distance between the ischial spines) was measured on an axial computed tomography slice. The operative time, blood loss, and time from the insertion of linear staplers to completion of clamping on the distal end of the rectum (clamp time) were compared between patients with narrow or wide pelvises. RESULTS: Overall, 42 men and 20 women with low rectal cancer were assessed. The mean tumor size was 34.5 mm. Total or tumor-specific mesorectal excisions were performed in all cases; high ligation and resection of the inferior mesenteric arteries were carried out in 92% of patients. The mean operative time and blood loss were 206 minutes and 15 mL, respectively. Four patients (6.5%) experienced postoperative complications, including 2 anastomotic leaks (3.2%). The mean IS distance was 93.3 mm. In simple linear regression analysis, a shorter IS distance correlated with a longer operative time (R2=0.08, P=0.030) and the clamp time (R2=0.07, P=0.046). Using a receiver operating characteristic curve, a narrow pelvis was defined as an IS distance <94.7 mm. Multivariate regression analysis revealed that an IS distance <94.7 mm (odds ratio: 3.51; P=0.04) was independently associated with a longer clamp time. CONCLUSIONS: The IS distance is a simple and useful measurement for predicting the difficulty of laparoscopic low anterior resection.
• 肝切除におけるナビゲーション 3次元画像解析システムを応用した肝切除

  折茂 達也, 柿坂 達彦, 長津 明久, 相山 健, 脇坂 和貴, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (増刊) S170 - S170 1345-2843 2022/10
• 新型コロナウイルス感染蔓延下での長期待機後に脳死肝腎同時移植を実施した末期原発性硬化性胆管炎の1例

  植林 毅行, 後藤 了一, 山口 将功, 伊藤 啓一郎, 津坂 翔一, 原田 拓弥, 太田 拓児, 川村 典生, 渡辺 正明, 増谷 祥, 秋山 久, 田邉 起, 堀田 記世彦, 篠原 信雄, 嶋村 剛, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (10) 1839 - 1840 1345-2843 2022/10
• 生体肝移植後に発生した膵充実性偽乳頭腫瘍(Solid pseudopapillary neoplasm of pancreas,SPNP)に対し核出術を施行した1例

  津坂 翔一, 川村 典生, 植林 毅行, 竹元 小乃美, 原田 拓弥, 太田 拓児, 渡辺 正明, 後藤 了一, 蒲池 浩文, 神山 俊哉, 嶋村 剛, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (10) 1840 - 1840 1345-2843 2022/10
• 肝癌治療における肝移植の役割 Japan criteria導入後の変化と現状

  渡辺 正明, 嶋村 剛, 後藤 了一, 川村 典生, 太田 拓児, 武冨 紹信

  日本癌治療学会学術集会抄録集 60回 OF - 6 2022/10
• 肝癌に対する肝移植の新基準の適応状況 肝癌治療における肝移植の役割 Japan criteria導入後の変化と現状

  渡辺 正明, 嶋村 剛, 後藤 了一, 川村 典生, 太田 拓児, 武冨 紹信

  移植 (一社)日本移植学会 57 (総会臨時) 213 - 213 0578-7947 2022/10
• 肝移植後小児レシピエントに対する弱毒性ワクチン投与

  渡辺 正明, 嶋村 剛, 後藤 了一, 川村 典生, 太田 拓児, 武冨 紹信

  移植 (一社)日本移植学会 57 (総会臨時) 329 - 329 0578-7947 2022/10
• 生体肝移植ドナー長期経過後脂肪肝発生リスク因子の検討

  後藤 了一, 嶋村 剛, 太田 拓児, 川村 典生, 渡辺 正明, 武冨 紹信

  移植 (一社)日本移植学会 57 (総会臨時) 379 - 379 0578-7947 2022/10
• 肝細胞癌に対する肝移植 Japan criteria導入後の肝細胞癌に対する肝移植の現状と今後の課題

  渡辺 正明, 嶋村 剛, 藤吉 真人, 後藤 了一, 川村 典生, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (増刊) S124 - S124 1345-2843 2022/10
• 肝移植後の長期成績 生体ドナー術前Fib-4 indexの長期予後に及ぼす影響

  川村 典生, 嶋村 剛, 後藤 了一, 渡辺 正明, 太田 拓児, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (増刊) S125 - S125 1345-2843 2022/10
• ステージII大腸癌における静脈侵襲の再発に与える影響の検討

  市川 伸樹, 本間 重紀, 吉田 雅, 藤好 直, 松井 博紀, 柴田 賢吾, 武冨 紹信

  日本癌治療学会学術集会抄録集 60回 O52 - 2 2022/10
• コロナ禍ががん医療にもたらしたもの コロナ禍が消化器がん医療にもたらしたもの

  花崎 和弘, 前田 広道, 遠藤 英樹, 山本 博之, 宗景 匡哉, 日比 泰造, 掛地 吉弘, 武富 紹信, 北川 雄光, 森 正樹, 門田 守人

  日本癌治療学会学術集会抄録集 60回 SP3 - 3 2022/10
• コロナ禍ががん医療にもたらしたもの コロナ禍が消化器がん医療にもたらしたもの

  花崎 和弘, 前田 広道, 遠藤 英樹, 山本 博之, 宗景 匡哉, 日比 泰造, 掛地 吉弘, 武富 紹信, 北川 雄光, 森 正樹, 門田 守人

  日本癌治療学会学術集会抄録集 60回 SP3 - 3 2022/10
• 生体肝移植ドナー長期経過後脂肪肝発生リスク因子の検討

  後藤 了一, 嶋村 剛, 太田 拓児, 川村 典生, 渡辺 正明, 武冨 紹信

  移植 (一社)日本移植学会 57 (総会臨時) 379 - 379 0578-7947 2022/10
• ASO Visual Abstract: Hepatectomy is Beneficial for Select Patients with Multiple Hepatocellular Carcinomas.

  Tatsuya Orimo, Toshiya Kamiyama, Tatsuhiko Kakisaka, Akihisa Nagatsu, Yoh Asahi, Takeshi Aiyama, Hirofumi Kamachi, Akinobu Taketomi

  Annals of surgical oncology 29 (13) 8448 - 8448 2022/09/30
• Hepatectomy is Beneficial in Select Patients with Multiple Hepatocellular Carcinomas.

  Tatsuya Orimo, Toshiya Kamiyama, Tatsuhiko Kakisaka, Akihisa Nagatsu, Yoh Asahi, Takeshi Aiyama, Hirofumi Kamachi, Akinobu Taketomi

  Annals of surgical oncology 29 (13) 8436 - 8445 2022/09/13 

  BACKGROUND: A single hepatocellular carcinoma (HCC) is a good indication for hepatic resection regardless of tumor size, but the surgical indications for cases with multiple HCCs remain unclear. METHODS: We retrospectively reviewed the outcomes of hepatectomies for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, and B HCCs. We further subclassified stage A and B into A1 (single nodule <5 cm, or three or fewer nodules ≤3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥10 cm), B1 (two to three nodules >3 cm), and B2 (four or more nodules). RESULTS: A total of 1088 patients were enrolled, comprising 88 stage 0, 750 stage A (A1: 485; A2: 190; A3: 75), and 250 stage B (B1: 166; B2: 84) cases. The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (p < 0.0001). Significant differences in OS were found between stages A1 and A2 (p = 0.0118), A2 and A3 (p = 0.0013), and B1 and B2 (p = 0.0050), but not between stages A3 and B1 (p = 0.4742). In stage B1 patients, multivariate analysis indicated that Child-Pugh B cirrhosis was the only independent prognostic factor for the OS outcome. CONCLUSIONS: A hepatectomy should be considered for multiple HCCs if the number of tumors is three or fewer, especially in patients with no cirrhosis or in Child-Pugh A cases, because the long-term results are equivalent to those for a single HCC.
• 肝血管筋脂肪腫の1切除例

  佐々木 貴志, 甲谷 理紗子, 細田 峻一, 吉田 苑永, 得地 祐匡, 久保 彰則, 大原 正嗣, 須田 剛生, 中井 正人, 荘 拓也, 小川 浩司, 坂本 直哉, 相山 健, 武冨 紹信, 岡崎 ななせ, 松野 吉宏

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 131回・125回 40 - 40 2022/09
• IL-6の制御による大腸がんの肝転移に対する新規戦略(A novel strategy for liver metastasis of colon cancer by control of IL-6)

  北村 秀光, 豊島 雄二郎, 項 慧慧, 大野 陽介, 本間 重紀, 川村 秀樹, 高橋 典彦, 神山 俊哉, 谷野 美智枝, 武冨 紹信

  日本癌学会総会記事 81回 P - 1135 0546-0476 2022/09
• 内科・外科による消化器病共同診療の現況と展望 当院における潰瘍性大腸炎に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 桂田 武彦, 桜井 健介, 福島 新弥, 青山 慶哉, 坂本 直哉, 武冨 紹信

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 131回・125回 26 - 26 2022/09
• 内科・外科による消化器病共同診療の現況と展望 局所進行直腸癌における術前FOLFOX療法の有効性の検討(RNAC01試験)の解釈とその発展

  藤好 直, 本間 重紀, 市川 伸樹, 結城 敏志, 川本 泰之, 原田 一顕, 吉田 雅, 柴田 賢吾, 松井 博紀, 小松 嘉人, 坂本 直哉, 武冨 紹信

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 131回・125回 26 - 26 2022/09
• 大腸癌浸潤先進部の病理組織所見と遺伝子発現signature

  松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 江本 慎, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 75 (9) A180 - A180 0047-1801 2022/09
• ステージII大腸癌における脈管侵襲の再発に与える影響の検討

  松井 博紀, 本間 重紀, 吉田 雅, 藤好 直, 市川 伸樹, 柴田 賢吾, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 75 (9) A201 - A201 0047-1801 2022/09
• 早期S状結腸癌の内視鏡的粘膜切除1年後に生じた肝転移に対して肝拡大右葉切除術を施行し,さらにその5年後にS状結腸間膜再発を認めた一例

  三國 夢人, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 大塚 拓也, 三橋 智子, 本間 重紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 75 (9) A223 - A223 0047-1801 2022/09
• Exploration of the advantages of minimally invasive surgery for clinical T4 colorectal cancer compared with open surgery: A matched-pair analysis.

  Ken Imaizumi, Shigenori Homma, Yoichi Miyaoka, Hiroki Matsui, Nobuki Ichikawa, Tadashi Yoshida, Norihiko Takahashi, Akinobu Taketomi

  Medicine 101 (32) e29869  2022/08/12 

  The indications of minimally invasive surgery (MIS) for T4 colorectal cancer are controversial because the advantages of MIS are unclear. Therefore, we compared overall survival (OS) and recurrence-free survival (RFS) as the primary endpoint, and short-term outcome, alteration in perioperative laboratory data, and the interval of postoperative chemotherapy from operation as secondary endpoints, between MIS and open surgery (OPEN) using a matched-pair analysis. We explored the advantages of MIS for T4 colorectal cancer. In this retrospective single-institution study, we included 125 patients with clinical T4 colorectal cancer who underwent curative-intent surgery of the primary tumor between October 2010 and September 2019. Conversion cases were excluded. MIS patients were matched to OPEN patients (ratio of 1:2) according to tumor location, clinical T stage, and preoperative treatment. We identified 25 and 50 patients who underwent OPEN and MIS, respectively, including 31 with distant metastasis. Both groups had similar background characteristics. The rate of major morbidities (Clavien-Dindo grade > III) was comparable between the 2 groups (P = .597), and there was no mortality in either group. MIS tended to result in shorter postoperative hospitalization than OPEN (P = .073). Perioperative alterations in laboratory data revealed that MIS suppressed surgical invasiveness better compared to OPEN. Postoperative chemotherapy, especially for patients with distant metastasis who underwent primary tumor resection, tended to be started earlier in the MIS group than in the OPEN group (P = .075). OS and RFS were comparable between the 2 groups (P = .996 and .870, respectively). In the multivariate analyses, MIS was not a significant prognostic factor for poor OS and RFS. MIS was surgically safe and showed similar oncological outcomes to OPEN-with the potential of reduced invasiveness and enhanced recovery from surgery. Therefore, patients undergoing MIS might receive subsequent postoperative treatments earlier.
• 腹腔鏡下に完全摘除した後腹膜神経鞘腫の1例

  三國 夢人, 谷 道夫, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科系連合学会誌 日本外科系連合学会 47 (4) 596 - 602 0385-7883 2022/08 

  症例は35歳女性.検診で骨盤内腫瘤を指摘された.精査にて神経原性後腹膜腫瘍と診断され,腹腔鏡下後腹膜腫瘍摘出術を施行した.直腸を授動すると左S3神経孔から出る神経を根部とする腫瘍を認め,容易に神経孔から剥離でき,腹腔鏡下に周囲臓器を温存して腫瘍の完全摘除が可能であった.病理所見からschwannomaの術後診断であった.後腹膜神経鞘腫は外科的切除が第一選択であり,近年は腹腔鏡手術の有用性も報告されている.治療方針については拡大切除の必要性や再発・術後合併症によるQOL低下などを総合的に判断し,術中所見も加味して柔軟に対応する必要がある.今回われわれは過去の報告を踏まえて,診断から治療までの戦略を考察して報告する.(著者抄録)
• Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma

  Shunji Sano, Yoh Asahi, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Takeshi Aiyama, Keizo Kazui, Hiroki Shomura, Shinya Ueki, Yuzuru Sakamoto, Chisato Shirakawa, Hirofumi Kamachi, Hirokazu Sugino, Tomoko Mitsuhashi, Akinobu Taketomi

  INTERNATIONAL CANCER CONFERENCE JOURNAL 12 (1) 7 - 13 2192-3183 2022/08 

  Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
• STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model.

  Shuhei Kii, Hidemitsu Kitamura, Shinichi Hashimoto, Kazuho Ikeo, Nobuki Ichikawa, Tadashi Yoshida, Shigenori Homma, Mishie Tanino, Akinobu Taketomi

  Inflammation research : official journal of the European Histamine Research Society ... [et al.] 71 (9) 1079 - 1094 2022/08/01 

  BACKGROUND: The development of inflammatory bowel diseases is thought to be multifactorial, but the exact steps in pathogenesis are poorly understood. In this study, we investigated involvement of the activation of STAT1 signal pathway in the pathogenesis of an acute colitis model. METHODS: A dextran sulfate sodium-induced acute colitis model was established by using wild-type C57BL/6 mice and STAT1-deficient mice. Disease indicators such as body weight loss and clinical score, induction of cytokines, chemokines, and inflammatory cells were evaluated in the acute colitis model. RESULTS: Disease state was significantly improved in the acute colitis model using STAT1-deficient mice compared with wild-type mice. The induction of Ly6c-highly expressing cells in colorectal tissues was attenuated in STAT1-deficient mice. IL-6, CCL2, and CCR2 gene expressions in Ly6c-highly expressing cells accumulated in the inflamed colon tissues and were significantly higher than in Ly6c-intermediate-expressing cells, whereas TNF-α and IFN-α/β gene expression was higher in Ly6c-intermediate-expressing cells. Blockade of CCR2-mediated signaling significantly reduced the disease state in the acute colitis model. CONCLUSIONS: Two different types of Ly6c-expressing macrophages are induced in the inflamed tissues through the IFN-α/β-STAT1-mediated CCL2/CCR2 cascade and this is associated with the pathogenesis such as onset, exacerbation, and subsequent chronicity of acute colitis.
• Efficacy of chemotherapy for comorbid cancer in patients with simultaneous double cancers: a multicenter study.

  Makoto Sohda, Takehiko Yokobori, Akiharu Kimura, Takayuki Kosaka, Kazuhiro Yoshida, Kenichi Hakamada, Shoji Natsugoe, Akinobu Taketomi, Hiroshi Saeki, Ken Shirabe, Hiroyuki Kuwano

  Surgery today 53 (1) 98 - 108 2022/08/01 

  PURPOSE: Anticancer drugs for double cancers are selected based on their therapeutic effects on the target cancer, but there are insufficient data on the effects of anticancer drugs on comorbid cancer. We investigated the effect of chemotherapy on comorbid cancer in patients with simultaneous double cancers. METHODS: The subjects of this retrospective study were 51 patients with simultaneous double cancers at the time of receiving systemic chemotherapy. We evaluated the types of anticancer drugs used for double cancers, the therapeutic effects on targeted and comorbid cancers, and prognoses. RESULTS: Disease control was achieved for 90.9% of the target cancers and 90.7% of the comorbid cancers. The prognosis was significantly better when the disease was controlled, not only in the target cancer but also in the comorbid cancer. CONCLUSION: Physicians treating double cancers should develop treatment strategies focusing not only on the treatment for advanced cancer, but also on the course of comorbidities and the therapeutic effects of anticancer drugs. This study is important because it presents new possibilities to expand the indications for anticancer drugs, while allowing unnecessary clinical research to be avoided.
• Randomized phase III study of Gemcitabine, Cisplatin plus S-1 (GCS) versus Gemcitabine, Cisplatin (GC) for Advanced Biliary Tract Cancer (KHBO1401-MITSUBA).

  Tatsuya Ioka, Masashi Kanai, Shogo Kobayashi, Daisuke Sakai, Hidetoshi Eguchi, Hideo Baba, Satoru Seo, Akinobu Taketomi, Tadatoshi Takayama, Hiroki Yamaue, Masahiro Takahashi, Masayuki Sho, Keiko Kamei, Jiro Fujimoto, Masanori Toyoda, Junzo Shimizu, Takuma Goto, Yoshitaro Shindo, Kenichi Yoshimura, Etsuro Hatano, Hiroaki Nagano

  Journal of hepato-biliary-pancreatic sciences 30 (1) 102 - 110 2022/07/28 

  BACKGROUND: Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials could demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC. PATIENTS AND METHODS: We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. GCS regimen comprised gemcitabine (1,000 mg/m2 ) and cisplatin (25 mg/m2 ) infusion on day 1 and 80 mg/m2 of S-1 on days 1-7 every 2 weeks. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response rate (RR), and adverse events (AEs). This study is registered with Clinical trial identification: NCT02182778. RESULTS: Between July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidential interval [CI] 0.628-0.996; p = 0.046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI 0.577-0.970; p = 0.015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms. CONCLUSIONS: GCS is the first regimen which demonstrated the survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.
• ASO Visual Abstract: Versican Secreted by Cancer-Associated Fibroblasts Is a Poor Prognostic Factor in Hepatocellular Carcinoma.

  Koichi Kato, Moto Fukai, Kanako C Hatanaka, Akira Takasawa, Tomoyuki Aoyama, Takahiro Hayasaka, Yoshihiro Matsuno, Toshiya Kamiyama, Yutaka Hatanaka, Akinobu Taketomi

  Annals of surgical oncology 29 (11) 7147 - 7148 2022/07/28
• Impact of comorbid renal dysfunction in patients with hepatocellular carcinoma on long-term outcomes after curative resection.

  Yuzuru Sakamoto, Shingo Shimada, Toshiya Kamiyama, Ko Sugiyama, Yoh Asahi, Akihisa Nagatsu, Tatsuya Orimo, Tatsuhiko Kakisaka, Hirofumi Kamachi, Yoichi M Ito, Akinobu Taketomi

  World journal of gastrointestinal surgery 14 (7) 670 - 684 2022/07/27 

  BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM: To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS: We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m2; non-RD, EGFR ≥ 60 mL/min/1.73 m2) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m2; mild CKD, 30 ≤ EGFR < 60 mL/min/1.73 m2; control, EGFR ≥ 60 mL/min/1.73 m2) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 ± 53.0 mo. RESULTS: The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics, liver function, and other causes of death. CONCLUSION: Comorbid mild RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management, and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection.
• A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma.

  Takafumi Kondo, Shohei Honda, Hiromu Suzuki, Yoichi M Ito, Issei Kawakita, Kazuyoshi Okumura, Momoko Ara, Masashi Minato, Norihiko Kitagawa, Yukichi Tanaka, Mio Tanaka, Masato Shinkai, Tomoro Hishiki, Kenichiro Watanabe, Kohmei Ida, Atsushi Takatori, Eiso Hiyama, Akinobu Taketomi

  European journal of cancer (Oxford, England : 1990) 172 311 - 322 2022/07/08 

  INTRODUCTION: Hepatoblastoma (HB) is the most common paediatric liver tumour, and epigenetic aberrations may be important in HB development. Recently, the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) developed risk stratification based on clinicopathological factors. This study aimed to construct a more accurate model by integrating CHIC-HS with molecular factors based on DNA methylation. METHODS: HB tumour specimens (N = 132) from patients treated with the Japanese Pediatric Liver Tumors Group-2 protocol were collected and subjected to methylation analysis by bisulfite pyrosequencing. Associations between methylation status and clinicopathological factors, overall survival (OS), and event-free survival (EFS) were retrospectively analysed. We investigated the effectiveness of the evaluation of methylation status in each CHIC-HS risk group and generated a new risk stratification model. RESULTS: Most specimens (82%) were from post-chemotherapy tissue. Hypermethylation in ≥2 of the four genes (RASSF1A, PARP6, OCIAD2, and MST1R) was significantly associated with poorer OS and EFS. Multivariate analysis indicated that ≥2 methylated genes was an independent prognostic factor (hazard ratios of 6.014 and 3.684 for OS and EFS, respectively). Two or more methylated genes was also associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk and CHIC-intermediate (I) risk groups (3-year OS rates were 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model were 98%, 90%, and 62% (vs. CHIC-HS [96%, 82%, and 65%, respectively]), optimising CHIC-HS. CONCLUSIONS: Our proposed stratification system considers individual risk in HB and may improve patient clinical management.
• 結腸亜全摘術を行ったClostridioides difficile腸炎後横行結腸狭窄の1例

  原田 拓弥, 吉田 雅, 本間 重紀, 市川 伸樹, 大塚 拓也, 三橋 智子, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (7) 1325 - 1330 1345-2843 2022/07 

  症例は54歳,男性.腹痛を主訴に近医を受診し,門脈気腫症の診断.α-グルコシダーゼ阻害薬が原因と考えられ,またバイタルは保たれており臨床症状も軽度であったため,同薬剤の中止と抗菌薬投与による保存的加療が選択された.門脈気腫症は速やかに改善したが,Clostridioides difficile腸炎(以下CD腸炎)を発症.その後,巨大結腸症を発症し手術も考慮されたため当科に転院した.転院後,炎症や潰瘍は改善が見られたが,進行性の横行結腸狭窄を認め,完全閉塞も危惧されたため,結腸亜全摘を施行した.術後経過は問題なく,術後18日目に退院となり,現在,術後3年3ヵ月経過したが,狭窄の再発なく経過している.病理組織学的検査から感染性腸炎による狭窄と診断し,その原因としてCD腸炎が強く疑われた.CD腸炎の経過中には腸管狭窄も生じ得ることを念頭に置く必要がある.(著者抄録)
• Squeezingアプローチによる腹腔鏡下右側結腸切除

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 77回 O8 - 3 2022/07
• 直腸癌におけるCTによる側方リンパ節転移予測の検討

  江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 77回 P055 - 1 2022/07
• 潰瘍性大腸炎に対するTa-TME

  本間 重紀, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 77回 P090 - 2 2022/07
• 腹腔鏡下大腸手術前処置における腸管洗浄剤の有効性と安全性に関する多施設ランダム化比較試験

  吉田 雅, 本間 重紀, 市川 伸樹, 石津 寛之, 舩越 徹, 小池 雅彦, 今 裕史, 上泉 洋, 谷 安弘, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 77回 O14 - 1 2022/07
• 中規模病院におけるロボット支援下直腸手術の導入

  金沢 亮, 本間 重紀, 鈴木 麗美, 浜田 卓巳, 辻 健志, 谷 安弘, 河合 朋昭, 羽田 力, 上泉 洋, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 77回 P138 - 5 2022/07
• Liver metastasis 13 years after the resection of a malignant triton tumor originating in the duodenum

  Keita Ohashi, Yoh Asahi, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Yuzuru Sakamoto, Hirofumi Kamachi, Tomofumi Takagi, Takuya Otsuka, Tomoko Mitsuhashi, Shintaro Sugita, Tadashi Hasegawa, Akinobu Taketomi

  International Cancer Conference Journal 11 (3) 178 - 183 2022/07 

  This is an additional case report of a malignant triton tumor arising in the duodenum that was removed by pancreatoduodenectomy. Liver and gallbladder dysfunctions were detected in a regular blood examination during a follow-up for hypertension in a 62-year-old woman with a previous surgical history for a malignant Triton tumor in the duodenum 13 years ago. Further examinations revealed a metastatic liver tumor originating from the malignant triton tumor in the duodenum. Since the progression of the liver tumor was detected after radiation therapy, complete resection was performed by right hepatectomy. Curative hepatectomy resulted in disease-free survival for 1 year and 5 months in an extremely rare case of liver metastasis derived from a malignant triton tumor in the duodenum.
• Long-term quality of life of living liver donors: A Japanese nationwide survey.

  Nobuhisa Akamatsu, Kiyoshi Hasegawa, Kayo Nojiri, Kaori Muto, Junichi Shimizu, Etsuko Soeda, Naoki Kawagishi, Shigeru Marubashi, Koichi Mizuta, Toshimi Kaido, Akinobu Taketomi, Hideki Ohdan, Shinji Uemoto, Norihiro Kokudo

  Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 28 (11) 1800 - 1803 2022/06/02
• アルギナーゼ1を介したアルギニン代謝の活性化は大腸がんの肝転移巣形成と抗腫瘍免疫を制御する

  北村 秀光, 王 向東, 項 慧慧, 豊島 雄二郎, 沈 輝棟, 志智 俊介, 中本 裕紀, 木村 沙織, 杉山 昂, 本間 重紀, 宮城 洋平, 武冨 紹信

  日本がん免疫学会総会プログラム・抄録集 日本がん免疫学会 26回 147 - 147 2022/06
• Impact of Endoscopic Surgical Skill Qualification on Laparoscopic Resections for Rectal Cancer in Japan: The EnSSURE Study.

  Nobuki Ichikawa, Shigenori Homma, Koya Hida, Tomonori Akagi, Yasuyuki Kamada, Tomohiro Yamaguchi, Masaaki Ito, Fumio Ishida, Jun Watanabe, Daisuke Yamamoto, Hiroaki Iijima, Shigeki Yamaguchi, Masafumi Inomata, Yoshiharu Sakai, Takeshi Naitoh, Akinobu Taketomi

  Annals of surgery open : perspectives of surgical history, education, and clinical approaches 3 (2) e160  2022/06 

  OBJECTIVE: This cohort study investigated short- and long-term postoperative outcomes of laparoscopic procedures for rectal cancer performed with versus without certified surgeons. BACKGROUND: In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) evaluates surgical skills deemed essential for laparoscopic surgery; however, it is unknown whether this certification contributes to procedural safety. METHODS: Outcomes of laparoscopic rectal resections for cStage II and III rectal cancer performed from 2014 to 2016 at 56 Japanese hospitals were retrospectively reviewed. The impact of having versus not having certified surgeons on postoperative complications and other short- and long-term outcomes were assessed. In cases with ESSQS-certified surgeons, surgeons attended surgery in the capacity of an operator, assistant, scope operator, or advisor. RESULTS: Overall, 3188 procedures were analyzed, with 2644 procedures performed with and 544 without ESSQS-certified surgeons. A multivariate logistic regression model showed that the adjusted odds ratio of postoperative complications after procedures performed with ESSQS-certified surgeons was 0.68 (95% confidence interval, 0.51-0.91; P = 0.009). The adjusted odds ratios for conversion and pathological R0 resection rates with ESSQS-certified surgeons were 0.20 (P < 0.001) and 2.10 (P = 0.04), respectively. Multiple linear regression analyses showed significantly shorter surgical duration and more harvested lymph nodes for operations performed with ESSQS-certified surgeons. Multivariate Cox regression showed that the adjusted hazard ratios for poor overall and recurrence-free survival after operations performed with ESSQS-certified surgeons were 0.88 (P = 0.35) and 1.04 (P = 0.71), respectively. CONCLUSIONS: This study showed the superiority of the short-term postoperative results for laparoscopic rectal procedures performed with ESSQS-certified surgeons.
• Efficient multiple treatments including molecular targeting agents in a case of recurrent hepatocellular carcinoma, post-living donor liver transplantation.

  Reimi Suzuki, Ryoichi Goto, Norio Kawamura, Masaaki Watanabe, Yoshikazu Ganchiku, Kanako C Hatanaka, Yutaka Hatanaka, Toshiya Kamiyama, Tsuyoshi Shimamura, Akinobu Taketomi

  Clinical journal of gastroenterology 15 (4) 755 - 764 2022/05/30 

  Despite the promising efficacies of recently developed molecular targeting therapies for hepatocellular carcinoma, their role in liver transplantation is unknown. Here we report that multidisciplinary treatment, including novel molecular targeting therapy with lenvatinib, achieved long-term survival of a patient with post-liver transplantation recurrence of hepatocellular carcinoma. A 62 year-old man with hepatocellular carcinoma beyond the Milan criteria, arising from hepatitis B virus-associated cirrhotic liver, underwent living donor liver transplantation. However, alpha-fetoprotein level increased a month post-transplantation, and pleural dissemination and lung metastasis of hepatocellular carcinoma in the right lung were detected. The patient was initially treated with sorafenib and rapamycin, right pleurectomy and upper and middle lobectomies were attempted as the second treatment. However, remnant tumors started to grow. Subsequently, the newly molecular targeting agents; regorafenib and lenvatinib, approved for recurrent hepatocellular carcinoma in Japan, were administered. Lenvatinib efficiently reduced tumor volumes and the alpha-fetoprotein level, which contributed to maintaining better quality of life for 26 months as an outpatient. Unfortunately, sepsis caused by cholangitis and liver abscess required the discontinuation of lenvatinib, and the patient died 73 months after the recurrence of hepatocellular carcinoma. Multidisciplinary treatment including lenvatinib is potentially acceptable for recurrent hepatocellular carcinoma after liver transplantation.
• A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

  Takehito Otsubo, Shinjiro Kobayashi, Keiji Sano, Takeyuki Misawa, Satoshi Katagiri, Hisashi Nakayama, Shuji Suzuki, Manabu Watanabe, Shunichi Ariizumi, Michiaki Unno, Minoru Tanabe, Hiroaki Nagano, Norihiro Kokudo, Satoshi Hirano, Masafumi Nakamura, Ken Shirabe, Yasuyuki Suzuki, Masahiro Yoshida, Yasutsugu Takada, Toshio Nakagohri, Akihiko Horiguchi, Hideki Ohdan, Susumu Eguchi, Masayuki Ohtsuka, Masayuki Sho, Toshiki Rikiyama, Etsuro Hatano, Akinobu Taketomi, Tsutomu Fujii, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto, Tadahiro Takada, Itaru Endo

  Journal of hepato-biliary-pancreatic sciences 30 (1) 60 - 71 2022/05/24 

  BACKGROUND: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety. METHODS: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary. RESULTS: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037). CONCLUSIONS: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.
• IFN-α/β-mediated NK2R expression is related to the malignancy of colon cancer cells.

  Huihui Xiang, Yujiro Toyoshima, Weidong Shen, Xiangdong Wang, Naoki Okada, Shuhei Kii, Ko Sugiyama, Toshihiro Nagato, Hiroya Kobayashi, Kazuho Ikeo, Shinichi Hashimoto, Mishie Tanino, Akinobu Taketomi, Hidemitsu Kitamura

  Cancer science 113 (8) 2513 - 2525 2022/05/13 

  Neurokinin 2 receptor (NK2R), a G protein-coupled receptor for Neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and IFN-α/β stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a JAK1/2-dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of ERK1/2 levels of IFN-α/β-treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic-polycytidylic acid, a synthetic analog of double-stranded RNA, to CT26-bearing mice significantly suppressed tumorigenesis. NK2R-overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN-α/β-mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.
• Versican Secreted by Cancer-Associated Fibroblasts is a Poor Prognostic Factor in Hepatocellular Carcinoma.

  Koichi Kato, Moto Fukai, Kanako C Hatanaka, Akira Takasawa, Tomoyuki Aoyama, Takahiro Hayasaka, Yoshihiro Matsuno, Toshiya Kamiyama, Yutaka Hatanaka, Akinobu Taketomi

  Annals of surgical oncology 29 (11) 7135 - 7146 2022/05/11 

  BACKGROUND: Hepatocellular carcinoma (HCC) is highly recurrent. Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment, promote malignancy; however, the mechanisms underlying their actions are obscure. We aimed to identify CAF-specific proteins in HCC and determine whether they could be potential therapeutic targets. METHODS: Using comprehensive proteomic analysis of CAFs and noncancerous fibroblasts (NFs) primary-cultured from resected HCC specimens from the same patients, CAF-specific proteins were identified. Immunohistochemistry for versican (VCAN) was performed on cancerous tissues obtained from 239 patients with HCC. Conditioned medium from CAFs transfected with siRNA for VCAN was analyzed in vitro. RESULTS: CAFs significantly promoted HCC cell proliferation, migration, and invasion (p < 0.01, 0.01, and 0.01, respectively) compared with NFs. VCAN was upregulated in CAFs, and its stromal level correlated with poor differentiation (p = 0.009) and positive vascular invasion (p = 0.003). Stromal VCAN level was also associated with significantly lower overall (p = 0.002) and relapse-free (p < 0.001) survival rates. It also independently predicted prognosis and recurrence. VCAN-knockdown CAFs significantly suppressed HCC cell migration and invasion compared with negative control. CONCLUSIONS: VCAN secreted from CAFs promoted malignant transformation of HCC cells and has potential as a new therapeutic target in HCC.
• Gastric cancer complicated by paraneoplastic neurological syndrome which presented with extremity numbness: a case report.

  Takuto Yoshida, Hideki Kawamura, Kazuhiro Mino, Yuji Konishi, Tomoya Saito, Yuichi Shimizu, Akinobu Taketomi

  Surgical case reports 8 (1) 78 - 78 2022/04/28 

  BACKGROUND: Paraneoplastic neurological syndromes refer to a group of neurological disorders, which occur as distant effects of malignant tumors and are not caused by metastasis, nutritional disorders, or side effects of antitumor drugs. CASE PRESENTATION: A 70-year-old woman complained of a 1-month history of extremity numbness. Upon presentation to our hospital, she had worsening numbness, and experienced staggering and falling. Physical examination revealed diminished tendon reflexes in both lower limbs, stocking and glove-type abnormal sensation, and left-sided dominant high-steppage gait due to weakness of the bilateral tibialis anterior muscles. Blood tests indicated anemia, and upper gastrointestinal endoscopy revealed gastric cancer, leading to laparoscopic distal gastrectomy. A nerve conduction velocity test showed demyelinating peripheral neuropathy. Further blood tests and imaging studies ruled out nutritional disorders, such as vitamin deficiency, diabetes-related diseases, connective tissue diseases, and central nervous system metastasis, leading to the suspicion of paraneoplastic neurological syndrome. After laparoscopic distal gastrectomy, the progression of symptoms stopped, and with intravenous high-dose immunoglobulin and steroid therapy, the symptoms improved to only minor numbness in the peripheral limbs as of the 18-month follow-up. As of the 2-year follow-up, there has been no cancer recurrence or metastasis. CONCLUSIONS: When paraneoplastic neurological syndrome is suspected, early diagnosis and a multidisciplinary approach, including surgical treatment, are important before irreversible neurological damage occurs.
• A case of alveolar echinococcosis in the liver that ruptured into the pericardium treated by a combination of hepatectomy and albendazole.

  Yoichi Yamamoto, Yuzuru Sakamoto, Toshiya Kamiyama, Akihisa Nagatsu, Yoh Asahi, Tatsuya Orimo, Tatsuhiko Kakisaka, Hirofumi Kamachi, Takuya Otsuka, Tomoko Mitsuhashi, Akinobu Taketomi

  Surgical case reports 8 (1) 63 - 63 2022/04/08 

  BACKGROUND: Alveolar echinococcosis (AE) is a rare parasitic disease caused by the larva of Echinococcus multilocularis. It nearly always occurs in the liver, and cardiac involvement is extremely rare. Liver resection is the most effective intervention for AE because the only potentially curative treatment is removal of the lesion. Even when complete resection is not performed, long-term survival can be expected after surgical removal of most of the lesion with lifelong administration of albendazole (ABZ). CASE PRESENTATION: A 64-year-old man who lived in Hokkaido was referred to our hospital due to abnormalities in biliary enzymes. According to the findings from enhanced computed tomography and magnetic resource imaging of the abdomen, transthoracic echocardiography and serologic tests, he was diagnosed with hepatic AE with rupture into the pericardium. He underwent extended left hemi-hepatectomy with reconstruction of the inferior vena cava and opening of the pericardium with drainage as reduction surgery. Pathological examination revealed echinococcal infection in the pericardium as well as the liver. He started chemotherapy with 400 mg ABZ per Day 67 days after surgery. Although the surgical margin was positive in the pathological findings, he was alive 19 months later with no regrowth of the echinococcal lesion. CONCLUSION: AE with cardiac involvement is extremely rare. Even if the complete removal of cardiac-involved AE is not possible, surgical debulking with lifelong ABZ treatment can successfully manage the disease.
• 少子化社会と小児外科育成 北海道における小児外科診療の現状とこれから

  本多 昌平, 荒 桃子, 近藤 享史, 河北 一誠, 大場 豪, 山本 浩史, 浜田 弘巳, 縫 明大, 宮城 久之, 石井 大介, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 PD - 1 2022/04
• 肝細胞癌に対するsalvage liver transplantationの適応検討

  川村 典生, 嶋村 剛, 後藤 了一, 渡辺 正明, 巖築 慶一, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 2 2022/04
• 心停止肝に対する低温機械灌流の至適pHの検討

  坂本 聡大, 柴田 賢吾, 石川 隆壽, 藤好 真人, 巌築 慶一, 川村 典生, 渡辺 正明, 後藤 了一, 暮地本 宙己, 深井 原, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 6 2022/04
• アロ感作マウスを用いた異所性アロ心移植に対する抗CD3F(ab')2の効果の検討

  太田 拓児, 後藤 了一, 原田 拓弥, アグスティーナ・フォルジオニ, 巖築 慶一, 川村 典生, 渡辺 正明, 深井 原, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 1 2022/04
• マウスにおける抗CD80/86抗体で誘導した抑制性T細胞の検討

  原田 拓弥, 後藤 了一, Agustina Forgioni, 太田 拓児, 巖築 慶一, 渡辺 正明, 川村 典生, 深井 原, 内田 浩一郎, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 8 2022/04
• 肝移植後小児レシピエントに対する弱毒生ワクチン投与

  渡辺 正明, 後藤 了一, 川村 典生, 巌築 慶一, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 3 2022/04
• 生体肝移植で治療し得た肝内門脈肝静脈シャントの1例

  津坂 翔一, 巌築 慶一, 川村 典夫, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 RS - 5 2022/04
• 非アルコール性脂肪肝炎、非代償性肝硬変のhigh MELD例に実施した脳死肝移植の一例

  中村 恒星, 後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 森川 賢一, 小川 浩司, 坂本 直哉, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 RS - 2 2022/04
• 生体肝移植後、膵頭部に生じたSolid pseudopapillary neoplasmに核出術を施行した1例

  津坂 翔一, 荒 桃子, 河北 一誠, 川村 典生, 渡辺 正明, 後藤 了一, 本多 昌平, 蒲池 浩文, 神山 俊哉, 嶋村 剛, 武冨 紹信

  日本小児外科学会雑誌 (一社)日本小児外科学会 58 (3) 410 - 410 0288-609X 2022/04
• 大腸癌浸潤先進部の局所炎症反応と遺伝子発現signature

  松井 博紀, 畑中 佳奈子, 谷 道夫, 本間 重紀, 吉田 雅, 市川 伸樹, 江本 慎, 畑中 豊, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 4 2022/04
• 直腸癌症例におけるdouble-stapling technique吻合の縫合不全リスク因子の検討

  江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 8 2022/04
• 直腸癌局所再発に対するTp-TME

  本間 重紀, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 8 2022/04
• 腹腔鏡下に完全摘除した後腹膜神経鞘腫の一例

  三國 夢人, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 RS - 10 2022/04
• 人工甘味料の多量摂取が原因と考えられた直腸癌術後回腸ストマからのhigh output症候群の1例

  竹元 小乃美, 本間 重紀, 江本 慎, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 RS - 10 2022/04
• 小腸diffuse ganglioneuromatosisによる穿孔に対し緊急手術を要した一例

  浜田 和也, 島田 慎吾, 渋谷 一陽, 小柳 要, 本間 友樹, 橋本 卓, 阿部 厚憲, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 DP - 4 2022/04
• 3,5-dihydroxy-4-methoxybenzyl alcohol(DHMBA)は心筋細胞の冷保存傷害を軽減する

  深井 原, 大谷 晋太郎, 千葉 仁志, 惠 淑萍, 坂本 聡大, 柴田 賢吾, 石川 隆壽, 川村 典生, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 8 2022/04
• 腹腔鏡下直腸癌手術における技術認定取得医の役割別治療成績の検討 EnSSURE studyサブ解析

  清住 雄希, 山口 智弘, 池田 公治, 古城 憲, 稲田 涼, 大塚 幸喜, 古谷 晃伸, 市川 伸樹, 本間 重紀, 武冨 紹信, 内藤 剛

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 8 2022/04
• 分子標的薬時代後のBCLC stage C肝細胞癌の切除後成績の変化

  旭 火華, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 相山 健, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 5 2022/04
• 3,5-dihydroxy-4-methoxybenzyl alcohol(DHMBA)は心筋細胞の冷保存傷害を軽減する

  深井 原, 大谷 晋太郎, 千葉 仁志, 惠 淑萍, 坂本 聡大, 柴田 賢吾, 石川 隆壽, 川村 典生, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 8 2022/04
• Pancreatic morphological abnormality that was challenging to differentiate from an ectopic pancreas: a case report.

  Takuto Yoshida, Hideki Kawamura, Kazuhiro Mino, Yuji Konishi, Tomoya Saito, Yuichi Shimizu, Akinobu Taketomi

  Surgical case reports 8 (1) 55 - 55 2022/03/28 

  BACKGROUND: Protrusion of the lateral contour of the pancreatic head is a pancreatic morphological abnormality, which is known as rare shape atypia. We present a rare case of protrusion of the lateral contour of the pancreatic head, which was challenging to distinguish from an ectopic pancreas. CASE PRESENTATION: The patient was a 40-year-old man with a history of acute pancreatitis that occurred twice in the past. He complained of epigastric pain since the day before the visit; his blood workup showed high serum amylase level and a CT scan revealed a 25-mm-large mass with contrast effect from the anterior wall of the gastric pylorus to the duodenum and increased surrounding fatty tissue density. Endoscopic ultrasonography revealed a mass lesion in the gastric pylorus with continuity with the gastric wall and suspected partial continuity with the pancreatic head. Thus, the possibility of pancreatic morphological abnormality or an ectopic pancreas was considered. Following which, resection was attempted and intraoperative findings showed a wide extension of the pancreatic parenchyma from the pancreatic head to the anterior wall of the gastric pylorus to the duodenal bulb. Since the patient only had mild pancreatitis, the resection was judged to be too invasive and was completed by exploratory laparoscopy. CONCLUSIONS: Even if the findings on preoperative CT are suspicious for an ectopic pancreas or tumor, a pancreatic morphological abnormality, such as a protrusion of the lateral contour of the pancreatic head, should be included in the differential diagnosis.
• Laparoscopic liver resection for liver metastasis of leiomyosarcoma of the thigh: a case report.

  Shoichi Tsuzaka, Yoh Asahi, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Takeshi Aiyama, Takeyuki Uebayashi, Hirofumi Kamachi, Masatake Matsuoka, Kento Wakabayashi, Takuya Otsuka, Yoshihiro Matsuno, Akinobu Taketomi

  Surgical case reports 8 (1) 47 - 47 2022/03/21 

  BACKGROUND: Although there is no established treatment strategy for liver metastasis of leiomyosarcoma, liver resection has been reported to be effective in some cases. However, almost all liver resections performed for liver metastasis of primary leiomyosarcoma are reported to be open resections, and there are few reports of liver resection performed by laparoscopy. Here, we report a case of laparoscopic liver resection for liver metastasis of a leiomyosarcoma in the right thigh. CASE PRESENTATION: An 80-year-old man was diagnosed with leiomyosarcoma of the right thigh with liver metastasis. The primary tumor was first resected, and he was discharged on the 25th postoperative day. Four months after primary tumor resection, a laparoscopic right posterior sectionectomy was performed. There were no postoperative complications, and the patient was discharged on the 11th postoperative day with a histopathological diagnosis of liver metastasis of leiomyosarcoma and negative resection margins. Currently, 9 months have passed since the resection of the primary tumor, and 5 months have passed since the laparoscopic liver resection; there is no recurrence. CONCLUSIONS: The liver metastasis of leiomyosarcoma was successfully removed, with good short-term outcomes after the laparoscopic liver resection. Laparoscopic liver resection seems to be effective for liver metastasis of leiomyosarcoma, which is characterized by a high recurrence rate after surgery. However, more case studies may be necessary to examine the effectiveness and long-term results of laparoscopic liver resection for the treatment of liver metastasis of leiomyosarcoma.
• 巨大な肝内門脈肝静脈短絡を伴った自己免疫性肝硬変に対する生体肝移植

  津坂 翔一, 巌築 慶一, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (3) 602 - 602 1345-2843 2022/03
• 人工甘味料の大量摂取が原因と考えられた直腸癌術後回腸ストマからのhigh output症候群の1例

  竹元 小乃美, 本間 重紀, 江本 慎, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (3) 607 - 607 1345-2843 2022/03
• 肝細胞癌患者の治癒切除後長期予後における腎機能障害の影響

  坂本 譲, 神山 俊哉, 島田 慎吾, 相山 健, 旭 よう, 長津 明久, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 83 (3) 598 - 599 1345-2843 2022/03
• 肝移植適応疾患の病態解明と診療展開 当院におけるNASH肝硬変肝移植後NASH、NAFLD再発の検討

  後藤 了一, 嶋村 剛, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 119 (臨増総会) A218 - A218 0446-6586 2022/03
• Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer.

  Souvick Roy, Mitsuro Kanda, Sachiyo Nomura, Zhongxu Zhu, Yuji Toiyama, Akinobu Taketomi, James Goldenring, Hideo Baba, Yasuhiro Kodera, Ajay Goel

  Molecular cancer 21 (1) 42 - 42 2022/02/09 

  BACKGROUND: Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC. METHODS: We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies. RESULTS: We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation. CONCLUSIONS: We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.
• The impact of preformed donor‐specific antibodies in living donor liver transplantation according to graft volume

  Ryoichi Goto, Makoto Ito, Norio Kawamura, Masaaki Watanabe, Yoshikazu Ganchiku, Toshiya Kamiyama, Tsuyoshi Shimamura, Akinobu Taketomi

  Immunity, Inflammation and Disease 10 (3) e586  2050-4527 2022/01/22 

  INTRODUCTION: The roles of preformed anti-HLA donor-specific antibodies (DSAs) in liver transplantation remain controversial. We evaluated the impact of preformed DSAs in living donor liver transplantation. METHODS: Adults who underwent living donor liver transplantation (n = 175) in our institute were included in this study. Lymphocyte cytotoxicity test (LCT), flow cytometric crossmatch (FCXM), and single-antigen bead assays were performed. RESULTS: Among adult living donor liver transplantation recipients, 27 (16.5%) and 14 (8.5%) had pretransplant FCXM-positive findings and LCT-positive findings, respectively. FCXM-positive patients displayed a significantly worse 5-year graft survival rate (77.3%; vs. DSA-negative, 91.6%). Six of 14 LCT-positive patients exhibited graft loss shortly after transplantation (5-year survival rate: 57.1%). All LCT-positive patients with graft loss underwent left lobe living donor liver transplantation. Significantly lower ratio of graft volume relative to standard liver volume (32.9 ± 5.7%) and smaller graft size (365.3 ± 57.9 g) were observed in patients with graft loss (p < .03, vs. surviving grafts). Significantly higher DSA-mean fluorescence intensity (MFI) values were present in patients with graft loss (p = .0012, vs. surviving grafts). CONCLUSIONS: Patients with preformed DSAs exhibited worse graft outcomes in living donor liver transplantation. Higher DSA-MFI values and smaller graft size were associated with worse outcomes in LCT-positive patients. High-risk patients with preformed DSAs should be considered for appropriate graft selection and application of a desensitization protocol.
• Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

  Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Yosuke Togashi, Shohei Koyama, Daisuke Kotani, Shota Fukuoka, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Makoto Fukui, Masashi Wakabayashi, Naoki Nakamura, Motohiro Kojima, Hiroshi Kawachi, Richard Kirsch, Tsutomu Yoshida, Yutaka Suzuki, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino

  Clinical cancer research : an official journal of the American Association for Cancer Research 28 (6) 1136 - 1146 2022/01/21 

  PURPOSE: Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC. PATIENTS AND METHODS: In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated. RESULTS: Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes. CONCLUSIONS: CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.
• The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study.

  Nobuki Ichikawa, Shigenori Homma, Tohru Funakoshi, Masahiro Hattori, Masanori Sato, You Kamiizumi, Kazuyoshi Omori, Masaru Nomura, Ryoichi Yokota, Masahiko Koike, Hirofumi Kon, Keisa Takeda, Hiroyuki Ishizu, Shinichi Matsuoka, Kunihiro Hirose, Takahisa Ishikawa, Ryohei Murata, Hiroaki Iijima, Tadashi Yoshida, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi

  Surgery today 52 (8) 1134 - 1142 2022/01/05 

  PURPOSE: In this follow-up of the R-NAC-01 study, we assessed the long-term oncological benefit of four courses of modified leucovorin, 5-fluorouracil (FU), and oxaliplatin (mFOLFOX6) chemotherapy before rectal surgery. METHODS: In this prospective, multicenter study (UMIN 000012559) involving 11 hospitals in Japan, patients with lower rectal cancer underwent four cycles of mFOLFOX6 chemotherapy and subsequent surgery within four to six weeks. The 3-year recurrence-free survival and local recurrence rates were then reported. RESULTS: Of 41 patients (36 males, 5 females; mean age: 60.8 years old) who received 4 courses of chemotherapy, 40 underwent total mesorectal excision, and 1 underwent total pelvic exenteration. R0 resection was achieved in 40 patients, but none showed a pathological complete response. Twenty-nine patients received adjuvant chemotherapy for an average of 4 months. The 3 year recurrence-free survival and local recurrence rates in patients undergoing curable resection were 72.8% and 8.5%, respectively. cStage III patients with adjuvant chemotherapy had a significantly higher 3 year recurrence-free survival than those without adjuvant chemotherapy (76.6 vs. 40.0%, log-rank p = 0.03). CONCLUSION: Four courses of mFOLFOX6 chemotherapy before surgery may be a promising treatment strategy for locally advanced rectal cancer. Adjuvant chemotherapy might be needed for cStage III patients, even after four courses of neoadjuvant mFOLFOX6.
• Two-time perforation of the ileal J-pouch 6 and 18 years after restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis: a case report.

  Kengo Shibata, Shota Ebinuma, Sodai Sakamoto, Asami Suzuki, Yasunobu Terasaki, Akinobu Taketomi

  Surgical case reports 8 (1) 2 - 2 2022/01/04 

  BACKGROUND: Perforation of the ileal J-pouch after restorative proctocolectomy and ileal pouch-anal anastomosis are extremely rare. There has been no report of perforation of the ileal J-pouch occurring twice over several years. We report the first case of perforation at 6 and 18 years following restorative proctocolectomy. CASE PRESENTATION: The patient was a 52-year-old man who underwent a two-stage restorative proctocolectomy with a hand-sewn ileal J-pouch anal anastomosis due to familial adenomatous polyposis and sigmoid colon cancer at 34 years of age. At the age of 40, he underwent ileal pouch resection at its blind end, abdominal drainage, and anastomotic dilatation. The patient had a perforation of the blind end of the ileal J-pouch from increased intraluminal pressure, with anastomotic stricture and pervasive peritonitis. The patient had no symptoms for a few years; however, 18 years after the initial surgery and 12 years after the first perforation, the patient presented with severe abdominal pain. Computed tomography demonstrated pneumoperitoneum; accordingly, laparotomy was performed. Upon opening the abdominal cavity, contaminated ascites and inflammatory changes were documented involving the ileum. A 2-mm perforation involving the blind end of the ileal J-pouch was also observed and repaired, followed by temporary loop ileostomy creation. Postoperative endoscopy revealed an ulcer in the ileal J-pouch and a stricture located directly at the anastomosis. CONCLUSIONS: The blind end of the J-pouch repeatedly perforated over the years due to recurrent anastomotic stricture. Regular surveillance is, therefore, considered necessary for the release of stricture, maintenance of anastomotic patency, and prevention of ileal J-pouch perforation.
• Transumbilical Repair for Umbilical Hernia: A New Technique.

  Go Ohba, Hiroshi Yamamoto, Masashi Minato, Masato Nakayama, Shohei Honda, Akinobu Taketomi

  The American surgeon 31348211060438 - 31348211060438 2022/01/03 

  Although there are many reports on surgical repair for umbilical hernia, there is no standard procedure at present. Since 2012, we have performed surgery with transumbilical repair using an original procedure. With this procedure, a longitudinal incision is made in the umbilicus, and the fascial defect is closed. Excess skin is excised at a fixed length. The fascia and dermis are sutured vertically over a length of 15 mm. A total of 424 patients with pediatric umbilical hernia who underwent this procedure between September 2012 and December 2020 were reviewed. The mean operative duration was 52 minutes. All patients were followed up to 6 months after surgery. Postoperative complications included infection in 15 patients and wound granulation in 5 patients. The morphology of the umbilicus is natural and satisfying. We conclude that this procedure is safe and simple and the results are satisfactory.
• Transabdominal Ultrasonography for Preoperative Diagnosis of Lymph Node Metastasis in Colon Cancer: A Retrospective Cohort Study.

  Ken Imaizumi, Shigenori Homma, Mutsumi Nishida, Takeshi Soyama, Ryosuke Shimura, Yusuke Kudo, Satomi Omotehara, Isao Yokota, Ryo Takagi, Hiroki Matsui, Yoichi Miyaoka, Nobuki Ichikawa, Tadashi Yoshida, Norihiko Takahashi, Akinobu Taketomi

  Cancer diagnosis & prognosis 2 (2) 173 - 183 2022 

  BACKGROUND/AIM: Although computed tomography (CT) is the standard modality for diagnosing lymph node metastasis (LNM), transabdominal ultrasonography (US) can be useful due to its high spatial resolution and use of Doppler signals to precisely analyse lymph nodes. This study aimed to evaluate the accuracy of US for lymph node assessment, establish US-based diagnostic criteria for LNM, and compare the capability of US with that of CT for the diagnosis of LNM. PATIENTS AND METHODS: This retrospective, single-institution, cohort study included patients who underwent radical surgery for clinical stage 0-III colon cancer, between March 2012 and February 2019. RESULTS: Overall, 34.9% (66/189) of patients had pathological LNM. The optimal US diagnostic criteria were 1) short axis ≥7 mm and short/long ratio ≥0.75 and 2) at least two of the following: the absence of hilar echoes, expansive appearance, or peripheral/mixed vascularity by the colour Doppler and/or contrast-enhanced method. Compared to CT, US showed a higher diagnostic sensitivity (54.5% vs. 43.9%; p=0.296), higher concordance with the number of pathological LNM (correlation coefficient: US, 0.42; CT, 0.27) and pathological N diagnosis (weighted ĸ: US, 0.35; CT, 0.18), and higher sensitivity for advanced LNM, including multiple LNMs (47.4% vs. 18.4%; p=0.014) and N2 stage (27.8% vs. 5.6%; p=0.177). CONCLUSION: US has higher sensitivity than CT for diagnosing LNM in colon cancer, along with a more accurate preoperative diagnosis of the N stage. Additionally, US may be more helpful than CT alone for preoperatively deciding the appropriateness of neoadjuvant treatment in colon cancer with advanced LNM.
• Preventing Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy With Active Hexose-correlated Compound Derived From Lentinula edodes Mycelia.

  Toshiya Kamiyama, Tatsuya Orimo, Kenji Wakayama, Tatsuhiko Kakisaka, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Takeshi Aiyama, Hirofumi Kamachi, Akinobu Taketomi

  Integrative cancer therapies 21 15347354211073066 - 15347354211073066 2022 

  PURPOSE: Active hexose-correlated compound (AHCC), a standardized extract of cultured Lentinula edodes mycelia, exerts antitumor effects through anti-inflammatory and immune-modulatory functions. Adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy has not been established. The purpose of this study was to evaluate the efficacy and safety of AHCC as adjuvant therapy in patients with advanced HCC after curative hepatectomy. PATIENTS AND METHODS: The study design was single-armed, non-randomized, open (no one was blinded), and uncontrolled. Patients with HCC who underwent curative hepatectomy were treated with AHCC (1 g) 3 times daily orally for 2 years. The inclusion criteria were HCC diagnosed preoperatively as stages A and B of the Barcelona clinic liver cancer (BCLC) classification and alpha-fetoprotein × protein induced by vitamin K absence or antagonist II (PIVKA-II) ≥ 105 for stage A. RESULTS: A total of 29 patients were treated with AHCC, of which 25 (4 patients discontinued) were followed up. The 2-year recurrence-free survival rate after resection was 48% for those without discontinuations and 55.2% for all patients with a history of treatment. Serum albumin levels decreased to a minimum in the first postoperative month and gradually recovered to the preoperative level at 6 months. Almost no change in lymphocyte percentage was observed during follow-up. Inflammation-based prognostic scores were maintained at favorable levels after hepatectomy. Toxicity and adverse events were not observed in any patient. CONCLUSION: AHCC may be safe and effective in preventing HCC recurrence after curative hepatectomy, and further randomized trials of AHCC for its use in this setting are warranted.This clinical trial was registered in UMIN Clinical Trials Registry (ID UMIN000024396).
• [Successful treatment of a fulminant-type Wilson's disease with deceased donor liver transplantation after recovery from critical illness].

  Yosuke Wakui, Ryoichi Goto, Masaaki Watanabe, Norio Kawamura, Koji Ogawa, Tomoko Mitsuhashi, Tsuyoshi Shimamura, Akinobu Taketomi

  Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 119 (12) 1096 - 1102 2022 

  A 15-year-old female patient was diagnosed with a fulminant-type Wilson's disease. She had severe illness with a Model for End-Stage Liver Disease score of 25 and new Wilson Index score of 11. She underwent plasma exchanges, hemodiafiltration, and administration of fresh frozen plasma on consecutive days. Finally, she had recovered from severe illness and was discharged from the hospital. After 18 months of waiting time, she underwent deceased liver transplantation and returned to normal daily life. In Japan, the critical shortage of donated organs requires a long waiting time. Previous studies demonstrated that artificial liver support systems, including plasma exchange and hemodiafiltration, could be useful for a fulminant-type Wilson's disease. For such a disease, multidisciplinary bridging treatments are crucial for a successful liver transplantation.
• Living Donor Liver Transplantation for Hepatic Venoocclusive Disease/Sinusoidal Obstruction Syndrome Originating from Hematopoietic Stem Cell Transplantation.

  Kentaro Ichimura, Norio Kawamura, Ryoichi Goto, Masaaki Watanabe, Yoshikazu Ganchiku, Tsuyoshi Shimamura, Akinobu Taketomi

  Case reports in transplantation 2022 8361769 - 8361769 2022 

  Background: Venoocclusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening hematopoietic stem cell transplantation (HSCT) complication. Cases of mild and moderate VOD/SOS are self-limiting; however, the mortality for severe VOD/SOS has reached 80%. Recently, defibrotide became available and has been used for VOD/SOS; however, the outcome for patients with severe VOD/SOS is not satisfactory, and liver transplantation is attempted in these severe cases. Method: We describe a case of living donor liver transplantation (LDLT) for acute liver failure secondary to VOD/SOS that originates from HSCT. Result: Liver regeneration after LDLT was impaired, and several infections were developed before liver regeneration completion. Our patient suffered sepsis and finally died of multiorgan failure. Conclusion: Severe VOD/SOS originating from HSCT is associated with a very poor prognosis. The liver transplantation outcome for VOD/SOS has not been satisfied, but it may provide long-term survival if successful. We considered liver transplantation as a therapeutic option, especially in cases where sufficient graft volume is secured, considering impaired liver regeneration under bone marrow suppression after HSCT.
• 早期肝細胞癌に対する腹腔鏡下肝部分切除術の治療成績

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 相山 健, 蒲池 浩文, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO084 - 6 1344-6703 2021/12
• 腹腔鏡下に完全摘除した後腹膜神経鞘腫の1例

  三國 夢人, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  北海道外科雑誌 北海道外科学会 66 (2) 170 - 171 0288-7509 2021/12
• 横行結腸・脾彎曲・下行結腸癌に対する郭清手技と治療成績 下行結腸癌 下行結腸癌に対する腹腔鏡下左半結腸切除手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 谷 道夫, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) PD16 - 6 1344-6703 2021/12
• 鏡視下局所進行直腸癌切除後の局所再発に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO017 - 4 1344-6703 2021/12
• 低位前方切除術に対するdiverting stoma造設基準の妥当性に関する検討

  谷 道夫, 本間 重紀, 吉田 雅, 市川 伸樹, 江本 慎, 松井 博紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO141 - 1 1344-6703 2021/12
• 経会陰的内視鏡を併用した腹会陰式直腸切断術の初期経験

  松井 博紀, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 谷 道夫, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO166 - 6 1344-6703 2021/12
• 直腸癌に対するロボット支援手術導入初期成績の検討

  大野 陽介, 山本 寛大, 鈴木 琢士, 海老沼 翔太, 合地 美香子, 深作 慶友, 腰塚 靖之, 芝木 泰一郎, 柳田 尚之, 本間 重紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO208 - 3 1344-6703 2021/12
• Stage II-III直腸癌に対する腹腔鏡手術の治療成績

  江本 慎, 本間 重紀, 吉田 雅, 市川 伸樹, 松井 博紀, 谷 道夫, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) MO220 - 5 1344-6703 2021/12
• The incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer in Japanese hospitals: A large-scale clinical study

  Nobuki Ichikawa, Shigenori Homma, Tohru Funakoshi, Keisuke Obuchi, Takahiro Ohshima, Kazuhito Uemura, Hirofumi Kon, Yosuke Ohno, Ryoichi Yokota, Akinobu Taketomi

  ANNALS OF GASTROENTEROLOGICAL SURGERY 6 (3) 396 - 404 2475-0328 2021/12 

  Aim The aim of this retrospective study was to investigate the incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer. Methods This study involved 2017 patients with stages 0-III colorectal cancer who underwent laparoscopic surgery at 17 Japanese hospitals between January 2010 and December 2013. We assessed the incidence of postoperative cardiovascular thrombotic and haemorrhagic complications. Results Laparoscopic surgeries were performed in 1152 men and 865 women with 1405 colon and 612 rectal cancers, respectively. Overall, 3%, 38%, 17%, 8%, and 9% of patients had comorbidities of heart failure, high blood pressure, diabetes, history of stroke, and vascular disease, respectively. Antithrombotic agents were being consumed by 17% of patients. The types (and perioperative rest periods) of the antithrombotic agents were aspirin in 58% (18.6 days), clopidogrel in 19% (21.1 days), cilostazol in 13% (13.3 days), and warfarin potassium in 21% (14.6 days) of cases with antithrombotic agents. Surgical time and blood loss in the total cohort were 234 minutes and 56 mL. Four cases (0.2%) had cardiovascular thrombotic complications, including one severe cardiac infarction and one stroke with major sequelae (CHADS2 scores were 2 points in both cases). Hemorrhagic complications occurred in 19 cases (0.9%). In particular, the incidence of the major gastroduodenal haemorrhagic ulcer was higher in cases with antithrombotic agents than without them (0.05% vs 0%, P = .02). Conclusion The incidence of cardiovascular thrombotic complications was rare, although severe cardiac infarction and stroke could occur even after minimally invasive surgery in colorectal cancer.
• Meckel’s diverticulum with intraperitoneal hemorrhage in a child detected with screening laparoscopy: a case report

  Kazuki Wakizaka, Lee Wee Khor, Kazuya Annen, Tsuyoshi Fukushima, Mitsuko Furuya, Akinobu Taketomi

  Surgical Case Reports 7 (1) 2021/12 

  Abstract Background The most common presentation of symptomatic Meckel’s diverticulum (MD) are intestinal obstruction, gastrointestinal hemorrhage, and inflammation of the MD with or without perforation. Intraperitoneal hemorrhage because of MD is extremely rare. We report a case of MD with intraperitoneal hemorrhage in a child detected with screening laparoscopy. Case presentation An 11-year-old girl presented to another hospital with lower abdominal pain and vomiting that lasted for 2 days. Acute appendicitis was suspected, and she was referred to our department. Abdominal enhanced computed tomography showed an abscess in the lower abdomen with ascites in the pelvis. She was diagnosed with a localized intra-abdominal abscess and the decision was made to treat with antibiotics. However, her abdominal pain worsened, with abdominal distension, tenderness and guarding. She was diagnosed with panperitonitis and the decision was made for surgery 5 h after admission. During surgery, laparoscopic observation from the umbilical region revealed 200 ml of fresh blood throughout the peritoneal cavity, originating from the mesentery of the ileum. MD was observed with bleeding from the surrounding mesentery. Small bowel resection was performed, and the patient was discharged on the 5th postoperative day. Pathological findings revealed an MD containing ectopic gastric mucosa and small intestinal ulcer perforation at the base of the MD. Conclusions We report an extremely rare case of an MD with intraperitoneal hemorrhage in a child. In pediatric cases, it is possible that perforation with ectopic gastric mucosa may cause massive bleeding because of rupture of the surrounding mesenteric blood vessels.
• The impact of COVID-19 on surgical procedures in Japan: analysis of data from the National Clinical Database

  Norihiko Ikeda, Hiroyuki Yamamoto, Akinobu Taketomi, Taizo Hibi, Minoru Ono, Naoki Niikura, Iwao Sugitani, Urara Isozumi, Hiroaki Miyata, Hiroaki Nagano, Michiaki Unno, Yuko Kitagawa, Masaki Mori

  Surgery Today 0941-1291 2021/11/16 

  The spread of COVID-19 has restricted the delivery of standard medical care to surgical patients dramatically. Surgical triage is performed by considering the type of disease, its severity, the urgency for surgery, and the condition of the patient, in addition to the scale of infectious outbreaks in the region. The purpose of this study was to evaluate the impact of the COVID-19 pandemic on the number of surgical procedures performed and whether the effects were more prominent during certain periods of widespread infection and in the affected regions. We selected 20 of the most common procedures from each surgical field and compared the weekly numbers of each operation performed in 2020 with the respective numbers in 2018 and 2019, as recorded in the National Clinical Database (NCD). The surgical status during the COVID-19 pandemic as well as the relationship between surgical volume and the degree of regional infection were analyzed extensively. The rate of decline in surgery was at most 10–15%. Although the numbers of most oncological and cardiovascular procedures decreased in 2020, there was no significant change in the numbers of pancreaticoduodenectomy and aortic replacement procedures performed in the same period. The numbers of most surgical procedures decreased in 2020 as a result of the COVID-19 pandemic; however, the precise impact of surgical triage on decrease in detection of disease warrants further investigation.
• Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma.

  Yoh Asahi, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Takeshi Aiyama, Yuzuru Sakamoto, Hirofumi Kamachi, Akinobu Taketomi

  World journal of gastrointestinal surgery 13 (10) 1245 - 1257 2021/10/27 

  BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated. AIM: To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy. METHODS: Thirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively. RESULTS: The 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when ≤ 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473). CONCLUSION: Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that ≤ 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.
• Functional Roles of Graft Infiltrating Lymphocytes during Early Phase Post‐transplantation in Mouse Cardiac Transplantation Models

  Yoshikazu Ganchiku, Ryoichi Goto, Ryo Kanazawa, Takuji Ota, Kazuaki Shibuya, Yasutomo Fukasaku, Nozomi Kobayashi, Rumi Igarashi, Norio Kawamura, Masaaki Zaitsu, Masaaki Watanabe, Akinobu Taketomi

  Transplant International 0934-0874 2021/10/23
• 小児外科専門医不在・不足地域での小児外科医療 小児外科専門医不在・不足地域での小児外科医療 北海道における現況 民間病院の立場から

  大場 豪, 山本 浩史, 浜田 弘巳, 縫 明大, 石井 大介, 宮城 久之, 本多 昌平, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S171 - S171 1345-2843 2021/10
• 肝癌に対する肝移植の新たな適応基準に基づいた治療成績 肝細胞癌治療における肝移植の役割 Japan criteria導入後に予想される変化

  渡辺 正明, 後藤 了一, 川村 典生, 巌築 慶一, 嶋村 剛, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S166 - S166 1345-2843 2021/10
• conventional TME vs trans-anal TME適応の実際 骨盤内再発例に対するTp-TME

  本間 重紀, 谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S195 - S195 1345-2843 2021/10
• Stage II-III大腸癌におけるKlintrup gradeと予後

  松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 江本 慎, 谷 道夫, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S687 - S687 1345-2843 2021/10
• 直腸低位前方切除術に対する人工肛門造設基準の妥当性に関する検討

  谷 道夫, 松井 博紀, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S725 - S725 1345-2843 2021/10
• 進行結腸癌肥満症例に対する腹腔鏡下手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 谷 道夫, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S732 - S732 1345-2843 2021/10
• 脂肪肝の温阻血再灌流傷害に伴うリゾフォスファチジルイノシトールの変動と局在変化 イメージング質量分析による網羅的解析

  柴田 賢吾, 橋本 咲月, 早坂 孝宏, 深井 原, 島田 慎吾, 三野 和宏, 嶋村 剛, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 118 (臨増大会) A702 - A702 0446-6586 2021/10
• 移植後de novo発がんに関する諸問題 本邦の多施設共同研究による生体肝移植後グラフト肝に発生するde novo HCCのリスク因子の検討

  後藤 了一, 八木 真太郎, 小斉 侑希子, 嶋村 剛, 大段 秀樹, 島田 光生, 小倉 靖弘, 長谷川 潔, 吉住 朋晴, 前原 喜彦, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S233 - S233 1345-2843 2021/10
• 肝細胞癌に対する最新の集学的治療 術後再発肝細胞癌に対する分子標的薬使用の意義

  旭 よう, 神山 俊哉, 折茂 達也, 柿坂 達彦, 長津 明久, 相山 健, 蒲池 浩文, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 82 (増刊) S280 - S280 1345-2843 2021/10
• 大腸癌周術期治療の臨床開発と将来展望 進行直腸癌に対する化学放射線療法と免疫チェックポイント阻害剤を用いた術前治療

  塚田 祐一郎, 坂東 英明, 稲守 宏冶, 冨樫 庸介, 結城 敏志, 小松 嘉人, 本間 重紀, 武冨 紹信, 植村 守, 加藤 健志, 若林 将史, 佐藤 暁洋, 西川 博嘉, 伊藤 雅昭, 吉野 孝之

  日本癌治療学会学術集会抄録集 59回 SY2 - 4 2021/10
• Hepatectomy and immune checkpoint inhibitor treatment for liver metastasis originating from non-cutaneous melanoma: a report of three cases.

  Yoh Asahi, Toshiya Kamiyama, Tatshiko Kakisaka, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yuzuru Sakamoto, Takaya Ishikawa, Hirofumi Kamachi, Tomoko Mitsuhashi, Satoshi Takeuchi, Hirotoshi Dosaka-Akita, Akinobu Taketomi

  International cancer conference journal 10 (4) 274 - 279 2021/10 

  The outcomes of hepatectomy alone for liver metastasis derived from non-cutaneous melanoma are insufficient, and the outcomes of systemic therapy alone are also insufficient, even since the development of immune checkpoint inhibitors (ICIs). We report the cases of three patients, in whom liver metastasis derived from non-cutaneous melanoma was treated with hepatectomy combined with ICI therapy, which was administered in various settings. One patient received ICI treatment for recurrent melanoma and survived 107 months after the first hepatectomy, one patient received both preoperative and adjuvant ICI treatment and has been disease-free for 27 months, and another patient received postoperative ICI treatment after reduction hepatectomy and has been alive with disease for 47 months. Since long-term survival is possible, hepatectomy combined with ICI therapy should be considered for the treatment of liver metastasis derived from non-cutaneous melanoma.
• Anti-Donor Regulatory T-Cell Therapy in Adult-to-Adult Living Donor Liver Transplantation: A Case Report.

  Susumu Eguchi, Koichiro Uchida, Mitsuhisa Takatsuki, Satomi Okada, Masaaki Hidaka, Akihiko Soyama, Takanobu Hara, Hajime Matsushima, Tomohiko Adachi, Kazuhiro Nagai, Masaaki Watanabe, Akinobu Taketomi, Ko Okumura, Kenichiro Yamashita, Satoru Todo

  Transplantation proceedings 53 (8) 2570 - 2575 2021/09/10 

  We report on the case of a 50-year-old female patient with symptomatic polycystic liver disease who underwent living donor liver transplantation (LDLT) using right liver graft from her ABO-identical husband. To achieve operational tolerance, regulatory T-cell (T-reg)-based cell therapy was applied, following the protocol introduced by Todo et al. Briefly, donor lymphocytes were collected by leukapheresis 20 days before LDLT without any adverse events, and the cells were irradiated with a dose of 30 Gy and kept frozen. Lymphopheresis of the recipient was conducted in a similar manner 1 day before LDLT, and donor cells and recipient cells were cultured with anti-CD80/86 antibodies to induce the donor-specific T-reg. At 14 days of culture, the CD4+CD25+Foxp3+ cells had increased from 1.51% to 5.21%, and mixed lymphocyte reaction assay using an intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester-labeling technique revealed donor-specific hyporesponsiveness of CD4-positive lymphocytes. On postoperative day (POD) 13 (14 days of culture), these cells were infused to the recipient intravenously without any adverse events. Initial immunosuppression consisted of tacrolimus, steroid and mycophenolate mofetil (MMF), and cyclophosphamide (40 mg/kg) administered on POD 5. Both the steroid and MMF were continued until 4 weeks after LDLT, and the patient was discharged on POD 30 with normal liver function. On POD 52, the patient developed acute cellular rejection and received appropriate reinforcement of immunosuppressive therapy and is currently doing well with normal liver function 30 months after LDLT with reduced anti-donor allo-activity. In summary, T-reg therapy was safely performed in adult LDLT, and we are following the patient carefully to determine whether she can achieve operational tolerance in the future.
• Combination therapy for hepatocellular carcinoma with diacylglycerol kinase alpha inhibition and anti-programmed cell death-1 ligand blockade.

  Naoki Okada, Ko Sugiyama, Shunsuke Shichi, Yasuhito Shirai, Kaoru Goto, Fumio Sakane, Hidemitsu Kitamura, Akinobu Taketomi

  Cancer immunology, immunotherapy : CII 71 (4) 889 - 903 2021/09/05 

  Activation of diacylglycerol kinase alpha (DGKα) augments proliferation and suppresses apoptosis of cancer cells and induces T lymphocyte anergy. We investigated the dual effects of DGKα inhibition on tumorigenesis and anti-tumor immunity with the aim of establishing a novel therapeutic strategy for cancer. We examined the effects of a DGKα inhibitor (DGKAI) on liver cancer cell proliferation and cytokine production by immune cells in vitro and on tumorigenesis and host immunity in a hepatocellular carcinoma (HCC) mouse model. Oral DGKAI significantly suppressed tumor growth and prolonged survival in model mice. Tumor infiltration of T cells and dendritic cells was also enhanced in mice treated with DGKAI, and the production of cytokines and cytotoxic molecules by CD4+ and CD8+ T cells was increased. Depletion of CD8+ T cells reduced the effect of DGKAI. Furthermore, interferon-γ stimulation augmented the expression of programmed cell death-1 ligand (PD-L1) on cancer cells, and DGKAI plus an anti-PD-L1 antibody strongly suppressed the tumor growth. These results suggest that DGKα inhibition may be a promising new treatment strategy for HCC.
• 肝移植後小児レシピエントに対する弱毒生ワクチン投与

  渡辺 正明, 後藤 了一, 川村 典生, 巌築 慶一, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 56 (総会臨時) O12 - 5 0578-7947 2021/09
• 肝移植におけるABO不適合・抗体関連拒絶への対策 小児生体肝移植後de novo抗ドナー抗体陽性の線維化進行リスク因子の検討

  後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 長津 明久, 神山 俊哉, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 56 (総会臨時) SSY7 - 3 0578-7947 2021/09
• 肝細胞癌において血清中表皮型脂肪酸結合タンパク質は組織中発現レベルとは独立した予後不良因子である

  大平 将史, 横尾 英樹, 小川 浩司, 深井 原, 神山 俊哉, 坂本 直哉, 武冨 紹信

  日本癌学会総会記事 80回 [J14 - 4] 0546-0476 2021/09
• 当科におけるロボット支援下手術の初期成績

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (9) A109 - A109 0047-1801 2021/09
• ウルソデオキシコール酸内服によるクローン病患者の腸結石

  松井 博紀, 本間 重紀, 吉田 雅, 市川 伸樹, 江本 慎, 宮岡 陽一, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (9) A117 - A117 0047-1801 2021/09
• CTを用いた大腸癌の術前所属リンパ節転移の評価

  江本 慎, 本間 重紀, 市川 伸樹, 今泉 健, 吉田 雅, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (9) A135 - A135 0047-1801 2021/09
• 高齢者直腸癌に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (9) A149 - A149 0047-1801 2021/09
• Lateral lymph node recurrence of rectal cancer with a pathological complete response to chemotherapy confirmed by laparoscopic lateral lymph node dissection: A case report.

  Kazuki Wakizaka, Shigenori Homma, Nobuki Ichikawa, Tadashi Yoshida, Hiroki Matsui, Lee Wee Khor, Kazuya Annen, Tsuyoshi Fukushima, Akinobu Taketomi

  Asian journal of endoscopic surgery 15 (1) 216 - 219 2021/08/09 

  Lateral lymph node (LLN) metastasis is one of the forms of local recurrence after surgery for lower rectal cancer. We here present a case of LLN recurrence of rectal cancer that was shown by laparoscopic lateral lymph node dissection (LLND) to have a complete pathological response to chemotherapy. A 58-year-old man underwent open low anterior resection for lower rectal cancer. After detection of right LLN recurrence 43 months after the operation, 11 cycles of capecitabine, oxaliplatin, and bevacizumab chemotherapy were administered. Laparoscopic right LLND was performed 55 months after the first operation. Pathological examination revealed no viable tumor cells in the dissected lymph nodes. The patient remains alive without recurrence 61 months after the first surgery and 6 months after laparoscopic LLND. Laparoscopic LLND for LLN recurrence of rectal cancer is feasible and should be considered a valid treatment option.
• Combined treatment of an aortosplenic bypass followed by coil embolization in the treatment of pancreaticoduodenal artery aneurysms caused by median arcuate ligament compression: a report of two cases.

  Shuhei Kii, Hirofumi Kamachi, Daisuke Abo, Takuya Kato, Yousuke Tsuruga, Kenji Wakayama, Tatsuhiko Kakisaka, Takeshi Soyama, Toshiya Kamiyama, Tomonori Ooka, Satoru Wakasa, Akinobu Taketomi

  Surgical case reports 7 (1) 174 - 174 2021/08/04 

  BACKGROUND: Pancreaticoduodenal artery aneurysms (PDAAs) are rare visceral aneurysms, and prompt intervention/treatment of all PDAAs is recommended at the time of diagnosis to avoid rupture of aneurysms. Herein, we report two cases of PDAA caused by the median arcuate ligament syndrome, treated with surgical revascularization by aortosplenic bypass followed by coil embolization. CASE PRESENTATION: Case 1 A 54-year-old woman presented with a chief complaint of severe epigastralgia and was diagnosed with two large fusiform inferior PDAAs and celiac axis occlusion. To preserve the blood flow of the pancreatic head, duodenum, liver, and spleen, we performed elective surgery to release the MAL along with aortosplenic bypass. At 6 days postoperatively, transcatheter arterial embolization was performed. At the 8-year 6-month follow-up observation, no recurrent perfusion of the embolized PDAAs or rupture had occurred, including the non-embolized small PDAA, and the bypass graft had excellent patency. Case 2 A 39-year-old man who had been in good health was found to have a PDAA with celiac stenosis during a medical checkup. Computed tomography and superior mesenteric arteriography showed severe celiac axis stenosis and a markedly dilated pancreatic arcade with a large saccular PDAA. To preserve the blood flow of the pancreatic arcade, we performed elective surgery to release the MAL along with aortosplenic bypass. At 9 days postoperatively, transcatheter arterial embolization was performed. At the 6-year 7-month follow-up observation, no recurrent perfusion or rupture of the PDAA had occurred, and the bypass graft had excellent patency. CONCLUSION: Combined treatment with bypass surgery and coil embolization can be an effective option for the treatment of PDAAs associated with celiac axis occlusion or severe stenosis.
• High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection.

  Shingo Shimada, Toshiya Kamiyama, Tatsuya Orimo, Akihisa Nagatsu, Hirofumi Kamachi, Akinobu Taketomi

  Hepatobiliary surgery and nutrition 10 (4) 454 - 463 2021/08 

  Background: Currently, the population with type 2 diabetes mellitus (DM) is increasing worldwide. However, the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma (HCC) is unclear. Methods: We analyzed 756 patients with HCC who underwent hepatectomy. These patients were assigned to an HbA1c ≥7.0% (H-A1c; n=100) or HbA1c <7.0% (L-A1c; n=656) group depending on their HbA1c level at admission. We investigated prognoses, clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c, prognoses according to the treatment for DM were also investigated. Results: Among all patients and those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, overall survival (OS) and relapse-free survival (RFS) did not differ significantly between the H-A1c and L-A1c groups. In contrast, the 5-year OS rate of the H-A1c group was 55% and that of the L-A1c group 71% among patients without HBV and HCV (NBNC patients) (P=0.03). Among NBNC patients, the median RFS of the H-A1c group was 13 months, and that of the L-A1c group was 26 months (P=0.02). In addition, metformin use was an independent favorable factor for both OS and RFS. The H-A1c group had significantly higher rates of hyperbilirubinemia, wound infection, and pneumonia. Conclusions: HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in NBNC-HCC. High HbA1c may also be a risk factor for morbidities after hepatectomy. Metformin use may constitute a good option for NBNC patients with HCC.
• Hepatic Resection for Hepatocellular Carcinoma in the Era of Molecular-targeted Agents and Immune Checkpoint Inhibitors in Japan.

  Akinobu Taketomi

  JMA journal 4 (3) 241 - 245 2021/07/15 

  Hepatic resection or liver transplantation for hepatocellular carcinoma (HCC) represents the only chance for achieving a cure. For the past several decades in Japan, aggressive hepatic resection has been performed for advanced HCC, with consequent good outcomes. According to the 21st Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 38.3% of patients were treated with hepatic resection or liver transplantation as the initial treatment. The median overall survival of patients who underwent surgery was 57.0 months, and the 5- and 10-year survival rates were 48.4% and 25.2%, respectively. Since 1964, a total of 10,038 liver transplants (595 deceased-donor and 9,443 living-donor transplants) have been performed in Japan. Neoplastic disease, including HCC, was reported to be the third-most common cause of liver transplantation, and the cumulative 1-, 3-, 5-, and 10-year survival rates of living-donor liver transplants for HCC were 85.0%, 76.2%, 70.9%, and 63.1%, respectively. However, molecular-targeted agents, including sorafenib and lenvatinib, have recently been developed. Furthermore, a significantly longer survival with atezolizumab, which is an immune checkpoint inhibitor, plus bevacizumab was observed compared with sorafenib for unresectable HCC patients. Herein, we review the current status of hepatic resection and liver transplantation for HCC in Japan and discuss the role of hepatic resection in the era of molecular-targeted agents and immune checkpoint inhibitors, as well as the need for a definition of borderline resectable-HCC.
• Modified complete mesocolic excision with central vascular ligation by the squeezing approach in laparoscopic right colectomy.

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Shin Emoto, Ken Imaizumi, Yoichi Miyaoka, Hiroki Matsui, Akinobu Taketomi

  Langenbeck's archives of surgery 407 (1) 409 - 419 2021/07/13 

  PURPOSE: Complete mesocolic excision (CME) and central vascular ligation (CVL) are becoming the standard procedure in laparoscopic right-sided colectomy. However, the approach to CME and CVL has not been established, although several useful approaches have been reported. The squeezing approach described herein is a novel procedure to perform modified CME and CVL in laparoscopic right colectomy. METHODS: The squeezing approach features retroperitoneal mobilization followed by cranial mesocolic mobilization and lymph node dissection using a cranial approach followed by a caudal approach. Dissection of the regional lymph nodes along with central vascular ligation was performed along the anterior wall of the superior mesenteric vein. In total, 177 patients (mean age, 70.6 years; male-to-female ratio, 90:87) who underwent laparoscopic right-sided colectomy were retrospectively assessed. Descriptive statistics for patient characteristics were calculated. RESULTS: The mean operative time and blood loss were 169 min and 37 mL, respectively. Seven patients (4.0%) required conversion to open surgery, and major postoperative complications occurred in five patients (2.8%) with no anastomotic leakage. Histological R0 resection was achieved in all cases of stages 0-III colon cancer. The 5-year recurrence-free survival rates were 100% (n = 19), 100% (n = 40), 87% (n = 46), and 81% (n = 43) in pathological stages 0, I, II, and III, respectively. Node recurrence occurred in one case near the root of the middle colic artery. CONCLUSION: The novel squeezing approach in laparoscopic right colectomy could be safely performed in terms of the technical and oncological aspects.
• 高齢者に対する肝臓外科治療 後期高齢者における術前経皮経肝的門脈塞栓術の有用性の検討

  坂本 譲, 神山 俊哉, 島田 慎吾, 旭 よう, 長津 明久, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 PD5 - 7 2021/07
• BRA膵癌に対する治療戦略 BR膵癌に対するジェムシタビン併用術前化学放射線療法の成績

  蒲池 浩文, 折茂 達也, 柿坂 達彦, 島田 慎吾, 長津 明久, 旭 よう, 坂本 譲, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 O34 - 6 2021/07
• 本邦膵臓移植症例におけるrituximab(遺伝子組換え)に関する使用実態調査の結果 膵移植後rituximab使用4症例の報告

  伊藤 泰平, 剣持 敬, 栗原 啓, 會田 直弘, 後藤 了一, 渡辺 正明, 嶋村 剛, 武冨 紹信, 大島 稔, 岡野 圭一, 鈴木 康之, 中川 健, 江川 裕人

  移植 (一社)日本移植学会 56 (1) 35 - 42 0578-7947 2021/07 

  膵移植後に抗体関連型拒絶反応(AMR)を発現し、rituximabを使用した4例を報告した。移植時年齢は30歳代から50歳代で、男女各2例であった。AMRは移植後40日目から143日目に診断され、rituximabは拒絶反応発現から最短で1日、最長で20日に1回投与されていた。投与量は81mg/bodyが1例、200mg/bodyが3例で、AMR治療後の膵グラフト生着は1例(25%)で得られていた。有害事象としてはサイトメガロウイルス抗原血症による感染症が1例、骨髄抑制が2例で認められたが、いずれも回復し、患者生命予後に影響を与える有害事象はみられなかった。
• 再発直腸癌に対するTa-TME

  本間 重紀, 松井 博紀, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P033 - 4 2021/07
• 術前放射線化学療法後の局所進行直腸癌鏡視下根治術の短期成績に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P061 - 2 2021/07
• CTを用いた大腸癌の術前所属リンパ節転移の評価

  江本 慎, 本間 重紀, 市川 伸樹, 今泉 健, 吉田 雅, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P081 - 2 2021/07
• 大腸癌根治切除後の異時性遠隔転移に関わるリスク因子の探索

  沢田 尭史, 松井 博紀, 谷 道夫, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P084 - 1 2021/07
• 高齢者直腸癌に対する術式選択

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 宮岡 陽一, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P195 - 4 2021/07
• 浸潤先進部の新規病理所見であるInvasion front gradeによる大腸癌の予後層別化

  松井 博紀, 畑中 佳奈子, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 松野 吉宏, 畑中 豊, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P256 - 3 2021/07
• 大腸癌根治切除後の異時性遠隔転移に関わるリスク因子の探索

  沢田 尭史, 松井 博紀, 谷 道夫, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 P084 - 1 2021/07
• 本邦膵臓移植症例におけるrituximab(遺伝子組換え)に関する使用実態調査の結果 膵移植後rituximab使用4症例の報告

  伊藤 泰平, 剣持 敬, 栗原 啓, 會田 直弘, 後藤 了一, 渡辺 正明, 嶋村 剛, 武冨 紹信, 大島 稔, 岡野 圭一, 鈴木 康之, 中川 健, 江川 裕人

  移植 (一社)日本移植学会 56 (1) 35 - 42 0578-7947 2021/07
• 非大腸癌肝転移に対する肝切除の意義 悪性黒色腫肝転移に対する肝切除と免疫チェックポイント阻害剤の使用 3症例の検討

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 76回 RS18 - 3 2021/07
• Novel Prognostic Stratification Factor Based on the Pathological Profile of the Invasive Front in Colorectal Cancer.

  Hiroki Matsui, Shigenori Homma, Kanako C Hatanaka, Akifumi Sawada, Ken Imaizumi, Tadashi Yoshida, Nobuki Ichikawa, Shin Emoto, Yoichi Miyaoka, Norihiko Takahashi, Yoshihiro Matsuno, Yutaka Hatanaka, Akinobu Taketomi

  Anticancer research 41 (7) 3429 - 3438 2021/07 

  BACKGROUND/AIM: This study aimed to develop a new pathological finding, namely, invasion front grade and verify its clinical usefulness. MATERIALS AND METHODS: We re-examined haematoxylin-eosin-stained specimens in 162 stage II-III colorectal cancer patients who underwent radical resection. We assessed the desmoplastic reaction, Klintrup grade, and poorly differentiated cluster. These three findings were combined to form the invasion front grade (good prognosis group; Grade A, poor prognosis group; Grade B), and its reproducibility and prognostic stratification ability were statistically analysed. RESULTS: Invasion front grade was Grade A in 116 cases and Grade B in 46 cases, and its kappa coefficient was 0.81 for interobserver and 0.74 for intraobserver variability. The 3-year recurrence-free survival rates of Grade A and Grade B were 90.4% and 55.9%. Multivariate analysis showed that invasion front grade was an independent prognostic factor. CONCLUSION: Invasion front grade is useful as a prognostic stratification factor for stage II-III colorectal cancer.
• Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma.

  Yuichi Yoshida, Sachiyo Yoshio, Taiji Yamazoe, Taizo Mori, Yuriko Tsustui, Hironari Kawai, Shiori Yoshikawa, Takasuke Fukuhara, Toru Okamoto, Yoshihiro Ono, Yu Takahashi, Ryuki Hashida, Takumi Kawaguchi, Akinobu Taketomi, Tatsuya Kanto

  Cells 10 (6) 2021/06/14 

  Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients.
• A case report of percutaneous direct injection of N-butyl-2-cyanoacrylate (NBCA) to treat a pancreatic duodenal stump leak after a simultaneous pancreas and kidney transplantation.

  Chisato Shirakawa, Masaaki Watanabe, Tsuyoshi Shimamura, Yasuyuki Koshizuka, Norio Kawamura, Ryoichi Goto, Takeshi Soyama, Daiki Iwami, Kiyohiko Hotta, Akinobu Taketomi, Daisuke Abo

  Surgical case reports 7 (1) 139 - 139 2021/06/08 

  BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) is a treatment option for patients with end-stage renal disease due to type 1 diabetes mellitus. We report a patient with a refractory fistula due to leakage from the duodenal stump of the pancreas graft after an SPK with bladder drainage who was successfully treated with a percutaneous direct injection of N-butyl-2-cyanoacrylate (NBCA). CASE PRESENTATION: A 60-year-old female with a 33-year history of type 1 diabetes mellitus and a 10-year history of renal replacement therapy underwent an SPK in 2015. At the time of transplantation, an abdominal aortic aneurysm with a high risk of rupture was treated by a Y-graft replacement prior to the SPK. Bladder drainage of the pancreas graft was chosen to avoid a vessel graft infection. The patient's postoperative course was uneventful. The patient was discharged on postoperative day 93 with good-functioning pancreas and kidney grafts. One and a half years after the operation, the patient was found to have acute graft pancreatitis and a leak from the duodenal stump of the pancreas graft due to a paralytic neurogenic bladder. The insertion of an indwelling catheter into the bladder and the endoscopic-guided insertion of a catheter into the graft pancreatic duct through the duodenum/bladder anastomosis did not result in the closure of the fistula. Therefore, NBCA was injected at the site of the leak point using CT-guided technique. The fistula was completely closed immediately after the injection, with no recurrences of leaks. CONCLUSIONS: A percutaneous direct injection of NBCA is one of the treatment options to treat intractable fistulas.
• 【局所進行直腸癌の根治性向上に向けた集学的治療のupdate】

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  北海道外科雑誌 北海道外科学会 66 (1) 2 - 12 0288-7509 2021/06 

  直腸癌は結腸癌に比べ、遠隔転移のみならず局所再発が多い事が特徴で、局所治療を改善させる為の試みが歴史的に積み重ねられてきた。1982年にHealdらによってTME(total mesorectal excision:全直腸間膜切除)の概念が報告され、直腸固有筋膜に包まれたまま直腸を切除する事で、局所再発および生命予後が改善する事が示されたが、更に局所再発を減らす努力として、欧米では術前療法としての放射線療法が確立された。本編では、この放射線療法をめぐる歴史と論点をまとめた。また、近年では、術前放射線療法後にCR(complete response)となった症例に、手術を行わず経過をみるストラテジー(Watch and Wait)や、全身療法としての術後補助化学療法を術前に行う事で、治療の完遂率が上げ、遠隔転移の抑制を含め生命予後を改善させる事を目指すストラテジーTNT(total neoadjuavant therapy)が注目されており、これらについても論点をまとめた。(著者抄録)
• Comparison of laparoscopic and open hepatectomy with synchronous colectomy for colorectal cancer with synchronous liver metastasis(和訳中)

  Asahi Yoh, Kamiyama Toshiya, Kakisaka Tatsuhiko, Orimo Tatsuya, Nagatsu Akihisa, Sakamoto Yuzuru, Kamachi Hirofumi, Homma Shigenori, Ichikawa Nobuki, Yoshida Tadashi, Taketomi Akinobu

  日本肝胆膵外科学会・学術集会プログラム・抄録集 33回 291 - 291 2021/06
• 【局所進行直腸癌の根治性向上に向けた集学的治療のupdate】

  市川 伸樹, 本間 重紀, 吉田 雅, 江本 慎, 松井 博紀, 谷 道夫, 武冨 紹信

  北海道外科雑誌 北海道外科学会 66 (1) 2 - 12 0288-7509 2021/06 

  直腸癌は結腸癌に比べ、遠隔転移のみならず局所再発が多い事が特徴で、局所治療を改善させる為の試みが歴史的に積み重ねられてきた。1982年にHealdらによってTME(total mesorectal excision:全直腸間膜切除)の概念が報告され、直腸固有筋膜に包まれたまま直腸を切除する事で、局所再発および生命予後が改善する事が示されたが、更に局所再発を減らす努力として、欧米では術前療法としての放射線療法が確立された。本編では、この放射線療法をめぐる歴史と論点をまとめた。また、近年では、術前放射線療法後にCR(complete response)となった症例に、手術を行わず経過をみるストラテジー(Watch and Wait)や、全身療法としての術後補助化学療法を術前に行う事で、治療の完遂率が上げ、遠隔転移の抑制を含め生命予後を改善させる事を目指すストラテジーTNT(total neoadjuavant therapy)が注目されており、これらについても論点をまとめた。(著者抄録)
• Genomewide transcriptomic profiling identifies a gene signature for predicting recurrence in early-stage hepatocellular carcinoma.

  Tatsuhiko Kakisaka, Moto Fukai, Jasjit K Banwait, Toshiya Kamiyama, Tatsuya Orimo, Tomoko Mitsuhashi, Kensuke Yamamura, Takeo Toshima, Hideo Baba, Akinobu Taketomi, Ajay Goel

  Clinical and translational medicine 11 (6) e405  2021/06
• A case of laparoscopic hepatectomy for a primary hepatic neuroendocrine tumor.

  Yuzuru Sakamoto, Shingo Shimada, Toshiya Kamiyama, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Tatsuhiko Kakisaka, Hirofumi Kamachi, Tomoko Mitsuhashi, Akinobu Taketomi

  Clinical journal of gastroenterology 14 (3) 876 - 880 2021/06 

  Neuroendocrine tumors (NETs) account for approximately 1-2% of all gastrointestinal tumors. In particular, primary hepatic NETs (PHNETs) are extremely rare. A 42-year-old female patient was given a diagnosis of liver tumor after a medical check-up with ultrasonography. An enhanced CT scan and MRI were suggestive for a hepatic hemangioma or adenoma, but the possibility of hepatocellular carcinoma could not be denied. Moreover, this tumor grew larger, so we performed a laparoscopic partial hepatectomy for the diagnosis and treatment of the patient. Pathological examination revealed that the tumor cells were spindle-shaped, forming glandular-tubular structures, and had less visible nucleoli and increased mitotic figures on H&E staining. Immunohistochemical findings indicated that CK19, MOC-31, CD56, synaptophysin, and chromogranin A were positive; CK7, AFP, and glypican-3 were negative; and the Ki-67 index was 3.6%, so the final diagnosis was a PHNET G2. PHNETs differ from other NETs, as they do not produce biologically active polypeptides or amines. As a result, there are no manifestations of carcinoid syndrome. In addition, PHNETs grow slowly, and most patients show no symptoms in the early stages. Laparoscopic hepatectomy is a very useful procedure for diagnosis and treatment in such cases and can be performed safely.
• The impact of elastography with virtual touch quantification of future remnant liver before major hepatectomy.

  Shingo Shimada, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Yusuke Kudo, Mutsumi Nishida, Akinobu Taketomi

  Quantitative imaging in medicine and surgery 11 (6) 2572 - 2585 2021/06 

  Background: Liver elastography with virtual touch quantification (VTQ) measures the velocity of the shear wave generated by a short-duration acoustic force impulse, with values expressed in units of velocity (m/s). VTQ can evaluate right or left hepatic lobes separately. VTQ might be appropriate for the evaluation of future remnant liver after hepatectomy. Methods: We analyzed 95 patients underwent liver elastography with VTQ and both future remnant liver and resected side before hepatectomy of more than two sections, except for central bisectionectomy. We divided the patients into a high VTQ group (≥1.52 m/s, n=37, 39%) and a low VTQ group (<1.52 m/s, n=58, 61%) according to the VTQ of future remnant liver. Transient elastography could not be performed in 22 cases due to tumor size. We defined the group with liver stiffness measurement (LSM) ≥7.9 kPa as the high LSM group (n=29, 40%) and those with LSM <7.9 kPa as the low LSM group (n=44, 60%). We investigated the outcome after hepatectomy and the correlations between the VTQ of future remnant liver and other indicators for hepatic fibrosis. Results: The high VTQ group showed significantly higher postoperative ascites (19% vs. 3%; P=0.01), pathological fibrosis (19% vs. 5%; P=0.03), and rates of patients with postoperative T-bil ≥2.0 mg/dL (70% vs. 40%; P<0.01). The high LSM group showed no significant postoperative outcomes compared to the low LSM group. The high VTQ group showed a higher frequency of male gender (78% vs. 57%; P=0.03), higher indocyanine green retention rate at 15 min (ICGR15) (10.5% vs. 6.3%; P<0.01), hyaluronic acid (100 vs. 67 ng/mL; P=0.02), type IV collagen 7S (7.6 vs. 5.1 ng/mL; P<0.01), Mac-2 binding protein glycan isomer (M2BPGi) (1.19 vs. 1.00; P=0.01), Fibrosis-4 (FIB-4) index (2.25 vs. 1.76; P=0.01), and aspartate aminotransferase to platelet ratio index (APRI) score (0.64 vs. 0.41; P<0.01). We also observed an especially strong positive correlation between the high VTQ and hyaluronic acid or type IV collagen 7S. Conclusions: Elastography with VTQ for future remnant liver before major hepatectomy is an accurate and useful method as a preoperative evaluation.
• Diagnostic timing dependent characteristics of acute kidney injury following hepatectomy: a retrospective historical cohort analysis.

  Kazuyuki Mizunoya, Yasunori Yagi, Hirofumi Kamachi, Toshiya Kamiyama, Yuji Morimoto, Akinobu Taketomi

  HPB : the official journal of the International Hepato Pancreato Biliary Association 2021/05/18 

  BACKGROUND: The timing of diagnosis of post-hepatectomy acute kidney injury (AKI) has rarely been investigated. The aim of this retrospective study was to reveal the differences between AKI subtypes following hepatectomy, as classified by timing of diagnosis. METHOD: Post-hepatectomy AKI was classified as very transient AKI (vtAKI; criteria satisfied by the serum creatinine value immediately after surgery) or non-transient AKI (ntAKI; all other AKI types except for vtAKI). Multivariate logistic regression analyses for both AKI types were performed separately to identify differences in known perioperative AKI risk factors. The impacts of each AKI subtype on postoperative complications, hospital stay and renal outcome at discharge were also evaluated. RESULTS: AKI was diagnosed in 135 of 750 patients (18.0%); 82 and 53 patients were classified as vtAKI and ntAKI, respectively. In multivariate analysis, even among the perioperative factors associated with whole AKI, there were distinct relationships depending on vtAKI or ntAKI. Furthermore, only ntAKI was associated with postoperative complications, longer hospital stays and impaired renal function at discharge. CONCLUSIONS: Based on the results of this study, future post-hepatectomy AKI studies should only include ntAKI and exclude vtAKI, as vtAKI has minimal clinical impact despite accounting for a significant proportion of AKI patients. CLINICAL TRIAL REGISTRATIONS: None.
• Myostatin as a fibroblast-activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma.

  Sachiyo Yoshio, Tomonari Shimagaki, Ryuki Hashida, Takumi Kawaguchi, Yuriko Tsutsui, Yuzuru Sakamoto, Yuichi Yoshida, Hironari Kawai, Shiori Yoshikawa, Taiji Yamazoe, Taizo Mori, Yosuke Osawa, Shinji Itoh, Moto Fukai, Tomoharu Yoshizumi, Akinobu Taketomi, Masaki Mori, Tatsuya Kanto

  Hepatology research : the official journal of the Japan Society of Hepatology 51 (7) 803 - 812 2021/05/16 

  AIM: In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non-alcoholic fatty liver disease-hepatocellular carcinoma (NAFLD-HCC) without cirrhosis and on the progression of liver fibrosis. METHODS: Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. RESULTS: The median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2 /m2 , and the median body mass index was 23.4 kg/m2 . Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2 /m2 ). The etiologies of liver disease were hepatitis B virus (n = 61), hepatitis C virus (n = 86), and non-B non-C hepatitis (n = 87) including NAFLD (n = 74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in patients with no sarcopenia (n = 152). In patients without advanced liver fibrosis (Fibrosis stage, 0-2; n = 58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin. CONCLUSIONS: In patients with NAFLD-HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production.
• Transperineal total mesorectal excision for rectal cancer on the residual rectum after multiple abdominal surgeries in a patient with Crohn's disease: a case report.

  Shin Emoto, Shigenori Homma, Tadashi Yoshida, Nobuki Ichikawa, Yoichi Miyaoka, Hiroki Matsui, Ryo Takahashi, Keita Ishido, Takuya Otsuka, Tomoko Mitsuhashi, Takehiko Katsurada, Akinobu Taketomi

  Surgical case reports 7 (1) 122 - 122 2021/05/13 

  BACKGROUND: The improved prognosis of Crohn's disease may increase the opportunities of surgical treatment for patients with Crohn's disease and the risk of development of colorectal cancer. We herein describe a patient with Crohn's disease and a history of multiple surgeries who developed rectal stump carcinoma that was treated laparoscopically and transperineally. CASE PRESENTATION: A 51-year-old man had been diagnosed with Crohn's disease 35 years earlier and had undergone several operations for treatment of Crohn's colitis. Colonoscopic examination was performed and revealed rectal cancer at the residual rectum. The patient was then referred to our department. The tumor was diagnosed as clinical T2N0M0, Stage I. We treated the tumor by combination of laparoscopic surgery and concomitant transperineal resection of the rectum. While the intra-abdominal adhesion was dissected laparoscopically, rectal dissection in the correct plane progressed by the transperineal approach. The rectal cancer was resected without involvement of the resection margin. The duration of the operation was 3 h 48 min, the blood loss volume was 50 mL, and no intraoperative complications occurred. The pathological diagnosis of the tumor was type 5 well- and moderately differentiated adenocarcinoma, pT2N0, Stage I. No recurrence was evident 3 months after the operation, and no adjuvant chemotherapy was performed. CONCLUSION: The transperineal approach might be useful in patients with Crohn's disease who develop rectal cancer after multiple abdominal surgeries.
• The Phenolic Antioxidant 3,5-dihydroxy-4-methoxybenzyl Alcohol (DHMBA) Prevents Enterocyte Cell Death under Oxygen-Dissolving Cold Conditions through Polyphyletic Antioxidant Actions.

  Moto Fukai, Takuya Nakayabu, Shintaro Ohtani, Kengo Shibata, Shingo Shimada, Soudai Sakamoto, Hirotoshi Fuda, Takayuki Furukawa, Mitsugu Watanabe, Shu-Ping Hui, Hitoshi Chiba, Tsuyoshi Shimamura, Akinobu Taketomi

  Journal of clinical medicine 10 (9) 2021/05/04 

  Cold preservation in University of Wisconsin (UW) solution is not enough to maintain the viability of the small intestine, due to the oxidative stress. The novel phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has dual properties to reduce oxidative stress, radical scavenging, and antioxidant protein induction, in other cells. This study was designed to determine whether DHMBA reduces cold preservation injury of enterocytes, and to identify the effector site. Enterocytes were subjected to 48-h cold preservation under atmosphere in UW solution (±DHMBA), and then returned to normal culture to replicate reperfusion of the small intestine after cold preservation. At the end of cold preservation (ECP) and at 1, 3, 6, and 72 h after rewarming (R1h, R3h, R6h, and R72h), we evaluated cell function and the injury mechanism. The results showed that DHMBA protected mitochondrial function mainly during cold preservation, and suppressed cell death after rewarming, as shown by the MTT, ATP, mitochondrial membrane potential, LDH, and lipid peroxidation assays, together with enhanced survival signals (PI3K, Akt, p70S6K) and induction of antioxidant proteins (HO-1, NQO-1, TRX-1). We found that DHMBA mitigates the cold-induced injury of enterocytes by protecting the mitochondria through direct and indirect antioxidative activities.
• 粘膜下層浸潤直腸癌の治療成績

  吉田 雅, 本間 重紀, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (5) 325 - 325 0047-1801 2021/05
• 大腸癌肺転移切除後の予後に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (5) 344 - 344 0047-1801 2021/05
• アルギナーゼ1の発現とアルギニン代謝の活性化は、がんの悪性化と抗腫瘍免疫の抑制に関連する

  北村 秀光, 王 向東, 項 慧慧, 豊島 雄二郎, 沈 輝棟, 杉山 昂, 志智 俊介, 木村 沙織, 本間 重紀, 武冨 紹信

  日本がん免疫学会総会プログラム・抄録集 日本がん免疫学会 25回 160 - 160 2021/05
• 担がん生体におけるIFN-STAT1信号伝達経路の活性化は抗腫瘍エフェクター細胞の誘導に重要である

  沈 輝棟, 王 向東, 志智 俊介, 木村 沙織, 杉山 昂, 武冨 紹信, 北村 秀光

  日本がん免疫学会総会プログラム・抄録集 日本がん免疫学会 25回 134 - 134 2021/05
• 粘膜下層浸潤直腸癌の治療成績

  吉田 雅, 本間 重紀, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (5) 325 - 325 0047-1801 2021/05
• 大腸癌肺転移切除後の予後に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (5) 344 - 344 0047-1801 2021/05
• アルギナーゼ1の発現とアルギニン代謝の活性化は、がんの悪性化と抗腫瘍免疫の抑制に関連する

  北村 秀光, 王 向東, 項 慧慧, 豊島 雄二郎, 沈 輝棟, 杉山 昂, 志智 俊介, 木村 沙織, 本間 重紀, 武冨 紹信

  日本がん免疫学会総会プログラム・抄録集 日本がん免疫学会 25回 160 - 160 2021/05
• 【大腸癌肝転移の治療戦略の再考】JCOG0603の解釈と今後の展開 肝臓外科の立場から

  坂本 譲, 折茂 達也, 武冨 紹信

  外科 (株)南江堂 83 (6) 682 - 685 0016-593X 2021/05 

  ＜文献概要＞JCOG0603は,大腸癌肝転移切除後におけるアジュバント療法の優越性を検証したランダム化II/III相試験である.mFOLFOX6によるアジュバント療法は,無病生存期間(DFS)を有意に延長するものの全生存期間(OS)の延長には寄与せず,その適応は慎重に検討すべきである.肝転移切除後の再発抑制は重要であるものの,治療法として再肝切除は有用であり,きたるべき再切除に備えて残肝機能と全身状態を温存することも肝要である.
• Early administration of amatuximab, a chimeric high-affinity anti-mesothelin monoclonal antibody, suppresses liver metastasis of mesothelin-expressing pancreatic cancer cells and enhances gemcitabine sensitivity in a xenograft mouse model.

  Yuki Fujii, Hirofumi Kamachi, Fumihiko Matsuzawa, Tatsuzo Mizukami, Nozomi Kobayashi, Moto Fukai, Akinobu Taketomi

  Investigational new drugs 39 (5) 1256 - 1266 2021/04/27 

  Amatuximab is a promising therapeutic antibody targeting mesothelin, a 40-kDa glycoprotein that is highly expressed in pancreatic cancer. We investigated the effectiveness of early amatuximab treatment, imitating an adjuvant chemotherapy setting, and combination therapy with amatuximab and gemcitabine in liver metastasis of pancreatic cancer. Liver metastasis mouse models were established in 8-week-old male BALB/c nu/nu mice using the hemisplenic injection method. Tridaily amatuximab monotherapy or combination with gemcitabine was administered to the liver metastasis mouse model before metastatic lesions had formed huge masses. Gaussia luciferase-transfected AsPC-1 was used as a mesothelin-overexpressing pancreatic cancer cell line. The amount of liver metastases and the serum luciferase activity were significantly lower in the treatment groups than those in the control IgG group. Notably, the anti-tumor activity of gemcitabine was synergically enhanced by combination therapy with amatuximab. Furthermore, western blotting revealed that the high expression of phosphorylated c-Met and AKT in liver metastatic lesions treated with gemcitabine monotherapy was canceled by its combination with amatuximab. This result indicated that the observed synergic therapeutic effect may have occurred as a result of the inhibitory effect of amatuximab on the phosphorylation of c-Met and AKT, which were promoted by exposure to GEM. In conclusion, our study revealed that early administration of amatuximab alone or in combination with GEM significantly suppressed the liver metastases of mesothelin-expressing pancreatic cancer cells. A phase II clinical trial of amatuximab as part of an adjuvant chemotherapy regimen for resected pancreatic cancer is expected.
• 門脈還流異常症に対する治療適応時期 術後に肺高血圧症を発症した症例の経験から

  本多 昌平, 荒 桃子, 奥村 一慶, 近藤 享史, 河北 一誠, 後藤 了一, 辻岡 孝郎, 武田 充人, 嶋村 剛, 神山 俊哉, 武冨 紹信

  日本小児外科学会雑誌 (一社)日本小児外科学会 57 (2) 323 - 323 0288-609X 2021/04
• 肝・膵移植における最新の進歩と課題 脾摘の生体肝移植短期予後に及ぼす影響の検討

  川村 典生, 嶋村 剛, 後藤 了一, 渡辺 正明, 巖築 慶一, 長津 明久, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SY - 1 2021/04
• 心停止ドナー肝に対する機械灌流における水素ガスの有効性の検討

  坂本 聡大, 柴田 賢吾, 石川 隆壽, 島田 慎吾, 若山 顕治, 藤好 真人, 加藤 紘一, 巖築 慶一, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 深井 原, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 4 2021/04
• 球状肝細胞移植後のグラフトの動態

  渋谷 一陽, 渡辺 正明, 巖築 慶一, 後藤 了一, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 6 2021/04
• 生体肝移植後肝細胞癌再発に対し新規分子標的薬を含む集学的治療により長期生存が得られた一例

  鈴木 麗美, 後藤 了一, 巌築 慶一, 川村 典生, 渡辺 正明, 神山 俊哉, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 RS - 5 2021/04
• 肝腎症候群による腎不全併発非代償性肝硬変症例に対する、脳死肝単独と、脳死肝腎同時移植症例の比較検討

  伊藤 栄祐, 渡辺 正明, 渋谷 一陽, 巖築 慶一, 川村 典生, 後藤 了一, 堀田 記世彦, 篠原 信雄, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 RS - 6 2021/04
• 肥満合併肝細胞癌患者における肝切除の検討

  坂本 譲, 神山 俊哉, 島田 慎吾, 折茂 達也, 長津 明久, 旭 よう, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 8 2021/04
• 肝前区域切除術後に胆管狭窄に伴う肝後区域の萎縮を呈した2例

  石川 倫啓, 柿坂 達彦, 坂本 譲, 旭 よう, 長津 明久, 島田 慎吾, 折茂 達也, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 8 2021/04
• PIVKA-II高値を呈し切除に至った巨大肝細胞腺腫の1例

  高橋 直規, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 蒲池 浩文, 三橋 智子, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 54 (4) 253 - 261 0386-9768 2021/04 

  症例は18歳の男性で,健診でのγ-GTP高値と近医での腹部超音波検査で肝外側区に巨大腫瘤を認め,当院を紹介受診した.Dynamic CTで肝外側区に動脈相で濃染され,平衡相で造影効果が遷延する最大径18cmの腫瘤を認めた.PIVKA-IIは481mAU/mlと高値であった.肝細胞腺腫(hepatocellular adenoma;以下,HCAと略記)を第一に考えたが,肝細胞癌の可能性も除外できず,破裂の危険性も鑑みて切除の方針とし,肝左葉切除を施行した.病理組織検査では,HCAと診断された.免疫染色検査では,CD34(+),SAA(+),β-catenin(-),L-FABP(-)でinflammatory typeと分類された.術後経過は良好であり,第7病日に退院した.若年男性の巨大肝腫瘤の鑑別診断としてHCAも念頭に置く必要があり,外科的切除は診断および治療に寄与すると考えられた.(著者抄録)
• ハイリスク症例への大腸手術-いかに安全に行うか- 腹腔鏡下大腸切除における心血管塞栓性合併症の発症リスクに関する検討

  市川 伸樹, 本間 重紀, 舩越 徹, 大渕 佳祐, 大島 隆弘, 植村 一仁, 今 裕史, 大野 陽介, 横田 良一, 数井 啓蔵, 石川 隆壽, 水上 達三, 三野 和宏, 前田 好章, 吉田 雅, 下國 達志, 相山 健, 小野 仁, 森田 恒彦, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 WS - 2 2021/04
• 根治切除を施行したStage1-3大腸癌患者の再発予測における周術期リンパ球/C反応性蛋白比変化率の有用性

  吉田 拓人, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 1 2021/04
• 大腸がんの肝転移巣形成モデルにおけるメトホルミンの抗腫瘍効果

  木村 沙織, 本間 重紀, 志智 俊介, 沢田 尭史, 杉山 昴, 松田 博紀, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 北村 秀光, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
• CTを用いた大腸癌の術前所属リンパ節転移の評価

  江本 慎, 本間 重紀, 市川 伸樹, 今泉 健, 吉田 雅, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 1 2021/04
• 低分化胞巣と局所炎症反応によるStage II大腸癌の予後層別化

  松井 博紀, 畑中 佳奈子, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 松野 吉宏, 畑中 豊, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
• Ta-TMEを併用した潰瘍性大腸炎に対する手術手技

  本間 重紀, 松井 博紀, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 1 2021/04
• ハイリスク高齢者直腸癌に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 宮岡 陽一, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 6 2021/04
• 直腸癌における回腸diverting stoma造設後の入院期間に影響を与える因子の検討

  高橋 遼, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 6 2021/04
• 結腸直腸癌術前の深部静脈血栓症(DVT)のリスク因子及び術前D-dimerによるDVTスクリーニングについて

  宮岡 陽一, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 3 2021/04
• 小児領域における他診療科との合同手術 先天性門脈体循環シャントに対するIVR・外科治療戦略

  本多 昌平, 荒 桃子, 奥村 一慶, 近藤 享史, 河北 一誠, 後藤 了一, 阿保 大介, 工藤 與亮, 嶋村 剛, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 WS - 5 2021/04
• 肝がんマウスモデルにおいてDiacylglycerol Kinase α阻害は免疫チェックポイント阻害治療による抗腫瘍効果を増強させる

  志智 俊介, 北村 秀光, 杉山 昂, 岡田 尚樹, 木村 沙織, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 3 2021/04
• 消化器がんにおける新規治療標的Diacylglycerol kinase alphaの阻害と抗がん剤治療との併用療法に関する研究

  杉山 昂, 北村 秀光, 志智 俊介, 木村 沙織, 岡田 尚樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 2 2021/04
• 肝細胞癌切除例におけるCOPZ1発現と予後の検討

  加藤 拓也, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 1 2021/04
• ハイリスク症例への大腸手術-いかに安全に行うか- 腹腔鏡下大腸切除における心血管塞栓性合併症の発症リスクに関する検討

  市川 伸樹, 本間 重紀, 舩越 徹, 大渕 佳祐, 大島 隆弘, 植村 一仁, 今 裕史, 大野 陽介, 横田 良一, 数井 啓蔵, 石川 隆壽, 水上 達三, 三野 和宏, 前田 好章, 吉田 雅, 下國 達志, 相山 健, 小野 仁, 森田 恒彦, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 WS - 2 2021/04
• 根治切除を施行したStage1-3大腸癌患者の再発予測における周術期リンパ球/C反応性蛋白比変化率の有用性

  吉田 拓人, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 1 2021/04
• 大腸がんの肝転移巣形成モデルにおけるメトホルミンの抗腫瘍効果

  木村 沙織, 本間 重紀, 志智 俊介, 沢田 尭史, 杉山 昴, 松田 博紀, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 北村 秀光, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
• CTを用いた大腸癌の術前所属リンパ節転移の評価

  江本 慎, 本間 重紀, 市川 伸樹, 今泉 健, 吉田 雅, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 1 2021/04
• 低分化胞巣と局所炎症反応によるStage II大腸癌の予後層別化

  松井 博紀, 畑中 佳奈子, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 本間 重紀, 松野 吉宏, 畑中 豊, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
• Ta-TMEを併用した潰瘍性大腸炎に対する手術手技

  本間 重紀, 松井 博紀, 宮岡 陽一, 江本 慎, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 1 2021/04
• ハイリスク高齢者直腸癌に対する手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 江本 慎, 松井 博紀, 宮岡 陽一, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 6 2021/04
• 直腸癌における回腸diverting stoma造設後の入院期間に影響を与える因子の検討

  高橋 遼, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 6 2021/04
• 結腸直腸癌術前の深部静脈血栓症(DVT)のリスク因子及び術前D-dimerによるDVTスクリーニングについて

  宮岡 陽一, 本間 重紀, 市川 伸樹, 吉田 雅, 江本 慎, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 3 2021/04
• 肝細胞癌における術後末梢血白血球分画の術後早期再発の関連性

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 武冨 紹信

  肝臓 (一社)日本肝臓学会 62 (Suppl.1) A373 - A373 0451-4203 2021/04
• 進行肝細胞癌に対する集学的治療の意義-薬物療法は手術を変えたか- 根治切除不能肝細胞癌に対する減量肝切除/分子標的薬sequential治療の意義についての検討

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 島田 慎吾, 長津 明久, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 WS - 8 2021/04
• 肝細胞癌における間質Versicanの発現と予後に関する検討

  加藤 紘一, 深井 原, 坂本 譲, 旭 よう, 長津 明久, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 8 2021/04
• 肝細胞癌に対する肝切除後予後因子としてのGd-EOB-DTPA-MRIの意義

  島田 慎吾, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
• Propensity scoreを用いた解析によるvp3、4肝細胞癌の門脈腫瘍栓に対する術前放射線治療の有効性の検討

  柿坂 達彦, 神山 俊哉, 折茂 達也, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 加藤 徳雄, 畑中 佳奈子, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 3 2021/04
• EOB-MRIを用いた術後肝不全予測の有用性

  折茂 達也, 神山 俊哉, 柿坂 達彦, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 3 2021/04
• 局所進行膵癌に対するメトホルミン併用術前化学放射線療法の効果

  蒲池 浩文, 折茂 達也, 柿坂 達彦, 敦賀 陽介, 若山 顕示, 島田 慎吾, 長津 明久, 旭 よう, 坂本 譲, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 7 2021/04
• 腹腔鏡下肝切除における実質切離方法と成績の検討

  長津 明久, 神山 俊哉, 坂本 譲, 旭 よう, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 5 2021/04
• 肝エキノコックス症に対する下大静脈切除再建を伴う肝切除治療成績

  神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 1 2021/04
• 肥満合併肝細胞癌患者における肝切除の検討

  坂本 譲, 神山 俊哉, 島田 慎吾, 折茂 達也, 長津 明久, 旭 よう, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 8 2021/04
• 肝前区域切除術後に胆管狭窄に伴う肝後区域の萎縮を呈した2例

  石川 倫啓, 柿坂 達彦, 坂本 譲, 旭 よう, 長津 明久, 島田 慎吾, 折茂 達也, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 PS - 8 2021/04
• 心嚢穿破を伴う肝エキノコックス症に対して外科的治療が奏功した1例

  山本 葉一, 神山 俊哉, 柿坂 達彦, 折茂 達也, 旭 よう, 長津 明久, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 RS - 3 2021/04
• 十二指腸原発悪性Triton腫瘍術後13年目に発生した肝転移の一例

  大橋 慶太, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 大塚 拓也, 三橋 智子, 杉田 真太朗, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 RS - 9 2021/04
• 増大傾向を示す肝外門脈瘤に対し門脈形成術を施行した一例

  石川 昂弥, 長津 明久, 坂本 譲, 旭 よう, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 RS - 10 2021/04
• Establishment of a Cell Culture Model Permissive for Infection by Hepatitis B and C Viruses.

  Teruhime Otoguro, Tomohisa Tanaka, Hirotake Kasai, Nobuhiro Kobayashi, Atsuya Yamashita, Takasuke Fukuhara, Akihide Ryo, Moto Fukai, Akinobu Taketomi, Yoshiharu Matsuura, Kohji Moriishi

  Hepatology communications 5 (4) 634 - 649 2021/04 

  Compared with each monoinfection, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is well known to increase the risks of developing liver cirrhosis and hepatocellular carcinoma. However, the mechanism by which HBV/HCV coinfection is established in hepatocytes is not well understood. Common cell culture models for coinfection are required to examine viral propagation. In this study, we aimed to establish a cell line permissive for both HBV and HCV infection. We first prepared a HepG2 cell line expressing sodium taurocholate cotransporting polypeptide, an HBV receptor, and then selected a cell line highly permissive for HBV infection, G2/NT18-B. After transduction with a lentivirus-encoding microRNA-122, the cell line harboring the highest level of replicon RNA was selected and then treated with anti-HCV compounds to eliminate the replicon RNA. The resulting cured cell line was transduced with a plasmid-encoding CD81. The cell line permissive for HCV infection was cloned and then designated the G2BC-C2 cell line, which exhibited permissiveness for HBV and HCV propagation. JAK inhibitor I potentiated the HCV superinfection of HBV-infected cells, and fluorescence-activated cell-sorting analysis indicated that HBV/HCV double-positive cells accounted for approximately 30% of the coinfected cells. Among several host genes tested, cyclooxygenase-2 showed synergistic induction by coinfection compared with each monoinfection. Conclusion: These data indicate that our in vitro HBV/HCV coinfection system provides an easy-to-use platform for the study of host and viral responses against coinfection and the development of antiviral agents targeting HBV and HCV.
• Laparoscopic repair of inguinal hernia in a patient with a ventriculoperitoneal shunt: A case report.

  Yui Ishiguro, Takahisa Ishikawa, Takumi Hamada, Naoki Okada, Takahito Nakagawa, Seiji Kobayashi, Kazuhiro Ogasawara, Hiromasa Takahashi, Akinobu Taketomi

  Asian journal of endoscopic surgery 14 (2) 282 - 285 2021/04 [Refereed][Not invited]
   

  Laparoscopic surgery in patients with a ventriculoperitoneal (VP) shunt is reportedly associated with increased intracranial pressure secondary to high intraperitoneal pressure and retrograde infection due to intraperitoneal infection. We herein report the first case of transabdominal preperitoneal (TAPP) inguinal hernia repair without catheter manipulation for a patient with a VP shunt. A 69-year-old man with a VP shunt was suspected to have an inguinal hernia based on symptoms and examination findings. With a pneumoperitoneum pressure of 10 mm Hg, the VP shunt was not clamped and mesh was placed while confirming cerebrospinal fluid outflow from the tip of the catheter. The patient developed no shunt-associated complications and was discharged 3 days postoperatively. TAPP inguinal hernia repair without catheter manipulation is a potential surgical option for patients with a VP shunt.
• Triazolopyrimidine derivative NK026680 and donor-specific transfusion induces CD4+CD25+Foxp3+ T cells and ameliorates allograft rejection in an antigen-specific manner.

  Shin Emoto, Susumu Shibasaki, Akihisa Nagatsu, Ryoichi Goto, Hitoshi Ono, Yasutomo Fukasaku, Rumi Igarashi, Takuji Ota, Moto Fukai, Tsuyoshi Shimamura, Kan Saiga, Akinobu Taketomi, Masaaki Murakami, Satoru Todo, Kenichiro Yamashita

  Transplant immunology 65 101338 - 101338 2021/04 [Refereed][Not invited]
   

  We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination with donor-specific transfusion (DST). BALB/c (H-2d) heart graft were transplanted into C57BL/6 (H-2b) mice following intravenous injection of donor splenocytes (DST) and oral administration of NK026680. The NK026680 plus DST treatment markedly prolonged the survival time of the donor-graft, but not that of the 3rd party-graft (C3H; H-2k). Treg cells in the recipient spleen on day 0 expanded when stimulated with donor-antigens in vivo and in vitro. After heart transplantation, Treg cells accumulated into the graft and increased in the spleen. NK026680 plus DST also decreased activated CD8+ T cells in the spleen and inhibited infiltration of CD8+ T cells into the graft. Depletion of CD25+ cells inhibited the graft prolonging effect of the NK026680 plus DST treatment. NK026680 administration together with DST induces potent immunoregulatory effects in an antigen-specific manner, likely due to the in vivo generation of donor-specific Tregs.
• Serum fatty acid-binding protein 5 is a significant factor in hepatocellular carcinoma progression independent of tissue expression level.

  Masafumi Ohira, Hideki Yokoo, Koji Ogawa, Moto Fukai, Toshiya Kamiyama, Naoya Sakamoto, Akinobu Taketomi

  Carcinogenesis 42 (6) 794 - 803 2021/03/23 

  Fatty acid-binding protein 5 (FABP5) is highly expressed in hepatocellular carcinoma (HCC) tissues and is related to HCC progression. In this study, we analyzed the potential of serum FABP5 (sFABP5) as a tumor marker in HCC and its clinical significance in HCC progression. We compared the sFABP5 concentration in patients with HCC (HCC group) with that of patients with hepatitis without HCC (hepatitis group). Moreover, we measured the FABP5 expression levels in resected HCC tissues (tFABP5) and analyzed their relationship with sFABP5. We also performed cell-based assays using FABP5 knockout and overexpressing HCC cell lines to analyze the effect of extrinsic FABP5 on HCC cells. We showed that sFABP5 was not a useful tumor marker for HCC, as HCC and sFABP5 were not correlated. However, sFABP5 and tFABP5 significantly correlated with survival after surgery for HCC, while sFABP5 and tFABP5 were independent of each other. In cell-based assays, extrinsic FABP5 was taken up by HCC cell lines and positively affected cell survival under glucose-depleted conditions by complementing the endogenous FABP5 function. In conclusion, sFABP5 had a significant impact on HCC progression irrespective of tFABP5 by augmenting cell viability under glucose-depleted conditions. As tFABP5 and sFABP5 are important factors that are independent of each other in HCC progression, both of them should be considered independently in improving the prognosis of patients with HCC.
• 直腸癌術後局所再発症例に対して経会陰的内視鏡手術が有用であった2例

  宮岡 陽一, 本間 重紀, 市川 伸樹, 松井 博紀, 吉田 雅, 江本 慎, 今泉 健, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (3) 198 - 198 0047-1801 2021/03
• 腹腔鏡下肝切除における工夫とコツ(Synchronous laparoscopic hepatectomy and gastrointestinal surgery)

  Asahi Yoh, Kamiyama Toshiya, orimo Tatsuya, Shimada Shingo, Nagatsu Akihisa, Sakamoto Yuzuru, Kamachi Hirofumi, Taketomi Akinobu

  日本内視鏡外科学会雑誌 25 (7) WS20 - 5 1344-6703 2021/03
• 悪性黒色腫の肝転移に対して肝切除を行った4症例の報告

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 蒲池 浩文, 竹内 啓, 三橋 智子, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 118 (臨増総会) A390 - A390 0446-6586 2021/03
• 悪性黒色腫の肝転移に対して肝切除を行った4症例の報告

  旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 蒲池 浩文, 竹内 啓, 三橋 智子, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 118 (臨増総会) A390 - A390 0446-6586 2021/03
• 後期高齢者における経皮経肝的門脈塞栓術を要する大量肝切除の検討

  坂本 譲, 神山 俊哉, 島田 慎吾, 折茂 達也, 長津 明久, 旭 よう, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 128回・122回 57 - 57 2021/03
• Central Hepatectomy Versus Major Hepatectomy for Centrally Located Hepatocellular Carcinoma: A Propensity Score Matching Study.

  Tatsuya Orimo, Toshiya Kamiyama, Tatsuhiko Kakisaka, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Akinobu Taketomi

  Annals of surgical oncology 28 (11) 6769 - 6779 2021/03/01 

  BACKGROUND: In terms of anatomical liver sectionectomy approaches, both a central hepatectomy (CH) and major hepatectomy (MH) are feasible options for a centrally located hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the surgical outcomes of central HCC patients who underwent CH or MH. MH includes hemihepatectomy or trisectionectomy, whereas CH involves a left medial sectionectomy, right anterior sectionectomy, or central bisectionectomy. The surgical outcomes were compared before and after propensity score matching (PSM). RESULTS: A total of 233 patients were enrolled, including 132 in the CH group and 101 in the MH group. The MH group cases were pathologically more advanced and had poorer overall survival rates than the CH group. After PSM, 68 patients were selected into each group, both of which showed similar overall and recurrence-free survival outcomes. The CH group showed a tendency for a longer operation time; however, other perioperative outcomes were similar between the two groups. Multivariate analyses of our matched HCC patients revealed that the type of surgery (CH or MH) was not an independent prognostic factor. More patients in the matched CH group experienced a repeat hepatectomy for recurrence and no patients in this group underwent a preoperative portal vein embolization. CONCLUSIONS: The short- and long-term surgical outcomes of CH and MH for a centrally located HCC are similar under a matched clinicopathological background. CH has the advantage of not requiring a preoperative portal vein embolization and increased chances of conducting a repeat hepatectomy for recurrence.
• Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization.

  Yosuke Tsuruga, Toshiya Kamiyama, Hirofumi Kamachi, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Tatsuhiko Kakisaka, Akinobu Taketomi

  World journal of gastrointestinal surgery 13 (2) 153 - 163 2021/02/27 

  BACKGROUND: Preoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear. AIM: To investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and 99mTc-galactosyl-human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODS: Thirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and 99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D 99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D 99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV. RESULTS: FFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure. CONCLUSION: The functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.
• Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells.

  Fumihiko Matsuzawa, Hirofumi Kamachi, Tatsuzo Mizukami, Takahiro Einama, Futoshi Kawamata, Yuki Fujii, Moto Fukai, Nozomi Kobayashi, Yutaka Hatanaka, Akinobu Taketomi

  BMC cancer 21 (1) 200 - 200 2021/02/26 

  BACKGROUND: Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model. METHODS: We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer. RESULTS: Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes. CONCLUSIONS: Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.
• ASO Author Reflections: Anatomical Liver Sectionectomy for Centrally Located Hepatocellular Carcinoma.

  Tatsuya Orimo, Toshiya Kamiyama, Akinobu Taketomi

  Annals of surgical oncology 28 (11) 6780 - 6781 2021/02/25
• Ischemic proctitis 6 months after laparoscopic sigmoidectomy: a case report.

  Takuto Yoshida, Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Shin Emoto, Yoichi Miyaoka, Hiroki Matsui, Akinobu Taketomi

  Surgical case reports 7 (1) 54 - 54 2021/02/22 

  BACKGROUND: Ischemic colitis is a common disease; however, its pathophysiology remains unclear, especially in ischemic proctitis after sigmoidectomy. We present a rare case of ischemic proctitis 6 months after laparoscopic sigmoidectomy. CASE PRESENTATION: The patient was a 60-year-old man with hypertension, type 2 diabetes, and hyperlipidemia. He was a smoker. He underwent laparoscopic sigmoidectomy for pathological stage I sigmoid colon cancer and was followed up without any adjuvant therapy. Six months after his surgery, he complained of lower abdominal discomfort, bloody stools, and tenesmus. Colonoscopy showed extensive rectal ulcers between the anastomotic site and the anal canal, which was particularly severe on the anal side several centimeters beyond the anastomosis. We provided non-surgical management, including hyperbaric oxygen therapy. The rectal ulcers had healed 48 days after the therapeutic intervention. He has not experienced any recurrence for 3.5 years. CONCLUSIONS: While performing sigmoidectomy, it is important to consider the blood backflow from the anal side of the bowel carefully, especially for patients with risk factors of ischemic proctitis.
• Laparoscopic hepatectomy for hepatic angiomyolipoma with preoperative diagnosis of other malignancy: a report of 2 cases.

  Yoh Asahi, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yuzuru Sakamoto, Chihiro Ishizuka, Kazuya Hamada, Hirofumi Kamachi, Emi Takakuwa, Tomoko Mitsuhashi, Akinobu Taketomi

  Surgical case reports 7 (1) 44 - 44 2021/02/08 

  BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare liver tumor, and hepatectomy is the only effective treatment. Due to the difficulty of correct diagnosis of HAML before surgery by image studies, more than 36.6% of reported HAMLs are misdiagnosed as other malignant liver tumors before surgery. As there are only few reported cases in which HAMLs were removed using laparoscopic hepatectomy, the effectiveness of laparoscopic hepatectomy for such HAMLs in which are diagnosed as other malignant liver tumor before surgery has not been reported. Case presentation Case 1: a 58-year-old female with a history of treatment for autoimmune hepatitis was preoperatively diagnosed with hepatocellular carcinoma (size: 20 mm) in segment 7 (S7) of the liver. The tumor was removed by laparoscopic partial resection and was diagnosed as a HAML through a pathological examination. The patient's postoperative course was good, and she was recurrence-free at 37 months after the hepatectomy. Case 2: a 29-year-old female with a history of surgery for a right mature cystic teratoma was referred to our department to receive treatment for a growing 20-mm liver tumor with some calcification, which arose in S3 of the liver. A metastatic liver tumor derived from the mature cystic teratoma was suspected, and laparoscopic left lateral sectionectomy was performed. The liver tumor was diagnosed as a HAML after a pathological examination. The patient's postoperative course was unremarkable, and more than 54 months have passed since the hepatectomy without any recurrence. CONCLUSIONS: Two cases in which HAMLs were preoperatively diagnosed as other malignant liver tumor were successfully removed by laparoscopic hepatectomy with a correct postoperative diagnosis. Laparoscopic hepatectomy for the present 2 cases of HAML seemed to be effective for providing a correct diagnosis after the curative removement of liver tumor with a smaller invasion compared to open hepatectomy, and for denying risk of dissemination of the malignant tumor by needle biopsy that had to be considered before ruling out malignant tumor.
• 肝腎症候群を併発した非代償性肝硬変に対する脳死肝腎同時移植

  堀田 記世彦, 渡辺 正明, 川村 典生, 後藤 了一, 田邉 起, 嶋村 剛, 篠原 信雄, 武富 紹信

  日本臨床腎移植学会プログラム・抄録集 (一社)日本臨床腎移植学会 54回 134 - 134 2021/02
• 大腸癌同時性肝転移における術前化学療法の意義

  市川 伸樹, 神山 俊哉, 本間 重紀, 前田 好章, 篠原 敏樹, 敦賀 陽介, 数井 啓藏, 吉田 雅, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (2) 94 - 94 0047-1801 2021/02
• 大腸神経内分泌腫瘍の治療成績

  吉田 雅, 本間 重紀, 市川 伸樹, 松井 博紀, 宮岡 陽一, 今泉 健, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 74 (2) 119 - 119 0047-1801 2021/02
• What is optimal multidisciplinary management of advanced HCC? Tyrosine kinase inhibitor administration after the volume reduction hepatectectomy for highly advanced hepatocellular carcinoma(和訳中)

  Asahi Yoh, Kamiyama Toshiya, Orimo Tatsuya, Shimada Shingo, Nagatsu Akihisa, Sakamoto Yuzuru, Kamachi Hirofumi, Taketomi Akinobu

  日本肝胆膵外科学会・学術集会プログラム・抄録集 32回 260 - 260 2021/02
• 肝腎症候群を併発した非代償性肝硬変に対する脳死肝腎同時移植

  堀田 記世彦, 渡辺 正明, 川村 典生, 後藤 了一, 田邉 起, 嶋村 剛, 篠原 信雄, 武富 紹信

  日本臨床腎移植学会プログラム・抄録集 (一社)日本臨床腎移植学会 54回 134 - 134 2021/02
• Prognostic Significance of Circulating Tumor Cells with Mesenchymal Phenotypes in Patients with Gastric Cancer: A Prospective Study.

  Yui Ishiguro, Hideyasu Sakihama, Tadashi Yoshida, Nobuki Ichikawa, Shigenori Homma, Moto Fukai, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  Annals of surgical oncology 28 (2) 1178 - 1186 2021/02 [Refereed][Not invited]
   

  BACKGROUND: Circulating tumor cells (CTCs) have been shown to be heterogeneous. Focusing on the epithelial-mesenchymal transition and perioperative kinetics, we evaluated CTCs with mesenchymal phenotypes as a potential prognostic biomarker for patients with gastric cancer. METHODS: Peripheral blood was collected from 54 patients with gastric cancer before surgery and at 1 week and 1 month after surgery. CTCs were enriched using density-gradient centrifugation and magnetic-activated cell sorting (negative selection). Cell suspensions were characterized by multi-immunofluorescence staining against cytokeratin and N-cadherin, and by 4',6'-diamidino-2-phenyldole staining. RESULTS: CTCs were detected in five patients (17%) with early cancer and 14 patients (56%) with advanced cancer (p < 0.05). In our system, N-cadherin, but not cytokeratin, was expressed in the CTCs of 90% (19/21) of patients. Postoperative recurrence was detected in 10 patients, all of whom had N-cadherin+/cytokeratin-/CD45- CTCs preoperatively. Regarding perioperative kinetics, we divided patients into three risk groups: a high-risk group, with one or more preoperative CTCs and increased CTCs postoperatively; an intermediate-risk group, with one or more preoperative CTCs and decreased CTCs postoperatively; and a low-risk group, with no preoperative CTCs. Recurrence rates were 57% (4/7), 33% (4/12), and 6% (2/35), respectively. The relapse-free survival rate was lower in patients at high risk versus those at intermediate or low risk, for all patients (p = 0.00024) and in patients with advanced cancer (p = 0.00103). CONCLUSIONS: N-cadherin is a highly useful marker to detect CTCs lacking cytokeratin, and the perioperative kinetics of CTC numbers is beneficial in risk stratification for survival in patients with gastric cancer.
• A Case of Huge Hepatocellular Adenoma with an Elevated Serum PIVKA-II Level Treated with Hepatectomy

  Naoki Takahashi, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Hirofumi Kamachi, Tomoko Mitsuhashi, Akinobu Taketomi

  Japanese Journal of Gastroenterological Surgery 54 (4) 253 - 261 1348-9372 2021 

  The patient was an 18-year-old man with a high γ-GTP level and a huge tumor found in the lateral segment of the liver on abdominal US. He was admitted to our hospital. Dynamic CT showed a tumor of 18 cm in diameter in the left lateral segment. The tumor was strongly enhanced in the arterial phase and showed prolonged enhancement in the delayed phase. In addition, PIVKA-II was elevated to 481 mAU/ml. The diagnosis was suspected hepatocellular adenoma (HCA), but the possibility of hepatocellular carcinoma could not be ruled out. Given the risk of rupture, we decided to perform hepatectomy and we ultimately performed left hemihepatectomy. The tumor was finally diagnosed as inflammatory type of HCA (CD34 (+), serum-amyloid-A (+), β-catenin (−), liver fatty acid-binding protein (−)) by immunohistochemistry examination. The postoperative course was uneventful and the patient was discharged 7 days after surgery. HCA may be an appropriate differential diagnosis for a huge liver mass in a young patient, and surgical resection should be considered for diagnosis and treatment.
• A Case of Hepatocellular Carcinoma with Recurrence of Skeletal Muscle Metastasis to the Right Lower Leg 9 Years after Hepatectomy

  Hiromasa Namba, Toshiya Kamiyama, Shingo Shimada, Tatsuya Orimo, Akihisa Nagatsu, Hirofumi Kamachi, Ken Kuwahara, Emi Takakuwa, Yoshihiro Matsuno, Akinobu Taketomi

  Japanese Journal of Gastroenterological Surgery 54 (1) 16 - 24 1348-9372 2021 

  A 61-year-old man underwent right trisegmentectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) at age 52, and thoracoscopic left upper and lower lobe partial resection for lung metastases at age 56. At age 59, PIVKA-II was elevated, transcatheter arterial chemoembolization was performed for diagnosis of intrahepatic recurrence, and PIVKA-II also decreased. In the next year, PIVKA-II re-elevated and a tumor of 5 cm was found in the right gastrocnemius muscle. Needle biopsy was performed for diagnosis of skeletal muscle metastasis. Extended tumor resection and latissimus dorsi musculocutaneous flap and skin graft were performed. The histopathological diagnosis was metastasis of HCC, moderately to poorly differentiated, and venous invasion was observed. The patient is alive without recurrence 16 months after the last surgery. While skeletal muscle metastasis of HCC is rare, this case shows that a favorable prognosis is possible after tumor resection.
• Preoperative Elemental Diet before Laparoscopic Anterior Resection in Patients with Advanced Stenotic Rectal Cancer

  Tadashi Yoshida, Shigenori Homma, Nobuki Ichikawa, Hiroaki Iijima, Akinobu Taketomi

  JOURNAL OF THE ANUS RECTUM AND COLON 5 (4) 395 - 404 2021 

  Objectives: To evaluate the feasibility of our new preoperative enteral nutrition protocol using Elental (R) without mechanical bowel preparation (MBP) before laparoscopic anterior resection (LAR) in patients with advanced stenotic rectal cancer.Methods: Among 74 patients with advanced rectal cancer (clinical stages T3 and T4) scheduled to undergo LAR, 42 patients with stenotic rectal cancer were administered Elental (R) (900 kcal/day) without MBP before LAR (group S). Thirty-two patients without stenosis (group NS) did not receive preoperative nutritional support but underwent MBP.Results: Group S patients were maintained in a fasting state and received an elemental diet approximately 10 days preoperatively without severe adverse effects. The incidence of postoperative complications (Clavien-Dindo classification >= grade 2) was significantly lower in group S than that in group NS (adjusted odds ratio [OR]: 6.046, P = 0.008). Logistic regression analysis revealed that group NS exhibited higher risks of developing postoperative complications than those exhibited by group S (OR: 4.32, 95% confidence interval [CI]: 1.28-17.28, P = 0.018). Among preoperative characteristics, the clinical tumor stage indicated a significant intergroup difference. Thus, the clinical stage was selected as a covariate and adjusted in the logistic regression model to calculate a covariate-adjusted OR. Group NS exhibited a higher incidence of postoperative complications than group S (adjusted OR: 6.05, 95% CI: 1.58-28.35, P = 0.008).Conclusions: Administration of an elemental diet using Elental (R) without MBP before LAR is a feasible strategy in patients with advanced stenotic rectal cancer. Application of this research may encourage use of Elental (R) in the clinical setting.
• Preoperative Elemental Diet before Laparoscopic Anterior Resection in Patients with Advanced Stenotic Rectal Cancer.

  Tadashi Yoshida, Shigenori Homma, Nobuki Ichikawa, Hiroaki Iijima, Akinobu Taketomi

  Journal of the anus, rectum and colon 5 (4) 395 - 404 2021 

  OBJECTIVES: To evaluate the feasibility of our new preoperative enteral nutrition protocol using ElentalⓇ without mechanical bowel preparation (MBP) before laparoscopic anterior resection (LAR) in patients with advanced stenotic rectal cancer. METHODS: Among 74 patients with advanced rectal cancer (clinical stages T3 and T4) scheduled to undergo LAR, 42 patients with stenotic rectal cancer were administered ElentalⓇ (900 kcal/day) without MBP before LAR (group S). Thirty-two patients without stenosis (group NS) did not receive preoperative nutritional support but underwent MBP. RESULTS: Group S patients were maintained in a fasting state and received an elemental diet approximately 10 days preoperatively without severe adverse effects. The incidence of postoperative complications (Clavien-Dindo classification ≥ grade 2) was significantly lower in group S than that in group NS (adjusted odds ratio [OR]: 6.046, P = 0.008). Logistic regression analysis revealed that group NS exhibited higher risks of developing postoperative complications than those exhibited by group S (OR: 4.32, 95% confidence interval [CI]: 1.28-17.28, P = 0.018). Among preoperative characteristics, the clinical tumor stage indicated a significant intergroup difference. Thus, the clinical stage was selected as a covariate and adjusted in the logistic regression model to calculate a covariate-adjusted OR. Group NS exhibited a higher incidence of postoperative complications than group S (adjusted OR: 6.05, 95% CI: 1.58-28.35, P = 0.008). CONCLUSIONS: Administration of an elemental diet using ElentalⓇ without MBP before LAR is a feasible strategy in patients with advanced stenotic rectal cancer. Application of this research may encourage use of ElentalⓇ in the clinical setting.
• Ursodeoxycholic Acid Triggers Primary Enterolith Growth in a Crohn's Disease Patient with Jejunal Stenosis.

  Hiroki Matsui, Tadashi Yoshida, Shigenori Homma, Nobuki Ichikawa, Shin Emoto, Yoichi Miyaoka, Kensuke Sakurai, Shinsuke Odagiri, Takehiko Katsurada, Akinobu Taketomi

  Journal of the anus, rectum and colon 5 (4) 433 - 438 2021 

  Primary enteroliths associated with Crohn's disease have been considered to be rare and are most likely caused by severe ileal stenosis. Herein, we report the case of a primary enterolith possibly caused by mild jejunal stenosis in a Crohn's disease patient who received oral administration of ursodeoxycholic acid (UDCA). A 62-year-old woman with a 6-year history of Crohn's disease, currently in clinical remission, was on UDCA prescription for liver dysfunction. Magnetic resonance imaging and double-balloon endoscopy, which were performed to examine epigastric pain, revealed mild jejunal stenosis and an enterolith on the oral side. Since it was difficult to remove or crush the enterolith endoscopically, we decided to remove it surgically with the stenotic jejunum. Component analysis revealed that more than 98% of the enterolith was composed of UDCA; subsequently, oral administration of UDCA was discontinued. This case demonstrated that primary enterolith might develop in Crohn's disease patients with mild intestinal stenosis, and oral administration of UDCA can trigger an enterolith in such patients. Therefore, routine follow-up imaging is necessary for early detection. Oral UDCA should be administered with caution for Crohn's disease patients with stenosis of the proximal small intestine.
• The Efficacy of the Hepatocyte Spheroids for Hepatocyte Transplantation

  Kazuaki Shibuya, Masaaki Watanabe, Ryoichi Goto, Masaaki Zaitsu, Yoshikazu Ganchiku, Akinobu Taketomi

  Cell Transplantation 30 096368972110000 - 096368972110000 0963-6897 2021/01/01 

  The safety and short-term efficacy of hepatocyte transplantation (HCTx) have been widely proven. However, issues such as reduced viability and/or function of hepatocytes, insufficient engraftment, and lack of a long-term effect have to be overcome for widespread application of HCTx. In this study, we evaluated hepatocyte spheroids (HSs), formed by self-aggregation of hepatocytes, as an alternative to hepatocytes in single-cell suspension. Hepatocytes were isolated from C57BL/6 J mice liver using a three-step collagenase perfusion technique and HSs were formed by the hanging drop method. After the spheroids formation, the HSs showed significantly higher mRNA expression of albumin, ornithine transcarbamylase, glucose-6-phosphate, alpha-1-antitrypsin, low density lipoprotein receptor, coagulation factors, and apolipoprotein E (ApoE) than 2 dimensional (2D)-cultured hepatocytes ( p < 0.05). Albumin production by HSs was significantly higher than that by 2D-cultured hepatocytes (9.5 ± 2.5 vs 3.5 ± 1.8 μg/dL, p < 0.05). The HSs, but not single hepatocytes, maintained viability and albumin mRNA expression in suspension (92.0 ± 2.8% and 1.03 ± 0.09 at 6 h). HSs (3.6 × 10⁶ cells) or isolated hepatocytes (fSH, 3.6 × 10⁶ cells) were transplanted into the liver of ApoE knockout (KO-/-) mice via the portal vein. Following transplantation, serum ApoE concentration (ng/mL) of HS-transplanted mice (1w: 63.1 ± 56.7, 4w: 17.0 ± 10.9) was higher than that of fSH-transplanted mice (1 w: 33.4 ± 13.0, 4w: 13.7 ± 9.6). In both groups, the mRNA levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, MCP-1, and MIP-1β) were upregulated in the liver following transplantation; however, no significant differences were observed. Pathologically, transplanted HSs were observed as flat cell clusters in contact with the portal vein wall on day 7. Additionally, ApoE positive cells were observed in the liver parenchyma distant from the portal vein on day 28. Our results indicate that HS is a promising alternative to single hepatocytes and can be applied for HCTx.
• Combined Laparoscopic and Transperineal Endoscopic Pelvic Tumor Resection with Sacrectomy for Locally Recurrent Rectal Cancer.

  Hiroki Matsui, Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Shin Emoto, Ken Imaizumi, Yoichi Miyaoka, Akinobu Taketomi

  Journal of the anus, rectum and colon 5 (3) 327 - 333 2021 

  Pelvic tumor resection with sacrectomy for locally recurrent rectal cancer is a challenging operation with a high complication rate and poor prognosis. We report a case of pelvic tumor resection with sacrectomy by transperineal endoscopy following laparoscopic dissection for locally recurrent rectal cancer. A 70-year-old man underwent laparoscopic abdominoperineal resection for rectal cancer and was diagnosed with local pelvic recurrence on follow-up computed tomography (CT) three years postoperatively. As the recurrence was in contact with the front of the sacrum, we concluded that distal sacrectomy was necessary to ensure a surgical margin. We safely performed combined laparoscopic and transperineal endoscopic pelvic tumor resection with sacrectomy by exposing the surface of the sacrum from both abdominal and transperineal approach. The operative time was 200 minutes, with minimal blood loss. There was no tumor exposure on the surgically dissected surface, and the patient was discharged without complications 14 days postoperatively. Transperineal endoscopy may be useful for pelvic tumor resection with sacrectomy for locally recurrent rectal cancer.
• Acute Myocardial Infarction of the Left Main Coronary Artery Presenting with Cardiogenic Shock and Pulmonary Edema during Noncardiac Surgery.

  Sakae Takenaka, Takao Konishi, Tomoya Sato, Atsushi Tada, Takuya Koizumi, Yoshifumi Mizuguchi, Takahide Kadosaka, Ko Motoi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Miwa Sarashina, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Tatsuya Orimo, Hirofumi Kamachi, Akinobu Taketomi, Toshihisa Anzai

  Case reports in cardiology 2021 5460816 - 5460816 2021 

  Acute myocardial infarction (AMI) caused by severe stenosis of left main coronary artery (LMCA) presenting with cardiogenic shock and pulmonary edema during noncardiac surgery is uncommon, but a catastrophic event. A 77-year-old male with cholangiocarcinoma underwent hepatectomy. During the surgery, he presented with cardiogenic shock, which did not respond to infusion administration or vasopressor. A transesophageal echocardiogram revealed anterior, septal, and lateral severe hypokinesia and impaired left ventricular function. Emergent coronary angiogram showed severe stenosis of LMCA. The patient underwent primary percutaneous coronary intervention (PCI) under the support of intra-aortic balloon pump, followed by extracorporeal membrane oxygenation. The chest roentgenogram showed pulmonary edema. Two days after PCI, he successfully underwent hepatectomy and bile duct resection. Early identification of the cause of hemodynamic instability during noncardiac surgery and invasive strategy are important for minimizing the myocardial injury and improving clinical outcomes in AMI of LMCA.
• Impact of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging on the prognosis of hepatocellular carcinoma after surgery.

  Shingo Shimada, Toshiya Kamiyama, Tatsuhiko Kakisaka, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Daisuke Abo, Hirofumi Kamachi, Akinobu Taketomi

  JGH open : an open access journal of gastroenterology and hepatology 5 (1) 41 - 49 2021/01 

  Background and Aim: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has been recognized as a useful imaging technique to distinguish the biological behavior of hepatocellular carcinoma (HCC). Methods: We analyzed 217 hepatectomy recipients with HCCs measuring 10 cm or less. We divided the patients into a decreased intensity (DI) group (n = 189, 87%) and an increased or neutral intensity (INI) group (n = 28, 13%) according to the ratio of tumor intensity to liver intensity during the hepatobiliary phase (HBP). According to the ratio of the maximum tumor diameter (including peritumoral hypointensity) between HBP images and precontrast T1-weighted images (RHBPP), we divided the patients as follows: The group whose RHBPP was ≥1.036 was the high RHBPP group (n = 60, 28%), and the group whose RHBPP was <1.036 was the low RHBPP group (n = 157, 72%). We investigated the prognoses and clinicopathological characteristics of these patients. Results: DI versus INI was not a prognostic factor for either survival or recurrence; however, a high RHBPP was an independent predictor of unfavorable survival and recurrence in patients. In addition, the INI group showed significantly lower α-fetoprotein (AFP) levels and higher rates of well-differentiated HCC and ICGR15 ≥15% than the DI group. The high RHBPP group showed significantly higher rates of vascular invasion and poorly differentiated HCC than the low RHBPP group. Conclusions: A high RHBPP by EOB-MRI is a preoperative predictor of vascular invasion and an unfavorable prognostic factor for survival and recurrence. These patients might be considered for highly curative operations such as anatomical liver resection.
• Increased Frequency of Dysfunctional Siglec-7-CD57+PD-1+ Natural Killer Cells in Patients With Non-alcoholic Fatty Liver Disease.

  Yuzuru Sakamoto, Sachiyo Yoshio, Hiroyoshi Doi, Taizo Mori, Michitaka Matsuda, Hironari Kawai, Tomonari Shimagaki, Shiori Yoshikawa, Yoshihiko Aoki, Yosuke Osawa, Yuji Yoshida, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Takanori Ito, Takashi Honda, Yoshihiro Mise, Yoshihiro Ono, Yu Takahashi, Akio Saiura, Akinobu Taketomi, Tatsuya Kanto

  Frontiers in immunology 12 603133 - 603133 2021 

  Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that can develop into liver fibrosis and hepatocellular carcinoma. Natural killer (NK) cells have been shown to protect against liver fibrosis and tumorigenesis, suggesting that they may also play a role in the pathogenesis of NAFLD. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of inhibitory and activating receptors expressed by many cell types, including NK cells. Here, we investigated the phenotypic profiles of peripheral blood and intrahepatic NK cells, including expression of Siglecs and immune checkpoint molecules, and their association with NK cell function in patients with NAFLD. Immune cells in the peripheral blood of 42 patients with biopsy-proven NAFLD and 13 healthy volunteers (HVs) were identified by mass cytometry. The function of various NK cell subpopulations was assessed by flow cytometric detection of intracellular IFN-γ and CD107a/LAMP-1, a degranulation marker, after in vitro stimulation. We found that peripheral blood from NAFLD patients, regardless of fibrosis stage, contained significantly fewer total CD56+ NK cell and CD56dim NK cell populations compared with HVs, and the CD56dim cells from NAFLD patients were functionally impaired. Among the Siglecs examined, NK cells predominantly expressed Siglec-7 and Siglec-9, and both the expression levels of Siglec-7 and Siglec-9 on NK cells and the frequencies of Siglec-7+CD56dim NK cells were reduced in NAFLD patients. Notably, Siglec-7 levels on CD56dim NK cells were inversely correlated with PD-1, CD57, and ILT2 levels and positively correlated with NKp30 and NKp46 levels. Further subtyping of NK cells identified a highly dysfunctional Siglec-7-CD57+PD-1+CD56dim NK cell subset that was increased in patients with NAFLD, even those with mild liver fibrosis. Intrahepatic NK cells from NAFLD patients expressed elevated levels of NKG2D and CD69, suggesting a more activated phenotype than normal liver NK cells. These data identify a close association between NK cell function and expression of Siglec-7, CD57, and PD-1 that could potentially be therapeutically targeted in NAFLD.
• 生体肝ドナー術中所見により、生体肝移植術を断念した8例の検討

  川村 典生, 後藤 了一, 渡辺 正明, 巖築 慶一, 長津 明久, 神山 俊哉, 嶋村 剛, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P224 - 1 2020/12
• HEVによる昏睡型急性肝不全症例についての検討

  腰塚 靖之, 川村 典生, 渡辺 正明, 後藤 了一, 太田 稔, 山下 健一郎, 武冨 紹信, 嶋村 剛

  肝臓 (一社)日本肝臓学会 61 (12) 750 - 750 0451-4203 2020/12
• 潰瘍性大腸炎合併colitic cancerに対する腹腔鏡下大腸全摘術

  吉田 雅, 本間 重紀, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P112 - 6 2020/12
• Ta-TMEを併用した潰瘍性大腸炎に対する手術手技

  本間 重紀, 松井 博紀, 宮岡 陽一, 今泉 健, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P119 - 3 2020/12
• 一時的回腸人工肛門造設時の人工肛門合併症の検討

  宮岡 陽一, 今泉 健, 松井 博紀, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P166 - 3 2020/12
• 早期ステージ大腸癌根治切除後の異時性肝転移に関わるリスク因子の探索

  沢田 尭史, 松井 博紀, 宮岡 陽一, 今泉 健, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P178 - 1 2020/12
• 大腸癌の新規病理学的因子である線維性癌間質反応の臨床的有用性

  松井 博紀, 畑中 佳奈子, 宮岡 陽一, 今泉 健, 市川 伸樹, 吉田 雅, 本間 重紀, 松野 吉宏, 畑中 豊, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P196 - 3 2020/12
• 経腹壁超音波検査による結腸癌リンパ節転移診断精度に関連する臨床病理学的因子の同定

  今泉 健, 本間 重紀, 西田 睦, 松井 博紀, 宮岡 陽一, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P107 - 2 2020/12
• 腫瘍浸潤リンパ球の局在に注目した肝内胆管癌の臨床病理学的検討

  旭 よう, 畑中 佳奈子, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 坂本 譲, 蒲池 浩文, 畑中 豊, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 75回 P220 - 3 2020/12
• 原発性胆汁性胆管炎による非代償性肝硬変、腎不全に対し脳死下肝腎同時移植を実施した一例

  山本 啓一朗, 後藤 了一, 深澤 拓夢, 巖築 慶一, 川村 典生, 渡辺 正明, 小川 浩司, 堀田 記世彦, 岩見 大基, 篠原 信雄, 嶋村 剛, 武冨 紹信

  北海道外科雑誌 北海道外科学会 65 (2) 158 - 163 0288-7509 2020/12 

  今回、原発性胆汁性胆管炎による肝腎不全に対し脳死肝腎同時移植を施行したので報告する。症例は46歳女性。35歳頃、原発性胆汁性胆管炎と診断。43歳時に黄疸発症し、非代償性肝硬変(T-bil 7.4mg/dl、Child Turcotte Pugh(CTP)B9点、Model for End-stage Liver Disease(MELD)score 7点)で当院紹介。2年後に肝不全進行し(T-bil 15.9、CTP C12、MELD22)、脳死登録された。3ヵ月後、T-bil 21.1、CTP C12、MELD27と増悪し、肝腎症候群から透析導入となった。透析導入8週後に腎移植も脳死移植登録した。待機期間246日で脳死ドナー発生、肝腎同時移植を実施した。術後膵炎を認めたが、肝機能は良好に推移し、術後12日目で透析離脱、術後57日目で退院した。術後11ヵ月の時点で、経過良好で外来フォロー中である。今後、肝腎不全に陥った症例に対しても肝腎同時移植を施行することで長期予後改善の可能性が期待される。(著者抄録)
• 17歳男性に発生した肝細胞腺腫(径25cm)の1例

  石塚 千紘, 島田 慎吾, 神山 俊哉, 折茂 達也, 蒲池 浩文, 杉野 弘和, 三橋 智子, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 81 (12) 2500 - 2506 1345-2843 2020/12 

  症例は生来健康な17歳の男性.腹部膨満を契機に,肝右葉に径25cmの肝腫瘍が発見された.肝炎ウイルスマーカーは陰性,AFPは正常値でPIVKA-IIが12,738mAU/mlと異常高値を認めた.造影CTおよびMRIで腫瘍は漸増性の造影効果を伴っており,一部造影効果の乏しい不整形領域を認めた.腫瘍の大部分はEOB-MRIの肝細胞相で取り込み低下は軽度であり,肝細胞癌としては非典型的であったが悪性の可能性が否定できないことと破裂の危険性があることから手術適応と考え,肝右3区域切除を施行した.術後経過は良好で,術後13日目に退院となった.病理診断はβ-catenin活性化型肝細胞腺腫であり,悪性所見は認めなかった.PIVKA-IIは切除後速やかに低下した.今回,若年男性に発生した稀な巨大肝細胞腺腫の1切除例を経験したため,文献的考察を加えて報告する.(著者抄録)
• Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines.

  Hidenori Takahashi, Toshiya Kamiyama, Nozomi Hirane, Nozomi Kobayashi, Takeshi Aiyama, Akihisa Nagatsu, Shingo Shimada, Tatsuya Orimo, Tatsuhiko Kakisaka, Moto Fukai, Hideki Yokoo, Hirofumi Kamachi, Shin-Ichiro Nishimura, Akinobu Taketomi

  Oncology reports 44 (6) 2757 - 2769 2020/12 

  The N‑glycoforms of glycoproteins modify protein function and control a number of biological pathways. The aim of the present study was to investigate the correlation between alterations in N‑glycans and cancer aggressiveness in terms of cancer cell invasion ability. The expression of urokinase‑type plasminogen activator (uPA) and N‑acetylglucosaminyltransferase V (GnT‑V) in liver cancer cell lines was analyzed by western blotting. Cell invasiveness was analyzed by Matrigel invasion assays. uPA and GnT‑V expression in liver cancer cell lines was knocked down by RNA interference. Furthermore, uPA was overexpressed in liver cancer cells using lentiviral vectors, and a mutant strain of HepG2 cells overexpressing uPA deficient in N‑glycans was established. A glycoblotting‑assisted matrix‑assisted laser desorption/ionization‑time‑of‑flight/mass spectrometry‑based quantitative analysis of liver cancer cell lines was performed, in which invasiveness was altered by modifying the expression of uPA and GnT‑V. N‑glycan profiles were found to differ between the highly invasive liver cancer cell line HLE and the less invasive cell line HepG2. The expression of several N‑glycans, including a form with m/z=1892, was changed according to invasiveness controlled by knockdown and overexpression of uPA. The invasiveness of HepG2 cells with mutant uPA did not increase regardless of the level of expression of uPA. Following GnT‑V knockdown and N‑glycan alteration, uPA expression did not change, whereas cell invasiveness decreased. One N‑glycan (m/z=1892) was common among N‑glycans in the comparative analysis between HLE and HepG2, HLE and uPA knockdown HLE, HepG2 and uPA‑overexpressing HepG2, and HLE and GnT‑V knockdown HLE cells and among N‑glycan profiles in human uPA. Therefore, N‑glycosylation is an important factor controlling invasiveness of liver cancer cells, and a specific N‑glycan (m/z=1892) associated with the invasion of liver cancer cells via uPA was identified in the present study.
• De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience.

  Ryoichi Goto, Yukiko Kosai-Fujimoto, Shintaro Yagi, Tsuyoshi Kobayashi, Nobuhisa Akamatsu, Tsuyoshi Shimamura, Satoru Imura, Satoshi Ogiso, Shugo Mizuno, Mitsuhisa Takatsuki, Takasuke Fukuhara, Tatsuya Kanto, Susumu Eguchi, Katsuhiko Yanaga, Yasuhiro Ogura, Takumi Fukumoto, Mitsuo Shimada, Kiyoshi Hasegawa, Hideki Ohdan, Shinji Uemoto, Yuji Soejima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara

  Hepatology research : the official journal of the Japan Society of Hepatology 50 (12) 1365 - 1374 2020/12 [Refereed][Not invited]
   

  AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.
• 肝臓 再発・転移

  旭 よう, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 53 (Suppl.2) 235 - 235 0386-9768 2020/11
• 肝臓 周術期管理

  坂本 譲, 神山 俊哉, 島田 慎吾, 折茂 達也, 長津 明久, 旭 よう, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 53 (Suppl.2) 238 - 238 0386-9768 2020/11
• Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition.

  Kazuki Wakizaka, Toshiya Kamiyama, Kenji Wakayama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Hirofumi Kamachi, Hideki Yokoo, Moto Fukai, Nozomi Kobayashi, Tomoko Mitsuhashi, Akinobu Taketomi

  Oncology letters 20 (5) 268 - 268 2020/11 [Refereed][Not invited]
   

  Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.
• Risk factors for dysfunction of preoperative endoscopic biliary drainage for malignant hilar biliary obstruction.

  Ryo Sugiura, Masaki Kuwatani, Shin Kato, Kazumichi Kawakubo, Hirofumi Kamachi, Akinobu Taketomi, Takehiro Noji, Keisuke Okamura, Satoshi Hirano, Naoya Sakamoto

  Journal of hepato-biliary-pancreatic sciences 27 (11) 851 - 859 2020/11 [Refereed][Not invited]
   

  BACKGROUND: Few studies have focused on the risk factors for dysfunction of endoscopic biliary drainage (EBD) in preoperative patients with malignant hilar biliary obstruction (MHBO). METHODS: We searched the database between February 2011 and December 2018 and identified patients with MHBO who underwent radical operation. The rate of dysfunction of the initial EBD, risk factors for dysfunction of the initial EBD and survival after surgery were retrospectively evaluated. RESULTS: We analyzed a total of 131 patients [95 males (72.5%); mean age, 69.5 (±7.3) years; Bismuth-Corlette classification (BC) I/II/IIIa/IIIb/IV, 50/26/22/17/16; hilar cholangiocarcinoma/gall bladder cancer, 115/16]. Dysfunction of the initial EBD occurred in 28 patients (21.4%). The cumulative incidences of dysfunction of the initial EBD in all patients were 18.4%, 38.2% and 47.0% at 30, 60 and 90 days, respectively (Kaplan-Meier method). The rate of dysfunction of the initial EBD increased in patients with BC-IV (P = .03). Multivariate analysis showed that BC-IV and pre-EBD cholangitis were significantly associated with the occurrence of dysfunction of the initial EBD. Survival rates were not significantly different according to the initial biliary drainage methods and presence/absence of the initial EBD dysfunction. CONCLUSIONS: Dysfunction of the initial EBD frequently occurs in patients with the BC-IV and those with pre-EBD cholangitis.
• Intermittent pneumatic compression versus additional prophylaxis with enoxaparin for prevention of venous thromboembolism after laparoscopic surgery for gastric and colorectal malignancies: multicentre randomized clinical trial

  H. Kamachi, S. Homma, H. Kawamura, T. Yoshida, Y. Ohno, N. Ichikawa, R. Yokota, T. Funakoshi, Y. Maeda, N. Takahashi, T. Amano, A. Taketomi

  BJS open 4 (5) 804 - 810 2474-9842 2020/10/01 

  BACKGROUND: The role of antithrombotic chemoprophylaxis in prevention of venous thromboembolism (VTE) in laparoscopic surgery for gastric and colorectal malignancies is unknown. This study compared the addition of enoxaparin following intermittent pneumatic compression (IPC) with IPC alone in patients undergoing laparoscopic surgery for gastrointestinal malignancy. METHODS: In this multicentre RCT, eligible patients were older than 40 years and had a WHO performance status of 0 or 1. Exclusion criteria were prescription of antiplatelet or anticoagulant drugs and history of VTE. Patients were allocated to IPC or to ICP with enoxaparin in a 1 : 1 ratio. Stratification factors included sex, location of cancer, age 61 years and over, and institution. Enoxaparin was administered on days 1-7 after surgery. Primary outcome was VTE, evaluated by multidetector CT on day 7. RESULTS: Of 448 patients randomized, 208 in the IPC group and 182 in the IPC with enoxaparin group were evaluated. VTE occurred in ten patients (4·8 per cent) in the IPC group and six (3·3 per cent) in the IPC with enoxaparin group (P = 0·453). Proximal deep vein thrombosis and/or pulmonary embolism occurred in seven patients (3·4 per cent) in the IPC group and one patient (0·5 per cent) in the IPC with enoxaparin group (P = 0·050). All VTE events were asymptomatic and non-fatal. Bleeding occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient needed a transfusion. All bleeding events were managed by discontinuation of the drug. CONCLUSION: IPC with enoxaparin after laparoscopic surgery for gastric and colorectal malignancies did not reduce the rate of VTE. Registration number: UMIN000011667 ( https://www.umin.ac.jp/).
• 早期ステージ大腸癌根治切除後の異時性肝転移に関わるリスク因子の探索

  沢田 尭史, 市川 伸樹, 吉田 雅, 小林 希, 本間 重紀, 武冨 紹信

  日本癌学会総会記事 79回 PJ14 - 7 0546-0476 2020/10
• アルギナーゼ1の阻害は担がん生体内における大腸がん細胞の肝転移巣形成を減弱させる

  王 向東, 項 慧慧, 豊島 雄二郎, 杉山 昂, 志智 俊介, 沈 輝棟, 本間 重紀, 武冨 紹信, 北村 秀光

  日本癌学会総会記事 79回 OE10 - 6 0546-0476 2020/10
• DGKαの阻害は肝がんモデルマウスの抗腫瘍免疫状態を亢進する

  志智 俊介, 北村 秀光, 杉山 昂, 岡田 尚樹, 武冨 紹信

  日本癌学会総会記事 79回 OJ12 - 3 0546-0476 2020/10
• IL-6の欠損は生体内の抗腫瘍免疫を亢進し大腸がん細胞の肝転移巣形成を抑制する

  北村 秀光, 豊島 雄二郎, 項 慧慧, 大野 陽介, 本間 重紀, 川村 秀樹, 高橋 典彦, 神山 俊哉, 谷野 美智枝, 武冨 紹信

  日本癌学会総会記事 79回 OJ12 - 5 0546-0476 2020/10
• 消化器がんに対する新規治療標的Diacylglycerol kinaseα阻害と制癌剤投与併用効果の検証

  杉山 昂, 北村 秀光, 志智 俊介, 岡田 尚樹, 武冨 紹信

  日本癌学会総会記事 79回 OJ17 - 6 0546-0476 2020/10
• CMKLR1は肝癌幹細胞標的治療のための候補分子である

  谷 道夫, 津田 真寿美, 鈴鹿 淳, 王 磊, 武冨 紹信, 田中 伸哉

  日本癌学会総会記事 79回 PJ14 - 1 0546-0476 2020/10
• Xenograftマウスモデルを用いた抗メソテリン抗体の早期投与による膵癌肝転移抑制効果の検討

  藤居 勇貴, 蒲池 浩文, 深井 原, 折茂 達也, 坂本 譲, 旭 よう, 長津 明久, 島田 慎吾, 柿坂 達彦, 神山 俊哉, 武冨 紹信

  日本癌学会総会記事 79回 OJ14 - 4 0546-0476 2020/10
• 肝切除を施行後集学的治療にて長期生存が得られているG-CSF産生肝細胞癌の1例

  坂本 譲, 神山 俊哉, 旭 よう, 長津 明久, 島田 慎吾, 折茂 達也, 柿坂 達彦, 蒲池 浩文, 武冨 紹信

  日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 58回 P - 190 2020/10
• A rare case of cavernous hemangioma accompanied with diffuse hepatic hemangiomatosis.

  Takuji Ota, Toshiya Kamiyama, Takuya Kato, Takayuki Hanamoto, Kunihiro Hirose, Noriyuki Otsuka, Shinichi Matsuoka, Akinobu Taketomi

  Surgical case reports 6 (1) 251 - 251 2020/10/01 [Refereed][Not invited]
   

  BACKGROUND: Hepatic cavernous hemangioma (CH) is the most common hepatic benign tumor. Most cases are solitary, asymptomatic, and found incidentally. In symptomatic cases with rapidly growing tumors and coagulopathy, surgical treatment is considered. In rare cases, diffuse hepatic hemangiomatosis (DHH) is reported as a comorbidity. The etiology of DHH is unknown. CASE PRESENTATION: A 29-year-old female patient had a history of endometriosis treated with oral contraceptives. Hepatic CH was incidentally detected in the segment IVa of the liver according to the Couinaud classification. Follow-up computed tomography (CT) and ultrasound sonography showed the growth of the lesion and formation of multiple new lesions near the first. Enhanced CT and magnetic resonance imaging (MRI) revealed that the new lesions were different from CH. Although oral contraceptives were stopped, all lesions grew in size. Malignancy and possibility of rupture of these tumors were considered due to the clinical course, and we opted for surgical removal of the tumors. Left liver lobectomy and cholecystectomy were performed. Surgical findings were small red spot spreading and a mass in segment IV of the liver. Pathological examination revealed a circumscribed sponge-like tumor with diffuse irregular extension to the adjacent area. Both of the lesions consisted of blood-filled dilated vascular spaces lined by flat endothelium without atypia. The diagnosis was hepatic CH with DHH. The patient was discharged on postoperative day 12 uneventfully. CONCLUSION: We report the successful resection of CH with DHH. The case findings suggest a relationship between oral contraceptive use and enlargement of CH and DHH. Although DHH has been poorly understood, a few previously published cases reported DHH occurrence in patients using oral contraceptives. In such cases, the decision to perform surgical resection should be made after careful examination.
• Intestinal anisakiasis with severe intestinal ischemia caused by extraluminal live larvae: a case report.

  Kengo Shibata, Yuichi Yoshida, Yoichi Miyaoka, Shin Emoto, Tomoaki Kawai, Seiji Kobayashi, Kazuhiro Ogasawara, Akinobu Taketomi

  Surgical case reports 6 (1) 253 - 253 2020/10/01 [Refereed][Not invited]
   

  BACKGROUND: Anisakiasis is a parasitic infection caused by Anisakis worms found in raw fish. Most cases of anisakiasis occur in the stomach and rarely occur in the intestine. It is extremely rare for live larvae to break through the intestine into the mesentery and cause severe intestinal ischemia. Anisakiasis can be treated conservatively, because the larvae will die in approximately 1 week, but, sometimes, a serious condition can arise, as in this case. We report the first case of extraluminal anisakiasis in which a live Anisakis worm caused severe intestinal ischemia. CASE PRESENTATION: The patient was a 26-year-old woman who ate squid a week prior. She had abdominal pain and was admitted to our emergency department. On physical examination, abdominal guarding and rebound tenderness were present in her lower abdomen. Contrast-enhanced computed tomography showed ascites, the whirl sign, localized submucosal edema of the intestinal wall, and a dilated small bowel segment with edema. We suspected the strangulated small bowel obstruction based on the CT-scan findings. To rule out the strangulated small bowel obstruction, laparoscopic exploration was performed. Bloody ascites in the pouch of Douglas and severe inflammation in 20 cm of the ileum were observed. An Anisakis larva had perforated the intestinal wall and was found alive in the mesentery. The ileum had developed a high degree of ischemia, so the affected section was resected. Histopathological examination revealed that the Anisakis worm body was in the inflamed mesentery and caused a high degree of ischemia in the intestinal tract. The patient was discharged 9 days after surgery. CONCLUSIONS: A living Anisakis larva punctured the mesentery of the small intestine, resulting in severe intestinal ischemia. As seen in this case, intestinal anisakiasis may cause serious symptoms, and a low threshold for performing diagnostic laparoscopy for the early diagnosis of bowel ischemia secondary to anisakiasis can be useful in determining the definite diagnosis and indications for resection.
• ASO Author Reflections: Is Hepatectomy Plus Diaphragmatic Resection for Hepatocellular Carcinoma with Diaphragmatic Involvement Justified?

  Tatsuya Orimo, Toshiya Kamiyama, Akinobu Taketomi

  Annals of surgical oncology 27 (11) 4164 - 4165 2020/10 [Refereed][Not invited]
  
• Hepatectomy Combined with Diaphragmatic Resection for Hepatocellular Carcinoma with Diaphragmatic Involvement: A Propensity Score-Matched Analysis.

  Tatsuya Orimo, Toshiya Kamiyama, Kenji Wakayama, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Akinobu Taketomi

  Annals of surgical oncology 27 (11) 4153 - 4163 2020/10 [Refereed][Not invited]
   

  PURPOSE: We evaluated the short- and long-term surgical outcomes of hepatectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) with diaphragmatic involvement. METHODS: We retrospectively reviewed the surgical outcomes of HCC patients with diaphragmatic resection (DR group) and HCC patients without diaphragmatic resection (non-DR group). We applied 1:1 propensity score matching (PSM) to these subjects. RESULTS: The study included 46 patients in DR group and 828 patients in non-DR group. The DR group cases were pathologically more advanced, and both overall and relapse-free survival among the patients in this group with pathological diaphragmatic invasion were similar to cases with pathological diaphragmatic fibrous adhesion. There were 40 patients from each group subjected to PSM. In these matched cohorts, there was no statistically significant difference between the two groups regarding perioperative outcomes, overall survival, and relapse-free survival. Multivariate analyses of our matched HCC patients revealed that alpha-fetoprotein expression and tumor size were independent prognostic factors for overall survival and poor differentiation for relapse-free survival, whereas neither diaphragmatic invasion nor diaphragmatic resection were prognostic indicators. The most frequent site of recurrence in non-DR group was the liver, whereas the most frequent site of recurrence in DR group was the lung before and after PSM. CONCLUSIONS: The short- and long-term surgical outcomes of DR HCC cases are equivalent to their non-DR counterparts under a matched clinicopathological background. Hepatectomy combined with DR is an acceptable treatment for HCC with either diaphragmatic fibrous adhesion or diaphragmatic invasion.
• Second Case of Deceased Donor Liver Transplantation in a Patient Co-infected with HIV and HCV in Japan: Special Reference to the Management of Complicated Coagulopathy Due to a Diverse Spectrum of Preformed Anti-HLA Antibodies.

  Norio Kawamura, Ryoichi Goto, Yasuyuki Koshizuka, Masaaki Watanabe, Tomomi Suzuki, Tomoyuki Endo, Takeshi Kondo, Akinobu Taketomi, Tsuyoshi Shimamura

  Japanese journal of infectious diseases 73 (5) 369 - 372 2020/09/24 [Refereed][Not invited]
   

  We report the second case of deceased donor liver transplantation in a patient co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in Japan. A 48-year-old patient with hemophilia A was infected with HIV and HCV through contaminated factor VIII concentrate in his childhood and developed cirrhosis and hepatocellular carcinoma. The patient was on the transplant list for a deceased donor liver. The patient had broad spectrum anti-HLA class I and II antibodies, which may be attributed to repeated whole blood transfusions in the past. Catastrophic coagulopathy during the surgery was predicted because of the underlying hemophilic status and severe thrombocytopenia requiring HLA-matched platelet products, which are difficult to obtain quickly. To maintain adequate platelet counts (> 5 × 104/µL) while awaiting liver transplantation, a thrombopoietin receptor agonist and rituximab were administered. During surgery, factor VIII concentrate was administered according to a previously planned protocol. Adequate hemostasis was obtained, and the operation was completed without uncontrollable coagulopathy. The postoperative course was uneventful, and the patient was discharged on postoperative day 41. Detailed planning is required for surgical patients with hemophilia and HIV/HCV cirrhosis, especially for those with a diverse spectrum of anti-HLA antibodies.
• 局所進行大腸癌に対する治療戦略【International】術前FOLFOX療法が切除可能局所進行直腸癌の予後に及ぼす影響 The R-NAC-01 study(The survival impact of preoperative FOLFOX in resectable locally advanced rectal cancer: The R-NAC-01 study)

  市川 伸樹, 本間 重紀, 舩越 徹, 服部 優宏, 佐藤 正法, 上泉 洋, 大森 一吉, 野村 克, 横田 良一, 小池 雅彦, 今 裕史, 武田 圭佐, 石津 寛之, 廣瀬 邦弘, 蔵谷 大輔, 石川 隆壽, 村田 竜平, 吉田 雅, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 PD - 5 2020/08
• 大腸癌肝転移に対する免疫組織化学染色を併用した遺伝子コピー数解析の有用性

  沢田 尭史, 松井 博紀, 宮岡 陽一, 今泉 健, 市川 伸樹, 吉田 雅, 本間 重紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 4 2020/08
• 胃癌患者における循環腫瘍細胞(CTC)の臨床的意義 特に上皮間葉転換と周術期動態に注目して

  石黒 友唯, 崎浜 秀康, 吉田 雅, 市川 伸樹, 本間 重紀, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 3 2020/08
• 若年性大腸癌の臨床病理学的特徴

  吉田 雅, 本間 重紀, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 7 2020/08
• 肝がんモデルを用いたDiacylglicerol Kinaseα阻害による抗腫瘍エフェクター細胞の活性化機序解明

  志智 俊介, 岡田 尚樹, 杉山 昂, 北村 秀光, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 3 2020/08
• Diacylglycerol kinase alpha阻害は抗がん剤投与による抗腫瘍効果を増強する

  杉山 昂, 北村 秀光, 志智 俊介, 岡田 尚樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 5 2020/08
• 肝細胞癌に対する減容肝切除術の結果(Result of Volume Reduction Hepatectectomy for Hepatocellular Carcinoma)

  Asahi Yoh, Kamiyama Toshiya, Orimo Tatsuya, Shimada Shingo, Nagatsu Akihisa, Sakamoto Yuzuru, Kamachi Hirofumi, Taketomi Akinobu

  薬理と臨床 30 (3) 182 - 182 0917-3994 2020/08
• 肝腎症候群による腎不全を伴った原発性胆汁性胆管炎、非代償性肝硬変に対し脳死肝移植を施行した3例の検討

  鈴木 大喜, 後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 山本 啓一朗, 深澤 拓夢, 堀田 記世彦, 岩見 大基, 篠原 信雄, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 RS - 10 2020/08
• リンパ球の再構築による移植片局所免疫機能解析法の開発

  巌築 慶一, 後藤 了一, 大田 拓児, 金沢 亮, 川村 典生, 財津 雅昭, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 3 2020/08
• 脳死肝移植後早期グラフト機能不全(Early Graft Dysfunction)並びに短期成績の検討

  川村 典生, 嶋村 剛, 後藤 了一, 渡辺 正明, 巖築 慶一, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 5 2020/08
• 小腸冷保存中の酸素供給が抗酸化治療の有効性に与える影響の検討

  深井 原, 柴田 賢吾, 坂本 聡大, 島田 慎吾, 加藤 紘一, 藤好 真人, 若山 顕治, 石川 隆壽, 川村 典生, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 8 2020/08
• 移植医療における細胞治療の有用性

  渡辺 正明, 渋谷 一陽, 後藤 了一, 川村 典生, 巌築 慶一, 腰塚 靖之, 嶋村 剛, 深井 原, 藤堂 省, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 8 2020/08
• 肝移植術後合併症予測モデルに基づいた支援プログラムに関するアンケート調査

  佐藤 直哉, 丸橋 繁, 掛地 吉弘, 武富 紹信, 高田 泰次, 梅下 浩司, 江川 裕人, 大段 秀樹, 瀬戸 泰之, 後藤 満一

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 53 (8) 617 - 626 0386-9768 2020/08 

  目的:これまでに我々は本邦における肝移植術後合併症・死亡予測モデルを構築し,2018年11月にNational Clinical Databaseのフィードバック機能として実装した.本研究では,予測モデルに基づいた肝移植支援プログラムについて,肝移植を実施する医療現場での感想を明らかにすることを目的とした.方法:2018年度日本肝移植研究会施設会員全121施設における医師・看護師・コーディネーターを対象として,無記名式アンケート郵送調査を行った.結果:37施設(回収率30.6%)より回答が得られ,内訳は医師数64名,看護師5名,コーディネーター10名であった.医師を対象としたアンケートでは,リスクモデルによる術後合併症予測発生率の妥当性について,「そう思う」が65.6%,「どちらでもない」が28.1%であった.また,症例ごとの合併症予測によりグラフト選択,手術適応の判断および周術期管理に影響があると回答した医師は,それぞれ63%,45%,42%と最多であった.また,患者説明や若手の教育に利用可能であるとの回答は,医師でおよそ60%,看護師・コーディネーターでは100%であった.結語:本研究により,肝移植支援プログラムにおける合併症予測の妥当性は広く認識され,最適な術式の検討に加えて,患者への術前説明,医療者の教育ツールなどへの幅広い活用も可能であることが示された.(著者抄録)
• 転移性肝癌に対する肝切除の位置付け 大腸癌肝転移に対する外科切除成績の意義の検討 傾向スコアマッチングによる解析

  長津 明久, 神山 俊哉, 坂本 譲, 旭 よう, 島田 慎吾, 折茂 達也, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 WS - 1 2020/08
• 肝細胞癌原発巣切除12年後の横隔膜上リンパ節再発に対しリンパ節摘出術を行った一例

  深澤 拓夢, 神山 俊哉, 長津 明久, 坂本 譲, 旭 よう, 島田 慎吾, 折茂 達也, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 RS - 8 2020/08
• 亜区域切除以上の肝切除を施行した80歳以上高齢者肝細胞癌の切除成績と予後因子

  島田 慎吾, 神山 俊哉, 折茂 達也, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 5 2020/08
• EOB-MRIを用いた肝細胞癌術後肝不全予測の有用性

  折茂 達也, 神山 俊哉, 島田 慎吾, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 1 2020/08
• 肝細胞癌におけるWnt5aの発現についての検討

  脇坂 和貴, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 旭 よう, 坂本 譲, 蒲池 浩文, 三橋 智子, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 6 2020/08
• 抗メソテリン抗体amatuximabによる膵癌肝転移形成阻害効果の検討

  藤居 勇貴, 蒲池 浩文, 折茂 達也, 坂本 譲, 旭 よう, 長津 明久, 島田 慎吾, 深井 原, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 SF - 4 2020/08
• Siglec-7はNAFLD患者における肝臓の炎症および線維化関連因子である

  坂本 譲, 由雄 祥代, 旭 よう, 長津 明久, 島田 慎吾, 折茂 達也, 蒲池 浩文, 神山 俊哉, 考藤 達哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 4 2020/08
• 肝細胞癌に対する減量肝切除術の検討

  旭 よう, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 坂本 譲, 蒲池 浩文, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 4 2020/08
• バイオマテリアルによる肝癌幹細胞の新規誘導法の開発とその解析

  谷 道夫, 津田 真寿美, 鈴鹿 淳, 王 磊, 杉野 弘和, 谷川 聖, 石田 雄介, グン 剣萍, 田中 伸哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 6 2020/08
• COVID-19: clinical issues from the Japan Surgical Society.

  Masaki Mori, Norihiko Ikeda, Akinobu Taketomi, Yo Asahi, Yoshio Takesue, Tatsuya Orimo, Minoru Ono, Takashi Kuwayama, Seigo Nakamura, Yohei Yamada, Tatsuo Kuroda, Kenji Yuzawa, Taizo Hibi, Hiroaki Nagano, Michiaki Unno, Yuko Kitagawa

  Surgery today 50 (8) 794 - 808 2020/08 [Refereed][Not invited]
   

  In this unprecedented COVID-19 pandemic, several key issues must be addressed to ensure safe treatment and prevent rapid spread of the virus and a consequential medical crisis. Careful evaluation of a patient's condition is crucial for deciding the triage plan, based on the status of the disease and comorbidities. As functionality of the medical care system is greatly affected by the environmental situation, the treatment may differ according to the medical and infectious disease circumstances of the institution. Importantly, all medical staff must prevent nosocomial COVID-19 by minimizing the effects of aerosol spread and developing diagnostic and surgical procedures. Polymerase chain reaction (PCR) screening for COVID-19 infection, particularly in asymptomatic patients, should be encouraged as these patients are prone to postoperative respiratory failure. In this article, the Japan Surgical Society addresses the general principles of surgical treatment in relation to COVID-19 infection and advocates preventive measures against viral transmission during this unimaginable COVID-19 pandemic.
• Prognostic impact of CD8+ T cell distribution and its association with the HLA class I expression in intrahepatic cholangiocarcinoma.

  Yoh Asahi, Kanako C Hatanaka, Yutaka Hatanaka, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yuzuru Sakamoto, Hirofumi Kamachi, Nozomi Kobayashi, Moto Fukai, Akinobu Taketomi

  Surgery today 50 (8) 931 - 940 2020/08 [Refereed][Not invited]
   

  PURPOSE: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. METHODS: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). RESULTS: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). CONCLUSION: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma.
• Predictive value of gadoxetic acid enhanced magnetic resonance imaging for posthepatectomy liver failure after a major hepatectomy.

  Tatsuya Orimo, Toshiya Kamiyama, Hirofumi Kamachi, Shingo Shimada, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Daisuke Abo, Akinobu Taketomi

  Journal of hepato-biliary-pancreatic sciences 27 (8) 531 - 540 2020/08 [Refereed][Not invited]
   

  BACKGROUND: We assessed the usefulness of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging for the prediction of posthepatectomy liver failure (PHLF) after a major hepatectomy. METHODS: We reviewed 140 cases involving a hepatectomy of two or more sections between 2010 and 2016 (study cohort). We used the standardized remnant hepatocellular uptake index (SrHUI) which was calculated by: SrHUI = future remnant liver volume × [(signal intensity of remnant liver on hepatobiliary phase images/signal intensity of spleen on hepatobiliary phase images) - 1]/body surface area. Validation of the SrHUI was performed in another cohort of 52 major hepatectomy cases between 2017 and 2018 (validation cohort). RESULTS: The SrHUI of patients with PHLF was significantly lower than that of non-PHLF cases. Receiver operating characteristic analysis and the Youden index revealed that the SrHUI cutoff value for the prediction of PHLF and PHLF grade ≥ B were 0.313 L/m2 and 0.257 L/m2 , respectively. In the validation cohort, the cutoff value of SrHUI for the prediction of PHLF or PHLF grade ≥ B had a sensitivity of 75.0% or 88.8%, and specificity of 78.1% or 91.6%, respectively. CONCLUSIONS: The SrHUI value is a predictor for PHLF after a major hepatectomy.
• Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria.

  Takuya Sho, Goki Suda, Koji Ogawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Jun Ito, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Katsumi Terasita, Tomofumi Takagi, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto

  Hepatology research : the official journal of the Japan Society of Hepatology 50 (8) 966 - 977 2020/08 [Refereed][Not invited]
   

  AIM: This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial). METHODS: In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression-free-survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial. RESULTS: Of the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child-Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child-Pugh-score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS. CONCLUSION: Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.
• Imaging Mass Spectrometry Reveals the Changes in the Taurine Conjugates of Dihydroxycholanoic Acid During Hepatic Warm Ischemia and Reperfusion in a Rat Model

  Kengo Shibata, Takahiro Hayasaka, Satsuki Hashimoto, Kohei Umemoto, Takahisa Ishikawa, Sodai Sakamoto, Koichi Kato, Shingo Shimada, Norio Kawamura, Kenji Wakayama, Nozomi Kobayashi, Yuka Hama, Moto Fukai, Tsuyoshi Shimamura, Akinobu Taketomi

  Transplantation Proceedings 52 (6) 1880 - 1883 1873-2623 2020/07/01 

  Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.
• Novel immunological approach to asses donor reactivity of transplant recipients using a humanized mouse model.

  Yasutomo Fukasaku, Ryoichi Goto, Yoshikazu Ganchiku, Shin Emoto, Masaaki Zaitsu, Masaaki Watanabe, Norio Kawamura, Moto Fukai, Tsuyoshi Shimamura, Akinobu Taketomi

  Human immunology 81 (7) 342 - 353 2020/07 [Refereed][Not invited]
   

  In organ transplantation, a reproducible and robust immune-monitoring assay has not been established to determine individually tailored immunosuppressants (IS). We applied humanized mice reconstituted with human (hu-) peripheral blood mononuclear cells (PBMCs) obtained from living donor liver transplant recipients to evaluate their immune status. Engraftment of 2.5 × 106 hu-PBMCs from healthy volunteers and recipients in the NSG mice was achieved successfully. The reconstituted lymphocytes consisted mainly of hu-CD3+ lymphocytes with predominant CD45RA-CD62Llo TEM and CCR6-CXCR3+CD4+ Th1 cells in hu-PBMC-NSG mice. Interestingly, T cell allo-reactivity of hu-PBMC-NSG mice was amplified significantly compared with that of freshly isolated PBMCs (p < 0.05). Furthermore, magnified hu-T cell responses to donor antigens (Ag) were observed in 2/10 immunosuppressed recipients with multiple acute rejection (AR) experiences, suggesting that the immunological assay in hu-PBMC-NSG mice revealed hidden risks of allograft rejection by IS. Furthermore, donor Ag-specific hyporesponsiveness was maintained in recipients who had been completely weaned off IS (n = 4), despite homeostatic proliferation of hu-T cells in the hu-PBMC-NSG mice. The immunological assay in humanized mice provides a new tool to assess recipient immunity in the absence of IS and explore the underlying mechanisms to maintaining operational tolerance.
• Post-transplant indolent T cell lymphoproliferative disorder in living donor liver transplantation: a case report.

  Ryoichi Goto, Norio Kawamura, Masaaki Watanabe, Yasuyuki Koshizuka, Souichi Shiratori, Momoko Ara, Shohei Honda, Tomoko Mitsuhashi, Yoshihiro Matsuno, Tsuyoshi Shimamura, Akinobu Taketomi

  Surgical case reports 6 (1) 147 - 147 2020/06/26 [Refereed][Not invited]
   

  BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) of T cell type has been rarely reported. Accurate diagnosis of this life-threatening rare form of PTLD is important for the treatment strategy. CASE PRESENTATION: A 7-year-old boy had severe diarrhea and weight loss progressively at 7 years post-living donor liver transplantation (LDLT) for biliary atresia. Endoscopy in the gastrointestinal (GI) tract revealed multiple erosions and ulcer lesions with prominent intraepithelial lymphocytosis in the duodenum and terminal ileum. Immunohistochemical examination demonstrated that these accumulated lymphocytes mainly comprised small- to medium-sized T cells expressing CD3, CD4, CD5, CD7, and CD103, but lacking CD8, CD56, and Epstein-Barr virus-encoded small RNAs. In addition, T cell receptor β gene rearrangement was detected by polymerase chain reaction analysis. Comprehensively, the lesions were best interpreted as post-transplant indolent T cell lymphoproliferative disorder (LPD) of the intestine. Clinical remission was achieved by reducing the immunosuppressant. CONCLUSION: A rarely reported indolent type of T cell LPD in post-LDLT was diagnosed by direct inspection and histological investigation. Although the histological classification and therapeutic strategy for post-transplant indolent T cell LPD have not been established, reducing immunosuppression allowed complete remission in our case. To prevent the incidence of PTLD and de novo malignancy, developing a methodology to set a proper dose of immunosuppressant is required.
• Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy.

  Shingo Shimada, Toshiya Kamiyama, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Akinobu Taketomi

  World journal of surgical oncology 18 (1) 122 - 122 2020/06/10 [Refereed][Not invited]
   

  OBJECTIVES: The aim was to evaluate the prognostic factors, clinicopathological characteristics, and surgical outcomes after hepatectomy in very elderly patients with hepatocellular carcinoma (HCC). METHODS: We analyzed 796 patients with HCC from 2000 to 2017. Patients aged 80 years or older were classified into the very elderly group (group VE; n = 49); patients younger than 80 years old and aged 65 years or older were classified into the elderly group (group E; n = 363), and patients younger than 65 years old were classified into the young group (group Y; n = 384). We investigated the prognoses, clinicopathological characteristics, and surgical outcomes after hepatectomy. RESULTS: The number of surgical procedures and outcomes, including morbidities, was not significantly different. Groups VE, E, and Y showed similar prognoses in terms of both survival and recurrence. In group VE, prothrombin activity (PA) < 80% and PIVKA-II ≥ 400 mAU/ml were unfavorable factors for survival, and PIVKA-II ≥ 400 mAU/ml and the presence of portal venous invasion (PVI), hepatic venous invasion, and fibrosis were unfavorable factors for recurrence. In group E, ChE < 180 IU/l, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and hepatic venous invasion (HVI) were unfavorable factors for survival, and ChE < 180 IU/l, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and HVI were unfavorable factors for recurrence. In group Y, AFP ≥ 20 ng/ml, the presence of multiple tumors, poor differentiation, PVI, HVI, and blood loss ≥ 400 ml were unfavorable factors for survival, and PA < 80%, albumin < 3.5 g/dl, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, poor differentiation, and PVI were unfavorable factors for recurrence. CONCLUSIONS: Tumor factors might have limited influence on the prognosis of very elderly patients, and liver function reserve might be important for the long-term survival of very elderly patients. Hepatectomy can be performed safely, even in very elderly patients. Hepatectomy should not be avoided in very elderly patients with HCC if patients have a good general status because these patients have the same prognoses as nonelderly individuals.
• Impact of technically qualified surgeons on laparoscopic colorectal resection outcomes: results of a propensity score‐matching analysis

  N. Ichikawa, S. Homma, T. Funakoshi, T. Ohshima, K. Hirose, K. Yamada, H. Nakamoto, K. Kazui, R. Yokota, T. Honma, Y. Maeda, T. Yoshida, T. Ishikawa, H. Iijima, T. Aiyama, A. Taketomi

  BJS Open 4 (3) 486 - 498 2474-9842 2020/06
• Long-term prognostic factors of patients with hepatocellular carcinoma who survive over 10 years after hepatectomy.

  Shingo Shimada, Toshiya Kamiyama, Tatsuya Orimo, Akihisa Nagatsu, Yoh Asahi, Yuzuru Sakamoto, Hirofumi Kamachi, Akinobu Taketomi

  Journal of surgical oncology 121 (8) 1209 - 1217 2020/06 [Refereed][Not invited]
   

  BACKGROUND AND OBJECTIVES: The aim was to evaluate long-term prognostic factors in hepatocellular carcinoma (HCC) patients who survived over 10 years after hepatectomy and compare prognostic factors between patients with recurrence who died and survived 10 years after initial hepatectomy. METHODS: We analyzed the HCC patients without recurrence over 10 years after hepatectomy (n = 35), those with recurrence who survived over 10 years (n = 48), and those who died within 10 years (n = 132). RESULTS: The rate of recurrence was 16.3%, 10-year overall survival rate was 38.6%, and the 10-year recurrence-free survival (RFS) rate was 16.7%. Nonviral, solitary tumor, well differentiation, and without severe fibrosis were independent favorable factors for long-term RFS. High cholinesterase levels, small tumors and without portal vein invasion were independent favorable factors for long-term survival among patients with recurrence. Long-term survivors with recurrence showed significantly low early recurrence, extrahepatic recurrence, multiple intrahepatic recurrences. CONCLUSION: Important factors for long-term prognoses in HCC patients were a solitary tumor, small tumors, and no advanced fibrosis. A treatment for nonviral hepatitis is needed to achieve long-term RFS. Even patients who relapse might survive long term if they have a late or solitary intrahepatic recurrence, nonsevere cirrhosis, and curative treatment at recurrence.
• An increase in the peripheral lymphocyte-to-monocyte ratio after primary site resection is associated with a prolonged survival in unresectable colorectal carcinoma.

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Tomoko Mitsuhashi, Hiroaki Iijima, Kazuhiro Ogasawara, Keizo Kazui, You Kamiizumi, Futoshi Kawamata, Akinobu Taketomi

  Surgery today 50 (6) 604 - 614 2020/06 [Refereed][Not invited]
   

  PURPOSE: The prognostic benefits of primary tumor resection in patients with unresectable distant metastatic colorectal cancer remain unclear. A high pre-treatment lymphocyte-to-monocyte ratio (LMR) was previously shown to be associated with a better prognosis. We assessed whether or not primary tumor resection was associated with an improved survival if the peripheral lymphocyte-to-monocyte ratio increased after primary site resection. METHODS: The survival in 64 and 59 patients with and without primary tumor resection, respectively, was retrospectively compared. After resection, the survival in 39 patients with a postoperatively increased LMR (LMR-increase) and 25 patients with a decreased LMR (LMR-decrease) was compared. RESULTS: Primary tumor resection prolonged the median survival more frequently in cases of non-differentiated adenocarcinoma, obstructive symptoms, high serum albumin levels, and no lymph-node metastasis than in others. Cox regression showed that the potential independent prognostic variable was non-resection of the primary lesion. After resection, the median survival in the LMR-increase vs. LMR-decrease groups was significantly different (27.3 vs. 20.8 months). There were no marked differences in patient background characteristics between the groups, except for in the number of pre-operative peripheral blood lymphocytes. The resected specimens showed significantly lower CD8+:CD163+ invading leukocyte ratios in the LMR-increase group than in the LMR-decrease group. CONCLUSIONS: Primary tumor resection in patients with unresectable metastatic colorectal cancer may be associated with an improved survival, especially when the LMR is increased after primary tumor resection.
• Hypermethylation of CSF3R is a novel cisplatin resistance marker and predictor of response to postoperative chemotherapy in hepatoblastoma.

  Sunao Fujiyoshi, Shohei Honda, Masashi Minato, Momoko Ara, Hiromu Suzuki, Eiso Hiyama, Akinobu Taketomi

  Hepatology research : the official journal of the Japan Society of Hepatology 50 (5) 598 - 606 2020/05 [Refereed][Not invited]
   

  AIM: Most hepatoblastoma patients undergo pre/postoperative cisplatin treatment. Approximately 20% patients are cisplatin resistant, and show poor prognosis and high recurrence rates. However, some cisplatin-sensitive patients show early recurrence. We consider that a small population of cisplatin-resistant cells may remain after preoperative chemotherapy. Previous studies showed a correlation between DNA hypermethylation and hepatoblastoma progression. Here, we examined whether DNA hypermethylation was related to cisplatin resistance and could be a potential indicator for cisplatin as postoperative chemotherapy. METHODS: We extracted DNA from 43 resected hepatoblastoma tumors. Methylation array analyses were performed in 11 samples, including six cisplatin-sensitive and five cisplatin-resistant samples. We also performed cDNA microarray analysis in parental and cisplatin-resistant HuH6 cells. Through comparison of the datasets, we selected the strongest correlated cisplatin-resistant candidate gene. Using bisulfite pyrosequencing, the candidate gene methylation level was assessed in 38 cisplatin-sensitive patients after checking its usefulness as a substitute modality of methylation array. Correlations between the methylation status and clinical data were analyzed. RESULTS: CSF3R was the strongest correlated variable. Bisulfite pyrosequencing analysis also confirmed CSF3R was significantly hypermethylated in cisplatin-resistant patients. Among the 38 cisplatin-sensitive patients, recurrence curves showed that the CSF3R high methylation patients had significantly higher recurrence than CSF3R low methylation patients. The recurrence curve of methylation high patients was similar to that of cisplatin-resistant patients. CONCLUSIONS: Our findings suggested that CSF3R hypermethylation was related to cisplatin resistance in HB patients and could be a predictor of postoperative chemotherapy, and indicate that CSF3R high methylation patients should be treated with non-CDDP regimens.
• Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma.

  Masafumi Ohira, Tomoharu Yoshizumi, Kyohei Yugawa, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Takashi Motomura, Yohei Mano, Takeo Toshima, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Masaki Mori

  Surgery today 50 (4) 379 - 388 0941-1291 2020/04 [Refereed][Not invited]
   

  PURPOSE: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). METHODS: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. RESULTS: The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. CONCLUSIONS: Our IS scoring system may predict long-term outcomes after surgery for MF-ICC.
• 病的先進部を伴った年長小児の腸重積症3例の経験

  鈴木 琢士, 荒 桃子, 河北 一誠, 本多 昌平, 高桑 恵美, 武富 紹信

  日本小児外科学会雑誌 (一社)日本小児外科学会 56 (2) 227 - 227 0288-609X 2020/04
• 南回りB2/3胆管を伴う肝左葉グラフトを用いた生体肝移植の一例

  高橋 直規, 後藤 了一, 財津 雅昭, 川村 典生, 渡辺 正明, 神山 俊哉, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 54 (6) 299 - 303 0578-7947 2020/04 

  症例は20歳代女性で、生体肝移植ドナーとして、肝左葉グラフト採取術施行目的に入院となった。MRCPでは、短い左肝管とそこから分岐する平行から下に凸に走行するB2-3が疑われたが、術前には明らかな走行異型は指摘できなかった。肝左葉グラフト採取術を施行したところ、肝門部剥離の際に門脈左枝の尾側やや後方に南回りB2/3を認識した。術中胆道造影で、総肝管より左肝管が分岐した直後に、北回りB4と南回りB2/3の分岐異型を認めた。C-armによるリアルタイム胆管造影で切離予定ラインを確認しつつ血管鉗子をかけ、ドナー残存胆管に狭窄が無く、可及的にグラフト胆管が長く残る位置で胆管を切離、北回りB4と南回りB2/3の2穴となった。肝左葉グラフト採取後、バックテーブルでB2/3を十分に剥離してB4と緊張のない形で一穴化し、レシピエント側でこれと胆管空腸吻合を実施した。胆管空腸吻合部にはB2/3、B4それぞれにRTBD tubeを挿入し、吻合後の胆道造影で狭窄、胆汁漏がないことを確認した。ドナーは術後1日目に血清の総ビリルビン値5.0mg/dL、直接ビリルビン値0.2mg/dLと間接優位のビリルビン上昇とPT-INR 1.34と上昇を認めた。術後2日目には、総ビリルビン値2.4mg/dL、PT-INR 1.30と改善し、中肝静脈灌流領域の鬱血に伴う変化と考えられた。以後、経過良好で、予定通り術後14日で退院となった。
• Preoperative chemotherapy in colorectal cancer patients with synchronous liver metastasis.

  Nobuki Ichikawa, Toshiya Kamiyama, Hideki Yokoo, Shigenori Homma, Yoshiaki Maeda, Toshiki Shinohara, Yosuke Tsuruga, Keizo Kazui, Hiroaki Iijima, Tadashi Yoshida, Akinobu Taketomi

  Molecular and clinical oncology 12 (4) 374 - 383 2020/04 [Refereed][Not invited]
   

  The response to preoperative chemotherapy is useful for predicting prognosis in unresectable and resectable disease. However, the prognostic benefit of chemotherapy prior to hepatectomy in patients with colorectal carcinoma and resectable or marginally resectable liver metastases remains unclear. The present study investigated the effect of preoperative chemotherapy on the prognosis of patients with colorectal cancer and resectable or marginally resectable synchronous liver metastasis. A total of 106 patients were retrospectively reviewed, who underwent hepatectomy for colorectal metastasis. The prognosis of 64 patients who received neoadjuvant chemotherapy (NAC) were compared with the 42 patients who did not (non-NAC). Furthermore, a total of 43 patients who responded to chemotherapy were compared with the 21 who did not. Preoperative chemotherapy was administered for 5.7 months, wherein 50 patients (78%) received a single regimen, and 54 (84%) received oxaliplatin. There were more patients with <3 metastases and maximum diameters <5 cm in the non-NAC group. The median survival time was 86.0 and 71.6 months in the NAC and non-NAC groups, respectively (P=0.33). Subgroup analysis on the basis of tumor size and number showed no prognostic differences between the two groups. The median survival time was longer in responders than in non-responders (85 vs. 56 months; P=0.01). However, the median relapse-free survival was equivalent in both groups (16.4 and 10.7 months). Preoperative chemotherapy did not prolong survival. Furthermore, it did not prevent recurrence, even in clinical responders. Therefore, it should not be routinely offered to patients with resectable liver metastasis before their hepatectomy.
• Serum soluble sialic acid-binding immunoglobulin-like lectin-7 concentration as an indicator of liver macrophage activation and advanced fibrosis in patients with non-alcoholic fatty liver disease.

  Yuzuru Sakamoto, Sachiyo Yoshio, Hiroyoshi Doi, Hironari Kawai, Tomonari Shimagaki, Taizo Mori, Michitaka Matsuda, Yoshihiko Aoki, Yosuke Osawa, Yuji Yoshida, Taeang Arai, Norio Itokawa, Takanori Ito, Yuya Seko, Kanji Yamaguchi, Yoshihito Itoh, Yoshihiro Mise, Akio Saiura, Akinobu Taketomi, Tatsuya Kanto

  Hepatology research : the official journal of the Japan Society of Hepatology 50 (4) 466 - 477 1386-6346 2020/04 [Refereed][Not invited]
   

  AIM: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Because liver fibrosis is associated with the long-term prognosis of patients with NAFLD, there is an urgent need for non-invasive markers of liver fibrosis. Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an immunomodulatory molecule expressed on various immune cells, including macrophages, which plays a key role in liver inflammation and fibrosis in NAFLD. We aimed to determine whether serum levels of soluble Siglec-7 (sSiglec-7) could have utility at a marker of fibrosis in this patient population. METHODS: We examined serum samples from 93 NAFLD patients and 19 healthy donors for macrophage-associated protein, including sSiglec-7, soluble CD163, and YKL-40, and examined their correlation with liver fibrosis scores, tissue elastography, and histological findings. Independent factors associated with advanced fibrosis were analyzed using a logistic regression model and a decision tree. To clarify the source of sSiglec-7, we examined its expression in liver tissue-derived macrophages and cultured monocyte-derived macrophages. RESULTS: Serum sSiglec-7 levels were significantly higher in NAFLD patients compared with healthy donors, and correlated positively with sCD163 and YKL-40 levels. Serum sSiglec-7 was an independent diagnostic marker with high specificity (96.3%) for advanced fibrosis (F3 and F4) in NAFLD patients. Siglec-7 was mainly expressed on CCR2+ macrophages in the liver, and sSiglec-7 production by monocyte-derived macrophages in vitro was increased after stimulation by pro-inflammatory factors. CONCLUSIONS: Elevated serum sSiglec-7 could serve as an independent marker with high specificity for advanced liver fibrosis in patients with NAFLD.
• Impaired O-Glycosylation at Consecutive Threonine TTX Motifs in Mucins Generates Conformationally Restricted Cancer Neoepitopes.

  Shun Hayakawa, Takahiko Matsushita, Yasuhiro Yokoi, Hajime Wakui, Fayna Garcia-Martin, Hiroshi Hinou, Koji Matsuoka, Kazuhiro Nouso, Toshiya Kamiyama, Akinobu Taketomi, Shin-Ichiro Nishimura

  Biochemistry 59 (12) 1221 - 1241 2020/03/31 [Refereed][Not invited]
   

  Autoantibody signatures of circulating mucin fragments stem from cancer tissues, and microenvironments are promising biomarkers for cancer diagnosis and therapy. This study highlights dynamic epitopes generated by aberrantly truncated immature O-glycosylation at consecutive threonine motifs (TTX) found in mucins and intrinsically disordered proteins (IDPs). NMR analysis of synthetic mucin models having glycosylated TTX motifs and colonic MUC2 tandem repeats (TRs) containing TTP and TTL moieties unveils a general principle that O-glycosylation at TTX motifs generates a highly extended and rigid conformation in IDPs. We demonstrate that the specific conformation of glycosylated TTX motifs in MUC2 TRs is rationally rearranged by concerted motions of multiple dihedral angles and noncovalent interactions between the carbohydrate and peptide region. Importantly, this canonical conformation of glycosylated TTX motifs minimizes steric crowding of glycans attached to threonine residues, in which O-glycans possess restricted orientations permitting further sugar extension. An antiadhesive microarray displaying synthetic MUC2 derivatives elicited the presence of natural autoantibodies to MUC2 with impaired O-glycosylation at TTX motifs in sera of healthy volunteers and patients diagnosed with early stage colorectal cancer (CRC). Interestingly, autoantibody levels in sera of the late stage CRC patients were distinctly lower than those of early stage CRC and normal individuals, indicating that the anti-MUC2 humoral response to MUC2 neoepitopes correlates inversely with the CRC stage of patients. Our results uncovered the structural basis of the creation of dynamic epitopes by immature O-glycosylation at TTX motifs in mucins that facilitates the identification of high-potential targets for cancer diagnosis and therapy.
• Increase of Akkermansia muciniphila by a Diet Containing Japanese Traditional Medicine Bofutsushosan in a Mouse Model of Non-Alcoholic Fatty Liver Disease.

  Mitsue Nishiyama, Nobuhiro Ohtake, Atsushi Kaneko, Naoko Tsuchiya, Sachiko Imamura, Seiichi Iizuka, Shiori Ishizawa, Akinori Nishi, Masahiro Yamamoto, Akinobu Taketomi, Toru Kono

  Nutrients 12 (3) 2020/03/20 [Refereed][Not invited]
   

  Non-alcoholic fatty liver disease (NAFLD) is considered a worldwide healthcare problem that mirrors the increased prevalence of obesity. Gut microbiota plays a crucial role in the progression and treatment of NAFLD. Bofutsushosan (BTS), a pharmaceutical-grade Japanese traditional medicine, has long been prescribed in Japan for obesity and obesity-related syndrome. Although BTS has been reported to exert an anti-obesity effect in obese patients as well as various obesity-model animals, its effect on gut microbiota is unknown. Here, the effects of BTS on obesity, liver damage, and the gut microbiome in genetically obese mice, ob/ob, were studied. Seven-week-old ob/ob mice were fed a standard diet with (BTS group) or without (CONT group) 5% BTS for 4 weeks. By comparison to the CONT group, the BTS group showed reduced body weight gain and hyperlipidemia as well as improved liver function. Moreover, gut microbiota in the CONT and BTS group formed a significantly different cluster. Specifically, the genera Akkermansia, Bacteroides and an unknown genus of the family Enterobacteriaceae expanded dramatically in the BTS group. Noteworthy, the population of Akkermansia muciniphila, which is reported to elicit an anti-obesity effect and improve various metabolic abnormalities, was markedly increased (93-fold) compared with the CONT group. These results imply that BTS may be a promising agent for treating NAFLD.
• 高度肥満を伴う腹腔鏡下スリーブ状胃切除後のHCCに対して腹腔鏡下肝左葉切除を施行した一例

  長津 明久, 神山 俊哉, 坂本 譲, 旭 よう, 島田 慎吾, 折茂 達也, 蒲池 浩文, 武冨 紹信

  日本消化器病学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 126回 66 - 66 2020/03 [Refereed][Not invited]
  
• CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma.

  Kazuki Wakizaka, Hideki Yokoo, Toshiya Kamiyama, Tatsuhiko Kakisaka, Masafumi Ohira, Michio Tani, Koichi Kato, Yuki Fujii, Ko Sugiyama, Akihisa Nagatsu, Shingo Shimada, Tatsuya Orimo, Hirofumi Kamachi, Ryosuke Matsuoka, Akinobu Taketomi

  Hepatology research : the official journal of the Japan Society of Hepatology 50 (2) 258 - 267 1386-6346 2020/02 [Refereed][Not invited]
   

  AIM: A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. METHODS: We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. RESULTS: Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. CONCLUSIONS: INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.
• 当院で管理中の先天性門脈体循環シャント6例の検討

  辻岡 孝郎, 泉 岳, 武田 充人, 小杉山 清隆, 山澤 弘州, 阿部 二郎, 谷口 宏太, 佐々木 大輔, 永井 礼子, 本多 昌平, 荒 桃子, 阿保 大介, 曽山 武士, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 神山 俊哉, 武冨 紹信, 真部 淳

  日本小児科学会雑誌 (公社)日本小児科学会 124 (2) 250 - 250 0001-6543 2020/02
• Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting

  Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto

  JGH OPEN 4 (1) 54 - 60 2397-9070 2020/02 [Refereed][Not invited]
   

  Background and AimLenvatinib has been recently approved as a first-line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child-Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real-world setting.MethodsAmong patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis.ResultsA total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups.ConclusionLenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.
• Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting.

  Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto

  JGH open : an open access journal of gastroenterology and hepatology 4 (1) 54 - 60 0168-8278 2020/02 [Refereed][Not invited]
   

  Background and Aim: Lenvatinib has been recently approved as a first-line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child-Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real-world setting. Methods: Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results: A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion: Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.
• Proficiency Level of Novice Technically Qualified Surgeons in Laparoscopic Rectal Resection.

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Hiroaki Iijima, Futoshi Kawamata, Susumu Sibasaki, Hideki Kawamura, Nozomi Minagawa, You Kamiizumi, Yasutomo Fukasaku, Akinobu Taketomi

  Surgical laparoscopy, endoscopy & percutaneous techniques 30 (1) 49 - 54 2020/02 [Refereed][Not invited]
   

  The actual proficiency levels of surgeons after their qualification by the Endoscopic Surgical Skill Qualification System have not been established. This study aimed to investigate whether technically qualified surgeons could safely perform laparoscopic low anterior resection and to evaluate the proficiency level at the time of certification acquisition. A total of 46 patients (mean age, 63.3 y; male to female ratio, 29:17) who underwent low anterior resection were included. Outcomes of 46 low anterior resections for rectal cancer performed by 3 novice surgeons certified by the Endoscopic Surgical Skill Qualification System from 2013 to 2018 at 2 hospitals were retrospectively assessed. The mean operative time and blood loss were 201 minutes and 12.9 mL, respectively. One patient (2.2%) required conversion to open surgery, and major postoperative complications occurred in 4 patients (8.6%), including anastomotic leakage in 2 patients (4.3%). Histologic R0 resection was achieved in all cases. The operative time moving average for the 3 surgeons gradually decreased from 233 to 158 minutes. In cumulative sum charts, the operative time values continuously decreased after the 12th case compared with the target operative time (180 min). In conclusion, surgeons can safely perform laparoscopic low anterior resection just after their qualification but have the potential to further attain proficiency.
• Outcome of Living-Donor Liver Transplantation Using Grafts from Donors Treated for Fatty Liver.

  Yuki Fujii, Norio Kawamura, Masaaki Zaitsu, Masaaki Watanabe, Ryoichi Goto, Toshiya Kamiyama, Akinobu Taketomi, Tsuyoshi Shimamura

  Annals of transplantation 25 e920677  2020/01/10 [Refereed][Not invited]
   

  BACKGROUND The aim of this study was to determine the efficacy of treating donors' fatty liver (FL) and to assess early graft function in recipients who received treated FL grafts in living-donor liver transplantation (LDLT). MATERIAL AND METHODS Data were collected for adult-to-adult LDLTs. Donors diagnosed with FL (FL group) received diet-exercise and pharmacological treatment. The perioperative findings and early transplanted graft function were compared with those of donors without FL (non-FL group) during the same period. RESULTS Of 30 donors, 8 were determined to have FL. The median duration of treatment for FL was 58 days. The liver-to-spleen attenuation ratios on CT scan in the FL group were significantly improved after treatment: 0.95 (0.62-1.06) to 1.2 (1.12-1.46) (P=0.003). Liver biopsy prior to donor surgery showed ≤10% fatty infiltration. Postoperative laboratory findings of the donors in the FL group were comparable to those in the non-FL group: maximum alanine transaminase (189.6±94.7 IU/L vs. 196.8±57.4) and maximum total bilirubin (2.2±1.1 mg/dL vs. 1.7±0.5 mg/dL). No major complications were observed after donor hepatectomy in either group. There were no significant differences between the 2 groups in early graft function, as evaluated by laboratory data, ascites volume, and bile production 2 weeks postoperatively. Graft and patient survival were 100% in both groups at 3 months. CONCLUSIONS Preoperative intentional treatment for FL was effective. Early graft function and donor postoperative course were comparable in the 2 groups. These results suggest that well-treated steatotic grafts can be used without jeopardizing donor safety.
• Ki67 expression and localization of T cells after neoadjuvant therapies as reliable predictive markers in rectal cancer.

  Ken Imaizumi, Toshihiro Suzuki, Motohiro Kojima, Manami Shimomura, Naoki Sakuyama, Yuichiro Tsukada, Takeshi Sasaki, Yuji Nishizawa, Akinobu Taketomi, Masaaki Ito, Tetsuya Nakatsura

  Cancer science 111 (1) 23 - 35 1347-9032 2020/01 [Refereed][Not invited]
   

  Chemoradiotherapy (CRT) is the standard neoadjuvant therapy for locally advanced rectal cancer (RC). However, neoadjuvant chemotherapy (NAC) also shows favorable outcomes. Although the immunological environment of RC has been thoroughly discussed, the effect of NAC on it is less clear. Here, we investigated the immunological microenvironment, including T cell infiltration, activation, and topological distribution, of resected RC tissue after neoadjuvant therapies and evaluated the correlation between T cell subsets and patient prognosis. Rectal cancer patients (n = 188) were enrolled and categorized into 3 groups, namely CRT (n = 41), NAC (n = 46), and control (surgery alone; n = 101) groups. Characterization of residual carcinoma cells and T cell subsets in resected tissues was performed using multiplex fluorescence immunohistochemistry. The densities of total and activated (Ki67high ) T cells in tissues after NAC, but not CRT, were higher than in control. In both CRT and NAC groups, patients presenting with higher treatment effects showed aggressive infiltration of T cell subsets into carcinomas. Multivariate analyses of pathological and immunological features and prognosis revealed that carcinoma Ki67high CD4+ T cells after CRT and stromal Ki67high CD8+ T cells after NAC are important prognostic factors, respectively. Our results suggest that evaluation of T cell activation with Ki67 expression and its tumor localization can be used to determine the prognosis of advanced RC after neoadjuvant therapies.
• Questionnaire survey on a support program based on real-time risk models of postoperative morbidity and mortality for liver transplants

  Naoya Sato, Shigeru Marubashi, Yoshihiro Kakeji, Akinobu Taketomi, Yasutsugu Takada, Koji Umeshita, Hiroto Egawa, Hideki Ohdan, Yasuyuki Seto, Mitsukazu Gotoh

  Japanese Journal of Gastroenterological Surgery 53 (8) 617 - 626 1348-9372 2020 

  A real-time risk model of postoperative mortality and morbidity for liver transplants was previously developed using the Japanese national clinical database and registry of the Japanese liver transplant society. This study aims to investigate the prediction property of the risk model and its impact on transplantation planning and utility for informed consent and educational information. Materials and Methods: We conducted an anonymous questionnaire survey targeting transplant physicians, nurses, and coordinators at all liver transplantation facilities in Japan. Result: The response rate of facilities was 30.6%, comprising of 64 transplant surgeons, 5 nurses, and 10 coordinators. Regarding prediction property, 65.6% of surgeons responded with "agree" in the questionnaire, whereas 28.1% responded with "neither agree nor disagree. " Additionally, the proportion of surgeons who agreed that the prediction of the real-time risk model could influence graft selection, transplant indication, and postoperative managements was 63%, 45%, and 42%, respectively, indicating dominant responses. Almost 60% of transplant surgeons and 100% of nurses and coordinators agreed that predicting postoperative mortality and morbidity using the real-time risk model could have some benefits in obtaining informed consent or education for students and young residents. Conclusion: This study demonstrates that the property of predicting postoperative mortality and morbidity using the real-time risk model was agreed by most liver transplant surgeons and that prediction using the risk models could be used for multiple purposes, such as planning optimal liver transplantation, informed consent procedure, and education for students or young residents. © 2020 The Japanese Society of Gastroenterological Surgery.
• 【ここがキモ!いまはこうする 肝疾患vs.薬物療法 肝機能評価&薬物性肝障害マネジメントに強くなる】(第9章)慢性肝不全と肝移植 慢性肝不全に対する肝移植

  巖築 慶一, 後藤 了一, 武富 紹信

  薬事 (株)じほう 62 (2) 464 - 473 0016-5980 2020/01 

  ＜Key Points＞・非代償性の末期肝不全に対する根本治療として肝移植が選択される。・肝移植の適応疾患は多岐にわたる。わが国では生体肝移植の割合が多いが、脳死ドナーからの臓器提供数は増加傾向にある。・生体肝移植では、健常者であるドナーの健康と安全へ最大限配慮する必要がある。・移植後は拒絶反応の抑制のために免疫抑制薬の投与が必要となるが、薬物相互作用や血中濃度に注意する必要がある。・移植後の原病の再発がしばしば問題となるが、HCVを中心に新規薬剤が登場し治療概念が急速に変化しつつある。(著者抄録)
• A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas.

  Shohei Honda, Aniruddha Chatterjee, Anna L Leichter, Hisayuki Miyagi, Masashi Minato, Sunao Fujiyoshi, Momoko Ara, Norihiko Kitagawa, Mio Tanaka, Yukichi Tanaka, Masato Shinkai, Kanako C Hatanaka, Akinobu Taketomi, Michael R Eccles

  Frontiers in oncology 10 513601 - 513601 2020 

  Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients.
• Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis.

  Takeshi Aiyama, Tatsuya Orimo, Hideki Yokoo, Takanori Ohata, Kanako C Hatanaka, Yutaka Hatanaka, Moto Fukai, Toshiya Kamiyama, Akinobu Taketomi

  PloS one 15 (9) e0239462  2020 [Refereed][Not invited]
   

  This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.
• IL6 Modulates the Immune Status of the Tumor Microenvironment to Facilitate Metastatic Colonization of Colorectal Cancer Cells.

  Yujiro Toyoshima, Hidemitsu Kitamura, Huihui Xiang, Yosuke Ohno, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Toshiya Kamiyama, Mishie Tanino, Akinobu Taketomi

  Cancer immunology research 7 (12) 1944 - 1957 2326-6066 2019/12 [Refereed][Not invited]
   

  It is unknown as to how liver metastases are correlated with host immune status in colorectal cancer. In this study, we found that IL6, a proinflammatory cytokine produced in tumor-bearing states, promoted the metastatic colonization of colon cancer cells in association with dysfunctional antitumor immunity. In IL6-deficient mice, metastatic colonization of CT26 cells in the liver was reduced, and the antitumor effector function of CD8+ T cells, as well as IL12 production by CD11c+ dendritic cells, were augmented in vivo IL6-deficient mice exhibited enhanced IFN-AR1-mediated type I interferon signaling, which upregulated PD-L1 and MHC class I expression on CT26 cells. In vivo injection of anti-PD-L1 effectively suppressed the metastatic colonization of CT26 cells in Il6-/- but not in Il6+/+ mice. Finally, we confirmed that colorectal cancer patients with low IL6 expression in their primary tumors showed prolonged disease-free survival. These findings suggest that IL6 may be a promising target for the treatment of metastasis in colorectal cancers by improving host immunity.
• 炎症性腸疾患に対する腹腔鏡下手術 潰瘍性大腸炎に対する腹腔鏡下手術成績

  吉田 雅, 本間 重紀, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) WS3 - 8 1344-6703 2019/12
• 当院におけるcT4b結腸癌に対する腹腔鏡手術の短期成績

  今泉 健, 本間 重紀, 松井 博紀, 宮岡 陽一, 市川 伸樹, 吉田 雅, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) SF018 - 1 1344-6703 2019/12
• 腹腔鏡下右半結腸切除D3郭清の定型化

  市川 伸樹, 本間 重紀, 吉田 雅, 今泉 健, 松井 博紀, 宮岡 陽一, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) SF021 - 6 1344-6703 2019/12
• 大腸憩室に対する腹腔鏡下手術の検討

  松井 博紀, 本間 重紀, 浜田 和也, 宮岡 陽一, 今泉 健, 市川 伸樹, 吉田 雅, 高橋 典彦, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) SF103 - 4 1344-6703 2019/12
• 腹腔鏡下肝切除により切除した肝血管筋脂肪腫の3例

  旭 よう, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 蒲池 浩文, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) MO070 - 5 1344-6703 2019/12
• 当科における肝細胞癌に対する腹腔鏡下肝切除の長期成績

  長津 明久, 神山 俊哉, 旭 よう, 島田 慎吾, 折茂 達也, 蒲池 浩文, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) MO187 - 6 1344-6703 2019/12
• 多数のリンパ節転移を伴った神経内分泌腫瘍の2切除例

  坂本 譲, 蒲池 浩文, 折茂 達也, 旭 よう, 長津 明久, 島田 慎吾, 神山 俊哉, 武冨 紹信

  北海道外科雑誌 北海道外科学会 64 (2) 212 - 212 0288-7509 2019/12 [Refereed][Not invited]
  
• Daikenchuto, a traditional Japanese herbal medicine, promotes colonic transit by inducing a propulsive movement pattern.

  Kunitsugu Kubota, Akihito Mase, Hiroaki Matsushima, Naoki Fujitsuka, Masahiro Yamamoto, Yuji Morine, Akinobu Taketomi, Toru Kono, Mitsuo Shimada

  Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 31 (11) e13689  1350-1925 2019/11 [Refereed][Not invited]
   

  BACKGROUND: The traditional Japanese herbal medicine, daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon. METHODS: The entire colon or segments of the proximal colon in rats were isolated and placed in Krebs solution. The motility of the colon was evaluated by analyzing spatiotemporal maps of diameter derived from video imaging and measuring the intraluminal pressure in the anal end of the proximal colon, and the transit time of a plastic bead through the entire isolated colon. KEY RESULTS: Several types of propagating contractions were observed in the isolated entire colon. When DKT was added to Krebs solution, the frequency of large-extent anal propagating contractions increased. DKT treatment increased the intraluminal pressure in the isolated proximal colon, which was related to the propagating contractions. This effect was abolished by treatment with the neural blocker tetrodotoxin. These findings suggest DKT induced peristaltic contractions in the isolated colon. DKT accelerated colonic transit activity, which was related to peristaltic contractions induction in the colon. These effects were also observed in the colons treated with bethanechol and the active ingredient of DKT, hydroxy-α-sanshool. CONCLUSIONS AND INFERENCES: Daikenchuto could enhance colonic transit activity by inducing peristaltic contractions, which may be mediated by the activation of the enteric nervous system in the colon.
• Heavy Water (D2O) Containing Preservation Solution Reduces Hepatic Cold Preservation and Reperfusion Injury in an Isolated Perfused Rat Liver (IPRL) Model.

  Shingo Shimada, Moto Fukai, Kengo Shibata, Sodai Sakamoto, Kenji Wakayama, Takahisa Ishikawa, Norio Kawamura, Masato Fujiyoshi, Tsuyoshi Shimamura, Akinobu Taketomi

  Journal of clinical medicine 8 (11) 2019/11/01 [Refereed][Not invited]
   

  BACKGROUND: Heavy water (D2O) has many biological effects due to the isotope effect of deuterium. We previously reported the efficacy of D2O containing solution (Dsol) in the cold preservation of rat hearts. Here, we evaluated whether Dsol reduced hepatic cold preservation and reperfusion injury. METHODS: Rat livers were subjected to 48-hour cold storage in University of Wisconsin (UW) solution or Dsol, and subsequently reperfused on an isolated perfused rat liver. Graft function, injury, perfusion kinetics, oxidative stress, and cytoskeletal integrity were assessed. RESULTS: In the UW group, severe ischemia and reperfusion injury (IRI) was shown by histopathology, higher liver enzymes leakage, portal resistance, and apoptotic index, oxygen consumption, less bile production, energy charge, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (versus control). The Dsol group showed that these injuries were significantly ameliorated (versus the UW group). Furthermore, cytoskeletal derangement was progressed in the UW group, as shown by less degradation of α-Fodrin and by the inactivation of the actin depolymerization pathway, whereas these changes were significantly suppressed in the Dsol group. CONCLUSION: Dsol reduced hepatic IRI after extended cold preservation and subsequent reperfusion. The protection was primarily due to the maintenance of mitochondrial function, cytoskeletal integrity, leading to limiting oxidative stress, apoptosis, and necrosis pathways.
• Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.

  Tomonari Shimagaki, Sachiyo Yoshio, Hironari Kawai, Yuzuru Sakamoto, Hiroyoshi Doi, Michitaka Matsuda, Taizo Mori, Yosuke Osawa, Moto Fukai, Takeshi Yoshida, Yunfei Ma, Tomoyuki Akita, Junko Tanaka, Akinobu Taketomi, Rikinari Hanayama, Tomoharu Yoshizumi, Masaki Mori, Tatsuya Kanto

  Scientific reports 9 (1) 15788 - 15788 2019/10/31 [Refereed][Not invited]
   

  Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 - 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC.
• 進行胆道癌に対する無作為化第III相試験 Gem+Cisplatin vs Gem+Cisplatin+S1

  近本 亮, 金井 雅史, 小林 省吾, 江口 英利, 瀬尾 智, 岡部 弘尚, 橋本 大輔, 山下 洋市, 武富 紹信, 吉村 健一, 波多野 悦朗, 永野 浩昭, 馬場 秀夫, 井岡 達也

  日本癌治療学会学術集会抄録集 57回 RT13 - 5 2019/10
• 胆道癌におけるGCS療法の炎症マーカーの意義 MITSUBA/KHBO1401-1B

  大鶴 徹, 坂井 大介, 金井 雅史, 小林 省吾, 江口 英利, 馬場 秀夫, 瀬尾 智, 武富 紹信, 吉村 健一, 波多野 悦郎, 永野 浩昭, 井岡 達也

  日本癌治療学会学術集会抄録集 57回 O21 - 4 2019/10
• マスサイトメトリーを用いたNAFLD患者における免疫病態の網羅的解析

  坂本 譲, 由雄 祥代, 河合 裕成, 島垣 智成, 森 泰三, 松田 道隆, 土肥 弘義, 青木 孝彦, 吉田 祐士, 新井 泰央, 糸川 典夫, 大澤 陽介, 考藤 達哉, 武冨 紹信

  肝臓 (一社)日本肝臓学会 60 (Suppl.2) A683 - A683 0451-4203 2019/10 [Refereed][Not invited]
  
• PREDICTION OF HEPATIC WARM ISCHEMIA AND REPERFUSION INJURY BY LYSOPHOSPHOLIPIDS - COMPREHENSIVE ANALYSIS BY IMAGING MASS SPECTROMETRY (IMS)

  Shibata Kengo, Hayasaka Takahiro, Fukai Moto, Kato Koichi, Ishikawa Takahisa, Umemoto Kohei, Shimada Shingo, Kobayashi Nozomi, Shimamura Tsuyoshi, Kimura Taichi, Taketomi Akinobu

  TRANSPLANT INTERNATIONAL 32 283  0934-0874 2019/10 [Refereed][Not invited]
  
• 生体肝移植におけるヒト化マウス新規免疫モニタリング法の有用性の検討

  深作 慶友, 後藤 了一, 巖築 慶一, 渡辺 正明, 川村 典生, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 54 (総会臨時) 240 - 240 0578-7947 2019/09
• 移植後早期グラフト浸潤リンパ球の抗原特異性に関する基礎的検討

  巌築 慶一, 後藤 了一, 太田 拓児, 金沢 亮, 川村 典生, 財津 雅昭, 渡辺 正明, 深井 元, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 54 (総会臨時) 240 - 240 0578-7947 2019/09
• 集学的治療により長期生存を得たStageIV直腸癌の1例

  山本 啓一朗, 本間 重紀, 吉田 雅, 市川 伸樹, 今泉 健, 宮岡 陽一, 松井 博紀, 結城 敏志, 武冨 紹信

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 125回・119回 45 - 45 2019/09
• アルギナーゼ1遺伝子発現とその活性は大腸がん細胞の増殖を亢進する(Arginase-1 gene expression and the activity augment the proliferation of colon cancer)

  Wang Xiangdong, 項 慧慧, 豊島 雄二郎, 杉山 昂, 沈 輝棟, 本間 重紀, 武冨 紹信, 北村 秀光

  日本癌学会総会記事 78回 E - 2094 0546-0476 2019/09
• IL-6関連マイクロRNAの新規機能とその担がん生体におけるバイオマーカーとしての有用性(A novel function of IL-6-related microRNA and the usefulness as a biomarker for evaluation of tumor-bearing state)

  北村 秀光, 豊島 雄二郎, 項 慧慧, 大竹 淳矢, 大野 陽介, 本間 重紀, 武冨 紹信

  日本癌学会総会記事 78回 P - 2230 0546-0476 2019/09
• NK2R介した神経ペプチドシグナルの遮断は大腸がん細胞の悪性化を抑制する(Blockade of NK2R-mediated neuropeptide signaling suppresses malignancy of colon cancer cells)

  項 慧慧, 豊島 雄二郎, 橋本 真一, 池尾 一穂, 小林 博也, 本間 重紀, 川村 秀樹, 高橋 典彦, 武冨 紹信, 北村 秀光

  日本癌学会総会記事 78回 E - 3010 0546-0476 2019/09
• The feasibility of laparoscopic gastrectomy for remnant gastric cancer

  Hideki Kawamura, Susumu Shibasaki, Tadashi Yoshida, Tatsushi Shimokuni, Hideyasu Sakihama, Shigenori Homma, Masahiro Takahashi, Akinobu Taketomi

  International Surgery 103 (9-10) 435 - 442 0020-8868 2019/09 

  We compared laparoscopic gastrectomy for remnant gastric cancer (LRG) with open gastrectomy for remnant gastric cancer (ORG) to assess the safety and invasive nature of LRG. This study was a retrospective study. The study population consisted of 27 consecutive patients who underwent gastrectomy for remnant gastric cancer. Of these, 15 underwent ORG between January 2003 and April 2007, and 12 underwent LRG between May 2007 and January 2013. The operation time was not significantly different between the 2 groups. However, blood loss was significantly less in the LRG group than in the ORG group. No intraoperative blood transfusion was required. There was no significant difference in morbidity rate between the LRG (1/12, 8.3%) and ORG (4/15, 26.7%) groups, and no patients died in either group. Body temperature on postoperative day (POD) 7 (P = 0.034); systolic blood pressure on PODs 6 (P = 0.042) and 7 (P = 0.035); and heart rate on POD 7 (P = 0.049) were significantly lower in the LRG group than in the ORG group. No significant differences were observed in white blood cell count, or C-reactive protein and serum albumin levels between the groups. Serum total protein levels were significantly higher on POD 1 (P = 0.020), and the number of lymphocytes was significantly higher on POD 7 in the LRG group than in the ORG group (P = 0.036). Pain scores on POD 7 were significantly lower in the LRG group than in the ORG group (P = 0.033). LRG is a technically feasible and safe procedure.
• 当院における原発性胆汁性胆管炎に対する生体・脳死肝移植症例の特徴

  後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 神山 俊哉, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 54 (総会臨時) 222 - 222 0578-7947 2019/09
• 【内科医に求められる他科の知識-専門家が伝えるDo/Don't】(第1章)外科 C.消化器外科 肝細胞がん

  脇坂 和貴, 武冨 紹信

  内科 (株)南江堂 124 (3) 1752 - 1755 0022-1961 2019/09
• 肝細胞癌に対する減量肝切除術の検討

  旭 よう, 神山 俊哉, 折茂 達也, 島田 慎吾, 長津 明久, 蒲池 浩文, 武冨 紹信

  日本消化器病学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 125回 63 - 63 2019/09 [Refereed][Not invited]
  
• 孤立性に右心室転移をきたした肝細胞癌の1例

  齋藤 智哉, 長津 明久, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (9) 1739 - 1743 1345-2843 2019/09 [Refereed][Not invited]
   

  症例は68歳,男性.検診を契機に肝内側区に17cm大の腫瘤性病変を指摘され,肝細胞癌の診断で肝左葉切除を施行した.1年4ヵ月後,労作時呼吸困難があり近医を受診.右室に3cm大の充実性腫瘤を認め,肝細胞癌の右心室内転移疑いの診断となった.心不全を呈し,頓死の危険性もあるため,右室腫瘍切除術および三尖弁置換術を施行した.術後経過は良好で,術後15日目に退院となった.病理は肝細胞癌の右心室転移の所見であった.術後3ヵ月目のCTで第四腰椎骨転移・右肺転移・右横隔膜角転移を認め,ソラフェニブによる分子標的療法を開始したが,間質性肺炎などの副作用が生じたため中止し,以後緩和医療の方針となった.転移巣摘出から1年1ヵ月経過した現在も生存中である.肝細胞癌フォロー中に,心不全兆候を呈した場合には,心転移を念頭に置いた精査の必要がある.肝細胞癌の孤立性心転移に対して確立された治療法はなく,今後も検討が必要である.(著者抄録)
• Prediction of urinary retention after surgery for rectal cancer using voiding efficiency in the 24 h following Foley catheter removal.

  Ken Imaizumi, Yuichiro Tsukada, Yoshinobu Komai, Shogo Nomura, Koji Ikeda, Yuji Nishizawa, Takeshi Sasaki, Akinobu Taketomi, Masaaki Ito

  International journal of colorectal disease 34 (8) 1431 - 1443 0179-1958 2019/08 [Refereed][Not invited]
   

  PURPOSE: Postoperative urinary retention is a common adverse effect after rectal surgery. Current methods for assessing postoperative urinary retention (residual urine volume) are inaccurate and unable to predict long-term retention. Voiding efficiency is an effective indicator of postoperative urinary retention in urological and gynaecological fields, but not in colorectal surgery. We aimed to determine whether voiding efficiency in the initial 24 h after urinary catheter removal was more effective in predicting the incidence of postoperative urinary retention than residual urine volume. METHODS: In this retrospective, observational study using prospectively collected data from patients who visited the colorectal department of a single institution, 549 patients who underwent rectal cancer surgery between April 2012 and May 2016 were initially enrolled, of which 46 were excluded and 503 finally included. RESULTS: The incidence of postoperative urinary retention was 18.5% (93/503). Multivariable logistic regression analyses revealed that the association of postoperative urinary retention with voiding efficiency < 50% was stronger than that with residual urine volume > 100 mL (odds ratio, 38.30 (residual urine volume) and 138.0 (voiding efficiency)). Voiding efficiency was significantly lower in patients with long-term than in those with short-term postoperative urinary retention (adjusted p value = 0.02), whereas residual urine volume was not different between the two groups. Multivariable logistic regression analysis for long-term postoperative urinary retention showed the strongest association with voiding efficiency < 20% (odds ratio, 25.70). CONCLUSIONS: Voiding efficiency is a more effective predictor of postoperative urinary retention than residual urine volume in rectal cancer patients.
• Preoperative FOLFOX in resectable locally advanced rectal cancer can be a safe and promising strategy: the R-NAC-01 study.

  Nobuki Ichikawa, Shigenori Homma, Tohru Funakoshi, Masahiro Hattori, Masanori Sato, You Kamiizumi, Kazuyoshi Omori, Masaru Nomura, Ryoichi Yokota, Masahiko Koike, Hirofumi Kon, Keisa Takeda, Hiroyuki Ishizu, Kunihiro Hirose, Daisuke Kuraya, Takahisa Ishikawa, Ryohei Murata, Hiroaki Iijima, Futoshi Kawamata, Tadashi Yoshida, Yosuke Ohno, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi

  Surgery today 49 (8) 712 - 720 0941-1291 2019/08 [Refereed][Not invited]
   

  PURPOSE: The aim of this study was to assess the safety of rectal surgery after 5-fluorouracil-leucovorin-oxaliplatin chemotherapy (FOLFOX6). METHODS: This was a prospective, multicenter study in 11 Japanese hospitals. We included patients with rectal cancer who received 4 courses of modified FOLFOX6 (mFOLFOX6) before rectal surgery and examined the postoperative complication rate, the clinicopathological response, and the rate of chemotherapy-related adverse events (UMIN 000012559). RESULTS: The study population included 36 men and 5 women. The average age of the patients was 60.8 years and the average body mass index was 23.1 kg/m2. After 4 courses of chemotherapy, grade 2 peripheral nerve disorder and other grade 3 adverse events were seen in 3 patients each (7.3%). Twenty-eight (73.7%) and 8 (21.1%) patients underwent low anterior resection and abdominoperineal resection, respectively. The pelvic nerves were preserved in 35 patients. Surgical morbidity (grade ≥ 3) occurred in 4 patients (10.5%). Anastomotic leakage occurred after surgery in 2 patients (7.1%). No patients achieved pathologically complete remission. However, downstaging of the clinical stage and N stage was seen in 17 (41.5%) and 22 (53.7%) patients, respectively. CONCLUSIONS: Surgery after four courses of mFOLFOX6 chemotherapy can be a safe and promising strategy for patients with locally advanced rectal cancer.
• Short-term and Long-term Outcomes Following Laparoscopic Gastrectomy for Advanced Gastric Cancer Compared With Open Gastrectomy.

  Kazuaki Shibuya, Hideki Kawamura, Shusaku Takahashi, Yosuke Ohno, Nobuki Ichikawa, Tadashi Yoshida, Shigenori Homma, Hiroyuki Ishizu, Masahiro Takahashi, Akinobu Taketomi

  Surgical laparoscopy, endoscopy & percutaneous techniques 29 (4) 297 - 303 1530-4515 2019/08 [Refereed][Not invited]
   

  INTRODUCTION: To investigate the oncological feasibility and technical safety of laparoscopic gastrectomy with D2 lymphadenectomy for advanced gastric cancer. METHODS: A total of 186 advanced gastric cancer patients treated by gastrectomy with D2 lymphadenectomy were eligible for inclusion including those with invasion into the muscularis propria, subserosa, and serosa without involvement of other organs, and stages N0-2 and M0. We retrospectively compared the short-term and long-term outcomes between laparoscopic gastrectomy and open gastrectomy. RESULTS: We analyzed short-term outcomes by comparing distal with total gastrectomy results. We found no significant difference for distal gastrectomy for postoperative morbidity [laparoscopic vs. open: n=4 (4.6%) vs. n=1 (3.6%); P=1.00]. We also found no significant difference in postoperative morbidity for total gastrectomy [laparoscopic vs. open: n=2 (4.0%) vs. n=1 (4.0%); P=1.00]. No deaths occurred in any group.The entire cohort analysis revealed no statistically significant differences in overall-free or recurrence-free survival between the laparoscopic and open groups. For overall survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.29 and 0.27, respectively), and for pathologic stage II or III (P=0.88 and 0.86, respectively). For recurrence-free survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.63 and 0.60, respectively), and for pathologic stage II or III (P=0.98 and 0.72, respectively). CONCLUSION: Laparscopic gastrectomy for advanced gastric cancer compared favorably with open gastrectomy regarding short-term and long-term outcomes.
• Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.

  Makoto Chuma, Hidenori Toyoda, Juntaro Matsuzaki, Yoshimasa Saito, Takashi Kumada, Toshifumi Tada, Yuji Kaneoka, Atsuyuki Maeda, Hideki Yokoo, Koji Ogawa, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Keiichi Yazawa, Kazuhisa Takeda, Chikara Kunisaki, Katsuaki Ogushi, Satoshi Moriya, Koji Hara, Akito Nozaki, Masaaki Kondo, Hiroyuki Fukuda, Kazushi Numata, Katsuaki Tanaka, Shin Maeda, Naoya Sakamoto

  Hepatology research : the official journal of the Japan Society of Hepatology 49 (7) 810 - 822 1386-6346 2019/07 [Refereed][Not invited]
   

  AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.
• Current status of hepatopulmonary syndrome in liver transplantation in Japan: a Japanese multicenter analysis.

  Yoshihito Kotera, Hiroto Egawa, Satoshi Ogata, Satoshi Teramukai, Toshimi Kaido, Ken Shirabe, Akinobu Taketomi, Yasutugu Takada, Masakazu Yamamoto, Hiroki Yamaue

  Journal of hepato-biliary-pancreatic sciences 26 (7) 292 - 299 1868-6974 2019/07 [Refereed][Not invited]
   

  BACKGROUND: Hepatopulmonary syndrome (HPS) negatively affects the outcomes of deceased donor liver transplantation (LT). METHODS: We retrospectively reviewed the clinical records of patients with HPS who underwent LT and studied the impact of risk factors on clinical outcomes to determine strategies to overcome complications. Patients with symptoms of hypo-oxygenemia and a shunt ratio >15% on 99mTc-MAA lung perfusion scintigraphy were defined as having HPS. RESULTS: Forty-eight patients in 10 centers were enrolled. Diseases included biliary atresia, liver cirrhosis, non-alcoholic steatohepatitis, congenital hepatic fibrosis, and others. The length of ICU stay was 2-170 days. The respirator was used for 41.6% of patients on post-operative day (POD) 3 and 20.8% on POD 14. The patient survival rate was 87% at 1 year and 82% at 5 years. The causes of hospital mortality were sepsis, thrombotic microangiopathy, intracranial bleeding, pulmonary fibrosis, and transplant rejection. An amount of shunt ratio prior to LT was a significant risk factor for hospital mortality. Hypoxia from POD 3 to POD 14 was a risk factor for biliary stenosis. The shunt ratio of all surviving patients significantly improved. CONCLUSION: Although LT is feasible for patients with HPS, early transplantation and avoiding hypo-oxygenemia immediately after transplantation are important.
• 【新しい肝予備能評価とPVEによる肝切除治療戦略】

  島田 慎吾, 神山 俊哉, 折茂 達也, 長津 明久, 旭 よう, 若山 顕治, 敦賀 陽介, 横尾 英樹, 蒲池 浩文, 武冨 紹信

  北海道外科雑誌 北海道外科学会 64 (1) 2 - 7 0288-7509 2019/06 [Refereed][Not invited]
   

  肝胆道悪性腫瘍に対する大量肝切除を安全に施行するために門脈塞栓術(PVE)は有用な方法である。PVEはMakuuchiらやKinoshitaらが臨床応用し、今や広く普及している。肝切除においては肝予備能で決まる切除量の安全限界内での過不足ない肝切除が求められる。しかしながら、PVEを施行しても十分に予定残肝の肥大が得られない症例も存在する。また、PVE後に肝体積の変化のみならず肝臓の「機能」が非塞栓葉にシフトすることも注目されている。当科では安全な肝切除を行うために、大量肝切除の際には積極的にPVEを用いている。また、これまでPVEにおける門脈血流変化と非塞栓葉の体積変化について評価を行ってきた。当科における肝予備能評価とPVEを用いた肝切除戦略、PVE後の変化および非塞栓葉増大に関わる因子について述べる。(著者抄録)
• Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers.

  Kazuki Wakizaka, Hideki Yokoo, Toshiya Kamiyama, Masafumi Ohira, Koichi Kato, Yuki Fujii, Ko Sugiyama, Naoki Okada, Takanori Ohata, Akihisa Nagatsu, Shingo Shimada, Tatsuya Orimo, Hirofumi Kamachi, Akinobu Taketomi

  Journal of gastroenterology and hepatology 34 (6) 1074 - 1080 0815-9319 2019/06 [Refereed][Not invited]
   

  BACKGROUND AND AIM: Combined hepatocellular-cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. METHODS: We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. RESULTS: The incidences of hepatitis B virus and high α-fetoprotein and protein induced by vitamin K absence or antagonists-II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5-year overall survival and disease-free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease-free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. CONCLUSIONS: The clinical features of CHC, including sex, hepatitis B virus infection, α-fetoprotein, and protein induced by vitamin K absence or antagonists-II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.
• Diacylglycerol kinase α-selective inhibitors induce apoptosis and reduce viability of melanoma and several other cancer cell lines.

  Atsumi Yamaki, Rino Akiyama, Chiaki Murakami, Saki Takao, Yuki Murakami, Satoru Mizuno, Daisuke Takahashi, Sayaka Kado, Akinobu Taketomi, Yasuhito Shirai, Kaoru Goto, Fumio Sakane

  Journal of cellular biochemistry 120 (6) 10043 - 10056 0730-2312 2019/06 [Refereed][Not invited]
   

  Diacylglycerol (DG) kinase (DGK), which phosphorylates DG to generate phosphatidic acid (PA), consists of ten isozymes (α-к). Recently, we identified a novel small molecule inhibitor, CU-3, that selectively inhibits the activity of the α isozyme. In addition, we newly obtained Compound A, which selectively and strongly inhibits type I DGKs (α, β, and γ). In the present study, we demonstrated that both CU-3 and Compound A induced apoptosis (caspase 3/7 activity and DNA fragmentation) and viability reduction of AKI melanoma cells. Liquid chromatography-mass spectrometry revealed that the production of 32:0- and 34:0-PA species was commonly attenuated by CU-3 and Compound A, suggesting that lower levels of these PA molecular species are involved in the apoptosis induction and viability reduction of AKI cells. We determined the effects of the DGKα inhibitors on several other cancer cell lines derived from refractory cancers. In addition to melanoma, the DGKα inhibitors enhanced caspase 3/7 activity and reduced the viability of hepatocellular carcinoma, glioblastoma, and pancreatic cancer cells, but not breast adenocarcinoma cells. Interestingly, Western blot analysis indicated that the DGKα expression levels were positively correlated with the sensitivity to the DGK inhibitors. Because both CU-3 and Compound A induced interleukin-2 production by T cells, it is believed that these two compounds can enhance cancer immunity. Taken together, our results suggest that DGKα inhibitors are promising anticancer drugs.
• Long-term donor quality of life after living donor liver transplantation in Japan.

  Yuki Morooka, Koji Umeshita, Akinobu Taketomi, Ken Shirabe, Tomoharu Yoshizumi, Mayumi Yamamoto, Tsuyoshi Shimamura, Akihiko Oshita, Hideki Ohdan, Naoki Kawagishi, Kuniko Hagiwara, Hidetoshi Eguchi, Hiroaki Nagano

  Clinical transplantation 33 (6) e13584  0902-0063 2019/06 [Refereed][Not invited]
   

  AIMS: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. METHODS: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. RESULTS: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale. CONCLUSIONS: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis.
• 初発大腸癌に対する腹腔鏡下大腸切除術の治療成績

  吉田 雅, 本間 重紀, 大野 陽介, 市川 伸樹, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 72 (5) 278 - 278 0047-1801 2019/05
• 原発性大腸癌における占拠部位別の治療成績

  吉田 雅, 本間 重紀, 大野 陽介, 市川 伸樹, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 72 (5) 308 - 308 0047-1801 2019/05
• 当院における小腸腫瘍の経験

  市川 伸樹, 本間 重紀, 吉田 雅, 本多 昌平, 川俣 太, 柴崎 晋, 川村 秀樹, 荒 桃子, 河北 一誠, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 72 (5) 327 - 327 0047-1801 2019/05
• pT1(SM)早期大腸癌の臨床病理学的特徴と治療成績

  吉田 雅, 本間 重紀, 川俣 太, 市川 伸樹, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 72 (5) 363 - 363 0047-1801 2019/05
• 術前診断に苦慮した回盲部炎症性偽腫瘍の1例

  南波 宏征, 吉田 雅, 川俣 太, 市川 伸樹, 柴崎 晋, 本間 重紀, 川村 秀樹, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (5) 1022 - 1022 1345-2843 2019/05
• 濾胞性リンパ腫を合併した早期横行結腸癌の1切除例

  佐藤 彩, 本間 重紀, 市川 伸樹, 柴崎 晋, 吉田 雅, 川俣 太, 川村 秀樹, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (5) 1022 - 1022 1345-2843 2019/05
• 胆道閉鎖症術後の生体肝移植適応因子

  本多 昌平, 荒 桃子, 河北 一誠, 後藤 了一, 渡辺 正明, 川村 典生, 財津 雅昭, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 8 2019/04
• 当科における脳死肝移植前抗ドナーHLA抗体値の推移の検討

  金沢 亮, 後藤 了一, 巌築 慶一, 財津 雅昭, 川村 典夫, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 6 2019/04
• 小児生体肝移植後の肝動脈血栓症発症に及ぼす血管因子の検討

  原田 拓弥, 川村 典生, 財津 雅昭, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 7 2019/04
• 早期移植片浸潤リンパ球の拒絶反応における役割に関する基礎的検討

  巌築 慶一, 後藤 了一, 金沢 亮, 渋谷 一陽, 深作 慶友, 川村 典生, 財津 雅昭, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 3 2019/04
• HEV急性肝不全5例の検討

  市村 健太郎, 川村 典生, 財津 雅昭, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 8 2019/04
• 当院における小児生体肝移植後門脈合併の検討

  佐藤 彩, 後藤 了一, 財津 雅昭, 川村 典生, 渡辺 正明, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 7 2019/04
• リンパ球-単球比を用いた肝移植後の急性拒絶反応と治療の評価

  財津 雅昭, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 5 2019/04
• 肝細胞移植における球状肝細胞の有用性

  渋谷 一陽, 渡辺 正明, 巌築 慶一, 金沢 亮, 腰塚 靖之, 財津 雅昭, 川村 典生, 後藤 了一, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 8 2019/04
• 【新 手術記録の書き方】結腸・直腸・肛門の手術/大腸癌 鏡視下手術 腹腔鏡下結腸右半切除術

  市川 伸樹, 本間 重紀, 吉田 雅, 武冨 紹信

  消化器外科 (株)へるす出版 42 (5) 633 - 637 0387-2645 2019/04
• 大腸癌診療におけるprecision medicine ゲノム解析を利用した大腸癌原発巣およびその肝転移巣に対するprecision medicine

  川俣 太, 本間 重紀, Patch Ann-Marie, 沢田 尭史, 市川 伸樹, 吉田 雅, 柴崎 晋, Waddell Nicola, Whitehall Vicki, Leggett Barbara, 深井 原, 川村 秀樹, 神山 俊哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 WS - 9 2019/04
• 所属リンパ節に乳癌と結腸癌の転移が混在した上行結腸癌の一切除例

  和久井 洋佑, 本間 重紀, 吉田 雅, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 RS - 1 2019/04
• 大腸癌肝転移に対するprecision medicineにおける免疫組織化学染色を併用したゲノム解析の有用性の検討

  沢田 尭史, 川俣 太, 市川 伸樹, 吉田 雅, 柴崎 晋, 本間 重紀, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 7 2019/04
• DSS誘発大腸炎モデルの病態発症におけるSTAT1を介したシグナルカスケードの関与

  木井 修平, 北村 秀光, 岡田 尚樹, 項 慧慧, 杉山 昂, 川俣 太, 大野 陽介, 市川 伸樹, 吉田 雅, 柴崎 晋, 本間 重紀, 川村 秀樹, 高橋 典彦, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 1 2019/04
• 局所進行直腸癌における術前mFOLFOX6療法後の手術の安全性(R-NAC-01試験)

  市川 伸樹, 本間 重紀, 船越 徹, 服部 優宏, 佐藤 正法, 上泉 洋, 大森 一吉, 野村 克, 横田 良一, 小池 雅彦, 今 裕史, 武田 圭佐, 石津 寛之, 廣瀬 邦弘, 蔵谷 大輔, 石川 隆壽, 村田 竜平, 吉田 雅, 川俣 太, 皆川 のぞみ, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 SF - 6 2019/04
• 潰瘍性大腸炎に対する手術方針と術後成績

  吉田 雅, 本間 重紀, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 2 2019/04
• 当院での腸閉塞に対し実施した高気圧酸素療法の治療成績の検討

  田仲 大樹, 本間 重紀, 吉田 雅, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 7 2019/04
• バイオマテリアルによる肝癌幹細胞の新規誘導法

  谷 道夫, 津田 真寿美, 鈴鹿 淳, 王 磊, 杉野 弘和, 谷川 聖, 石田 雄介, グン 剣萍, 田中 伸哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 6 2019/04
• NAFLD患者の病態におけるNK細胞Sgilec-7の意義

  坂本 譲, 由雄 祥代, 河合 裕成, 島垣 智成, 森 泰三, 松田 道隆, 大澤 陽介, 深井 原, 神山 俊哉, 考藤 達哉, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 119回 PS - 5 2019/04 [Refereed][Not invited]
  
• Case of chronic pain after laparoscopic percutaneous extraperitoneal closure in an adolescent girl with inguinal hernia in which open repair was effective.

  Takahisa Ishikawa, Makoto Nishikawa, Hiroki Nakamoto, Ryoji Yokoyama, Akinobu Taketomi

  Asian journal of endoscopic surgery 12 (2) 211 - 213 1758-5902 2019/04 [Refereed][Not invited]
   

  Chronic pain after laparoscopic percutaneous extraperitoneal closure is very rare. Here, we report a case of chronic pain after laparoscopic percutaneous extraperitoneal closure in an adolescent patient with inguinal hernia who underwent open repair. A 15-year-old girl was diagnosed with a left indirect inguinal hernia, and laparoscopic percutaneous extraperitoneal closure was performed. However, 6 months later, after strenuous exercise, she developed localized pain around the hernia site. Her pain was well controlled by internal treatment but failed to completely resolve. The pain type was somatic, Tinel's sign was negative, and there was no recurrence of the inguinal hernia. Because she strongly wished to undergo surgery, the Potts procedure with removal of the ligature and excision of the round ligament was performed. Her pain improved after surgery, and further medical treatment was not required. The Potts procedure may be an effective treatment for chronic pain such as in this case.
• Prognoses and Clinicopathological Characteristics for Hepatocellular Carcinoma Originating from the Caudate Lobe After Surgery.

  Shingo Shimada, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Akihisa Nagatsu, Takanori Ohata, Hirofumi Kamachi, Akinobu Taketomi

  World journal of surgery 43 (4) 1085 - 1093 0364-2313 2019/04 [Refereed][Not invited]
   

  BACKGROUND: The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS: We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS: HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION: HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.
• USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.

  Shinji Kusakabe, Tatsuya Suzuki, Yukari Sugiyama, Saori Haga, Kanako Horike, Makoto Tokunaga, Junki Hirano, He Zhang, David Virya Chen, Hanako Ishiga, Yasumasa Komoda, Chikako Ono, Takasuke Fukuhara, Masahiro Yamamoto, Masahito Ikawa, Takashi Satoh, Shizuo Akira, Tomohisa Tanaka, Kohji Moriishi, Moto Fukai, Akinobu Taketomi, Sachiyo Yoshio, Tatsuya Kanto, Tetsuro Suzuki, Toru Okamoto, Yoshiharu Matsuura

  Journal of virology 93 (6) 0022-538X 2019/03/15 [Refereed][Not invited]
   

  Hepatitis C virus (HCV) utilizes cellular factors for efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of deubiquitinating enzymes (DUBs) or overexpression of nonspecific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up RNA interference (RNAi) screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR-122 cells) but not in a nonhepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responses in vitro and in vivo We also found that USP15-deficient Huh7 cells showed reductions in the amounts of lipid droplets (LDs), and the addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and the formation of LDs.IMPORTANCE Although ubiquitination has been shown to play important roles in the HCV life cycle, the roles of deubiquitinating enzymes (DUBs), which cleave ubiquitin chains from their substrates, in HCV propagation have not been investigated. Here, we identified USP15 as a DUB regulating HCV propagation. USP15 showed no interaction with viral proteins and no participation in innate immune responses. Deficiency of USP15 in Huh7 cells resulted in suppression of the translation of HCV RNA and reduction in the amounts of lipid droplets, and the addition of fatty acids partially restored the production of infectious HCV particles. These data suggest that USP15 participates in HCV propagation in hepatic cells through the regulation of viral RNA translation and lipid metabolism.
• 術前診断が困難であった劇症型Clostridium difficile腸炎による著明な結腸狭窄に対して結腸亜全摘術を施行した1例

  原田 拓弥, 本間 重紀, 吉田 雅, 川俣 太, 市川 伸樹, 柴崎 晋, 大塚 拓也, 三橋 智子, 武冨 紹信

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 124回・118回 57 - 57 2019/03
• 潰瘍性大腸炎に対する手術方針と術後成績

  吉田 雅, 本間 重紀, 市川 伸樹, 川俣 太, 柴崎 晋, 武冨 紹信

  日本消化器病学会雑誌 (一財)日本消化器病学会 116 (臨増総会) A403 - A403 0446-6586 2019/03
• 80歳以上の高齢者肝細胞癌に対する肝切除の成績と予後因子

  横尾 英樹, 神山 俊哉, 島田 慎吾, 折茂 達也, 長津 明久, 浦池 浩文, 武冨 紹信

  日本消化器病学会北海道支部例会プログラム・抄録集 日本消化器病学会-北海道支部 124回 46 - 46 2019/03 [Refereed][Not invited]
  
• Hepatic hypertrophy and hemodynamics of portal venous flow after percutaneous transhepatic portal embolization.

  Shingo Shimada, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Kenji Wakayama, Akihisa Nagatsu, Tatsuhiko Kakisaka, Hirofumi Kamachi, Daisuke Abo, Yusuke Sakuhara, Akinobu Taketomi

  BMC surgery 19 (1) 23 - 23 2019/02/18 [Refereed][Not invited]
   

  BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.
• Two-stage surgery for intraperitoneal and retroperitoneal multicentric liposarcoma causing hydronephrosis: a case report.

  Ryohei Murata, Tadashi Yoshida, Nobuhiro Kobayashi, Yoshito Watanabe, Shigenori Homma, Hayato Echizenya, Akinobu Taketomi

  Surgical case reports 5 (1) 18 - 18 2019/02/04 [Refereed][Not invited]
   

  BACKGROUND: Liposarcoma is a soft tissue sarcoma of adipocyte origin. Liposarcoma represents 20-30% of adult soft tissue tumors, which was most frequently seen in the retroperitoneal space in 45% and abdominal space in only 5% of cases, but the multicentric case is unknown. Herein, we describe a rare case of multicentric, large, intra-abdominal and retroperitoneal liposarcoma, one of which had caused infection and pressing the right ureter causing hydronephrosis, which was resected by two-stage surgery. CASE PRESENTATION: The patient was a 46-year-old man who was referred for abdominal bloating and fatigue. Enhanced computed tomography showed a 23-cm intra-abdominal tumor and a 14.6-cm left retroperitoneal tumor. The intra-abdominal tumor which compressed the right ureter caused right unilateral hydronephrosis and deteriorated the renal function. The intra-abdominal tumor had also formed an intra-abdominal abscess. We performed emergent laparotomy and resected the intra-abdominal tumor. After the recovery of renal function, we resected the residual retroperitoneal tumor. Histopathological examination showed both tumors to be myxoid/round cell type liposarcoma. Considering clinical findings and their location, he was diagnosed with multicentric liposarcoma. He underwent adjuvant chemotherapy and has been alive without any recurrence for 9 months after the operation. CONCLUSIONS: We successfully resected large intra-abdominal and retroperitoneal multicentric myxoid/round cell liposarcomas. A two-stage surgery was a rational choice as it provides time to confirm the recovery of renal function.
• 南回りB2/3胆管を伴う肝左葉グラフトを用いた生体肝移植の一例

  高橋 直規, 後藤 了一, 渡辺 正明, 川村 典生, 財津 雅昭, 神山 俊哉, 嶋村 剛, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (2) 439 - 439 1345-2843 2019/02
• 腹腔鏡下大腸切除における技術認定の位置付け

  市川 伸樹, 本間 重紀, 吉田 雅, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (2) 436 - 436 1345-2843 2019/02
• 肝細胞癌大腸転移と腺癌が混在した上行結腸癌の一切除例

  田仲 大樹, 本間 重紀, 吉田 雅, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 80 (2) 446 - 446 1345-2843 2019/02
• Pediatric fitz-hugh-curtis syndrome diagnosed by magnetic resonance imaging

  Kazuaki Shibuya, Hisayuki Miyagi, Shohei Honda, Akinobu Taketomi

  African Journal of Paediatric Surgery 16 (1) 33 - 34 0974-5998 2019/01/01 

  A 17-year-old girl, who had a sexual intercourse history, presented with fever and right upper quadrant pain. On physical examination, tenderness and percussion tender were identified at that quadrant point, but cervical motion tenderness was not identified. Plane X-ray, abdominal ultrasonography, and nonenhanced abdominal computed tomography, because of contrast agent allergy, showed no specific findings. Nonenhanced magnetic resonance imaging (MRI) demonstrated the high-intensity area in the surface and subcapsule of the liver. From vaginal discharge, polymerase chain reaction for Chlamydia trachomatis was positive. Considered physical and MRI findings, Fitz-Hugh-Curtis syndrome was diagnosed. After Azithromycin administering (1000 mg/day), she got better and discharged.
• Six cases of simultaneous reduced port laparoscopic surgery for synchronous gastric and colorectal cancer

  Tadashi Yoshida, Hideki Kawamura, Shigenori Homma, Susumu Shibasaki, Tatsushi Shimokuni, Hideyasu Sakihama, Norihiko Takahashi, Akinobu Taketomi

  International Surgery 103 (5-6) 248 - 254 0020-8868 2019 

  We report 6 cases of simultaneous resection of synchronous gastric and colorectal cancer using a multichannel port and an additional 5-mm port. This is the first report of simultaneous gastric and colorectal resection using a reduced port technique. A multichannel port was inserted into an umbilical incision, and another 5-mm port in the right flank region. We named this approach ‘‘dual port surgery.’’ This report includes a 76-year-old man who underwent total gastrectomy and left hemicolectomy, a 70-year-old woman who underwent distal gastrectomy and high anterior resection, a 75-year-old man who underwent distal gastrectomy and right hemicolectomy, a 72-year-old man who underwent total gastrectomy and sigmoidectomy, a 67-year-old man who underwent distal gastrectomy and high anterior resection, and a 57-year-old woman who underwent distal gastrectomy and right hemicolectomy. All operations were successful. All patients recovered quickly, and were discharged without any intra- or postoperative complications. On a median follow-up of 14.5 months, all patients remain well with no evidence of recurrent malignancy. This is the first report of simultaneous reduced port laparoscopic surgery for synchronous gastric and colorectal cancer. This procedure was performed safely and successfully.
• Laparoscopic abdominoperineal resection with lateral lymph node dissection for advanced rectal and prostate cancer with synchronous lateral lymph node metastases.

  Takahisa Ishikawa, Shigenori Homma, Makoto Nishikawa, Hiroki Nakamoto, Ryoji Yokoyama, Akinobu Taketomi

  Asian journal of endoscopic surgery 12 (1) 118 - 121 1758-5902 2019/01 [Refereed][Not invited]
   

  Here we report a case of advanced rectal and prostate cancer with synchronous lateral lymph node (LLN) metastases that was treated with laparoscopic surgery. A 71-year-old man presented with fecal occult blood and was diagnosed with rectal cancer. A metastatic right LLN was suspected after CT examination of a 19-mm lymph node (proximal internal iliac artery region) and a 13-mm lymph node (distal internal iliac artery region) in the right lateral region. We planned neoadjuvant chemotherapy to suppress local and distant recurrence. This treatment decreased the size of the primary rectal tumor. We performed laparoscopic abdominoperineal resection and right LLN dissection. The histopathological diagnosis was LLN metastases from the rectal and prostate cancers. It is rare for synchronous metastases from rectal and prostate cancers to be observed in the LLN. It may be difficult to determine an appropriate treatment strategy in cases like this.
• Simultaneous Laparoscopic Cholecystectomy and Combined Endoscopic and Laparoscopic Surgery for an Endoluminal Tumor of the Sigmoid Colon: A Case Report.

  Hiroki Nakamoto, Makoto Nishikawa, Takahisa Ishikawa, Ryouji Yokoyama, Akinobu Taketomi

  The American journal of case reports 20 1 - 4 2019/01/01 [Refereed][Not invited]
   

  BACKGROUND One treatment for colon endoluminal tumors is endoscopic resection, i.e., endoscopic mucosal resection (EMR). In this report we describe a case of an endoluminal tumor resected safely and completely by combined endoscopic and laparoscopic surgery (CELS). CASE REPORT A 70-year-old female was admitted to our hospital for cholelithiasis, and we planned a cholecystectomy. She had a surgical history for endometrial cancer, and she was taking amlodipine 2.5 mg/day for hypertension. A preoperative colonoscopy for screening revealed an 18-mm endoluminal tumor in the sigmoid colon. We tried to resect it by EMR, but flexion of the colon, which was considered to be due to adhesion from the former surgical treatment, was severe, so it was difficult to resect the endoluminal tumor by endoscopy. We conducted laparoscopic cholecystectomy and sigmoid colon mobilization. Sigmoid colon flexion was released, enabling us to conduct EMR to the endoluminal tumor. No intraoperative or postoperative complications were observed. CONCLUSIONS CELS can make an endoluminal tumor resectable by EMR without colon resection, and performing simultaneous CELS and laparoscopic cholecystectomy is less invasive.
• "Real-time" risk models of postoperative morbidity and mortality for liver transplants.

  Shigeru Marubashi, Naoaki Ichihara, Yoshihiro Kakeji, Hiroaki Miyata, Akinobu Taketomi, Hiroto Egawa, Yasutsugu Takada, Koji Umeshita, Yasuyuki Seto, Mitsukazu Gotoh

  Annals of gastroenterological surgery 3 (1) 75 - 95 2019/01 [Refereed][Not invited]
   

  Aim: A comprehensive description of morbidity and mortality risk factors for post liver transplant has not been available to date. In this study, we established real-time risk models of postoperative morbidities and mortality in liver transplant recipients using two Japanese nationwide databases. Methods: Data from two Japanese nationwide databases were combined and used for this study. We developed real-time prognostic models for morbidity and mortality from a derivation cohort (n = 1472) and validated the findings with an independent cohort (n = 395). Preoperative variables (C1), preoperative and intraoperative variables (C2), and all variables including postoperative morbidities within 30 days (C3) were analyzed to evaluate the independent risk factors for postoperative morbidity and mortality. Results: We established real-time risk models for morbidity and mortality. Areas under the curve (AUC) of C1 and C2 risk models for mortality were 0.74 (0.63-0.82) and 0.79 (0.69-0.86), respectively. Multivariate logistic analysis using C3 showed that hemoglobin <10 g/dL, operative time (hours), and five postoperative morbidities (prolonged ventilation >48 hours, coma >24 hours, renal dysfunction, postoperative systemic sepsis, and serum total bilirubin ≥10 mg/dL) represented independent risk factors for mortality (AUC = 0.87, 95% confidence interval [CI]: 0.78-0.93). Conclusions: Real-time risk models of postoperative morbidities and mortality at various perioperative time points in liver transplant recipients were established. These novel approaches may improve postoperative outcomes of liver transplant recipients. Furthermore, these real-time risk models may be applicable to other surgical procedures.
• Hepatocellular carcinoma producing granulocyte colony-stimulating factor: diagnosis and treatment.

  Yuzuru Sakamoto, Toshiya Kamiyama, Hideki Yokoo, Shingo Shimada, Takahiro Einama, Kenji Wakayama, Tatsuya Orimo, Hirofumi Kamachi, Tomoaki Naka, Tomoko Mitsuhashi, Akinobu Taketomi

  International cancer conference journal 8 (1) 12 - 16 2019/01 [Refereed][Not invited]
   

  Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that is synthesized by stromal cells in bone marrow. Several cases of G-CSF-producing malignant tumors in various organs have been reported, but it is extremely rare in hepatocellular carcinoma (HCC). Here, we report a rare case of HCC producing G-CSF. The patient presented with a continuous fever and had a huge liver mass in the right lobe with portal vein tumor thrombus (PVTT) in the right first branch. He had marked granulocytosis, and his serum level of G-CSF was elevated. A complete curative liver resection was performed after preoperative radiotherapy to PVTT. The pathological findings of the resected specimen revealed poorly/moderately differentiated HCC, and immunohistochemical staining of G-CSF was negative the first time it was tested, but the second time, it was positive in the cytoplasm of other tumor cells of HCC. Only a few cases of G-CSF-producing HCC have been reported, and they resulted in rapid tumor growth, metastases, and poor prognosis. In our case with PVTT, there was no liver recurrence, although multiple lung metastases occurred at 8 months after curative resection. We should consider G-CSF-producing HCC and diagnose promptly when encountering liver tumor patients with leukocytosis, and we should perform multimodal treatment including radiation, radical surgery, and chemotherapy.
• 生体肝移植後肝動脈血栓症に対する肝動脈再建において端側吻合を用いた1例

  和久井 洋佑, 財津 雅昭, 渡辺 正明, 川村 典生, 後藤 了一, 嶋村 剛, 武冨 紹信, 大岡 智学, 松居 喜郎

  北海道外科雑誌 北海道外科学会 63 (2) 165 - 165 0288-7509 2018/12
• 所属リンパ節に乳癌と結腸癌の転移が混在した上行結腸癌の1切除例

  田仲 大樹, 本間 重紀, 吉田 雅, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  北海道外科雑誌 北海道外科学会 63 (2) 167 - 167 0288-7509 2018/12
• 抗血小板・抗凝固薬服用症例に対する腹腔鏡下大腸切除術

  吉田 雅, 本間 重紀, 川俣 太, 市川 伸樹, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 23 (7) OS20 - 3 1344-6703 2018/12
• 腹腔鏡下低位前方切除において狭骨盤が手術操作に与える影響に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 23 (7) OS87 - 5 1344-6703 2018/12
• Lipidomic Analysis in Liver Cancer Cells Regulated FABP5 Expression

  Hayasaka Takahiro, Ohata Takanori, Yokoo Hideki, Kobayashi Nozomi, Kamiyama Toshiya, Taketomi Akinobu

  CANCER SCIENCE 109 929  1349-7006 2018/12 [Refereed][Not invited]
  
• Post-reperfusion hydrogen gas treatment ameliorates ischemia reperfusion injury in rat livers from donors after cardiac death: a preliminary study.

  Takahisa Ishikawa, Shingo Shimada, Moto Fukai, Taichi Kimura, Kouhei Umemoto, Kengo Shibata, Masato Fujiyoshi, Sunao Fujiyoshi, Takahiro Hayasaka, Norio Kawamura, Nozomi Kobayashi, Tsuyoshi Shimamura, Akinobu Taketomi

  Surgery today 48 (12) 1081 - 1088 0941-1291 2018/12 [Refereed][Not invited]
   

  BACKGROUND AND PURPOSE: We reported previously that hydrogen gas (H2) reduced hepatic ischemia and reperfusion injury (IRI) after prolonged cold storage (CS) of livers retrieved from heart-beating donors. The present study was designed to assess whether H2 reduced hepatic IRI during donation of a cardiac death (DCD) graft with subsequent CS. METHODS: Rat livers were harvested after 30-min cardiac arrest and stored for 4 h in University of Wisconsin solution. The graft was reperfused with oxygenated buffer, with or without H2 (H2 or NT groups, respectively), at 37° for 90 min on isolated perfused rat liver apparatus. RESULTS: In the NT group, liver enzyme leakage, apoptosis, necrosis, energy depletion, redox status, impaired microcirculation, and bile production were indicative of severe IRI, whereas in the H2 group these impairments were significantly suppressed. The phosphorylation of cytoplasmic MKK4 and JNK were enhanced in the NT group and suppressed in the H2 group. NFkB-p65 and c-Fos in the nucleus were unexpectedly unchanged by IRI regardless of H2 treatment, indicating the absence of inflammation in this model. CONCLUSION: H2 was observed to ameliorate IRI in the DCD liver by maintaining microcirculation, mitochondrial functions, and redox status, as well as suppressing the cytoplasmic MKK4-JNK-mediated cellular death pathway.
• Rare case of idiopathic sclerosing cholangitis, which was difficult to distinguish from cholangiocarcinoma: A case report.

  Shunsuke Shichi, Takahiro Einama, Mayu Suzuki, Hiroki Matsui, Ryo Kanazawa, Kazuaki Shibuya, Takashi Suzuki, Fumihiko Matsuzawa, Kohei Nakachi, Taku Hashimoto, Nobuo Kondo, Hironori Abe, Akinobu Taketomi

  Experimental and therapeutic medicine 16 (6) 5224 - 5226 1792-0981 2018/12 [Refereed][Not invited]
   

  It is often difficult to correctly diagnose patients who present with dilation of the bile duct. Cholangiocarcinoma, primary sclerosing cholangitis (PSC) and immunoglobulin (Ig)G4-related sclerosing cholangitis must be considered as potential diagnoses for these cases. The current study presents a 73-year-old female patient who presented with a high fever and abdominal pain. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography revealed stenosis and dilation of the intrahepatic bile duct without solid components. It was suspected that the patient had intrahepatic cholangiocarcinoma. A left liver lobectomy, cholecystectomy and distal gastrectomy combined with a D2 lymph node dissection were performed. A pathological examination of the liver revealed increased fibrosis in the stroma, irregular bile duct dilation and clusters of inflamed lymph cells. No carcinoma or IgG4-positive plasma cells were observed and the typical findings of PSC were not detected. Based on these clinical and pathological results, the diagnosis was idiopathic sclerosing cholangitis, which is particularly rare. It is often difficult to preoperatively differentiate between cholangiocarcinoma and benign bile duct stenosis.
• Laparoscopic Surgery for the Treatment of Mesenteric Phlebosclerosis.

  Tadashi Yoshida, Shigenori Homma, Yosuke Ohno, Nobuki Ichikawa, Hideki Kawamura, Ryo Sato, Tomoyuki Ohta, Teppei Imamoto, Yoshihiro Matsuno, Akinobu Taketomi

  The American surgeon 84 (12) e544-e546 - e546 0003-1348 2018/12/01 [Refereed][Not invited]
  
• 内視鏡外科技術認定取得時の腹腔鏡下低位前方切除における習熟度と安全性に関する検討

  市川 伸樹, 本間 重紀, 吉田 雅, 大野 陽介, 川村 秀樹, 上泉 洋, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 51 (Suppl.2) 165 - 165 0386-9768 2018/11
• Impact of tumor localization on the outcomes of surgery for an intrahepatic cholangiocarcinoma.

  Tatsuya Orimo, Toshiya Kamiyama, Tomoko Mitsuhashi, Hirofumi Kamachi, Hideki Yokoo, Kenji Wakayama, Shingo Shimada, Akihisa Nagatsu, Akinobu Taketomi

  Journal of gastroenterology 53 (11) 1206 - 1215 0944-1174 2018/11 [Refereed][Not invited]
   

  BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) shows differing clinical outcomes depending on its localization. METHODS: We reviewed the surgical outcomes of 104 ICC patients who underwent liver resection at our institution. We divided ICC into hilar type (HICC) and peripheral type (PICC) depending on positive contact with the hepatic hilum on preoperative computed tomography (CT). RESULTS: The survival outcomes were significantly poorer in HICC patients. HICCs showed a larger tumor size and more frequent bile duct invasion, lymph node metastasis, and non-curative resection than PICC. Resections for HICC had greater blood loss and required a longer operation time, larger hepatectomy, and more frequent extrahepatic bile duct resection. HICCs, even if small in size, also showed a greater tendency to metastasize to the lymph nodes of the hepatoduodenal ligament. Univariate analysis of the ICCs in our current cohort revealed that tumor size, multiple tumors, bile duct invasion, lymph node metastasis, non-curative resection, and HICC are associated with a poorer overall survival outcome. Multivariate analysis indicated that multiple tumors and non-curative resection were independent prognostic factors for survival. Among the curative resection cases, however, survival did not differ significantly between HICC and PICC. The accuracy rate of our CT-based classification for the pathological classification was 81.7%. CONCLUSIONS: HICC shows more frequent bile duct invasion and lymph node metastasis, requires more extensive surgery, and has a higher rate of non-curative resection than PICC. However, if curative resection is achieved, the survival outcomes are expected to be equivalent between HICC and PICC.
• Cytoplasmic CD133 expression correlates with histologic differentiation and is a significant prognostic factor in extrahepatic bile duct cancer and gallbladder cancer.

  Tatsuzo Mizukami, Hirofumi Kamachi, Tomoko Mitsuhashi, Takahiro Einama, Yutaka Hatanaka, Toshiya Kamiyama, Akinobu Taketomi

  Oncology letters 16 (5) 6423 - 6430 1792-1074 2018/11 [Refereed][Not invited]
   

  Prominin-1 (CD133) is one of the most important stem cell markers among various malignant tumor types, but the clinicopathological significance of CD133 expression in intrahepatic cholangiocarcinoma remains controversial. To the best of our knowledge, there have been no reports on extrahepatic bile duct cancer (EHBDCA) and gallbladder cancer (GBCA). The present study examined the clinicopathological significance of CD133 expression in EHBDCA and GBCA. Immunohistochemistry was used to evaluate CD133 expression in resected specimens obtained from 82 patients with EHBDCA and GBCA, and this expression was compared with the clinicopathological parameters and survival data of the patients. Cytoplasmic CD133 expression was identified in 20 patients, and its incidence was significantly associated with histopathological grade (P=0.035), pT factor (P=0.020) and recurrence (P=0.046). Survival analysis revealed that cytoplasmic CD133 expression in patients was significantly associated with a poorer overall survival (OS) and relapse-free survival (RFS) compared with those without cytoplasmic expression (5-year OS rate, 11.6% vs. 39.1%; 3-year RFS rate, 12.5% vs. 42.0%, respectively). Multivariate analysis revealed that cytoplasmic CD133 expression was an independent prognostic factor for OS and RFS (P=0.0036 and P<0.0001, respectively). To the best of our knowledge, this is the first report demonstrating that cytoplasmic CD133 expression was associated with histologic differentiation, cancer progression, recurrence and poor prognosis in EHBDCA and GBCA. CD133 expression may be a useful marker for clinical prognosis in patients with EHBDCA and GBCA.
• Endoscopic Retrograde Cholangiopancreatography (ERCP) with Laparotomic Small-Intestinal Incision Approach for Extraction of a Common Bile Duct (CBD) Stone Following Total Gastrectomy and Roux-en-Y (R-Y) Anastomosis: A Case Report.

  Hiroki Nakamoto, Makoto Nishikawa, Takahisa Ishikawa, Ryouji Yokoyama, Akinobu Taketomi

  The American journal of case reports 19 1175 - 1178 2018/10/03 [Refereed][Not invited]
   

  BACKGROUND Endoscopic retrograde cholangiopancreatography for common bile duct stone in patients who underwent gastrectomy and Roux-en-Y anastomosis is challenging. We report a case in which we performed endoscopic retrograde cholangiopancreatography through a small-intestinal incision approach for a common bile duct stone, which had developed after total gastrectomy and Roux-en-Y anastomosis. CASE REPORT An 86-year-old woman with a history of laparoscopic-assisted total gastrectomy and R-Y anastomosis and incision of the common bile duct and cholecystectomy for common bile duct stone by open surgery 3 years ago presented with abdominal pain. Examination revealed a 10-mm stone in the lower part of common bile duct. We planned a combined endoscopic and open surgical approach. An incision on the Y limb of the Roux-en-Y anastomosis 20 cm from the jejunojejunal anastomosis and insertion of an endoscope through this opening were performed to extract the common bile duct stone. The patient was discharged on postoperative day 22 without complications. CONCLUSIONS For a patient with a common bile duct stone, who underwent gastrectomy and Roux-en-Y anastomosis, with firm adhesions at the porta hepatis, combined endoscopy and open surgery using a small-intestinal incision approach can be effective when small-bowel endoscopes are unavailable or the cannulation to Vater's papilla by them is difficult.
• The anti-mesothelin monoclonal antibody amatuximab enhances the anti-tumor effect of gemcitabine against mesothelin-high expressing pancreatic cancer cells in a peritoneal metastasis mouse model.

  Tatsuzo Mizukami, Hirofumi Kamachi, Yuki Fujii, Fumihiko Matsuzawa, Takahiro Einama, Futoshi Kawamata, Nozomi Kobayashi, Yutaka Hatanaka, Akinobu Taketomi

  Oncotarget 9 (73) 33844 - 33852 2018/09/18 [Refereed][Not invited]
   

  Pancreatic cancer often has a very poor prognosis, even after complete resection. The recurrence of hepatic and peritoneal metastases is an important prognostic factor; therefore, the development of improved adjuvant therapy is urgently required. Mesothelin is a cell surface glycoprotein whose expression is restricted to a variety of cancer types, including pancreatic cancer. This expression pattern makes mesothelin an attractive target for cancer therapy, and several agents targeting mesothelin are currently in clinical trials. Here, we used the chimerized high-affinity anti-mesothelin monoclonal antibody amatuximab to investigate its effect on peritoneal metastasis. We used the AsPC-1 pancreatic cancer cell line engineered to express Gaussia luciferase (Gluc), (AsPC-1-Gluc) for in vivo experiments. Results showed that while amatuximab was not directly cytotoxic on an AsPC-1-Gluc tumor cells in a peritoneal metastasis model, it prevented the formation of tumor growth. In combination therapy with gemcitabine, amatuximab exhibited synergistic killing. Our results suggest that blockade of mesothelin by amatuximab may be a useful strategy for preventing the peritoneal dissemination of pancreatic cancer under an adjuvant setting.
• 本邦の膵島移植の今後の展開 本邦での膵島移植の成績改善に向けて 我々のこれまでの取り組みとこれからの展開

  渡辺 正明, 腰塚 靖之, 渋谷 一陽, 蔵谷 大輔, 吉田 雅, 後藤 了一, 財津 雅昭, 川村 典生, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 53 (総会臨時) 276 - 276 0578-7947 2018/09
• 生体肝移植後の原発性胆汁性胆管炎再発による肝硬変に対して脳死再移植を施行した1例

  財津 雅昭, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 53 (総会臨時) 534 - 534 0578-7947 2018/09
• IL-6を標的としたTh1型抗腫瘍免疫応答の導入による新規がん免疫治療の可能性(Lack of IL-6 in tumor microenvironment augments type-1 anti-tumor immune responses)

  大野 陽介, 北村 秀光, 豊島 雄二郎, Xiang Huihui, 角田 健太郎, 金海 俊, 本間 重紀, 川村 秀樹, 高橋 典彦, 武冨 紹信

  日本癌学会総会記事 77回 1986 - 1986 0546-0476 2018/09
• 遠隔転移を有する大腸癌に対する治療戦略 ゲノム解析を利用した大腸癌原発巣およびその肝転移巣に対する新規治療戦略

  川俣 太, 沢田 尭史, 市川 伸樹, 吉田 雅, 柴崎 晋, 本間 重紀, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 71 (抄録号) A57 - A57 0047-1801 2018/09
• pT1(SM)早期大腸癌の臨床病理学的特徴と治療成績

  吉田 雅, 本間 重紀, 川俣 太, 市川 伸樹, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 71 (抄録号) A142 - A142 0047-1801 2018/09
• 肝細胞癌術後経過中に認めた肝細胞癌大腸転移と上行結腸癌の衝突癌の一切除例

  沢田 尭史, 本間 重紀, 吉田 雅, 市川 伸樹, 川俣 太, 柴崎 晋, 川村 秀樹, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 71 (抄録号) A167 - A167 0047-1801 2018/09
• DSS誘発性大腸炎モデルにおけるSTAT1シグナルの関与

  木井 修平, 北村 秀光, 項 慧慧, 豊島 雄二郎, 岡田 尚樹, 杉山 昂, 川俣 太, 大野 陽介, 市川 伸樹, 吉田 雅, 柴崎 晋, 本間 重紀, 川村 秀樹, 高橋 典彦, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 71 (抄録号) A190 - A190 0047-1801 2018/09
• 抗ドナーHLA抗体陽性の肝移植の短期・長期成績と問題点 De novoドナー特異的HLA抗体陽性の生体肝グラフト線維化進行症例の特徴

  後藤 了一, 川村 典生, 渡辺 正明, 財津 雅昭, 嶋村 剛, 武冨 紹信

  移植 (一社)日本移植学会 53 (総会臨時) 255 - 255 0578-7947 2018/09
• 大腸癌同時性肝転移における術前化学療法の意義

  市川 伸樹, 神山 俊哉, 横尾 英樹, 本間 重紀, 前田 好章, 濱田 朋倫, 篠原 敏樹, 敦賀 陽介, 数井 啓蔵, 吉田 雅, 川俣 太, 柴崎 晋, 川村 秀樹, 蒲池 浩文, 折茂 達也, 島田 慎吾, 長津 明久, 大畑 多嘉宣, 武冨 紹信

  日本大腸肛門病学会雑誌 (一社)日本大腸肛門病学会 71 (抄録号) A139 - A139 0047-1801 2018/09 [Refereed][Not invited]
  
• R0 Resection for Locally Advanced Pancreatic Cancer with Low-dose Gemcitabine with Wide Irradiation Area as Neoadjuvant Chemoradiotherapy.

  Kamachi H, Tsuruga Y, Orimo T, Wakayama K, Shimada S, Nagatsu A, Yokoo H, Kamiyama T, Katoh N, Taketomi A

  In vivo (Athens, Greece) 32 (5) 1183 - 1191 0258-851X 2018/09 [Refereed][Not invited]
   

  BACKGROUND: Local antitumor efficacy and the outcome of neoadjuvant chemoradiotherapy (NACRT) with low-dose gemcitabine and wide irradiation area for borderline resectable and unresectable pancreatic cancer were evaluated. PATIENTS AND METHODS: Thirty-four cases of borderline resectable and unresectable pancreatic cancer were recruited. Three-dimensional conformal radiotherapy to the pancreatic bed and the region scheduled for lymph node dissection was performed to a total dose of 50.4 Gy28 fractions with gemcitabine at a dose of 150 mg/m2 weekly. Clinical and pathological results were examined. RESULTS: Twenty-seven patients (79.4%) completed the protocol. Grade 3/4 leucopenia (n=10), and grade 3 anorexia (n=1) occurred. Seven cases were excluded (two refused treatment; five had progressive disease), 20 underwent laparotomy, and 16 resected (47.1%) cases achieved R0 resection. Median survival time, and 3-year and 5-year survival rates were 39.0 months, and 56.3% and 28.1% in resected cases, respectively. CONCLUSION: NACRT with low-dose gemcitabine and wide irradiation area achieved 100% R0 resection and acceptable prognosis.
• Current Status of Surgical Incisions Used in Donors During Living Related Liver Transplantation-A Nationwide Survey in Japan.

  Shirabe K, Eguchi S, Okajima H, Hasegawa K, Marubashi S, Umeshita K, Kawasaki S, Yanaga K, Shimada M, Kaido T, Kawagishi N, Taketomi A, Mizuta K, Kokudo N, Uemoto S, Maehara Y, Japanese Liver Transplantation Society

  Transplantation 102 (8) 1293 - 1299 0041-1337 2018/08 [Refereed][Not invited]
  
• Optimal resection area for superior mesenteric artery nerve plexuses after neoadjuvant chemoradiotherapy for locally advanced pancreatic carcinoma.

  Takahiro Einama, Hirofumi Kamachi, Yosuke Tsuruga, Toshihiro Sakata, Kazuaki Shibuya, Yuzuru Sakamoto, Shingo Shimada, Kenji Wakayama, Tatsuya Orimo, Hideki Yokoo, Toshiya Kamiyama, Norio Katoh, Yusuke Uchinami, Tomoko Mitsuhashi, Akinobu Taketomi

  Medicine 97 (31) e11309  0025-7974 2018/08 [Refereed][Not invited]
   

  Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.
• Differential diagnosis of a large size tumor in the retroperitoneum: A case report of retroperitoneal lipoblastoma

  Hisayuki Miyagi, Shohei Honda, Masashi Minato, Akihiro Iguchi, Emi Takakuwa, Akinobu Taketomi

  African Journal of Paediatric Surgery 15 (3-4) 151 - 153 0974-5998 2018/07/01 

  Lipoblastoma can arise almost anywhere within the soft tissues, especially in the extremities. It is rarely seen retroperitoneally. A 3-year-old girl presented with a palpable abdominal mass underwent an exploratory laparotomy with resection of the retroperitoneal mass. Based on histopathologic and cytogenetic features, a final diagnosis of lipoblastoma was rendered. At 18-month follow-up, she had no evidence of recurrence.
• The Immune Monitoring for Operationally Tolerant Recipients Following a Regulatory T cell-based Cell Therapy

  Goto Ryoichi, Zaitsu Masaaki, Nagatsu Akihisa, Emoto Shin, Fukasaku Yasutomo, Ganchiku Yoshikazu, Watanabe Masaaki, Oura Tetsu, Ota Minoru, Suzuki Tomomi, Taketomi Akinobu, Shimamura Tsuyoshi, Todo Satoru, Yamashita Kenichiro

  TRANSPLANTATION 102 S330  0041-1337 2018/07 [Refereed][Not invited]
  
• Carcinoma in the residual rectum of a long-standing Crohn's disease patient following subtotal colectomy: A case report.

  Kazuaki Shibuya, Shigenori Homma, Tadashi Yoshida, Yosuke Ohno, Nobuki Ichikawa, Hideki Kawamura, Teppei Imamoto, Yoshihiro Matsuno, Akinobu Taketomi

  Molecular and clinical oncology 9 (1) 50 - 53 2049-9450 2018/07 [Refereed][Not invited]
   

  The development of colorectal cancer in long-standing Crohn's disease (CD) patients has become a major complication. Therapeutic guidelines for CD-associated cancer (CDAC) have already been established in Western countries; however, specific guidelines are not currently available in Japan. Surveillance of the residual intestine for cancer screening is important for long-standing CD patients. The present case report describes the occurrence of rectal carcinoma in a patient with a 25-year history of CD. A 37-year-old male with a 17-year history of CD underwent semi-emergent subtotal colectomy and ileostomy for bowel obstruction secondary to the transverse colon stenosis, and multiple severe stenosis and inflammation. Postoperatively, the patient resumed pharmacological treatment and underwent follow-up colonoscopies at ~1-2-year intervals. Despite continued pharmacological treatment, inflammation continued in the residual rectum. A total of 8 years following the primary operation, colonoscopy revealed inflammatory polyposis at the remnant rectum, which was diagnosed as adenocarcinoma. The interval between the last colonoscopy was 16 months. The patient then underwent laparoscopic abdominoperineal resection, and remained without recurrence for 12 months following resection. Thus, in long-standing CD patients, annual colonoscopy of the residual intestine may be considered for cancer screening, and specific surveillance guidelines for CDAC should be established.
• Tumor budding and human chorionic gonadotropin-β expression correlate with unfavorable patient outcome in colorectal carcinoma.

  Yuji Konishi, Futoshi Kawamata, Hiroshi Nishihara, Shigenori Homma, Yasutaka Kato, Masumi Tsuda, Shinji Kohsaka, Takahiro Einama, Cheng Liu, Tadashi Yoshida, Akihisa Nagatsu, Mishie Tanino, Shinya Tanaka, Hideki Kawamura, Toshiya Kamiyama, Akinobu Taketomi

  Medical oncology (Northwood, London, England) 35 (7) 104 - 104 1357-0560 2018/06/11 [Refereed][Not invited]
   

  Tumor budding is thought to represent a manifestation of epithelial-to-mesenchymal transition (EMT) and it has been correlated with poor patient outcomes in colorectal cancer (CRC). Our group recently demonstrated that human chorionic gonadotropin-β (hCGβ) modulates EMT in CRC. In the current study, based on the likely relationships between tumor budding and hCGβ expression, we examined their clinicopathologic significance in CRC. Twenty-eight of 80 (35.0%) CRC showed tumor budding. Tumor budding significantly correlated with lymph node metastasis (P < 0.01), pathologic stage (P < 0.01), lymphatic invasion (P = 0.044), and vascular invasion (P = 0.013). Thirteen of 80 (16.3%) CRC were hCGβ positive on immunohistochemistry. More tumor buds were present in the hCGβ-positive cases (P < 0.01), and tumor budding was significantly correlated with hCGβ positivity (P < 0.01). Cases with both tumor budding and hCGβ expression had the poorest prognosis compared with all other groups (P < 0.01). In conclusion, tumor budding and hCGβ expression are closely associated with EMT, and they are independent prognostic factors in CRC. They identify patients with an "EMT phenotype" who may respond to targeted molecular therapies.
• Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.

  Hiromi Sawai, Nao Nishida, Seik-Soon Khor, Masao Honda, Masaya Sugiyama, Natsumi Baba, Kayoko Yamada, Norie Sawada, Shoichiro Tsugane, Kazuhiko Koike, Yuji Kondo, Hiroshi Yatsuhashi, Shinya Nagaoka, Akinobu Taketomi, Moto Fukai, Masayuki Kurosaki, Namiki Izumi, Jong-Hon Kang, Kazumoto Murata, Keisuke Hino, Sohji Nishina, Akihiro Matsumoto, Eiji Tanaka, Naoya Sakamoto, Koji Ogawa, Kazuhide Yamamoto, Akihiro Tamori, Osamu Yokosuka, Tatsuo Kanda, Isao Sakaida, Yoshito Itoh, Yuichiro Eguchi, Satoshi Oeda, Satoshi Mochida, Man-Fung Yuen, Wai-Kay Seto, Yong Poovorawan, Nawarat Posuwan, Masashi Mizokami, Katsushi Tokunaga

  Scientific reports 8 (1) 7958 - 7958 2018/05/21 [Refereed][Not invited]
   

  We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10-4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 × 10-12; rs1110446: OR = 1.79, P = 1.66 × 10-13; and rs3094137: OR = 1.73, P = 7.09 × 10-9). We then performed two-field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A * 33:03 (OR = 1.97, P = 4.58 × 10-4) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A*33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region.
• Usefulness of Plain Computed Tomography with Swallowing of Gastrografin^TM for the Diagnosis of a Late-Onset Iatrogenic Diaphragmatic Hernia following Biopsy of a Diaphragmatic Tumor: Report of a Case.

  Asahi Y, Honda S, Okada T, Miyagi H, Kaneda M, Iguchi A, Kaga K, Taketomi A

  Case reports in gastroenterology 12 (2) 271 - 276 2018/05 [Refereed][Not invited]
  
• Transparenchymal glissonean approach: a novel surgical technique for advanced perihilar bile duct cancer

  Hirofumi Kamachi, Toshiya Kamiyama, Yousuke Tsuruga, Tatsuya Orimo, Kenji Wakayama, Shingo Shimada, Tatsuhiko Kakisaka, Hideki Yokoo, Kenichiro Yamashita, Akinobu Taketomi

  Langenbeck's Archives of Surgery 403 (3) 387 - 394 1435-2451 2018/05/01 [Refereed][Not invited]
   

  Purpose: To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA) it comprises intra-hepatic exposure and dissection of the Glisson’s sheath to gain access to the hepatic artery and portal vein for reconstruction. Methods: Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson’s sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. Results: TGA was performed in 9 patients 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0 months. Conclusions: TGA is feasible with acceptable prognosis and expands the surgical opportunities.
• Pancreaticoduodenectomy with Preservation of Collateral Circulation or Revascularization for Biliary Pancreatic Cancer with Celiac Axis Occlusion: A Report of 2 Cases.

  Kazuaki Shibuya, Hirofumi Kamachi, Tatsuya Orimo, Akihisa Nagatsu, Shingo Shimada, Kenji Wakayama, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi

  The American journal of case reports 19 413 - 420 2018/04/09 [Refereed][Not invited]
   

  BACKGROUND In cases of celiac axis occlusion requiring pancreaticoduodenectomy for malignancy, both oncologic curability and control of hepatic arterial flow must be considered, but the operative strategy is undeveloped. CASE REPORT Case 1: A 74-year-old man was diagnosed with hilar cholangiocarcinoma with celiac axis stenosis. The collateral from the superior mesenteric artery ran through the pancreas head but no invasion was observed in preoperative imaging. Hepatopancreatoduodenectomy with preservation of a collateral was performed. Case 2: A 69-year-old woman was diagnosed with pancreas head cancer with celiac axis occlusion. The collateral from the superior mesenteric artery ran through pancreas head and tumor invasion was observed. Pancreaticoduodenectomy with bypass revascularization using a vein graft was performed. Both operations were performed safely oncologically under preoperative planning that was based on computed tomographic angiography. The operative procedure was ultimately determined by evaluation of perioperative blood flow under Doppler ultrasonography after clamping the gastroduodenal artery. CONCLUSIONS Preoperative simulations of arterial revascularization and perioperative evaluation of blood flow are necessary for the success of this procedure.
• [A Case of Locally Advanced Intrahepatic Cholangiocarcinoma Successfully Treated by Conversion Surgery after Hepatic Arterial Infusion Chemotherapy and Radiation Therapy].

  Ko Sugiyama, Toshiya Kamiyama, Takumi Ohmura, Akihisa Nagatsu, Shingo Shimada, Takahiro Einama, Kenji Wakayama, Tatsuya Orimo, Hideki Yokoo, Hirofumi Kamachi, Akinobu Taketomi

  Gan to kagaku ryoho. Cancer & chemotherapy 45 (4) 664 - 666 0385-0684 2018/04 [Refereed][Not invited]
   

  The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in diameter low-density mass in hepatic segments 4 and 8 as the main locus. This tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to invade to left and right Gleason's sheath, and radical cure was judged impossible. After hepatic arterial chemotherapy and radiotherapy were performed, tumor shrinkage was confirmed, and tumor markers also became negative. So he was referred to our hospital for surgical indication. CT revealed that the tumor did not invade to the left Gleason's sheath. After percutaneous transhepatic portal embolization, hepatic right trisectionectomy was performed. He was administered gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after surgery, the patient is alive without relapse. Preoperative hepatic arterial chemotherapy and radiotherapy could be an effective treatment for unresectable locally advanced intrahepatic cholangiocarcinoma.
• Single-stage operation for perforated choledochal cyst

  Go Ohba, Hiroshi Yamamoto, Masato Nakayama, Shohei Honda, Akinobu Taketomi

  Journal of Pediatric Surgery 53 (4) 653 - 655 1531-5037 2018/04/01 [Refereed][Not invited]
   

  Background: The option of either single- or two-staged cyst excision has been proposed for perforated choledochal cysts (CCs), but which of the two methods is more effective remains controversial. We examined the complications and short-term outcomes of single-stage excision of perforated and non-perforated CCs. Methods: The medical records of patients treated for CCs from 2003 to 2016 were retrospectively reviewed. Outcomes were compared between patients with perforated CCs (Group A) and non-perforated CCs (Group B). The operative time, intraoperative bleeding, length of stay, and postoperative complications were analyzed. Results: Group A comprised 6 patients (2 males, 4 females mean age, 29 months), and Group B comprised 26 patients (2 males, 24 females mean age, 41 months). All patients underwent single-stage complete excision with Roux-en-Y hepaticojejunostomy. There were no significant differences in the operative time, bleeding, and/or length of stay. There were no operative deaths or complications such as anastomosis leakage or postoperative cholangitis, but a pancreatic fistula developed in one patient in Group A and two in Group B. Conclusion: Single-stage excision for a perforated CC is feasible if the patient's condition is stable. Levels of evidence: Treatment Study, LEVELIII.
• L-Carnitine supplementation reduces the general fatigue of cancer patients during chemotherapy.

  Matsui H, Einama T, Shichi S, Kanazawa R, Shibuya K, Suzuki T, Matsuzawa F, Hashimoto T, Homma S, Yamamoto J, Taketomi A, Abe H

  Molecular and clinical oncology 8 (3) 413 - 416 2049-9450 2018/03 [Refereed][Not invited]
   

  L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease). The patients were administered 1,500 mg/day of levocarnitine per os, and the change in mean daily fatigue from the baseline to 8 weeks was assessed using the Brief Fatigue Inventory. The change in the plasma levels of albumin and the lymphocyte counts from the baseline to 8 weeks were also assessed. LC supplementation reduced general fatigue in all cases. Moreover, LC supplementation maintained the plasma levels of albumin and lymphocyte counts during chemotherapy, and enabled patients to continue chemotherapy sequentially without dose reduction. Therefore, LC supplementation improved general fatigue in all the examined cancer patients during chemotherapy. This treatment may make improve the tolerability of chemotherapy in cancer patients by reducing general fatigue and improving the nutritional status.
• Curative resection of pancreatic ductal adenocarcinoma developing in the remnant pancreas 13 years after distal pancreatectomy for intraductal papillary mucinous neoplasms: A case report.

  Einama T, Kamachi H, Sakata T, Shibata K, Wakizaka K, Sugiyama K, Shibuya K, Shimada S, Wakayama K, Orimo T, Yokoo H, Kamiyama T, Mitsuhashi T, Taketomi A

  Molecular and clinical oncology 8 (3) 417 - 420 2049-9450 2018/03 [Refereed][Not invited]
  
• Laparoscopic total gastrectomy for advanced gastric cancer in a patient with situs inversus totalis.

  Kengo Shibata, Hideki Kawamura, Nobuki Ichikawa, Kazuaki Shibuya, Tadashi Yoshida, Yosuke Ohno, Shigenori Homma, Akinobu Taketomi

  Asian journal of endoscopic surgery 11 (1) 39 - 42 1758-5902 2018/02 [Refereed][Not invited]
   

  Situs inversus totalis (SIT) is a rare congenital anomaly. Generally, laparoscopic surgery is difficult to perform in patients with SIT because of both the potential challenges associated with unexpected vascular anomalies and the lack of standardized strategy for handling such cases. This is the first report of laparoscopic total gastrectomy with lymph node dissection for advanced gastric cancer in a patient with SIT. A 79-year-old man with SIT was diagnosed with advanced gastric cancer. We performed laparoscopic total gastrectomy with modified D2 lymph node dissection (D2 without splenectomy) and esophagojejunal anastomosis using an overlap method involving retrocolic Roux-en-Y reconstruction. The total operating time was 232 min, and blood loss was 110 mL. There were no postoperative complications. In summary, laparoscopic total gastrectomy for gastric cancer can be performed safely, even in a patient with SIT.
• Copy number profiles of paired primary and metastatic colorectal cancers.

  Futoshi Kawamata, Ann-Marie Patch, Katia Nones, Catherine Bond, Diane McKeone, Sally-Ann Pearson, Shigenori Homma, Cheng Liu, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Nozomi Kobayasi, Hideki Yokoo, Moto Fukai, Hiroshi Nishihara, Toshiya Kamiyama, Matthew E Burge, Christos S Karapetis, Akinobu Taketomi, Barbara Leggett, Nicola Waddell, Vicki Whitehall

  Oncotarget 9 (3) 3394 - 3405 2018/01/09 [Refereed][Not invited]
   

  Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. The genomic differences between the tumor and paired metastases revealed an average copy number discordance of 22.0%. The pairs of tumor samples collected prior to treatment revealed significantly higher copy number differences compared to post-therapy liver metastases (P = 0.014). Loss of heterozygosity acquired in liver metastases was significantly higher in previously treated liver metastasis samples compared to treatment naive liver metastasis samples (P = 0.003). Amplification of the clinically actionable genes ERBB2, FGFR1, PIK3CA or CDK8 was observed in the metastatic tissue of 4 patients but not in the paired primary CRC. These examples highlight the intra-patient genomic discrepancies that can occur between metastases and the primary tumors from which they arose. We propose that precision medicine strategies may therefore identify different actionable targets in metastatic tissue, compared to primary tumors, due to substantial genomic differences.
• Reduced port laparoscopic TME with coloanal anastomosis

  Shigenori Homma, Futoshi Kawamata, Susumu Shibasaki, Takahisa Ishikawa, Tadashi Yoshida, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  Surgical Techniques in Rectal Cancer: Transanal, Laparoscopic and Robotic Approach 257 - 268 2018/01/01 [Refereed][Not invited]
   

  We began performing a single-incision plus one additional port laparoscopyassisted anterior resection of the rectum (SILS+1-AR) in August 2010. In recent years, intersphincteric resection (ISR) is proposed as a means of offering sphincter preservation in patients with very low rectal cancer and has become an accepted surgical procedure. Moreover, the procedure of ultralow anterior resection mainly includes an ISR for sphincter-saving operation. Therefore, we applied SILS+1 partial ISR in cases of rectal cancer located within 5 cm from the anal verge. In the SILS+1-AR without ISR, a 3-cm trans-umbilical incision was made, and the SILS™ port was inserted, and an additional 12-mm trocar was placed in the right lower quadrant. In the SILS+1 partial ISR, a SILS™ port was placed in the right lower quadrant at the intended ileostomy site, and a 5-mm trocar was inserted at the umbilicus at the subsequent drain site. The surgical procedure of partial ISR included five stages: colonic mobilization, pelvic dissection with total mesorectal excision (TME), transabdominal dissection of the intersphincteric space, stapled coloanal anastomosis, and diverting stoma. All postoperative outcomes were satisfactory (data not shown). Reduced port laparoscopic TME for rectal carcinoma with or without ISR can be performed safely, and its feasibility depends on proper selection of patients.
• IL-6 suppresses dendritic cell-mediated antitumor immunity and promotes liver metastasis of colorectal cancer cells

  Toyoshima Yujiro, Xiang Huihui, Terada Satoshi, Okada Naoki, Kii Shuhei, Ohno Yosuke, Homma Shigenori, Kawamura Hideki, Takahashi Norihiko, Taketomi Akinobu, Kitamura Hidemitsu

  CANCER SCIENCE 109 299 - 299 1349-7006 2018/01 [Refereed][Not invited]
  
• Surgical outcomes in gastroenterological surgery in Japan: Report of National Clinical database 2011-2016.

  Yoshihiro Kakeji, Arata Takahashi, Harushi Udagawa, Michiaki Unno, Itaru Endo, Chikara Kunisaki, Akinobu Taketomi, Akira Tangoku, Tadahiko Masaki, Shigeru Marubashi, Kazuhiro Yoshida, Mitsukazu Gotoh, Hiroyuki Konno, Hiroaki Miyata, Yasuyuki Seto

  Annals of gastroenterological surgery 2 (1) 37 - 54 2018/01 [Refereed][Not invited]
   

  The National Clinical Database (NCD) of Japan started its registration in 2011 and over 9 000 000 cases from more than 5000 facilities were registered over a 6-year period. This is the report of NCD based upon gastrointestinal surgery information in excess of 3 200 000 cases from 2011 to 2016 adding data of complications. About 70% of all gastrointestinal surgeries were carried out at certified institutions, and the percentage of surgeries done at certified institutions was particularly high for the esophagus (92.4% in 2016), liver (88.4%), pancreas (89.8%), and spleen (86.8%). The percentage of anesthesiologist participation was more than 90% for almost all organs, except 85.7% for the rectum and anus. Approximately, more than two-thirds of the surgeries were carried out with the participation of a board-certified surgeon. Although patients have been getting older, mortalities have not been increasing. There were differences in the incidence of complications according to organ site and procedure. Remarkably, mortality rates of low anterior resection were very low, and those of hepatectomy and acute diffuse peritonitis surgery have been gradually decreasing. Although the complication rates were gradually increasing for esophagectomy or pancreaticoduodenectomy, the mortality rates for these procedures were decreasing. Nationwide, this database is expected to ensure the quality of the board-certification system and surgical outcomes in gastroenterological surgery.
• A staged operation for anopenile urethral fistula.

  Kawakita I, Honda S, Miyagi H, Minato M, Okumura K, Taketomi A

  African journal of paediatric surgery : AJPS 15 (1) 48 - 49 0189-6725 2018/01 [Refereed][Not invited]
  
• Supervision by a technically qualified surgeon affects the proficiency and safety of laparoscopic colectomy performed by novice surgeons.

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Yosuke Ohno, Hideki Kawamura, You Kamiizumi, Hiroaki Iijima, Akinobu Taketomi

  Surgical endoscopy 32 (1) 436 - 442 0930-2794 2018/01 [Refereed][Not invited]
   

  BACKGROUND: The use of laparoscopic colectomy is becoming widespread and acquisition of its technique is challenging. In this study, we investigated whether supervision by a technically qualified surgeon affects the proficiency and safety of laparoscopic colectomy performed by novice surgeons. METHODS: The outcomes of 23 right colectomies and 19 high anterior resections for colon cancers performed by five novice surgeons (experience level of <10 cases) between 2014 and 2016 were assessed. A laparoscopic surgeon qualified by the Endoscopic Surgical Skill Qualification System (Japan Society for Endoscopic Surgery) participated in surgeries as the teaching assistant. RESULTS: In the right colectomy group, one patient (4.3%) required conversion to open surgery and postoperative morbidities occurred in two cases (8.6%). The operative time moving average gradually decreased from 216 to 150 min, and the blood loss decreased from 128 to 28 mL. In the CUSUM charts, the values for operative time decreased continuously after the 18th case, as compared to the Japanese standard. The values for blood loss also plateaued after the 18th case. In the high anterior resection group, one patient (5.2%) required conversion to open surgery and no postoperative complication occurred in any patient. The operative time moving average gradually decreased from 258 to 228 min, and the blood loss decreased from 33 to 18 mL. The CUSUM charts showed that the values of operative time plateaued after the 18th case, as compared to the Japanese standard. In the CUSUM chart for blood loss, no distinguishing peak or trend was noted. CONCLUSIONS: Supervision by a technically qualified surgeon affects the proficiency and safety of laparoscopic colectomy performed by novice surgeons. The trainee's learning curve in this study represents successful mentoring by the laparoscopic surgeon qualified by the Endoscopic Surgical Skill Qualification System.
• Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis.

  Futoshi Kawamata, Hiroshi Nishihara, Shigenori Homma, Yasutaka Kato, Masumi Tsuda, Yuji Konishi, Lei Wang, Shinji Kohsaka, Cheng Liu, Tadashi Yoshida, Mishie Tanino, Shinya Tanaka, Hideki Kawamura, Toshiya Kamiyama, Akinobu Taketomi

  The American journal of pathology 188 (1) 204 - 215 0002-9440 2018/01 [Refereed][Not invited]
   

  Ectopic production of free β human chorionic gonadotropin (hCGβ) has been associated with aggressive behavior in non-trophoblastic tumors. hCGβ shares common evolutionary sequences with transforming growth factor-β (TGF-β), which represents a major driving force of epithelial-to-mesenchymal transition (EMT). In this study, we examined the biological roles of hCGβ during EMT and its clinical significance in colorectal cancer (CRC) progression. Eighty CRC specimens and 54 preoperative serum samples were analyzed. hCGβ-overexpressing human CRC cell lines were examined for invasiveness and tumorigenicity, and the expression of EMT-associated genes was investigated. In human CRC, histologic hCGβ positivity [13/80 (16.3%)] was lower than serologic hCGβ positivity [13/54 (24.1%)]. However, it was significantly correlated with several clinicopathological features and unfavorable outcome (P < 0.05). hCGβ-overexpressing cell lines had increased invasiveness, migratory ability, and metastatic potential in mice (P < 0.01). Western blot, PCR, and microarray analyses showed hCGβ altered expression of EMT-related genes, including E-cadherin, phosphorylated SMAD2, SNAIL, and TWIST. hCGβ-induced SNAIL and TWIST overexpression levels were reversible by type I and type II TGF-β receptor inhibitors (P < 0.05). hCGβ thus induces EMT via the TGF-β signaling pathway, and it may represent a molecular target in CRC treatment.
• One-Stage Laparoscopic Surgery for Pulmonary Sequestration and Hiatal Hernia in a 2-Year-Old Girl.

  Hisayuki Miyagi, Shohei Honda, Hiromi Hamada, Masashi Minato, Momoko W Ara, Akinobu Taketomi

  European journal of pediatric surgery reports 6 (1) e11-e14 - e14 2194-7619 2018/01 [Refereed][Not invited]
   

  We herein report a case of one-stage laparoscopic surgery for extralobar pulmonary sequestration (EPS) and hiatal hernia. Our patient was a 2-year-old girl who was diagnosed as a mediastinal mass lesion. Postnatal computed tomography revealed that the mediastinal mass was an EPS. Two weeks after birth, the patient developed gastroesophageal reflux (GER), and esophagography showed a hiatal hernia. At 2 years of age, she underwent one-stage laparoscopic Nissen's fundoplication for GER with resection of the EPS in the posterior mediastinum. The sequestrated lung was grasped via the esophageal hiatus; three aberrant blood vessels were dissected to allow removal of the sequestration through the umbilical port site. The esophageal hiatus was repaired and Nissen's fundoplication was performed laparoscopically. The patient's postoperative course was uneventful, with no recurrence of GER symptoms for 1 year. We conclude that one-stage laparoscopic surgery is useful for patients with EPS and hiatal hernia.
• Spontaneous regression of transverse colon cancer: a case report.

  Chida K, Nakanishi K, Shomura H, Homma S, Hattori A, Kazui K, Taketomi A

  Surgical case reports 3 (1) 65 - 65 2017/12 [Refereed][Not invited]
   

  Spontaneous regression (SR) of many malignant tumors has been well documented, with an approximate incidence of one per 60,000-100,000 cancer patients. However, SR of colorectal cancer (CRC) is very rare, accounting for less than 2% of such cases. We report a case of SR of transverse colon cancer in an 80-year-old man undergoing outpatient follow-up after surgical treatment of early gastric cancer. Colonoscopy (CS) revealed a Borrmann type II tumor in the transverse colon measuring 30 × 30 mm. Because the patient underwent anticoagulant therapy, we did not perform a biopsy at that time. A second CS was performed 1 week after the initial examination and revealed tumor shrinkage to a diameter of 20 mm and a shift to the Borrmann type III morphology. Biopsy revealed a poorly differentiated adenocarcinoma. One week after the second CS, we performed a partial resection of the transverse colon and D2 lymph node dissection. Histopathology revealed inflammatory cell infiltration and fibrosis from the submucosal to muscularis propria layers in the absence of cancer cells, leading to pathological staging of pStage 0 (T0N0). The patient had an uneventful recovery, and CS performed at 5 months postoperatively revealed the absence of a tumor in the colon and rectum. The patient continues to be followed up as an outpatient at 12 months postoperatively, and no recurrence has been observed.
• Anastomotic complications after laparoscopic total gastrectomy with esophagojejunostomy constructed by circular stapler (OrVil((TM))) versus linear stapler (overlap method)

  Hideki Kawamura, Yosuke Ohno, Nobuki Ichikawa, Tadashi Yoshida, Shigenori Homma, Masahiro Takahashi, Akinobu Taketomi

  SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES 31 (12) 5175 - 5182 0930-2794 2017/12 [Refereed][Not invited]
   

  Esophagojejunostomy after laparoscopic total gastrectomy (LTG) is the most technically difficult type of anastomosis; thus, anastomotic complications such as leakage and stenosis sometimes occur. Identification of the safest anastomotic procedure is important for successful LTG. We have performed LTG since 2004 either with a circular stapler using an OrVil((TM)) anvil or via the overlap Orringer method with a linear stapler. This retrospective study aimed to determine which method results in a lower incidence of anastomotic complications in patients undergoing LTG. Data on 188 consecutive patients who underwent LTG between April 2004 and August 2016 were retrospectively reviewed. Patients were divided into those who underwent esophagojejunostomy performed via a circular stapler using an OrVil((TM)) anvil (group C, n = 49) or via the overlap method (group L, n = 139). Anastomotic complications occurred in five of 188 esophagojejunostomies (2.7%). They comprised three cases of leakage (1.6%), and two of stenosis (1.1%). There was no significant difference in patient characteristics or hematological variables between groups C and L. There was no significant difference between groups in operation time, blood loss, lymph node dissection, and intraoperative anastomotic problems. The rate of anastomotic complications was significantly lower in group L (0.7%, 1/139) than in group C (8.2%, 4/49; p = 0.005). In particular, anastomotic leakage in group L tended to be lower (0.7% 1/139) than in group C (4.1% 2/49), although this difference was not significant. The rate of anastomotic stenosis in group L was significantly lower (0%, 0/139) than in group C (4.1%, 2/49; p = 0.017). Furthermore multivariate analysis showed anastomotic procedure was an independent factor for anastomotic complication. There were fewer anastomotic complications after overlap esophagojejunostomy than after esophagojejunostomy via the OrVil((TM)) procedure, especially regarding anastomotic stenosis. We therefore recommend the overlap technique when performing esophagojejunostomy.
• Usefulness of PET/CT for early detection of internal malignancies in patients with Muir-Torre syndrome: report of two cases.

  Yui Ishiguro, Shigenori Homma, Tadashi Yoshida, Yosuke Ohno, Nobuki Ichikawa, Hideki Kawamura, Hiroo Hata, Satoru Kase, Susumu Ishida, Hiromi Okada-Kanno, Kanako C Hatanaka, Akinobu Taketomi

  Surgical case reports 3 (1) 71 - 71 2017/12 [Refereed][Not invited]
   

  BACKGROUND: Muir-Torre syndrome (MTS) is a rare autosomal dominant genodermatosis caused by mutations in mismatch repair genes. It is characterized by the presence of at least one sebaceous skin tumor associated with internal malignancies. Whether positron emission tomography/computed tomography (PET/CT) is useful for the detection of malignancies in patients with MTS has not been determined. We herein report two cases in which PET/CT was useful for the diagnosis and follow-up of internal malignancies in patients with MTS. CASE PRESENTATION: In case 1, a 57-year-old woman underwent excision of a sebaceous carcinoma on the left upper eyelid. She underwent follow-up PET/CT once yearly thereafter. Forty-two months after the eyelid surgery, PET/CT showed intense tracer uptake in the right lower abdomen. An ascending colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. In case 2, a 77-year-old man presented for evaluation of three continuous papules with telangiectasia on his right cheek. Examination of a skin biopsy specimen of the cheek papule revealed a sebaceous carcinoma. He underwent PET/CT to detect other malignancies. PET/CT showed intense tracer uptake in the sigmoid colon. A sigmoid colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. Both patients underwent resection of their tumors, and both were still free of recurrence of the sebaceous and colon carcinomas at the time of this writing. CONCLUSION: PET/CT is a reliable imaging modality for the detection of internal malignancies and is useful for the diagnosis and follow-up of MTS.
• Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial (vol 47, pg 1060, 2017)

  Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa

  SURGERY TODAY 47 (12) 1539 - 1540 0941-1291 2017/12 [Refereed][Not invited]
   

  In the original publication, the article category was published as "Review Article". The correct category should read as "Original Article".
• Serosal Laceration During Firing of Powered Linear Stapler Is a Predictor of Staple Malformation

  Fumihiko Matsuzawa, Shigenori Homma, Tadashi Yoshida, Yuji Konishi, Susumu Shibasaki, Takahisa Ishikawa, Hideki Kawamura, Norihiko Takahashi, Hiroaki Iijima, Akinobu Taketomi

  SURGICAL INNOVATION 24 (6) 590 - 597 1553-3506 2017/12 [Refereed][Not invited]
   

  Background. Although several types of staplers have been developed, staple-line leaks have been a great problem in gastrointestinal surgery. Powered linear staplers were recently developed to further reduce the risk of tissue trauma during laparoscopic surgery. The aim of this study was to identify the factors that predict staple malformation and determine the effect of precompression and slow firing on the staple formation of this novel powered stapling method. Methods. Porcine stomachs were divided using an endoscopic powered linear stapler with gold reloads. We divided the specimens into 9 groups according to the precompression time (0/60/180 seconds) and firing time (0/60/180 seconds). The occurrence and length of laceration and the shape of the staples were evaluated. We examined the factors influencing successful stapling and investigated the key factors for staple malformation. Results. Precompression significantly decreased the occurrence and length of serosal laceration. Precompression and slow firing significantly improved the optimal stapling formation rate. Univariate analysis showed that the precompression time (0 seconds), firing time (0 seconds), and presence of serosal laceration were significantly associated with a low optimal formation rate. Multivariate analysis showed that these three factors were associated independently with low optimal formation rate and that the presence of serosal laceration was the only factor that could be detected during the stapling procedure. Conclusions. We have shown that serosal laceration is a predictor of staple malformation and demonstrated the importance of precompression and slow stapling when using the powered stapling method.
• Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal Surgical Skills in a General Hospital

  Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Yosuke Ohno, Hideki Kawamura, Kazuki Wakizaka, Kazuaki Nakanishi, Keizo Kazui, Hiroaki Iijima, Hiroki Shomura, Tohru Funakoshi, Shiro Nakano, Akinobu Taketomi

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 27 (6) 479 - 484 1530-4515 2017/12 [Refereed][Not invited]
   

  Objective:We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital.Materials and Methods:A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19).Results:Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon.Conclusions:Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.
• Laparoscopic anterior resection for rectal cancer in a patient with a ventriculoperitoneal shunt.

  Ishikawa T, Nishikawa M, Nakamoto H, Yokoyama R, Taketomi A

  Asian journal of endoscopic surgery 11 (3) 259 - 261 1758-5902 2017/12 [Refereed][Not invited]
  
• 先天性胆道拡張症に発生した多発胆道癌に対し、生体肝移植と膵頭十二指腸切除を同時に実施した1例

  腰塚 靖之, 川村 典生, 渡辺 正明, 後藤 了一, 太田 稔, 川久保 和道, 桑谷 将城, 山下 健一郎, 武冨 紹信, 蒲池 浩文, 神山 俊哉, 嶋村 剛

  移植 (一社)日本移植学会 52 (4-5) 454 - 455 0578-7947 2017/11
• Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience

  Toru Ikegami, Yoshihide Ueda, Nobuhisa Akamatsu, Kohei Ishiyama, Ryoichi Goto, Akihiko Soyama, Kaori Kuramitsu, Masaki Honda, Masahiro Shinoda, Tomoharu Yoshizumi, Hideaki Okajima, Yuko Kitagawa, Yukihiro Inomata, Yonson Ku, Susumu Eguchi, Akinobu Taketomi, Hideki Ohdan, Norihiro Kokudo, Mitsuo Shimada, Katsuhiko Yanaga, Hiroyuki Furukawa, Shinji Uemoto, Yoshihiko Maehara

  CLINICAL TRANSPLANTATION 31 (11) 0902-0063 2017/11 [Refereed][Not invited]
   

  The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.
• 胃癌術前診断における経腹超音波検査の有用性

  市川 伸樹, 川村 秀樹, 吉田 雅, 大野 陽介, 本間 重紀, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (Suppl.2) 185 - 185 0386-9768 2017/10
• 腹腔鏡下大腸切除術における腹部手術既往の影響

  吉田 雅, 本間 重紀, 大野 陽介, 市川 伸樹, 川村 秀樹, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (Suppl.2) 352 - 352 0386-9768 2017/10
• NASHによる非代償性肝硬変に対する生体肝移植の成績

  長津 明久, 吉住 朋晴, 下川 雅弘, 坂田 一仁, 川崎 淳司, 吉田 佳弘, 間野 洋平, 本村 貴志, 伊藤 心二, 播本 憲史, 原田 昇, 後町 武志, 池上 徹, 池田 哲夫, 副島 雄二, 武冨 紹信, 前原 喜彦

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (Suppl.2) 513 - 513 0386-9768 2017/10
• 胃癌術前診断における経腹超音波検査の有用性

  市川 伸樹, 川村 秀樹, 吉田 雅, 大野 陽介, 本間 重紀, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (Suppl.2) 185 - 185 0386-9768 2017/10
• Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

  Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Junya Ohtake, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  CANCER SCIENCE 108 (10) 1947 - 1952 1349-7006 2017/10 [Refereed][Not invited]
   

  Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor-infiltrating CD11b(+)CD11c(+) cells isolated from colorectal cancer tissues showed strong induction of the IL-6 gene, downregulated surface expression of human leukocyte antigen (HLA)-DR, and an attenuated T cell-stimulating ability compared with those from peripheral blood mononuclear cells, suggesting that the tumor microenvironment suppresses antitumor effector cells. Invitro experiments revealed that IL-6-mediated STAT3 activation reduced surface expression of HLA-DR on CD14(+) monocyte-derived DC. Moreover, we confirmed that cyclooxygenase 2, lysosome protease and arginase activities were involved in the IL-6-mediated downregulation of the surface expression levels of HLA class II on human DC. These findings suggest that IL-6-mediated STAT3 activation in the tumor microenvironment inhibits functional maturation of DC to activate effector T cells, blocking introduction of antitumor immunity in cancers. Therefore, we propose in this review that blockade of the IL-6/STAT3 signaling pathway and target molecules in DC may be a promising strategy to improve the efficacy of immunotherapies for cancer patients.
• Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy

  Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura

  CANCER SCIENCE 108 (10) 1959 - 1966 1349-7006 2017/10 [Refereed][Not invited]
   

  Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In the present study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells were highly accumulated in tumor sites under the IL-6-deficient condition. In addition, higher numbers of interferon (IFN)--producing T cells were present in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26 cells were enhanced under the IL-6-deficient condition in vivo and by IFN- stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD-L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on these findings, we speculate that a lack of IL-6 produced in tumor-bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL-6 signaling may be a promising target for the development of effective cancer immunotherapies.
• Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy

  Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura

  Cancer Science 108 (10) 1959 - 1966 1349-7006 2017/10/01 [Refereed][Not invited]
   

  Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In the present study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8+ T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells were highly accumulated in tumor sites under the IL-6-deficient condition. In addition, higher numbers of interferon (IFN)-γ-producing T cells were present in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26 cells were enhanced under the IL-6-deficient condition in vivo and by IFN-γ stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD-L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on these findings, we speculate that a lack of IL-6 produced in tumor-bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL-6 signaling may be a promising target for the development of effective cancer immunotherapies.
• Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

  Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Junya Ohtake, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  Cancer Science 108 (10) 1947 - 1952 1349-7006 2017/10/01 [Refereed][Not invited]
   

  Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor-infiltrating CD11b+CD11c+ cells isolated from colorectal cancer tissues showed strong induction of the IL-6 gene, downregulated surface expression of human leukocyte antigen (HLA)-DR, and an attenuated T cell-stimulating ability compared with those from peripheral blood mononuclear cells, suggesting that the tumor microenvironment suppresses antitumor effector cells. In vitro experiments revealed that IL-6-mediated STAT3 activation reduced surface expression of HLA-DR on CD14+ monocyte-derived DC. Moreover, we confirmed that cyclooxygenase 2, lysosome protease and arginase activities were involved in the IL-6-mediated downregulation of the surface expression levels of HLA class II on human DC. These findings suggest that IL-6-mediated STAT3 activation in the tumor microenvironment inhibits functional maturation of DC to activate effector T cells, blocking introduction of antitumor immunity in cancers. Therefore, we propose in this review that blockade of the IL-6/STAT3 signaling pathway and target molecules in DC may be a promising strategy to improve the efficacy of immunotherapies for cancer patients.
• Mesothelin-Specific Immune Responses and Targeted Immunotherapy for Mesothelin-Expressing Tumors

  Takahiro Einama, Futoshi Kawamata, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Fumihiko Matsuzawa, Tatsuzo Mizukami, Yuji Konishi, Toshiya Kamiyama, Junji Yamamoto, Akinobu Taketomi, Satoru Todo

  EBIOMEDICINE 24 16 - 17 2352-3964 2017/10 [Refereed][Not invited]
  
• Salvage Hepatectomy for recurrent hepatocellular carcinoma after radiofrequency ablation and/or transcatheter arterial chemoembolization: a propensity score-mmatched analysis

  Orimo T, Kamiyama T, Yokoo H, Wakayama K, Shimada S, Einama T, Kamachi H, Taketomi A

  Digestive Surgery 2017/09 [Refereed][Not invited]
  
• Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial

  Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa

  SURGERY TODAY 47 (9) 1060 - 1071 0941-1291 2017/09 [Refereed][Not invited]
   

  Background The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. Methods At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. Results The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. Conclusion The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.
• Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma

  Hirotaka Shoji, Sachiyo Yoshio, Yohei Mano, Hiroyoshi Doi, Masaya Sugiyama, Yosuke Osawa, Kiminori Kimura, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Yoshihiko Aoki, Moto Fukai, Akinobu Taketomi, Masashi Mizokami, Tatsuya Kanto

  INTERNATIONAL JOURNAL OF CANCER 141 (5) 1011 - 1017 0020-7136 2017/09 [Refereed][Not invited]
   

  Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). Delta TEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the Delta TEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that Delta TEMs [hazard ratio (HR) = 8.53, 95% confidence interval (CI) = 1.51-48.16, p=0.015] and Child-Pugh class (HR=5.59, 95% CI=1.06-29.63, p=0.043) were independently associated with overall survival. Our results suggest that Delta TEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC.
• Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation and/or Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

  Orimo T, Kamiyama T, Yokoo H, Wakayama K, Shimada S, Einama T, Kamachi H, Taketomi A

  Digestive surgery 35 (5) 427 - 434 0253-4886 2017/09 [Refereed][Not invited]
   

  AIM: We aimed to evaluate the short- and long-term surgical outcomes of salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and/or transcatheter arterial chemoembolization (TACE). METHODS: We reviewed the surgical outcomes of 90 recurrent HCC patients after RFA and/or TACE (salvage group) and 490 HCC patients without preoperative treatment (primary group). We performed 1:1 propensity score matching (PSM) between the 2 groups and matched 87 patients in each group. RESULTS: Before PSM, the salvage group was pathologically more advanced than the primary group. After PSM, there were no significant differences in the clinicopathological features between the groups. The outcomes of propensity score-matched groups were compared and there was no statistically significant difference between the 2 groups regarding perioperative outcomes and survival. Univariate and multivariate analyses of propensity score-matched HCC patients revealed that stage, tumor size, differentiation, and portal vein invasion were independent prognostic factors for survival. Preoperative RFA and/or TACE was not a prognostic factor in a propensity score-matched cohort. CONCLUSIONS: The short- and long-term surgical outcomes of the primary and salvage groups were similar under the matched clinicopathological background. Salvage hepatectomy might be an acceptable treatment for recurrent HCC patients after RFA and/or TACE.
• Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience

  Yoshihide Ueda, Toru Ikegami, Nobuhisa Akamatsu, Akihiko Soyama, Masahiro Shinoda, Ryoichi Goto, Hideaki Okajima, Tomoharu Yoshizumi, Akinobu Taketomi, Yuko Kitagawa, Susumu Eguchi, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara

  JOURNAL OF GASTROENTEROLOGY 52 (8) 986 - 991 0944-1174 2017/08 [Refereed][Not invited]
   

  The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation. A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan. Fifty-four patients were treated with sofosbuvir and ledipasvir. Thirty-eight patients (70%) were treatment experienced, including 17 patients who had undergone prior direct-acting-antiviral-based triple therapy. Ten patients had resistance-associated substitutions at L31 or Y93 in the NS5A region of the HCV genome. Fifty-three patients completed the 12-week treatment protocol; treatment was discontinued in one patient who developed pneumonia at 4 weeks and died thereafter. All 53 patients who completed the treatment regimen achieved a sustained virological response 12 weeks after completion of treatment. Treatment was well tolerated in most patients, but seven patients developed serious adverse events, including hemorrhagic duodenal ulcers (n = 3), infection (n = 2), pleural effusion (n = 1), and alveolar hemorrhage (n = 1). Sofosbuvir and ledipasvir treatment without ribavirin for 12 weeks was highly effective in achieving a sustained virological response in Japanese patients who developed recurrent HCV genotype 1b infection after living donor liver transplantation.
• Clinicopathological Characteristics of Hepatocellular Carcinoma with Microscopic Portal Venous Invasion and the Role of Anatomical Liver Resection in These Cases

  Shingo Shimada, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Kenji Wakayama, Takahiro Einama, Tatsuhiko Kakisaka, Hirofumi Kamachi, Akinobu Taketomi

  WORLD JOURNAL OF SURGERY 41 (8) 2087 - 2094 0364-2313 2017/08 [Refereed][Not invited]
   

  Background The aims of this study were to investigate predictive factors for microscopic portal venous invasion (mPVI) in hepatocellular carcinoma (HCC) and whether anatomical liver resection (ALR) was useful in such cases. Methods We analyzed 852 patients with HCC without macroscopic portal venous invasion who were treated at our hospital between January 1990 and May 2014. These patients were stratified into a microscopic portal venous invasion group (mPVI group; n = 153) and non-microscopic portal venous invasion group (NmPVI group; n = 699). Results PIVKA-II >= 100 mAU/ml, a tumor size >= 5 cm, a confluent lesion, and poor differentiation were found to be independent risk factors for mPVI. Among the mPVI group who had single HCC under 5 cm, serum albumin level <4.0 g/dl, PIVKA-II >= 100 mAU/ml, a positive surgical margin, and non-ALR (NALR) were independent unfavorable prognostic factors for overall survival (OS). PIVKA-II >= 100 mAU/ml, a positive surgical margin and NALR were independent unfavorable prognostic factors for relapse-free survival (RFS). ALR was significantly favorable factor for both OS and RFS of the mPVI group who had single HCC under 5 cm. Conclusions Even if no portal venous invasion is detectable in HCC patients preoperatively, a PIVKA-II >= 100 mAU/ml, tumor size >= 5 cm, and a confluent lesion indicate a high risk of mPVI. ALR should be considered for the patients with these characteristics because it is a favorable prognostic factor in these cases with mPVI.
• Two cases of melanomas paradoxically metastasizing to the intestinal tract during nivolumab therapy

  Hajime Miyazawa, Teruki Yanagi, Yasuyuki Yamaguchi, Keisuke Imafuku, Shinya Kitamura, Hiroo Hata, Jiro Uehara, Nobuki Ichikawa, Yosuke Ohno, Tadashi Yoshida, Shigenori Homma, Hideki Kawamura, Akinobu Taketomi, Hiroshi Shimizu

  JOURNAL OF DERMATOLOGY 44 (8) 959 - 962 0385-2407 2017/08 [Refereed][Not invited]
   

  We report two cases of melanomas in patients who developed intestinal metastasis despite other metastatic sites responding to nivolumab and despite the patients having favorable findings such as vitiligo and normal lactate dehydrogenase. The first case is an 85-year-old man who had been administrated nivolumab for lung/cutaneous metastases. After 22 courses of nivolumab therapy, fever and anorexia had appeared and his bodyweight had decreased. An intussusception on the ileocecal valve was revealed by computed tomography, and emergency surgery revealed metastatic lesions on the colon. The second case is an 87-year-old woman treated with nivolumab for lymph node metastases. After 10 courses, laboratory tests had revealed anemia and positive fecal occult blood. Her bodyweight had decreased. Capsule endoscopy showed scattered tumors and clots, indicating metastases of melanoma. The frequency of symptomatic intestinal metastasis of melanoma is very low. Further, intestinal metastasis of melanoma is difficult to detect through routine examinations. Our cases suggest that fecal occult blood test and decreased bodyweight are indications of intestinal metastases.
• DaMab-2: Anti-Human DGKα Monoclonal Antibody for Immunocytochemistry

  Tomoyuki Nakano, Satoshi Ogasawara, Toshiaki Tanaka, Yasukazu Hozumi, Satoru Mizuno, Eri Satoh, Fumio Sakane, Naoki Okada, Akinobu Taketomi, Ryusuke Honma, Takuro Nakamura, Noriko Saidoh, Miyuki Yanaka, Shunsuke Itai, Saori Handa, Yao-Wen Chang, Shinji Yamada, Mika K. Kaneko, Yukinari Kato, Kaoru Goto

  Monoclonal Antibodies in Immunodiagnosis and Immunotherapy 36 (4) 181 - 184 2167-9436 2017/08/01 [Refereed][Not invited]
   

  Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic acid serve as signaling molecules, DGK is regarded as a hub between diacylglycerol-mediated and phosphatidic acid-mediated signaling. One of the 10 DGK isozymes, DGKα, is shown to be involved in T cell function. Transfection studies using tagged expression vectors revealed that DGKα localizes to the cytoplasm and nucleus and translocates to the plasma membrane in response to T cell receptor stimulation. However, a limited number of studies reported the localization of native protein of DGKα in tissues and cells. In this study, we immunized mice with recombinant DGKα and developed several anti-DGKα monoclonal antibodies (mAbs). One of the established anti-DGKα mAbs is a clone DaMab-2 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, DaMab-2 recognized only DGKα, and did not react with the other isozymes, such as DGKγ, DGKζ, DGKη, and DGKδ. Importantly, DaMab-2 is very useful in immunocytochemical analysis of human cultured cells, indicating that DaMab-2 is advantageous to analyze the localization and function of DGKα.
• The Balance Between Surgical Resident Education and Patient Safety in Laparoscopic Colorectal Surgery: Surgical Resident's Performance has No Negative Impact

  Shigenori Homma, Futoshi Kawamata, Tadashi Yoshida, Yosuke Ohno, Nobuki Ichikawa, Susumu Shibasaki, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 27 (4) 295 - 300 1530-4515 2017/08 [Refereed][Not invited]
   

  Objective: This study aimed to evaluate the feasibility and effectiveness of a comprehensive theoretical and hands-on training program in performing laparoscopic colonic resections under supervision of an expert surgeon. Materials and Methods: Laparoscopic right colectomy was performed in 78 patients (10 with benign disease, 68 with carcinoma). Demographic, intraoperative, pathologic examination, and short-term outcome data were retrospectively compared between 25 patients operated by surgical residents (R group) and 53 patients operated by senior surgeons (S group). The residents who performed surgeries in the R group had between 1 and 6 years after graduation; no experience with open or laparoscopic colorectal surgery was necessary. The residents completed a training program under supervision of a single expert laparoscopic colorectal surgeon, which included 6 steps, from basic skills to certification. Results: There were no differences in patient age, sex, and body mass index between the R and S groups. Significantly more patients in the R group had early cancer and benign lesions (P < 0.05). Thirteen of the 16 residents (81.2 %) had not had prior experience with colonic resection. The time of suturing and knot tying in the dry box did not differ between residents and senior surgeons (68 and 69 s, respectively). All the residents performed laparoscopic right colectomy without intraoperative complications. There were no significant differences in operating time (R group: 173 +/- 34 min, S group: 172 +/- 52 min), mean estimated blood loss (50 +/- 111 vs. 49 +/- 100 mL), number of lymph nodes dissected (20.8 +/- 12.8 vs. 17.1 +/- 9.0), and mean postoperative hospital stay (9.1 +/- 3.3 vs. 10.7 +/- 4.1 d). On the basis of the year of their residency period, all 3 residents at 6 years after graduation had far greater experience than the other residents and therefore performed the surgery with minor verbal support from the expert. However, residents with 1 or 2 years after graduation had to receive guidance provision by the expert during surgery. Conclusions: When supervised and led by an expert laparoscopic surgeon, surgical residents are capable of performing laparoscopic surgery without negative effects on outcomes.
• Survival outcomes of hepatectomy for stage B Hepatocellular carcinoma in the BCLC classification

  Toshiya Kamiyama, Tatsuya Orimo, Kenji Wakayama, Shingo Shimada, Akihisa Nagatsu, Hideki Yokoo, Hirofumi Kamachi, Kenichiro Yamashita, Tsuyoshi Shimamura, Akinobu Taketomi

  WORLD JOURNAL OF SURGICAL ONCOLOGY 15 (1) 156  1477-7819 2017/08 [Refereed][Not invited]
   

  Background: Because hepatectomy is not recommended in patients with stage B hepatocellular carcinoma (HCC) of the Barcelona Clinic Liver Cancer (BCLC) staging, we evaluated the survival outcomes of hepatectomy for stage B in the BCLC system. Methods: Data were collected from 297 consecutive adult stage B patients who underwent curative hepatectomy for HCC between 1996 and 2014 in Hokkaido University Hospital. Overall survival (OS), disease-free survival (DFS), and risk factors were analyzed using the Kaplan-Meier method. Independent prognostic factors were evaluated using a Cox proportional hazards regression model. AP-factor (alpha-fetoprotein [AFP] x protein induced by vitamin K absence or antagonism factor II [PIVKA-II]) was categorized according to the serum concentrations of AFP and PIVKA-II: AP1 (AFP < 200 ng/ml and PIVKA-II < 100 mAU/ml), AP2 (AFP x PIVKA-II < 10(5)), and AP3 (AFP x PIVKA-II >= 10(5)). Results: There were 130 deaths among our 297 stage B patients (43.8%). The causes of death in these cases were HCC recurrence (n = 106; 81.5%), liver failure (n = 7; 5.4%), and other causes (n = 17; 16.1%). The operative mortality rate was 0.34% (1/297). The 5-year OS and DFS rates for the stage B cases were 54.3 and 21.9%, respectively. By multivariate analysis, tumor number and AP-factor were risk factors for both survival and recurrence that were tumor related and could be evaluated preoperatively. The study patients with stage B HCC were classified into three groups by tumor number (B1, 1; B23, 2 or 3; B4over: >= 4) and into three groups stratified by AP-factor (AP1, AP2, and AP3). The 5-year OS rates of B1, B23, and B4over were 63.6, 52.3, and 29.0%. The 5-year OS rates of AP1, AP2, and AP3 were 67.6, 65.2, and 39.1%. Stratified by the 5-year OS rate, stage B HCC patients were classified into three subgroups (A-C). The 5-year OS rates of groups A (B1 or B23 and AP-1 or AP-2), B (B1 or B23 and AP-3, or B4over and AP-1 or AP-2), and C (B4over and AP-3) were 69.5, 43.7, and 21.3%. Conclusion: Stage B HCC patients with a tumor number <= 3 and/or AP-factor < 1 x 10(5) show acceptable 5-year OS rates and could be treated by hepatectomy.
• Petersen's hernia after living donor liver transplantation.

  Sakamoto S, Goto R, Kawamura N, Koshizuka Y, Watanabe M, Ota M, Suzuki T, Abo D, Yamashita K, Kamiyama T, Taketomi A, Shimamura T

  Surgical case reports 3 (1) 89 - 89 2017/08 [Refereed][Not invited]
   

  BACKGROUND: Hepaticojejunostomy may be used for biliary reconstruction in certain cases of liver transplantation. In this occasion, Roux-en-Y biliary reconstruction is predominantly performed. Petersen's hernia is an internal hernia that can occur after Roux-en-Y reconstruction, and it may lead to extensive ischemic changes affecting incarcerated portions of the small bowel or Roux limb resulting in severe complications with a poor prognosis. CASE PRESENTATION: The present case was a 44-year-old male who underwent living donor liver transplantation (LDLT) for familial amyloid polyneuropathy and in whom biliary reconstruction was performed with Roux-en-Y hepaticojejunostomy. Two years after liver transplantation, symptomatic bowel strangulation was diagnosed by CT examination and emergent surgery was performed accordingly. On exploration, an ischemic limb associated with Petersen's hernia was observed. Although repositioning of the incarcerated bowel loop gradually improved the color of the limb, the limb failed to completely recover to a normal color. To allow accurate evaluation for the viability of the limb, we decided to perform a second-look operation after 48 h. On re-exploration, the surface of the limb remained a dark color; however, intraoperative endoscopic findings revealed only partial necrosis of the mucosa. Next, we resected the portion of ischemic damaged limb only following side-to-side jejunojejunostomy. Consequently, redoing of biliary reconstruction could be avoided and the original hepaticojejunostomy site was preserved. Although the stricture of the remnant Roux limb occurred 1 month thereafter, it was successfully managed by balloon dilation via percutaneous transhepatic biliary drainage route. CONCLUSIONS: The occurrence of Petersen's hernia should always be considered in cases of liver transplantation with Roux-en-Y biliary reconstruction. On the basis of an accurate assessment of the extent of jejunal limb injury, reanastomosis of the hepaticojejunostomy, a potentially high-risk surgical procedure, can be avoided in emergent situations.
• 肝細胞癌切除後再発におけるソラフェニブ治療の有効性

  横尾 英樹, 神山 俊哉, 折茂 達也, 若山 顕治, 永生 高広, 島田 慎吾, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 72回 PL15 - 3 2017/07
• 自然退縮を来した肝静脈腫瘍栓を伴う肝細胞癌の1例

  村田 竜平, 神山 俊哉, 菅野 宏美, 横尾 英樹, 折茂 達也, 若山 顕治, 島田 慎吾, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (7) 535 - 543 0386-9768 2017/07 [Not refereed][Not invited]
   

  症例は67歳の男性で,慢性B型肝炎,アルコール性肝障害にて近医通院中,血液検査にてAFP 9,133ng/mlと高値であり,腹部超音波検査とCTから肝S1/8の48mm大の肝細胞癌と診断され,当科紹介となった.診断より2ヵ月後の入院時のCTでは腫瘍は造影効果に乏しく,中肝静脈腫瘍栓を伴っており,AFPは54.7ng/mlと著明に低下していた.低分化型肝細胞癌の診断にて尾状葉・中肝静脈合併左肝切除を施行した.切除標本の病理組織学的検査所見では,病変および肝静脈腫瘍栓は線維芽細胞の増生や組織球・リンパ球を主体とする炎症性細胞の浸潤を認める壊死組織であり,viableな癌細胞は認めず,肝細胞癌が自然消退したものと考えられた.肝細胞癌の完全自然退縮は極めてまれであり,腫瘍が残存していることが多いため,壊死を疑う症例でも外科的治療介入を考慮するべきである.(著者抄録)
• Hepatectomy for liver metastasis from gastrointestinal stromal tumor in the era of imatinib mesylate: a case series study.

  Kawamura N, Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Wakayama K, Tsuruga Y, Kamachi H, Hatanaka K, Taketomi A

  International cancer conference journal 6 (3) 121 - 125 2017/07 [Refereed][Not invited]
   

  The prognosis of metastatic gastrointestinal stromal tumor (GIST) has improved since the introduction of imatinib mesylate; however, acquired resistance has been reported, so alternative treatment option is needed. We evaluated the efficacy of hepatectomy for metastatic GIST. Six patients with liver metastases from GIST underwent hepatectomy. Four were treated with imatinib mesylate before hepatectomy, and all the patients were treated with imatinib mesylate after hepatectomy. Patients were followed-up for a mean duration of 113.5 months after hepatectomy. Complete resection was accomplished in four patients, with incomplete resection performed in the remaining two patients due to peritoneal dissemination. One patient with incomplete resection died 10 months after surgery. One patient with complete resection has survived without disease progression since initial hepatectomy. The remaining four patients with progressive disease during imatinib mesylate treatment developed tumor recurrence and three of them underwent a second hepatectomy. These three patients underwent complete resection during repeat surgery. In total, three patients died during the follow-up period, all of whom had tumors of small intestine origin. Primary tumor site (small intestine vs. others) was identified as a risk factor of mortality (P = 0.02). Although not statistically significant, there was a trend toward better outcomes in patients with exon 11 mutations. Surgical resection for metastatic GIST was shown to be effective and needed to achieve a better prognosis. Repeat hepatectomy demonstrated efficacy in selected patients. Hepatectomy should be considered based on tumor characteristics such as primary tumor site and c-KIT mutation status.
• In, Situ Posterior Graft Segmentectomy for Large-for-Size Syndrome in Deceased Donor Liver Transplantation in Adults: A Case Report

  A. Nagatsu, T. Yoshizumi, T. I. Kegami, N. Harimoto, N. Harada, Y. Soejima, A. Taketomi, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 49 (5) 1199 - 1201 0041-1345 2017/06 [Refereed][Not invited]
   

  Large-for-size syndrome (LFSS) is controversial in pediatric living donor liver transplantation patients and is associated with a poor graft outcome. Similar situations in deceased donor liver transplantation (DDLT) in adults have not been reported frequently, and there are no official guidelines worldwide. Deceased donation is extremely limited in Japan, and when a larger liver is allocated for a very sick small recipient in Japan, transplantation with a plan to address LFSS might be necessary. The patient is a 58-year-old female patient who had acute liver failure with coma. The graft-recipient weight ratio (GRWR) was 2.74%. Although the graft was enlarged by reperfusion, the intraoperative Doppler ultrasound, performed after reperfusion, showed sufficient graft in-flow and outflow. However, when the liver graft was situated appropriately into the right phrenic space supported by the rib cage and diaphragm, the blood flow in the hepatic vein and portal vein was significantly reduced. Graft blood flow did not improve without removing it from the right subphrenic space. Therefore, we decided to perform an in situ graft posterior segmentectomy, so that the graft right lobe was properly accommodated in the patient's right subphrenic space. After the segmentectomy of the graft, an intraoperative Doppler sonogram showed significantly improved blood flow. LFSS could be a significant operative challenge in adult DDLT, especially in areas with limited chances of DDLT. In situ posterior segmentectomy in the demarcated area could be a solution for treating patients with LFSS.
• Combination of neutrophil-to-lymphocyte ratio and early des--carboxyprothrombin change ratio as a useful predictor of treatment response for hepatic arterial infusion chemotherapy against advanced hepatocellular carcinoma

  Seiji Tsunematsu, Goki Suda, Kazushi Yamasaki, Megumi Kimura, Izumi Takaaki, Machiko Umemura, Jun Ito, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto

  HEPATOLOGY RESEARCH 47 (6) 533 - 541 1386-6346 2017/05 [Refereed][Not invited]
   

  AimHepatic arterial infusion chemotherapy (HAIC) is a potent therapeutic option for advanced hepatocellular carcinoma (HCC). However, there are few known predictive factors of treatment response to HAIC. We clarified the most accurate predictive factors early on in treatment.MethodsStudy subjects were 70 patients with advanced HCC who had been treated with HAIC. We assessed the relationships between patient characteristics, change ratios of early tumor markers, tumor response, progression-free survival (PFS), and overall survival.ResultsAfter two courses of HAIC, 1 (1.4%), 16 (22.9%), 30 (42.8%), and 23 (32.9%) of the 70 patients showed complete response, partial response, stable disease, and progressive disease, respectively. Overall survival was related to Child-Turcotte-Pugh score, extrahepatic metastasis, and the des--carboxyprothrombin (DCP) response. Univariate and multivariate analyses identified the neutrophil-to-lymphocyte ratio (NLR) and DCP response as significant determinants of treatment response and PFS. Progression-free survival with a low NLR (<2.87) was significantly longer than with a high NLR (median, 8.4months vs. 2.8months, respectively). Progression-free survival was 7.2months for patients with a responsive DCP (<0.7) and 2.3months for an unresponsive DCP (0.7). Additionally, even with baseline high NLR, patients with responsive DCP achieved better PFS.ConclusionBaseline NLR and early DCP response were significant predictors of treatment response and PFS after HAIC for patients with advanced HCC. The combination of baseline NLR and early DCP response could be accurate and useful predictive factors of response to HAIC and could help optimize treatments for patients with advanced HCC.
• Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition

  Takanori Ohata, Hideki Yokoo, Toshiya Kamiyama, Moto Fukai, Takeshi Aiyama, Yutaka Hatanaka, Kanako Hatanaka, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Nozomi Kobayashi, Yoshihiro Matsuno, Akinobu Taketomi

  CANCER MEDICINE 6 (5) 1049 - 1061 2045-7634 2017/05 [Refereed][Not invited]
   

  Hepatocellular carcinoma (HCC) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid-binding protein 5 (FABP5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP5 expression and HCC malignant behavior remains unknown. We compared FABP5 expression and patient characteristics in paired HCC and adjacent noncancerous liver tissues from 243 patients who underwent surgical resection of primary HCC. Cell proliferation, invasion, and migration assays were performed in HCC cell lines overexpressing FABP5 or downregulated for FABP5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP5-positive staining (n = 139/243, 57.2%) was associated with poor prognosis and recurrence (P < 0.0001) and showed positive correlation with distant metastasis, tumor size and vascular invasion (P < 0.05). Cell proliferation, invasion, and migration in vitro were enhanced by upregulation of FABP5 and decreased by downregulation of FABP5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI1 in FABP5-overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E-cadherin and ZO-1 and decreased SNAI1 expression and nuclear translocation of beta-catenin by knockdown of FABP5. We revealed a significant role for FABP5 in HCC progression and metastasis through the induction of epithelial-to-mesenchymal transition. FABP5 may be a potential novel prognostic biomarker and new therapeutic target for HCC.
• Laparoscopic Cholecystectomy in a Child Using Slender Forceps.

  Shibuya K, Kawamura H, Tahara M, Takahashi M, Taketomi A

  APSP journal of case reports 8 (3) 18  2017/05 [Refereed][Not invited]
  
• 腹腔鏡下大腸切除術における腹部手術既往の影響

  吉田 雅, 本間 重紀, 大野 陽介, 市川 伸樹, 川村 秀樹, 武冨 紹信

  日本外科学会定期学術集会抄録集 (一社)日本外科学会 117回 SF - 2 2017/04
• 常染色体劣性多発性嚢胞腎に伴う肝線維症に対し脳死肝移植を施行した1例

  大平 将史, 後藤 了一, 腰塚 靖之, 神山 俊哉, 山下 健一郎, 武冨 紹信, 鈴木 友己, 嶋村 剛

  移植 (一社)日本移植学会 52 (1) 60 - 66 0578-7947 2017/04 [Not refereed][Not invited]
   

  症例は20歳男性で、生後4ヵ月時に腹部膨満を認め、腹部CT検査、腹部超音波検査にて両側腎臓と肝臓に多発する嚢胞を指摘された。3歳時に腎機能障害が出現し、臨床経過から常染色体劣性多発嚢胞腎(ARPKD)が疑われた。16歳時に肝腫大と肝内胆管拡張を認め、肝生検で肝線維化を認めた。臨床的にARPKDの診断基準を満たし、ARPKDに伴う先天性肝線維症と診断された。18歳時に食道静脈瘤を指摘され、内視鏡的静脈瘤結紮術を施行した。19歳時に脳死肝移植登録となった。医学的緊急度8点へ登録修正後138日目に脳死ドナーが発生し、肝移植目的で入院となった。術後は挿管状態のままICUに入室した。術後10日目に抜管し、術後12日目には一般病棟に帰室した。術後77日目に退院となった。周術期ならびに退院後2年迄は血液透析を導入することなく経過したが、次第に腎機能が悪化し、術後2年10ヵ月で血液透析導入となった。
• 家族性大腸腺腫症術後30年で発生した結腸人工肛門部癌の1例

  矢部 沙織, 本間 重紀, 吉田 雅, 下國 達志, 崎浜 秀康, 川村 秀樹, 三橋 智子, 岡田 宏美, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (4) 317 - 325 0386-9768 2017/04 [Not refereed][Not invited]
   

  症例は60歳の男性で,30年前に他院にて,家族性大腸腺腫症(familial adenomatous polyposis;以下,FAPと略記)に対し大腸亜全摘術,人工肛門造設術を施行され,通院は自己中断していた.2013年,人工肛門の変形・疼痛を主訴に当科を初診した.人工肛門粘膜面の不整,内腔の狭小化を認めた.下部消化管内視鏡検査では,人工肛門表面から口側5cmにわたりポリープが多発し,生検の結果は腺癌であった.人工肛門部癌の診断で,人工肛門を含めた腸管切除および回腸人工肛門造設術を施行した.術中,回盲弁と盲腸が残存しており,腫瘍は残存盲腸に発生したことが判明した.病理診断はpT2N1M0 Stage IIIaであった.術後補助化学療法としてCapeOXを6ヵ月間施行し,術後24ヵ月無再発生存中である.FAPは大腸癌発症率が高く大腸全摘が治療の基本であるが,本症例のように残存腸管のサーベイランスが不十分であった例や回腸人工肛門部癌の報告例もあり,長期的かつ定期的な観察が重要である.(著者抄録)
• Factors Associated with the Risk of Persistent Gastrostomy Site Infection Following Laparoscopic or Open Nissen Fundoplication

  Hisayuki Miyagi, Shohei Honda, Masahi Minato, Tadao Okada, Akinobu Taketomi

  African Journal of Paediatric Surgery 14 (2) 21 - 23 0974-5998 2017/04/01 [Refereed][Not invited]
   

  Background: Gastrostomy for feeding disorders or swallowing dysfunctions can be complicated by persistent gastrostomy site infection (PGSI). PGSI causes nutrient leakage, with dilated PGSI requiring gastrostomy reconstruction. The purpose of this study was to evaluate the causes, patient characteristics, and perioperative management of PGSI after Nissen fundoplication and gastrostomy for patients with gastro-oesophageal reflux. Patients and Methods: The records of all patients who underwent Nissen fundoplication and gastrostomy for gastro-oesophageal reflux over the past 12 years were retrieved. Risk factors were analysed, including age at surgery, gender, operative procedure, use of postoperative ventilator management, gastrostomy tube migration towards the pylorus, bacterial culture results, and length of hospital stay. PGSI as a cause of inflammation was analysed statistically. Results: Forty patients were identified, ranging in age from 1 to 49 years (median, 11 years) surgically. Twenty each underwent laparoscopic and open surgery, with all undergoing gastrostomy using the Stamm technique. Four patients developed PGSI. Gastrostomy tubes had migrated postoperatively to the pyloric side in three of these four patients (P < 0.005), increasing intragastric pressure. Three of these four patients also required positive pressure ventilation during the perioperative period (P < 0.001). Conclusion: PGSI correlates with the perioperative management of positive pressure and with increased intragastric pressure resulting from pyloric obstruction, which is caused by aberrant distribution of the gastrostomy tube to the pyloric side. Statistical Analysis Used: Factors in the two groups were compared statistically by Mann-Whitney U-test to determine whether PGSI caused inflammation. Statistical significance was defined as P < 0.05.
• Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition

  Ohata T, Yokoo H, Kamiyama T, Fukai M, Aiyama T, Hatanaka Y, Hatanaka K, Wakayama K, Orimo T, Kakisaka T, Kobayashi N, Matsuno Y, Taketomi A

  Cancer Medicine 2017/04 [Refereed][Not invited]
  
• Anal canal duplication presenting with abscess formation

  Shohei Honda, Masashi Minato, Hisayuki Miyagi, Hiromi Okada, Akinobu Taketomi

  PEDIATRICS INTERNATIONAL 59 (4) 500 - 501 1328-8067 2017/04 [Refereed][Not invited]
  
• Huge Hepatocellular Carcinoma Greater Than 10 cm in Diameter Worsens Prognosis by Causing Distant Recurrence After Curative Resection

  Kenji Wakayama, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Shingo Shimada, Takahiro Einama, Hirofumi Kamachi, Akinobu Taketomi

  JOURNAL OF SURGICAL ONCOLOGY 115 (3) 324 - 329 0022-4790 2017/03 [Refereed][Not invited]
   

  Background and Objectives: This study aimed to evaluate the impact of huge (>= 10 cm) hepatocellular carcinoma (HCC) to the recurrence pattern and the prognosis after hepatectomy. Methods: 574 patients who underwent hepatectomy by 17 surgeons (Open 536 and Laparoscopic 38) for HCC without major vascular invasion from 1990 to 2013 at single institute were retrospectively analyzed. Results: Huge tumor, age, HCV, multiple tumors and microscopic portal invasion are independent risk factors for overall survival (OS), and huge tumor, ICGR15 >= 16%, multiple tumors, moderate/poor histology, microscopic portal invasion and a positive pathological margin are risk factors for relapse-free survival (RFS). The 5-year OS and RFS of patients with huge HCC (n = 53) (42.9 and 14.2%) were significantly worse than those of patients with HCC <10 cm (n = 521) (71.3 and 33.1%). Huge tumor is an independent risk factor for initial extra-hepatic recurrence (Hazard ratio 7.86, P< 0.0001). The 5-year OS of patients with initial extra-hepatic recurrence (n = 55) was significantly worse than patients with intra-hepatic recurrence (n = 338) (16.8 vs. 50.5%). Conclusions: Huge HCC (>= 10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. (C) 2016 Wiley Periodicals, Inc.
• National Clinical Database(消化器外科領域) Annual Report 2015

  掛地 吉弘, 宇田川 晴司, 海野 倫明, 遠藤 格, 國崎 主税, 武冨 紹信, 丹黒 章, 正木 忠彦, 丸橋 繁, 吉田 和弘, 渡邉 聡明, 後藤 満一, 今野 弘之, 高橋 新, 宮田 裕章, 瀬戸 泰之, 一般社団法人National, Clinical Database

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 50 (2) 166 - 176 0386-9768 2017/02 [Not refereed][Not invited]
   

  一般社団法人National Clinical Database(NCD)のデータベース事業であり、2014年に施行・登録された消化器外科手術情報を追加し作成されたAnnual Report 2015について報告した。115の消化器外科専門医術式、および医療水準評価術式として定めた8術式の、2011年〜2014年までのデータを対象に経年的変化を検討した。消化器外科専門医115術式に関しては、NCDに登録された総数は2056325例で、臓器別では小腸・結腸(36.1%)が最も多かった。男女比は全体で約6:4で、全体の16.0%が80歳以上であった。手術は全体の約7割が認定施設で行われ、麻酔科医関与の比率は91.2%であった。次いで、主たる8術式に関しては、2014年の症例数での検討で、男女比は全ての術式で男性が多く、結腸右半切除術、急性汎発性腹膜炎手術で80歳以上の比率が高かった。概ね7割以上が認定施設で行われ、麻酔科医関与の比率は全ての術式で90%以上であった。
• Postoperative analgesia using fentanyl plus celecoxib versus epidural anesthesia after laparoscopic colon resection

  Tadashi Yoshida, Shigenori Homma, Susumu Shibasaki, Tatsushi Shimokuni, Hideyasu Sakihama, Norihiko Takahashi, Hideki Kawamura, Akinobu Taketomi

  SURGERY TODAY 47 (2) 174 - 181 0941-1291 2017/02 [Refereed][Not invited]
   

  Effective postoperative analgesia is essential to a patient's recovery after laparoscopic colon resection (LCR). We introduce a new analgesic protocol using fentanyl plus celecoxib following LCR. The subjects of this retrospective comparative study were 137 patients who underwent LCR, 63 of whom were treated with 72 h of epidural anesthesia (group E), and 74 of whom were treated with 24 h of fentanyl intravenous injection followed by 7 days of oral celecoxib (group FC). We evaluated the safety and efficacy of this new protocol. The combination of fentanyl and celecoxib maintained a low postoperative pain score (< 1.5, evaluated by the FACES Pain Scale) and reduced the need for rescue analgesic drugs for 7 days (groups E vs. FC: 5.39 +/- 3.77 vs. 2.79 +/- 2.92, p < 0.001). The postoperative hospital stay was almost equal for the two groups (E vs. FC: 11.1 +/- 4.5 vs. 10.3 +/- 4.8 days, p = 0.315). The operating room stay other than for surgery was significantly shorter for group FC (E vs. FC: 128.7 +/- 30.5 vs. 107.2 +/- 17.0 min, p < 0.001). Neither group experienced complications, apart from one group FC patient, who suffered transient nausea and vertigo. The new analgesic protocol using fentanyl plus celecoxib is an effective and time-saving strategy for LCR.
• Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer.

  Einama T, Abe H, Shichi S, Matsui H, Kanazawa R, Shibuya K, Suzuki T, Matsuzawa F, Hashimoto T, Kohei N, Homma S, Kawamura H, Taketomi A

  Molecular and clinical oncology 6 (2) 163 - 166 2049-9450 2017/02 [Refereed][Not invited]
   

  In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.
• Significance of preoperative fluorodeoxyglucose-positron emission tomography in prediction of tumor recurrence after liver transplantation for hepatocellular carcinoma patients: a Japanese multicenter study

  Yasutsugu Takada, Toshimi Kaido, Ken Shirabe, Hiroaki Nagano, Hiroto Egawa, Yasuhiko Sugawara, Akinobu Taketomi, Takeshi Takahara, Go Wakabayashi, Chikashi Nakanishi, Naoki Kawagishi, Akira Kenjo, Mitsukazu Gotoh, Yoshikazu Toyoki, Kenichi Hakamada, Masayuki Ohtsuka, Nobuhisa Akamatsu, Norihiro Kokudo, Kazuhisa Takeda, Itaru Endo, Hiroyuki Takamura, Hideaki Okajima, Hiroshi Wada, Shoji Kubo, Kaoru Kuramitsu, Yonson Ku, Kohei Ishiyama, Hideki Ohdan, Eitaro Ito, Yoshihiko Maehara, Masaki Honda, Yukihiro Inomata, Hiroyuki Furukawa, Shinji Uemoto, Hiroki Yamaue, Masaru Miyazaki, Tadahiro Takada

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 24 (1) 49 - 57 1868-6974 2017/01 [Refereed][Not invited]
   

  Background In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Methods From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5 months (range 1-125 months). Results Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level >= 115 ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level < 115 ng/ml and PET-negative status (n = 22) had a significantly lower 5-year recurrence rate than the other patients (n = 27, 19% vs. 53%, P = 0.019). Conclusions These results suggest that preoperative FDG-PET status offers additional information on HCC recurrence risk after LT. Over-MC patients with PET-negative status and lower AFP level may achieve successful outcome comparable to that of within-MC patients.
• Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver

  Shingo Shimada, Kenji Wakayama, Moto Fukai, Tsuyoshi Shimamura, Takahisa Ishikawa, Daisuke Fukumori, Maki Shibata, Kenichiro Yamashita, Taichi Kimura, Satoru Todo, Ikuroh Ohsawa, Akinobu Taketomi

  ARTIFICIAL ORGANS 40 (12) 1128 - 1136 0160-564X 2016/12 [Refereed][Not invited]
   

  Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 378 for 90 min on an isolated perfusion apparatus, comprising the H-2(+) and H-2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H-2(-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H-2(+) group, these harmful changes were significantly suppressed [vs. H-2(-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.
• Successful treatment of rectovaginal fistula and rectal stenosis due to perianal Crohn's disease by dual-port laparoscopic abdominoperineal resection: a report of two cases.

  Matsuzawa F, Homma S, Yoshida T, Shibasaki S, Minagawa N, Shimokuni T, Sakihama H, Kawamura H, Takahashi N, Taketomi A

  Surgical case reports 2 (1) 83 - 83 2016/12 [Refereed][Not invited]
   

  BACKGROUND: The incidence of rectovaginal fistula in women with Crohn's disease has been reported to be 3-10 %. Although rectovaginal fistulas can be managed medically and surgically, they have high rates of recurrence and complications. Rectal stenosis is another condition that occurs due to perianal Crohn's disease. A novel, minimally invasive procedure, dual-port laparoscopic abdominoperineal resection using a multichannel port, has been shown effective in patients with lower rectal cancer and patients with medically uncontrolled ulcerative colitis. This report describes the use of the same method for two patients with Crohn's disease-related rectovaginal fistula and rectal stenosis. CASE PRESENTATION: The first patient, a 22-year-old woman, was diagnosed with rectovaginal fistula and rectal stenosis due to perianal Crohn's disease 2 years earlier. Induction therapy with infliximab and endoscopic balloon dilatation did not improve her symptoms. The second patient, a 33-year-old woman, was also diagnosed with rectovaginal fistula and rectal stenosis due to perianal Crohn's disease, and medical treatment was also unsuccessful. Both patients underwent dual-port laparoscopic abdominoperineal resection using a multichannel port, with no perioperative and postoperative complications. CONCLUSION: These findings show that this reduced port method can be used to successfully treat patients with Crohn's disease-associated rectovaginal fistula and rectal stenosis.
• Solitary left axillary lymph node metastasis after curative resection of carcinoma at the colostomy site: a case report.

  Imaizumi K, Homma S, Yoshida T, Shimokuni T, Sakihama H, Takahashi N, Kawamura H, Takakuwa E, Taketomi A

  Surgical case reports 2 (1) 99 - 99 2016/12 [Refereed][Not invited]
   

  BACKGROUND: The incidence of axillary lymph node metastasis (ALNM) of colon cancer is very low, and there have been only a few reports of solitary ALNM. Neither the mechanism involved in solitary colon cancer ALNM nor the proper treatment has been elucidated. We encountered a case of solitary left ALNM after curative resection of carcinoma at the colostomy site. CASE PRESENTATION: A 53-year-old man underwent a Hartmann's operation for Hirschsprung disease during his adolescence. He complained of a mass of the descending colon and was diagnosed with colon cancer at the colostomy site with pagetoid spread to the adjacent skin. The cancer at the stoma site was resected, and a transverse colostomy was performed. Nine years later, his carbohydrate antigen (CA) 19-9 level was high during a health screening. On physical examination, adenopathy was palpated in the left axilla. Computed tomography (CT) demonstrated a lymph node in the left axillary fossa that was 33 mm in diameter, and (18)F-fluorodeoxyglucose positron emission tomography/CT showed high uptake in the lesion. We performed a curative resection of the left axillary lymph node. The lesion was pathologically diagnosed as left ALNM originating from the adenocarcinoma at the colostomy site. After lymph node resection, his serum CA19-9 level decreased compared to that observed at baseline. He has been receiving adjuvant chemotherapy (capecitabine plus oxaliplatin) without recurrence for 5 months after lymph node resection. CONCLUSIONS: The present case report shows that carcinoma at the colostomy site with pagetoid spread can metastasize to the axillary lymph nodes through superficial abdominal lymphatic pathways, and surgical resection followed by adjuvant chemotherapy may be a potent strategy to treat solitary colon cancer ALNM.
• Safety of Laparoscopic Colorectal Resection in Patients With Severe Comorbidities

  Nobuki Ichikawa, Shigenori Homma, Kazuaki Nakanishi, Keizo Kazui, Sayuri Kashiwakura, Masafumi Ohira, Takeshi Tsuji, Takashi Suzuki, Tomohiro Ishikawa, Akinobu Taketomi

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 26 (6) 503 - 507 1530-4515 2016/12 [Refereed][Not invited]
   

  We aimed to assess the safety of laparoscopic colorectal resection in patients with severe comorbidities. High operative risk was defined as an American Society of Anesthesiologists (ASA) class 3 score. Outcomes in 34 patients with an ASA score of 3 undergoing laparoscopic surgery (LAP3) were compared with 172 laparoscopic surgery patients with an ASA score <2 (LAP2) and 32 laparotomy patients with an ASA score of 3 (OP3). The postoperative complication rate in LAP3 was similar to that seen in LAP2 and significantly lower than that seen in OP3 (LAP2, 4.0%; LAP3, 5.9%; OP3, 31.2%). The incidence of postoperative hemorrhage, infection, ileus, and anastomotic leakage was similar between LAP3 and LAP2 and between LAP3 and OP3. However, the systemic complication rate in LAP3 was similar to that seen in LAP2 and significantly lower than that seen in OP3. Laparoscopic colorectal resection can be performed safely in patients with severe comorbidities.
• Models predicting the risks of six life-threatening morbidities and bile leakage in 14,970 hepatectomy patients registered in the National Clinical Database of Japan

  Hideki Yokoo, Hiroaki Miyata, Hiroyuki Konno, Akinobu Taketomi, Tatsuhiko Kakisaka, Norimichi Hirahara, Go Wakabayashi, Mitsukazu Gotoh, Masaki Mori

  MEDICINE 95 (49) e5466  0025-7974 2016/12 [Refereed][Not invited]
   

  To construct a robust morbidity risk-prediction model based on a Japanese nationwide web-based database of patients who underwent liver surgery. Although liver resection has become safer, patient mortality and morbidity still occur. This study investigated postoperative morbidity risks in patients who underwent hepatectomy in Japan at institutions registered in the National Clinical Database. This analysis involved 14,970 patients who underwent hepatectomy of more than 1 section, except for left lateral sectionectomy, during 2011 and 2012 at 1192 hospitals in Japan. Patients were randomized into 2 subsets, with 80% of patients analyzed for model development and the remaining 20% for model validation. Rates of 90-day inhospital mortality and overall morbidity were 3.7% and 25.7%, respectively. Rates of surgical site infection and bile leakage were 9.0% and 8.0%, respectively, but these morbidities showed little association with mortality. Rates of nonsurgical complications, including postoperative transfusion over 5 units, unexpected intubation, renal failure, cardiac events, septic shock, and postoperative pneumonia, ranged from 0.2% to 2.6%. These complications were highly associated with mortality, suggesting they were life-threatening. Risk models for morbidity yielded high C-indices for transfusion of over 5 units (0.758), unplanned intubation (0.755), renal failure (0.80), cardiac events (0.779), septic shock (0.783), pneumonia (0.768), and bile leakage (0.676). Preoperative parameters/comorbidities can accurately predict life-threatening complications after hepatectomy. These models allow early identification of patients at risk of mortality and may be useful in deciding on surgical interventions and in improving surgical quality.
• Sonazoid Can Help Visualize the Intraductal Spread of Breast Cancer

  Kazuaki Shibuya, Takahiro Einama, Hironori Abe, Ryo Kanazawa, Takashi Suzuki, Fumihiko Matsuzawa, Khor Lee Wee, Terumi Kaga, Etsuya Tamura, Akinobu Taketomi, Kenichi Kyuno

  AMERICAN SURGEON 82 (12) E352 - E354 0003-1348 2016/12 [Refereed][Not invited]
  
• 胃GISTに対する腹腔鏡下胃部分切除の方法と成績

  川村 秀樹, 吉田 雅, 下國 達志, 崎浜 秀康, 本間 重紀, 武冨 紹信, 高橋 昌宏

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 49 (Suppl.2) 325 - 325 0386-9768 2016/11
• LTx-PET study group of the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the Japanese Liver Transplantation Society. Significance of preoperative FDG-PET in prediction of tumor recurrence after liver transplantation for HCC patients: A Japanese m

  Takada Y, Kaido T, Shirabe K, Nagano H, Egawa H, Sugawara Y, Taketomi A, Takahara T, Wakabayashi G, Nakanishi C, Kawagishi N, Kenjo A, Gotoh M, Toyoki Y, Hakamada K, Ohtsuka M, Akamatsu N, Kokudo N, Takeda K, Endo I, Takamura H, Okajima H, Wada H, Kubo S, Kuramitsu K, Ku Y, Ishiyama K, Ohdan H, Ito E, Maehara Y, Honda M, Inomata Y, Furukawa H, Uemoto S, Yamaue H, Miyazaki M, Takada T

  J Hepatobiliary Pancreat Sci 2016/11 [Refereed][Not invited]
  
• Colorectal cancer-the history and current status of clinical and research-.

  Shigenori Homma, Tadashi Yoshida, Nobuki Ichikawa, Hideki Kawamura, Akinobu Taketomi

  Nihon rinsho. Japanese journal of clinical medicine 74 (11) 1781 - 1785 0047-1852 2016/11 [Refereed][Not invited]
   

  The history of clinical and research of colorectal cancer, beginning from surgery therapy, a variety of fields have evolved from there, the results have been stacked. Safety of the establishment and the usefulness of the proof of the surgery, the development of diagnostic methods, advances in chemotherapy, the discovery of hereditary colon cancer, due to the development and application of basic research to support these, research and treatment results for colorectal cancer. It has been made great strides. Advances in establishment and chemotherapy safe surgical treatment, even for colorectal cancer has been considered to unresectable ever, it has become possible to perform a surgical treatment in combination with perioperative chemotherapy. In addition, even for recurrent colon cancer, by combining the surgery therapy sure to allow timing as well as chemotherapy, likely to be observed extension of further survival are coming out Occurrence for colorectal cancer, by the elucidation of the treatment mechanism, to expect that the study of the optimization of colon cancer treatment progresses.
• 高度脈管侵襲を伴った肝癌に対する治療戦略 下大静脈、右心房腫瘍栓を伴った肝細胞癌に対する治療戦略

  若山 顕治, 神山 俊哉, 横尾 英樹, 島田 慎吾, 永生 高広, 折茂 達也, 蒲池 浩文, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 77 (増刊) 409 - 409 1345-2843 2016/10
• A comparison between fentanyl plus celecoxib therapy and epidural anesthesia for postoperative pain management following laparoscopic gastrectomy

  Susumu Shibasaki, Hideki Kawamura, Shigenori Homma, Tadashi Yosida, Shusaku Takahashi, Masahiro Takahashi, Norihiko Takahashi, Akinobu Taketomi

  SURGERY TODAY 46 (10) 1209 - 1216 0941-1291 2016/10 [Refereed][Not invited]
   

  To clarify the efficacy of postoperative pain management following laparoscopic gastrectomy (LG), we retrospectively compared pain assessments in patients who received fentanyl plus celecoxib with those who received epidural anesthesia. From 2011 to 2012, 55 consecutive LG patients at our institution received 48 h of epidural anesthesia for postoperative pain management (group-E). Since September 2013, epidural anesthesia was replaced with 24 h of intravenous fentanyl and 4 days of oral celecoxib. Thirty-three consecutive LG patients who received this analgesic method (group-FC) were included in this analysis. The severity of postoperative pain as assessed by the FACES Pain Rating Scale and the frequency of rescue pain medication were retrospectively compared between the two groups. No significant difference in the severity of postoperative pain on postoperative day (POD) 0 or 1 was observed between the two groups. In contrast, pain was significantly lower in group-FC than group-E on PODs 2, 3, 4, and 7. The total use of rescue pain medications during the first 7 days following LG did not differ between the two groups. Pain management using 24 h of intravenous fentanyl and 4 days of oral celecoxib is comparable to epidural anesthesia following LG.
• Our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe using a vessel sealing device (LigaSure (TM)) for huge hepatic tumors with diaphragm invasion

  Kenji Wakayama, Toshiya Kamiyama, Hideki Yokoo, Tatsuhiko Kakisaka, Tatsuya Orimo, Shingo Shimada, Yosuke Tsuruga, Hirofumi Kamachi, Akinobu Taketomi

  SURGERY TODAY 46 (10) 1224 - 1229 0941-1291 2016/10 [Refereed][Not invited]
   

  We describe and assess our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe to treat a huge hepatic tumor with diaphragm invasion. The right hepatic artery and portal vein were divided at the hepatic hilum, and the mesenteries were then dissected with a vessel sealing device (LigaSure Impact (TM)). The invaded diaphragm was dissected roundly using a vessel sealing device and the right lobe was partially mobilized. A soft catheter was then passed along the anterior aspect of the retrohepatic inferior vena cava and the liver parenchyma was dissected via a liver hanging maneuver. We performed eight hepatectomies using this technique. The median blood loss was 532.5 ml and the mean excised liver weight was 1859 g. Our results demonstrate the safety and efficiency of the preceding diaphragm resection and partial mobilization technique using a vessel sealing device for right hepatectomy to resect a very large tumor with diaphragm invasion.
• Impact of umbilical polyp resection: A report and literature review

  Hisayuki Miyagi, Shohei Honda, Masashi Minato, Tadao Okada, Kanako C. Hatanaka, Akinobu Taketomi

  African Journal of Paediatric Surgery 13 (4) 196 - 198 0974-5998 2016/10/01 [Refereed][Not invited]
   

  The preferred treatment for this lesion should be the total resection of the umbilical polyp with a mini-laparotomy because residual intestinal mucosa at the umbilicus can be confirmed to eliminate the risk of recurrence.
• 膵島移植の長期生着のための課題と克服 膵島移植におけるプロテアソーム阻害による早期グラフト障害の抑制

  小野 仁, 旭 よう, 吉田 雅, 腰塚 靖之, 渡辺 正明, 外丸 詩野, 江本 慎, 深井 原, 嶋村 剛, 武冨 紹信, 藤堂 省, 山下 健一郎

  移植 (一社)日本移植学会 51 (2-3) 273 - 273 0578-7947 2016/08 [Refereed][Not invited]
  
• Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus, Including Cases with Obstructive Jaundice

  Tatsuya Orimo, Toshiya Kamiyama, Hideki Yokoo, Kenji Wakayama, Shingo Shimada, Yosuke Tsuruga, Hirofumi Kamachi, Akinobu Taketomi

  ANNALS OF SURGICAL ONCOLOGY 23 (8) 2627 - 2634 1068-9265 2016/08 [Refereed][Not invited]
   

  This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved.
• The impact of preformed donor-specific antibodies in living donor liver transplantation depending on graft volume

  Goto Ryoichi, Koshizuka Yasuyuki, Kawamura Norio, Zaitsu Masaaki, Ota Minoru, Kamiyama Toshiya, Yamashita Kenichiro, Taketomi Akinobu, Shimamura Tsuyoshi

  TRANSPLANTATION 100 (7) S350  0041-1337 2016/07 [Refereed][Not invited]
  
• Strong cytoplasmic expression of NF-kappa B/p65 correlates with a good prognosis in patients with triple-negative breast cancer

  Motoi Baba, Masato Takahashi, Katsushige Yamashiro, Hideki Yokoo, Moto Fukai, Masanori Sato, Mitsuchika Hosoda, Toshiya Kamiyama, Akinobu Taketomi, Hiroko Yamashita

  SURGERY TODAY 46 (7) 843 - 851 0941-1291 2016/07 [Refereed][Not invited]
   

  Purpose Recent studies have indicated that constitutive NF-kappa B activity could be involved in the proliferation of triple-negative breast cancer. Methods The NF-kappa B/p65 expression and the effects of a NF-kappa B inhibitor, (-)-DHMEQ, were examined in triple-negative MDA-MB-231 breast cancer cells. Women with triple-negative breast cancer treated with neoadjuvant chemotherapy between 2002 and 2012 were retrospectively analyzed for their expression of NF-kappa B/p65, Bcl2 and Ki67 by immunohistochemistry in pre-and post-treatment specimens. The factors predicting the response to neoadjuvant chemotherapy and the prognosis were analyzed. Results NF-kappa B/p65 was predominantly expressed in the cytoplasm of MDA-MB-231 cells. Of 34 triple-negative breast cancer patients, positive staining for NF-kappa B/p65 expression was detected in the nuclei of a few cells in seven tumors before neoadjuvant chemotherapy, while the expression of NF-kappa B/p65 in the cytoplasm was detected in almost all tumor cells of 33 tumors. The expression levels of NF-kappa B/p65 were not associated with the response to neoadjuvant chemotherapy, although the cytoplasmic NF-kappa B/p65 staining intensity was significantly decreased in the post-treatment tumor samples compared with the pretreatment samples. All patients whose tumors showed strong cytoplasmic NF-kappa B/p65 expression before neoadjuvant chemotherapy are currently disease free. Conclusion Our results suggest that strong cytoplasmic NF-kappa B/p65 expression could be a prognostic marker for patients with triple-negative breast cancer.
• ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma

  Katsumi Terashita, Makoto Chuma, Yutaka Hatanaka, Kanako Hatanaka, Tomoko Mitsuhashi, Hideki Yokoo, Takumi Ohmura, Hiroyuki Ishizu, Shunji Muraoka, Atsushi Nagasaka, Takahiro Tsuji, Yoshiya Yamamoto, Nobuaki Kurauchi, Norihiko Shimoyama, Hidenori Toyoda, Takashi Kumada, Yuji Kaneoka, Atsuyuki Maeda, Koji Ogawa, Mitsuteru Natsuizaka, Hirofumi Kamachi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto

  JOURNAL OF CLINICAL PATHOLOGY 69 (7) 593 - 599 0021-9746 2016/07 [Refereed][Not invited]
   

  Background/Aim Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins. Methods We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated. Results ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan-Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival. Conclusions ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.
• Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy

  Rena Morita, Yoshihiko Hirohashi, Toshihiko Torigoe, Satoko Ito-Inoda, Akari Takahashi, Tasuku Mariya, Hiroko Asanuma, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Terufumi Kubo, Goro Kutomi, Toru Mizuguchi, Takeshi Terui, Kunihiko Ishitani, Satoshi Hashino, Toru Kondo, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi, Satoru Todo, Masahiro Asaka, Noriyuki Sato

  CLINICAL CANCER RESEARCH 22 (13) 3298 - 3309 1078-0432 2016/07 [Refereed][Not invited]
   

  Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy. Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model. Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model. Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. (C) 2016 AACR.
• Inquiries About Biomarkers of Acute Liver Failure in Patients Who Underwent Living Donor Liver Transplantation Using a Protein Chip Array.

  Yamashita YI, Yoshizumi T, Ikegami T, Uchiyama H, Tsujita E, Itoh S, Harimoto N, Soejima Y, Taketomi A, Baba H, Maehara Y

  Fukuoka igaku zasshi = Hukuoka acta medica 福岡医学会 107 (7) 131 - 135 0016-254X 2016/07 [Refereed][Not invited]
   

  The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. The recovery of consciousness in patients with acute liver failure (ALF) who underwent liver transplantation (LT) is sometimes drastic ; therefore, we thought that the causative agents of HE would change markedly peri-operatively in these patients. We examined the biomarkers including new agents in the serum of patients using the ProteinChip^【○!R】 System 4000 (Ciphergen Biosystems, Yokohama, JAPAN). Sixteen samples were obtained from four patients with ALF who underwent living donor LT (LDLT) at four time points ; pre-operative, one post-operative day (1POD), 3POD, and 7POD. We used three chips made by the Biomek2000 robot. All duplicated samples were assayed and analyzed using the CiphergenExpress^ data manager. We divided the peri-operative changes in the intensity of identified peaks into seven patterns. The number of peaks whose intensity shows significant changes peri-operatively reached 755. Of course, it is difficult to determine each structure in all 755 peaks ; therefore, we should narrow down the candidates for causative agents of HE in further studies. Our own results suggest that many difficulties lie ahead in determining the causative agent of HE.肝性脳症の原因物質はまだ同定されていない．我々は，肝移植を受けた急性肝不全患者の意識回復が時に劇的である事から，このような患者において肝性脳症の原因物質が周術期に劇的に変化していると考えた．そこで，肝性脳症の原因物質を同定するために，プロテインチップシステム4000^【○!R】 (サイファージェンバイオシステムズ，横浜)を用いて，患者血清中のバイオマーカーを検討した．生体肝移植を受けた急性肝不全患者4名より，周術期4 ポイント(手術前，術後1日，術後3日，術後7日)で血清を採取して，合計16のサンプルを得た．今回は，Biomek2000ロボットにより作製された3つのチップを使用した．測定はサンプル毎に2回行い，結果はCiphergenExpressTMデータマネージャーを用いて分析した．周術期における発現ピークの変動パターンを7 パターンに分割し，周術期に有意に変動した発現ピークとして755個を同定した．もちろん，755個の発現ピーク全ての構造を決定することは困難である．従って，我々は更に検討を重ね，肝性脳症の原因物質の候補を絞り込む必要がある．我々の今回の検討結果は，肝性脳症の原因物質を決定するには多くの困難が待ち受けていることを示唆している．
• Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

  Hirotaka Shoji, Sachiyo Yoshio, Yohei Mano, Erina Kumagai, Masaya Sugiyama, Masaaki Korenaga, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Hiroshi Aikata, Hideyuki Hyogo, Kazuaki Chayama, Tomohiko Ohashi, Kiyoaki Ito, Masashi Yoneda, Yuichi Nozaki, Takumi Kawaguchi, Takuji Torimura, Masanori Abe, Yoichi Hiasa, Moto Fukai, Toshiya Kamiyama, Akinobu Taketomi, Masashi Mizokami, Tatsuya Kanto

  SCIENTIFIC REPORTS 6 28814  2045-2322 2016/07 [Refereed][Not invited]
   

  Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387* IL-34 (pg/ml) + 0.3623* type IV collagen 7s (ng/ml) + 0.0184* age (year)-1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients.
• Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates

  Shohei Honda, Masashi Minato, Hiromu Suzuki, Masato Fujiyoshi, Hisayuki Miyagi, Masayuki Haruta, Yasuhiko Kaneko, Kanako C. Hatanaka, Eiso Hiyama, Takehiko Kamijo, Tadao Okada, Akinobu Taketomi

  CANCER SCIENCE 107 (6) 812 - 819 1347-9032 2016/06 [Refereed][Not invited]
   

  Hepatoblastoma (HB) is very rare but the most common malignant neoplasm of the liver occurring in children. Despite improvements in therapy, outcomes for patients with advanced HB that is refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the survival rate among this group, identification of novel prognostic markers and therapeutic targets is needed. We have previously reported that altered DNA methylation patterns are of biological and clinical importance in HB. In the present study, using genome-wide methylation analysis and bisulfite pyrosequencing with specimens from HB tumors, we detected nine methylated genes. We then focused on four of those genes, GPR180, MST1R, OCIAD2, and PARP6, because they likely encode tumor suppressors and their increase of methylation was associated with a poor prognosis. The methylation status of the four genes was also associated with age at diagnosis, and significant association with the presence of metastatic tumors was seen in three of the four genes. Multivariate analysis revealed that the presence of metastatic tumors and increase of methylation of GPR180 were independent prognostic factors affecting event-free survival. These findings indicate that the four novel tumor suppressor candidates are potentially useful molecular markers predictive of a poor outcome in HB patients, which may serve as the basis for improved therapeutic strategies when clinical trials are carried out.
• Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan

  Tomoharu Yoshizumi, Yasutsugu Takada, Ken Shirabe, Toshimi Kaido, Masaaki Hidaka, Masaki Honda, Takashi Ito, Masahiro Shinoda, Hideki Ohdan, Naoki Kawagishi, Yasuhiko Sugawara, Yasuhiro Ogura, Mureo Kasahara, Shoji Kubo, Akinobu Taketomi, Natsumi Yamashita, Shinji Uemoto, Hiroki Yamaue, Masaru Miyazaki, Tadahiro Takada, Yoshihiko Maehara

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 23 (6) 333 - 341 1868-6974 2016/06 [Refereed][Not invited]
   

  BackgroundThe natural history of human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) or HTLV-1 associated myelopathy, after liver transplantation is unclear.MethodsWe conducted a nationwide survey to investigate the impact of HTLV-1 status on living donor liver transplantation (LDLT) in Japan. We analyzed the cases of 82 HTLV-1-positive recipients and six HTLV-1-negative-before-LDLT recipients who received a hepatic graft from HTLV-1-positive donors.ResultsAdult T-cell leukemia developed in five recipients who ultimately died. Of these five, two received grafts from HTLV-1-positive donors and three from HTLV-1-negative donors. The 1-, 3-, and 5-year ATL development rates were 4.5%, 6.5%, and 9.2%, respectively. Fulminant hepatic failure as a pre-transplant diagnosis was identified as an independent risk factor for ATL development (P = 0.001). The 1-, 3-, and 5-year survival rates for HTLV-1-positive recipients who received grafts from HTLV-1-negative donors were 79.9%, 66.1%, and 66.1%, and from HTLV-1-positive donors were 83.3%, 83.3%, and 60.8%, respectively. The 1-year survival rate for HTLV-1-negative recipients who received grafts from HTLV-1-positive donors was 33.3%.ConclusionsFulminant hepatic failure is an independent risk factor for ATL development in HTLV-1-positive recipients. Grafts from HTLV-1-positive living donors can be transplanted into selected patients.
• Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

  Nako Maishi, Yusuke Ohba, Kosuke Akiyama, Noritaka Ohga, Jun-ichi Hamada, Hiroko Nagao-Kitamoto, Mohammad Towfik Alam, Kazuyuki Yamamoto, Taisuke Kawamoto, Nobuo Inoue, Akinobu Taketomi, Masanobu Shindoh, Yasuhiro Hida, Kyoko Hida

  SCIENTIFIC REPORTS 6 28039  2045-2322 2016/06 [Refereed][Not invited]
   

  Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-kappa B and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis.
• Epidermal Sutureless Closure of the Umbilical Base Following Laparoscopic Colectomy for Colon Cancer

  Susumu Shibasaki, Shigenori Homma, Tadashi Yoshida, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  INDIAN JOURNAL OF SURGERY 78 (3) 203 - 208 0972-2068 2016/06 [Refereed][Not invited]
   

  At our institute, a non-suturing method for closure of the umbilical epidermis has been used in laparoscopic colorectal resection to prevent umbilical wound infection. We performed a retrospective evaluation of the incidence of umbilical wound infection using this technique for patients with colorectal cancer. From 2010 to 2014, 178 consecutive patients underwent elective laparoscopic resection of colorectal cancer. The umbilical fascia was closed using interrupted multifilament absorbable sutures. The skin surface of the umbilicus was compressed using a cotton ball and sealed by water vapor-permeable film. Three (1.7 %) patients required conversion from laparoscopic to open surgery. The mean surgery time was 174 +/- 48 min, intraoperative blood loss was 29 +/- 75 mL, and postoperative hospital stay was 10.5 +/- 6.7 days. According to the Centers for Disease Control and Prevention criteria, umbilical superficial wound infection occurred in two (1.1 %) patients. The two patients recovered from their wound infections after a few days of drainage, and their hospital discharge was not delayed. Deep umbilical wound infection did not occur in any patient. Our non-suturing closure technique appeared to be effective in preventing wound infection after laparoscopic resection of colon cancer.
• Clinical impacts of mesothelin expression in gastrointestinal carcinomas.

  Takahiro Einama, Futoshi Kawamata, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Fumihiko Matsuzawa, Tatsuzo Mizukami, Yuji Konishi, Munenori Tahara, Toshiya Kamiyama, Okio Hino, Akinobu Taketomi, Satoru Todo

  World journal of gastrointestinal pathophysiology 7 (2) 218 - 22 2016/05/15 [Refereed][Not invited]
   

  Mesothelin, C-ERC/mesothelin is a 40-kDa cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura, peritoneum, and pericardium. Moreover, mesothelin has been shown to be overexpressed in several human cancers, including virtually all mesothelioma and pancreatic cancer, approximately 70% of ovarian cancer and extra bile duct cancer, and 50% of lung adenocarcinomas and gastric cancer. The full-length human mesothelin gene encodes the primary product, a 71-kDa precursor protein. The 71-kDa mesothelin precursor is cleaved into two products, 40-kDa C-terminal fragment that remains membrane-bound via glycosylphosphatidylinositol anchor, and a 31-kDa N-terminal fragment, megakaryocyte potentiating factor, which is secreted into the blood. The biological functions of mesothelin remain largely unknown. However, results of recent studies have suggested that the mesothelin may play a role of cell proliferation and migration. In pancreatic cancer, mesothelin expression was immunohistochemically observed in all cases, but absent in normal pancreas and in chronic pancreatitis. Furthermore, the expression of mesothelin was correlated with an poorer patient outcome in several human cancers. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. The present review discusses the expression and function of mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.
• Optimizing Small for Sized Graft: Our Experience in Living Donor Liver Transplantation Using GV/SV Less Than 35% Grafts

  Norio Kawamura, Masaaki Zaitsu, Yasuyuki Koshizuka, Ryoichi Goto, Tomomi Suzuki, Toshiya Kamiyama, Kenichiro Yamashita, Akinobu Taketomi, Tsuyoshi Shimamura

  TRANSPLANTATION 100 S103 - S103 0041-1337 2016/05 [Refereed][Not invited]
  
• Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation

  Kazutoyo Morita, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo-ichi Yamashita, Keishi Sugimachi, Norifumi Harimoto, Shinji Itoh, Tetsuo Ikeda, Yoshihiko Maehara

  LIVER TRANSPLANTATION 22 (5) 665 - 676 1527-6465 2016/05 [Refereed][Not invited]
   

  There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. Liver Transplantation 22 665-676 2016 AASLD.
• Significance of functional hepatic resection rate calculated using 3D CT/Tc-99m-galactosyl human serum albumin single-photon emission computed tomography fusion imaging

  Yosuke Tsuruga, Toshiya Kamiyama, Hirofumi Kamachi, Shingo Shimada, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Hideki Yokoo, Akinobu Taketomi

  WORLD JOURNAL OF GASTROENTEROLOGY 22 (17) 4373 - 4379 1007-9327 2016/05 [Refereed][Not invited]
   

  AIM: To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/Tc-99m-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making. METHODS: We enrolled 57 patients who underwent bi-or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and 99mTc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/Tc-99m-GSA SPECT fusion images. RESULTS: In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 +/- 19.9 and 44.5 +/- 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 +/- 0.19 vs 0.82 +/- 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien- Dindo grade >= 3) occurred in 17 patients (29.8%). There was no case of surgery-related death. CONCLUSION: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/ or a tumor volume of > 1000 mL.
• Resection of liver metastasis derived from alpha-fetoprotein-producing gastric cancer-report of 4 cases

  Asahi Yoh, Kamiyama Toshiya, Homma Shigenori, Hatanaka Kanako C, Yokoo Hideki, Nakagawa Takahito, Kamachi Hirofumi, Nakanishi Kazuaki, Tahara Munenori, Kakisaka Tatsuhiko, Wakayama Kenji, Todo Satoru, Taketomi Akinobu

  INTERNATIONAL CANCER CONFERENCE JOURNAL 5 (2) 98 - 103 2192-3183 2016/04 [Refereed][Not invited]
   

  As is the case for metastatic liver tumors derived from standard gastric cancers, there is no consensus about the optimal treatment for metastatic liver tumors derived from alpha-fetoprotein (AFP)-producing gastric cancer, including regarding the surgical indications for such lesions. We report the cases of 4 patients in whom metastatic liver tumors derived from AFP-producing gastric cancer that were curatively resected. One of the patients had a thrombus in his inferior vena cava at the time of the liver resection, and both the liver tumor and thrombus were completely removed. The patient has survived 93 months after receiving multidisciplinary therapy including partial pneumonectomy, chemotherapy, and radiotherapy and currently has no evaluable disease. Another patient has survived for 3 years without suffering any recurrence. Since long-term survival is possible, liver resection should be considered as a treatment for liver metastases from AFP-producing gastric cancers.
• Development and future directions of antiangiogenic therapy in hepatocellular carcinoma

  Akinobu Taketomi

  INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 21 (2) 205 - 205 1341-9625 2016/04 [Refereed][Not invited]
  
• Clinical trials of antiangiogenic therapy for hepatocellular carcinoma

  Akinobu Taketomi

  INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 21 (2) 213 - 218 1341-9625 2016/04 [Refereed][Not invited]
   

  Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of antiangiogenic agents in hepatocellular carcinoma. A systematic search of PubMed was performed to identify clinical trials of specific antiangiogenic agents in hepatocellular carcinoma treatment, particularly phase III trials involving treatment guidelines for advanced hepatocellular carcinoma. Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma. Two large-scale, randomized phase III trials using sorafenib involving patients with unresectable HCC showed a significant survival benefit compared with placebo control groups. However, subsequent phase III trials of antiangiogenic agents in hepatocellular carcinoma have failed to improve survival compared with standard treatment protocols using sorafenib. The efficacy of antiangiogenic agents in combination with other drugs, transarterial chemoembolization, and surgical resection is currently being investigated. Future research is expected to optimize antiangiogenic therapies in combination with standard treatment with sorafenib.
• Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis

  Nao Nishida, Jun Ohashi, Seik-Soon Khor, Masaya Sugiyama, Takayo Tsuchiura, Hiromi Sawai, Keisuke Hino, Masao Honda, Shuichi Kaneko, Hiroshi Yatsuhashi, Osamu Yokosuka, Kazuhiko Koike, Masayuki Kurosaki, Namiki Izumi, Masaaki Korenaga, Jong-Hon Kang, Eiji Tanaka, Akinobu Taketomi, Yuichiro Eguchi, Naoya Sakamoto, Kazuhide Yamamoto, Akihiro Tamori, Isao Sakaida, Shuhei Hige, Yoshito Itoh, Satoshi Mochida, Eiji Mita, Yasuhiro Takikawa, Tatsuya Ide, Yoichi Hiasa, Hiroto Kojima, Ken Yamamoto, Minoru Nakamura, Hiroh Saji, Takehiko Sasazuki, Tatsuya Kanto, Katsushi Tokunaga, Masashi Mizokami

  SCIENTIFIC REPORTS 6 24767  2045-2322 2016/04 [Refereed][Not invited]
   

  Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1*06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 x 10(-18)) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1*09:01, and *04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1*15:02-DQB1*06:01 and DRB1*13:02-DQB1*06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region.
• Does reduced-port laparoscopic surgery for medically uncontrolled ulcerative colitis do more harm than good?

  Shigenori Homma, Futoshi Kawamata, Susumu Shibasaki, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  Asian journal of endoscopic surgery 9 (1) 24 - 31 1758-5902 2016/02 [Refereed][Not invited]
   

  INTRODUCTION: Reduced-port laparoscopic surgery is a novel minimally invasive surgery. However, reduced-port surgery for ulcerative colitis (UC) remains controversial. Here, we describe the clinical outcomes of single-incision plus one port laparoscopic surgery (SILS + 1) for medically uncontrolled UC. METHODS: Between May 2011 and September 2014, 10 UC patients underwent SILS + 1 port surgery. All procedures were performed with the use of a SILS port and either a 5-mm or a 12-mm port placed at the planned ileostomy site. RESULTS: The median age of patients was 32 years (range, 22-53 years). Six patients underwent two-stage SILS + 1 port restorative proctocolectomy with ileal pouch-anal anastomosis, two patients underwent SILS + 1 total proctocolectomy, and the remaining two patients underwent SILS + 1 subtotal colectomy with subsequent three-stage SILS + 1 ileal pouch-anal anastomosis. The median operative time was 363.1 min (range, 253-465 min) and the median estimated blood loss was 29 mL (range, 0-100 mL). There were no conversions or additional ports required. Two patients previously underwent SILS + 1 subtotal colectomy, and in one of those patients, SILS + 1 ileal pouch-anal anastomosis was performed successfully 6 months after the previous surgery. There were no intra-abdominal adhesions, and no extra wounds were necessary because the previous stoma site had been used to access the SILS port. The median postoperative period was 24 months, during which five patients had their ileostomies closed. No patients reported occasional minor daily soiling or the need to wear a pad. CONCLUSION: Reduced-port laparoscopic surgery for medically uncontrolled UC is a feasible and safe procedure when performed by skilled surgeons.
• IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4(+) T cells

  Yosuke Ohno, Hidemitsu Kitamura, Norihiko Takahashi, Junya Ohtake, Shun Kaneumi, Kentaro Sumida, Shigenori Homma, Hideki Kawamura, Nozomi Minagawa, Susumu Shibasaki, Akinobu Taketomi

  CANCER IMMUNOLOGY IMMUNOTHERAPY 65 (2) 193 - 204 0340-7004 2016/02 [Refereed][Not invited]
   

  Immunosuppression in tumor microenvironments critically affects the success of cancer immunotherapy. Here, we focused on the role of interleukin (IL)-6/signal transducer and activator of transcription (STAT3) signaling cascade in immune regulation by human dendritic cells (DCs). IL-6-conditioned monocyte-derived DCs (MoDCs) impaired the presenting ability of cancer-related antigens. Interferon (IFN)-gamma production attenuated by CD4(+) T cells co-cultured with IL-6-conditioned MoDCs corresponded with decreased DC IL-12p70 production. Human leukocyte antigen (HLA)-DR and CD86 expression was significantly reduced in CD11b(+)CD11c(+) cells obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-6 treatment and was STAT3 dependent. Arginase-1 (ARG1), lysosomal protease, cathepsin L (CTSL), and cyclooxygenase-2 (COX2) were involved in the reduction of surface HLA-DR expression. Gene expressions of ARG1, CTSL, COX2, and IL6 were higher in tumor-infiltrating CD11b(+)CD11c(+) cells compared with PBMCs isolated from colorectal cancer patients. Expression of surface HLA-DR and CD86 on CD11b(+)CD11c(+) cells was down-regulated, and T cell-stimulating ability was attenuated compared with PBMCs, suggesting that an immunosuppressive phenotype might be induced by IL-6, ARG1, CTSL, and COX2 in tumor sites of colorectal cancer patients. There was a relationship between HLA-DR expression levels in tumor tissues and the size of CD4(+) T and CD8(+) T cell compartments. Our findings indicate that IL-6 causes a dysfunction in human DCs that activates cancer antigen-specific Th cells, suggesting that blocking the IL-6/STAT3 signaling pathway might be a promising strategy to improve cancer immunotherapy.
• Anatomical hepatectomy using indocyanine green fluorescent imaging and needle- guiding technique

  Toshiya Kamiyama, Tatsuhiko Kakisaka, Hideki Yokoo, Tatsuya Orimo, Kenji Wakayama, Hirofumi Kamachi, Yosuke Tsuruga, Akinobu Taketomi

  ICG Fluorescence Imaging and Navigation Surgery 305 - 313 2016/01/01 [Refereed][Not invited]
   

  Anatomical hepatectomy using indocyanine green (ICG) fluorescent imaging and the needle-guiding technique is described in this chapter. Using this procedure, the root of the portal vein of the segment including the hepatocellular carcinoma is punctured with a 22 G Cattelan needle under ultrasonography (US). After backflow is confirmed, 1 mL of diluted (twofold) ICG solution is injected into the branch of the portal vein and monitored by US. The surface of the liver is observed with the ICG fluorescent imaging system. This novel operative procedure using ICG fluorescent imaging is able to clearly visualize the margins between the liver segments. However, this method cannot be used to guide to the root of the relevant portal vein. In order to overcome this disadvantage, an indwelling needle (18 G/65 mm) is used to puncture the outside of the margin of the stained segments under US, and the tip of the outer needle is placed in close proximity of the portal vein. This needle-guiding technique can accurately be used to guide toward the root of the portal vein to be ligated. Moreover, counterstaining with ICG fluorescent imaging defines the avascular segment to be resected as the nonstaining area, and thus, the liver fed by the tumor-bearing portal vein can be successfully resected. Using the ICG fluorescent imaging and needle-guiding technique, anatomical hepatectomy can be performed correctly and safely.
• The efficacy of 99mTc-GSA SPECT/CT fusion image for evaluating preoperative hepatic function in a huge hepatic hemangioma

  Keigo Chida, Toshiya Kamiyama, Tatsuya Orimo, Hideki Yokoo, Hiromi Kanno, Akinobu Taketomi

  Japanese Journal of Gastroenterological Surgery (一社)日本消化器外科学会 49 (9) 882 - 888 1348-9372 2016 [Not refereed][Not invited]
   

  We report on a case of a large hepatic hemangioma in a 34-year-old woman who complained of nausea and abdominal pain. Abdominal CT revealed a 20 cm cavernous hemangioma in the right lobe of the liver, and she was referred to our department. During the follow-up period, abdominal pain worsened and the patient was immediately hospitalized. Preoperative abdominal CT showed a 23×15 cm mass with early phase peripheral nodular enhancements and late phase filling-in malformations in the anterior and medial segments of the liver. Stenosis was present in the right and middle hepatic veins, and collateral pathways had developed in the trisection of the right liver due to venous congestion. The left hepatic vein and umbilical portion of the portal vein were still patent. The effective resection ratio of the liver was estimated to be 80%. The functional resection ratio, calculated using technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin single photon emission CT/CT (99mTc-GSA SPECT/CT) fusion imaging, was, however, 39.2%. It was predicted that the remnant liver function would be sufficient, and a right trisectionectomy was performed. The postoperative course was uneventful, and the patient was discharged on postoperative day 14.
• Down Syndrome with Patent Ductus Venosus and Hepato-Biliary-Pancreatic Abnormalities

  Hiroshi Yamaguchi, Kiyotaka Kosugiyama, Shohei Honda, Okada Tadao, Akinobu Taketomi, Seido Iwata

  INDIAN JOURNAL OF PEDIATRICS 83 (1) 78 - 80 0019-5456 2016/01 [Refereed][Not invited]
   

  The association between Down syndrome and congenital portosystemic shunts, most commonly caused by patent ductus venosus, remains relatively unknown. The authors present a girl with Down syndrome with patent ductus venosus, pancreaticobiliary maljunction and paucity of interlobular bile ducts, presenting with neonatal cholestasis and transient abnormal myeloproliferative disorder. To the best of authors' knowledge, no report of the concurrent presence of the above in Down syndrome has been published.
• Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung

  Yuki Fujii, Shigenori Homma, Tadashi Yoshida, Akinobu Taketomi

  BMJ Case Reports 2016 1757-790X 2016 [Refereed][Not invited]
   

  A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported.
• Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals

  N. Nishida, J. Ohashi, M. Sugiyama, T. Tsuchiura, K. Yamamoto, K. Hino, M. Honda, S. Kaneko, H. Yatsuhashi, K. Koike, O. Yokosuka, E. Tanaka, A. Taketomi, M. Kurosaki, N. Izumi, N. Sakamoto, Y. Eguchi, T. Sasazuki, K. Tokunaga, M. Mizokami

  TISSUE ANTIGENS 86 (6) 406 - 412 0001-2815 2015/12 [Refereed][Not invited]
   

  Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1*05: 01 and *09:01, and three protective alleles, DPB1*02:01, *04:01, and *04: 02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02: 01, *04: 01, and *04: 02) and the susceptible allele DPB1*05: 01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.
• CXCL12-CXCR7 axis is important for tumor endothelial cell angiogenic property

  Kenji Yamada, Nako Maishi, Kosuke Akiyama, Mohammad Towfik Alam, Noritaka Ohga, Taisuke Kawamoto, Masanobu Shindoh, Norihiko Takahashi, Toshiya Kamiyama, Yasuhiro Hida, Akinobu Taketomi, Kyoko Hida

  INTERNATIONAL JOURNAL OF CANCER 137 (12) 2825 - 2836 0020-7136 2015/12 [Refereed][Not invited]
   

  We reported that tumor endothelial cells (TECs) differ from normal endothelial cells (NECs) in many aspects, such as gene expression profiles. Although CXCR7 is reportedly highly expressed in blood vessels of several tumors, its function in TECs is still unknown. To investigate this role, we isolated TECs from mouse tumor A375SM xenografts, and compared them with NECs from normal mouse dermis. After confirming CXCR7 upregulation in TECs, we analyzed its function using CXCR7 siRNA and CXCR7 inhibitor; CCX771. CXCR7 siRNA and CCX771 inhibited migration, tube formation and resistance to serum starvation in TECs but not in NECs. ERK1/2 phosphorylation was inhibited by CXCR7 knockdown in TECs. These results suggest that CXCR7 promotes angiogenesis in TECs via ERK1/2 phosphorylation. Using ELISA, we also detected CXCL12, a ligand of CXCR7, in conditioned medium from TECs, but not from NECs. CXCL12 neutralizing antibody significantly inhibited TEC random motility. VEGF stimulation upregulated CXCR7 expression in NECs, implying that VEGF mediates CXCR7 expression in endothelial cells. A CXCR7 inhibitor, CCX771 also inhibited tumor growth, lung metastasis and tumor angiogenesis in vivo. Taken together, the CXCL12-CXCR7 autocrine loop affects TEC proangiogenic properties, and could be the basis for an antiangiogenic therapy that specifically targets tumor blood vessels rather than normal vessels. What's new? While the chemokine receptor CXCR7 is expressed at high levels on blood vessels in several tumor types, its function in tumor endothelial cells is unclear. The present study suggests that CXCR7 may have a role in tumor angiogenesis and lung metastasis. CXCR7 and its ligand CXCL12 were found to facilitate tube formation and cell migration in tumor endothelial cells via autocrine signaling. In mice, blockade of CXCR7 with the inhibitory molecule CCX771 resulted in reduced tumor growth and tumor weight, as well as lnhibition of lung metastasis. Inhibition of CXCL12/CXCR7 may represent a promising antiangiogenic strategy.
• Dual-port laparoscopic abdominoperineal resection using the intended stoma site as the multichannel port

  Takahisa Ishikawa, Shigenori Homma, Susumu Shibasaki, Tadashi Yoshida, Nozomi Minagawa, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  SURGERY TODAY 45 (12) 1583 - 1587 0941-1291 2015/12 [Refereed][Not invited]
   

  We describe a novel minimally invasive procedure: dual-port laparoscopic abdominoperineal resection using a SILS (TM) port, and report our experience of using this to treat ten patients with lower rectal cancer. A SILS (TM) port was placed in the left lower quadrant at the intended colostomy site. A 5-mm trocar was inserted at the umbilicus at the subsequent drain site. Via a standard laparoscopic medial-to-lateral approach, the inferior mesenteric artery and vein were ligated and total mesorectal excision was performed. Via a perineal approach, the specimen was retrieved from the perineal wound, and a sigmoid colostomy was created at the site of the SILS (TM) port. Ten consecutive patients with lower rectal cancer at clinical stage T3 or lower underwent the procedure at our institution. The procedure was completed successfully in all patients, without any intraoperative problems and all postoperative outcomes were satisfactory. Thus, dual-port laparoscopic abdominoperineal resection can be performed safely and feasibly in selected patients.
• Strategy of Laparoscopic Partial Resection for Gastric Gastrointestinal Stromal Tumors According to the Growth Pattern

  Hideki Kawamura, Susumu Shibasaki, Tadashi Yoshida, Shigenori Homma, Masahiro Takahashi, Akinobu Taketomi

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 25 (6) E175 - E179 1530-4515 2015/12 [Refereed][Not invited]
  
• A PROTEASOME INHIBITOR, BORTEZOMIB PREVENTS PANCREATIC ISLET GRAFT LOSS AFTER TRANSPLANTATION.

  Hitoshi Ono, Yoh Asahi, Tadashi Yoshida, Yasuyuki Koshizuka, Masaaki Watanabe, Utano Tomaru, Nozomi Kobayashi, Shin Emoto, Moto Fukai, Tsuyoshi Shimamura, Akinobu Taketomi, Satoru Todo, Kenichiro Yamashita

  TRANSPLANTATION 99 (11) S122 - S122 0041-1337 2015/11 [Refereed][Not invited]
  
• A proteasome inhibitor, bortezomib prevents pancreatic islet graft loss after transplantation

  Hitoshi Ono, Yoh Asahi, Tadashi Yoshida, Yasuyuki Koshizuka, Masaaki Watanabe, Utano Tomaru, Nozomi Kobayashi, Shin Emoto, Moto Fukai, Tsuyoshi Shimamura, Akinobu Taketomi, Satoru Todo, Kenichiro Yamashita

  XENOTRANSPLANTATION 22 S75 - S75 0908-665X 2015/11 [Refereed][Not invited]
  
• Clinicopathological characteristics and diagnostic performance of Wisteria floribunda agglutinin positive Mac-2-binding protein as a preoperative serum marker of liver fibrosis in hepatocellular carcinoma

  Masato Fujiyoshi, Atsushi Kuno, Masanori Gotoh, Moto Fukai, Hideki Yokoo, Hirofumi Kamachi, Toshiya Kamiyama, Masaaki Korenaga, Masashi Mizokami, Hisashi Narimatsu, Akinobu Taketomi

  JOURNAL OF GASTROENTEROLOGY 50 (11) 1134 - 1144 0944-1174 2015/11 [Refereed][Not invited]
   

  Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+)-M2BP) is a novel serum marker of liver fibrosis identified in glycoproteomic biomarker screening studies, and its clinicopathological characteristics have yet to be elucidated sufficiently for clinical utilization. We retrospectively analyzed the clinicopathology data and serum WFA(+)-M2BP levels in 376 hepatocellular carcinoma patients undergoing liver surgery. WFA(+)-M2BP was quantified in frozen serum samples collected at the time of surgery using the FastLec-Hepa method. Significant independent determinants of serum WFA(+)-M2BP levels included pathological diagnosis of cirrhosis, female gender, hepatitis C virus (HCV) infection, and liver dysfunction characteristics, such as abnormal indocyanine green retention rate at 15 min, platelet counts, albumin levels, alanine aminotransferase levels, and total bilirubin levels. Serum WFA(+)-M2BP levels increased with the pathological fibrosis stage and liver dysfunction severity. HCV infection significantly affected serum WFA(+)-M2BP levels throughout the pathological and functional progression of liver fibrosis, and the effect of gender was significant only in F4 stage patients with severe liver dysfunction. The diagnostic thresholds for cutoff index values for cirrhosis were 1.435 and 4.615 in HCV-negative and HCV-positive patients, respectively. Serum WFA(+)-M2BP levels at the time of operation were a significant predictor of hepatocellular carcinoma recurrence and overall survival in both HCV-negative and HCV-positive patients. Serum WFA(+)-M2BP levels reflected both the pathological and functional progression of liver fibrosis comprehensively and continuously. Elevated WFA(+)-M2BP levels were a significant risk factor for tumor recurrence and decreased overall survival after liver surgery independent of HCV infection.
• [Efficacy of Sorafenib for Extrahepatic Recurrence of Hepatocellular Carcinoma after Liver Resection].

  Yokoo H, Kamiyama T, Kakisaka T, Orimo T, Wakayama K, Shimada S, Tsuruga Y, Kamachi H, Taketomi A

  Gan to kagaku ryoho. Cancer & chemotherapy 42 (12) 1497 - 1499 0385-0684 2015/11 [Refereed][Not invited]
   

  Sorafenib is the first molecularly targeted drug recommended as a treatment for advanced hepatocellular carcinoma (HCC). Herein, we report the efficacy of sorafenib for extrahepatic recurrence of HCC. From September 2004 to March 2015, 47 patients who were diagnosed with recurrent HCC after liver resection were treated with sorafenib. The overall response rate was 17.5% (complete response: CR 1, partial response: PR 6, stable disease: SD 17, progressive disease: PD 13, SD beyond PD 3), and the disease control rate was 67.5%. The median time to disease progression, including extrahepatic recurrence, was significantly better than in the group with only intrahepatic metastasis (p=0.034). Therefore, sorafenib might be an effective treatment for extrahepatic recurrence of HCC.
• [Effect of Preoperative Bowel Preparation on Surgical Site Infection in Liver Surgery].

  Orimo T, Kamiyama T, Yokoo H, Kakisaka T, Wakayama K, Tsuruga Y, Kamachi H, Taketomi A

  Gan to kagaku ryoho. Cancer & chemotherapy 42 (12) 1887 - 1889 0385-0684 2015/11 [Refereed][Not invited]
   

  BACKGROUND: In our institute, the protocol for preoperative bowel preparation before liver surgery has been changed from polyethylene glycol lavage (NiflecR: N group) to magnesium citrate (MagcorolR: M group). METHODS: Ninety patients who underwent hepatectomy without reconstruction of the bile duct, gastorectomy, or colorectal resection from 2012 to 2013 were enrolled in this study. The impacts of preoperative bowel preparation were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups in terms of surgical procedure, operative time, bleeding amount, and duration of postoperative hospital stay. Surgical-site infection did not occur in both groups. There were no significant differences in the white blood cell count and platelet count of the patients in both groups. The C-reactive protein level in the M group was significantly lower than that in the N group on days 1, 3, and 5 after the operation, whereas the ammonia level in the M group was significantly lower than that in the N group on day 5 after the operation. CONCLUSION: It is possible to simplify preoperative bowel preparation associated with liver surgery while ensuring appropriate safety.
• Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy

  Toshiya Kamiyama, Hideki Yokoo, Tatsuhiko Kakisaka, Tatsuya Orimo, Kenji Wakayama, Hirofumi Kamachi, Yosuke Tsuruga, Kenichiro Yamashita, Tsuyoshi Shimamura, Satoru Todo, Akinobu Taketomi

  HEPATOLOGY RESEARCH 45 (10) E21 - E31 1386-6346 2015/10 [Refereed][Not invited]
   

  AimTo evaluate the oncological implications of multiplication of -fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) in patients with hepatocellular carcinoma (HCC). MethodsData were prospectively collected from 516 consecutive patients who underwent a curative primary hepatectomy for HCC between 1998 and 2010. The AP-factor (AFPxPIVKA-II) was evaluated in relation to 2-year survival outcomes by receiver-operator curve analysis to determine the cut-off values. Patient survival, recurrence-free survival and risk factors were analyzed in accordance with the preoperative AP-factor. ResultsThe AP-factor was categorized into three groups depending on the serum concentrations of AFP and PIVKA-II as follows: AP1 (n=206; AFP<200ng/mL and PIVKA-II<100mAU/mL), AP2 (n=152; AFPxPIVKA-II<10(5)) and AP3 (n=158; AFPxPIVKA-II10(5)). The AP-factor was found to be significantly related to pathological factors such as differentiation, portal vein invasion, hepatic vein invasion and intrahepatic metastasis. Multivariate analysis was performed to identify the risk factors for survival and recurrence. Albumin, AP-factor and pathological factors including portal vein invasion, hepatic vein invasion and intrahepatic metastasis are independent risk factors for survival. Tumor number, AP-factor, and a non-cancerous liver were determinants of recurrence. ConclusionThe AP-factor is closely related to differentiation and microscopic vascular invasion, and was selected by multivariate analysis as an independent factor for survival and recurrence, in HCC. Patients hopeful of obtaining good outcomes after a hepatectomy could be selected by the AP-factor evaluation.
• Long-term and perioperative outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with propensity score matching: a multi-institutional Japanese study

  Takeshi Takahara, Go Wakabayashi, Toru Beppu, Arihiro Aihara, Kiyoshi Hasegawa, Naoto Gotohda, Etsuro Hatano, Yoshinao Tanahashi, Toru Mizuguchi, Toshiya Kamiyama, Tetsuo Ikeda, Shogo Tanaka, Nobuhiko Taniai, Hideo Baba, Minoru Tanabe, Norihiro Kokudo, Masaru Konishi, Shinji Uemoto, Atsushi Sugioka, Koichi Hirata, Akinobu Taketomi, Yoshihiko Maehara, Shoji Kubo, Eiji Uchida, Hiroaki Miyata, Masafumi Nakamura, Hironori Kaneko, Hiroki Yamaue, Masaru Miyazaki, Tadahiro Takada

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 22 (10) 721 - 727 1868-6974 2015/10 [Refereed][Not invited]
   

  Background The aim of this study was to compare the long-term outcomes and perioperative outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) between well-matched patient groups. Methods Hepatocellular carcinoma patients underwent primary liver resection between 2000 and 2010, were collected from 31 participating institutions in Japan and were divided into LLR (n = 436) and OLR (n = 2969) groups. A one-to-one propensity case-matched analysis was used with covariates of baseline characteristics, including tumor characteristics and surgical procedures of hepatic resections. Long-term and short-term outcomes were compared between the matched two groups. Results The two groups were well balanced by propensity score matching and 387 patients were matched. There were no significant differences in overall survival and disease-free survival between LLR and OLR. The median blood loss (158 g vs. 400 g, P < 0.001) was significantly less with LLR, and the median postoperative hospital stay (13 days vs. 16 days, P < 0.001) was significantly shorter for LLR. Complication rate (6.7% vs. 13.0%, P = 0.003) was significantly less in LLR. Conclusion Compared with OLR, LLR in selected patients with HCC showed similar long-term outcomes, associated with less blood loss, shorter hospital stay, and fewer postoperative complications.
• Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study

  Hideo Baba, Yoshifumi Baba, Shinji Uemoto, Kazuhiro Yoshida, Akio Saiura, Masayuki Watanabe, Yoshihiko Maehara, Eiji Oki, Yasuharu Ikeda, Hiroyuki Matsuda, Masakazu Yamamoto, Mitsuo Shimada, Akinobu Taketomi, Michiaki Unno, Kenichi Sugihara, Yutaka Ogata, Susumu Eguchi, Seigo Kitano, Kazuo Shirouzu, Yasumitsu Saiki, Hiroshi Takamori, Masaki Mori, Toshihiko Hirata, Go Wakabayashi, Norihiro Kokudo

  ONCOTARGET 6 (32) 34004 - 34013 1949-2553 2015/10 [Refereed][Not invited]
   

  Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.
• IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway

  Kentaro Sumida, Yosuke Ohno, Junya Ohtake, Shun Kaneumi, Takuto Kishikawa, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura

  SCIENTIFIC REPORTS 5 13650  2045-2322 2015/09 [Refereed][Not invited]
   

  Myeloid-derived suppressor cells (MDSCs) are immune negative regulators in the tumour microenvironment. Interleukin (IL)-11, a member of IL-6 family cytokines, functions through the unique receptor IL-11 receptor alpha coupled with the common signal transducer gp130. IL-11-gp130 signalling causes activation of the JAK/STAT3 pathway. IL-11 is highly upregulated in many types of cancers and one of the most important cytokines during tumourigenesis and metastasis. However, the precise effect of IL-11 on differentiation into MDSCs is still unknown. Here, we found that CD11b(+) CD14(+) monocytic MDSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors in the presence of IL-11. IL-11-conditioned PBMCs induced higher expression of immunosuppressive molecules such as arginase-1. A reduction of T-cell proliferation was observed when MDSCs generated in the presence of IL-11 were co-cultured with CD3/CD28-stimulated, autologous T cells of healthy donors. Culture of normal PBMCs with IL-11 led to STAT3 phosphorylation and differentiation into MDSCs via STAT3 activation. We confirmed expressions of both IL-11 and phosphorylated STAT3 in tumour tissues of colorectal cancer patients. These findings suggest that monocytic MDSCs may be induced by IL-11 in the tumour microenvironment. Thus, IL-11-mediated regulation in functional differentiation of MDSCs may serve as a possible target for cancer immunotherapy.
• Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial

  Fumihiko Matsuzawa, Kiyoka Omoto, Takahiro Einama, Hironori Abe, Takashi Suzuki, Jun Hamaguchi, Terumi Kaga, Mami Sato, Masako Oomura, Yumiko Takata, Ayako Fujibe, Chie Takeda, Etsuya Tamura, Akinobu Taketomi, Kenichi Kyuno

  SPRINGERPLUS 4 509  2193-1801 2015/09 [Refereed][Not invited]
   

  Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.
• Use of transabdominal ultrasonography to preoperatively determine T-stage of proven colon cancers

  Susumu Shibasaki, Norihiko Takahashi, Shigenori Homma, Mutsumi Nishida, Tatsushi Shimokuni, Tadashi Yoshida, Hideki Kawamura, Noriko Oyama-Manabe, Kohsuke Kudo, Akinobu Taketomi

  ABDOMINAL IMAGING 40 (6) 1441 - 1450 0942-8925 2015/08 [Refereed][Not invited]
   

  Purpose: Although noninvasive and highly informative, transabdominal ultrasonography (US) is not yet an accepted means of staging colorectal cancer preoperatively. This prospective study evaluated the diagnostic accuracy of US in preoperative staging of patients with resectable colon cancers. Methods: A total of 98 patients with primary colon cancer diagnosed by colonoscopy at our institute between January, 2011 and June, 2014 underwent preoperative ultrasonographic tumor staging. Depth of tumor infiltration (T-stage) was assessed by standard means (i.e., extent of mural involvement), analyzing agreement in US and histopathology determinations. Results: All but two colon cancers (at splenic flexure) were detected by US (98%, 96/98). Compared with histopathology, overall accuracy of US in determining T-stage was 64% (61/96), indicating moderate reproducibility (kappa coefficient 0.48; 95% CI 0.35-0.62; p < 0.001). Using a three-tier approach of graded muscularis propria (MP) involvement (Tis/T1, below MP; T2, within MP; and T3/T4, beyond MP), diagnostic agreement increased to 89% (85/96), with good agreement (kappa coefficient 0.77; 95% CI 0.64-0.90; p < 0.001). No tumor characteristics or patient demographics influenced diagnostic agreement at any site in the colon. Conclusions: Given the potential to yield valuable information while limiting patient discomfort, US should be reconsidered as a means of assessing colon cancer.
• Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma

  Seiji Tsunematsu, Makoto Chuma, Toshiya Kamiyama, Noriyuki Miyamoto, Satoshi Yabusaki, Kanako Hatanaka, Tomoko Mitsuhashi, Hirofumi Kamachi, Hideki Yokoo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Tatsuya Orimo, Kenji Wakayama, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Yoko Tsukuda, Takuya Sho, Goki Suda, Kenichi Morikawa, Mitsuteru Natsuizaka, Mitsuru Nakanishi, Koji Ogawa, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto

  ABDOMINAL IMAGING 40 (6) 1492 - 1499 0942-8925 2015/08 [Refereed][Not invited]
   

  Differentiating intrahepatic cholangiocarcinoma (ICC) from poorly differentiated hepatocellular carcinoma (p-HCC) is often difficult, but it is important for providing appropriate treatments. The purpose of this study was to examine the features differentiating ICC from p-HCC on contrast-enhanced dynamic-computed tomography (CT).This study examined 42 patients with pathologically confirmed ICC (n = 19) or p-HCC (n = 23) for which contrast-enhanced dynamic CT data were available. CT images were analyzed for enhancement patterns during the arterial phase, washout pattern, delayed enhancement, satellite nodules, capsular retraction, lesion shape, and presence of an intratumoral hepatic artery, intratumoral hepatic vein, intratumoral portal vein, and bile duct dilation around the tumor, portal vein tumor thrombus, lobar atrophy, or lymphadenopathy.Univariate analysis revealed the presence of rim enhancement (p = 0.037), lobulated shape (p = 0.004), intratumoral artery (p < 0.001), and bile duct dilation (p = 0.006) as parameters significantly favoring ICC, while a washout pattern significantly favored p-HCC (p < 0.001). Multivariate analysis revealed intratumoral artery as a significant, independent variable predictive of ICC (p = 0.037), and 15 ICCs (78.9%) showed this feature. Washout pattern was a significant, independent variable favoring p-HCC (p = 0.049), with 15 p-HCCs (65.2%) showing this feature.The presence of an intratumoral artery in the arterial phase on contrast-enhanced dynamic CT was a predictable finding for ICC, and the presence of a washout pattern was a predictable finding for p-HCC, differentiating between ICC and p-HCC.
• 肝multicystic biliary hamartomaの1切除例

  今井 敦, 鈴木 友己, 神山 俊哉, 河崎 秀陽, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 70回 P - 4 2015/07
• Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver

  Shingo Shimada, Moto Fukai, Kenji Wakayama, Takahisa Ishikawa, Nozomi Kobayashi, Taichi Kimura, Kenichiro Yamashita, Toshiya Kamiyama, Tsuyoshi Shimamura, Akinobu Taketomi, Satoru Todo

  SURGERY TODAY 45 (7) 892 - 903 0941-1291 2015/07 [Refereed][Not invited]
   

  Hydrogen sulfide (H2S) ameliorates hepatic ischemia and reperfusion injury (IRI), but the precise mechanism remains elusive. We investigated whether sodium hydrogen sulfide (NaHS), a soluble derivative of H2S, would ameliorate hepatic IRI, and if so, via what mechanism. Mice were subjected to partial warm ischemia for 75 min followed by reperfusion. Either NaHS or saline was administered intravenously 10 min before reperfusion. The liver and serum were collected 3, 6, and 24 h after reperfusion. In the NaHS(-) group, severe IRI was apparent by the ALT leakage, tissue injury score, apoptosis, lipid peroxidation, and inflammation (higher plasma TNF-alpha, IL-6, IL-1 beta, IFN-gamma, IL-23, IL-17, and CD40L), whereas IRI was significantly ameliorated in the NaHS(+) group. These effects could be explained by the augmented nuclear translocation of Nrf2, and the resulting up-regulation of HO-1 and thioredoxin-1. Phosphorylation of the PDK-1/Akt/mTOR/p70S6k axis, which is known to mediate pro-survival and anti-apoptotic signals, was significantly augmented in the NaHS(+) group, with a higher rate of PCNA-positive cells thereafter. NaHS ameliorated hepatic IRI by direct and indirect anti-oxidant activities by augmenting pro-survival, anti-apoptotic, and anti-inflammatory signals via mechanisms involving Nrf-2, and by accelerating hepatic regeneration via mechanisms involving Akt-p70S6k.
• 膵癌術前放射線化学療法における術前胆道ドレナージ法の検討

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 折茂 達也, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 27回 626 - 626 2015/06
• 肝疾患 肝細胞癌

  横尾 英樹, 神山 俊哉, 武冨 紹信

  消化器外科学レビュー (株)総合医学社 2015-'16 73 - 79 2015/04 

  2013年に、「科学的根拠に基づく肝癌診療ガイドライン」が4年ぶりに改定された。経皮的ラジオ波焼灼術、肝切除術、肝移植術が完全寛解を得られる可能性のある治療法であり、生存期間を延長させる治療法としては、肝動脈塞栓療法、分子標的治療薬などがある。今後期待される治療法としては、C型肝炎を背景とした肝細胞癌切除後の再発予防におけるレチノイドや直接作用型抗ウイルス製剤、肝動脈塞栓に使用可能なビーズ製剤、ソラフェニブ以外の分子標的治療薬の開発などが挙げられる。
• Importance of luminal membrane mesothelin expression in intraductal papillary mucinous neoplasms

  Takahiro Einama, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Hiromi Kanno, Marin Ishikawa, Futoshi Kawamata, Yuji Konishi, Masanori Sato, Munenori Tahara, Kuniaki Okada, Shunji Muraoka, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Hiroyuki Furukawa, Satoru Todo

  ONCOLOGY LETTERS 9 (4) 1583 - 1589 1792-1074 2015/04 [Refereed][Not invited]
   

  The present study demonstrated that luminal membrane mesothelin expression is a reliable prognostic factor in gastric cancer. Intraductal papillary mucinous neoplasms (IPMNs) often exhibit a spectrum of dysplasia, ranging between adenoma and carcinoma. Therefore, an immunohistochemical analysis of mesothelin expression in IPMN was performed in the present study, focusing on the localization of mesothelin. IPMNs were classified into two groups, IPMNs associated with invasive carcinoma and low-high (L-H) grade dysplasias. The tumors were classified as mesothelin-positive or -negative and in the mesothelin-positive cases, the localization of mesothelin was evaluated as luminal membrane- or cytoplasmic-positive. Among the 37 IPMNs, mesothelin expression was observed in 21 samples (56.8%), including 46.2% (12 out of 26) of the L-H dysplasia and 81.8% (9 out of 11) of the invasive carcinoma samples (P=0.071). Luminal membrane localization was observed in 10 samples (27%), including 15.4% (4/26) of the L-H dysplasia samples and 54.5% (6 out of 11) of the invasive carcinoma samples (P=0.022). Six patients experienced post-operative recurrence, with five of the recurrent tumors exhibiting mesothelin expression and all six exhibiting luminal membrane localization. It was concluded that immunohistochemical examinations for mesothelin expression and localization are clinically useful for prognostic assessments and decision making regarding further treatment subsequent to surgical procedures in patients with IPMN.
• Accurate diagnosis of axillary lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid.

  Matsuzawa F, Einama T, Abe H, Suzuki T, Hamaguchi J, Kaga T, Sato M, Oomura M, Takata Y, Fujibe A, Takeda C, Tamura E, Taketomi A, Kyuno K

  Molecular and clinical oncology 3 (2) 299 - 302 2049-9450 2015/03 [Refereed][Not invited]
  
• [Treatment strategy for the recurrence of HCV infection after liver transplantation in the era of DAA].

  Taketomi A

  Nihon rinsho. Japanese journal of clinical medicine 日本臨床社 73 (2) 312 - 316 0047-1852 2015/02 [Refereed][Not invited]
  
• Small-for-Size Syndrome

  Yuji Soejima, Ken Shirabe, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Akinobu Taketomi, Yoshihiko Maehara

  Transplantation of the Liver: Third Edition 719 - 728 2015/01/28 [Refereed][Not invited]
  
• IL-6/STAT3 signaling impaired induction of cancer-antigen specific T cells via down-regulation of dendritic cells in tumor microenvironment.

  Ohno Yosuke, Kitamura Hidemitsu, Ohtake Junya, Kaneumi Shun, Sumida Kentaro, Homma Shigenori, Kawamura Hideki, Takahashi Norihiko, Taketomi Akinobu

  JOURNAL OF CLINICAL ONCOLOGY 33 (3) 0732-183X 2015/01/20 [Refereed][Not invited]
  
• The differences in microorganism growth on various dressings used to cover injection sites: inspection of the risk of catheter-related bloodstream infections caused by Gram-negative bacilli

  Hideki Kawamura, Norihiko Takahashi, Masahiro Takahashi, Akinobu Taketomi

  SURGERY TODAY 44 (12) 2339 - 2344 0941-1291 2014/12 [Refereed][Not invited]
   

  Sepsis caused by Gram-negative bacilli (GNB) is the most serious catheter-related bloodstream infection. However, the cause(s) of GNB propagation on the skin around needle or catheter insertion sites remain unclear. This observational study aimed to assess the differences in the microbial growth among various types of dressings used to cover injection sites, with a particular focus on GNB. We analyzed the bacterial populations on three types of surgical dressings; Tegaderm I.V. (semi-permeable, 27 sheets), IV3000 (highly permeable, 34 sheets) and Tegaderm CHG (chlorhexidine-impregnated, 26 sheets). The peripheral catheter site dressing was replaced every 3 days or when there was leakage or pain at the catheter site. Bacterial growth was observed in all Tegaderm I.V. and IV3000 sheets and in only one (3.8 %) Tegaderm CHG sheet. The GNB detection rate was significantly lower in the IV3000 group (2.9 %) than in the Tegaderm I.V. group (63.0 %). No GNB growth was identified in the Tegaderm CHG group. Semi-permeable dressings were insufficient to prevent GNB infections, whereas highly permeable or chlorhexidine-impregnated dressings could prevent GNB infections. Chlorhexidine-impregnated dressings can control almost all bacterial growth.
• Chondroma of the diaphragm mimicking a giant liver tumor with calcification: report of a case

  Yoh Asahi, Toshiya Kamiyama, Kazuaki Nakanishi, Hideki Yokoo, Munenori Tahara, Akihiro Usui, Tohru Funakoshi, Masanori Sato, Ayami Sasaki, Yoshihiro Matsuno, Akinobu Taketomi, Satoru Todo

  SURGERY TODAY 44 (12) 2361 - 2365 0941-1291 2014/12 [Refereed][Not invited]
   

  Extraskeletal chondroma is an unusual benign tumor, which rarely arises in the diaphragm. We report a case of chondroma of the diaphragm in a 31-year-old woman. Initially, a benign liver tumor with calcification was suspected, based on pre and intraoperative examination findings. Although parts of the tumor were contiguous with the diaphragm, its connections with the diaphragm were much narrower than its connection with the liver, which suggested a liver tumor. Pathological examination subsequently revealed that the chondroma was contiguous with the diaphragm and that there was a distinct border between the tumor and the liver; thus, the tumor was diagnosed as a chondroma of the diaphragm.
• Suprabasin as a novel tumor endothelial cell marker

  Mohammad T. Alam, Hiroko Nagao-Kitamoto, Noritaka Ohga, Kosuke Akiyama, Nako Maishi, Taisuke Kawamoto, Nobuo Shinohara, Akinobu Taketomi, Masanobu Shindoh, Yasuhiro Hida, Kyoko Hida

  CANCER SCIENCE 105 (12) 1533 - 1540 1347-9032 2014/12 [Refereed][Not invited]
   

  Recent studies have reported that stromal cells contribute to tumor progression. We previously demonstrated that tumor endothelial cells (TEC) characteristics were different from those of normal endothelial cells (NEC). Furthermore, we performed gene profile analysis in TEC and NEC, revealing that suprabasin (SBSN) was upregulated in TEC compared with NEC. However, its role in TEC is still unknown. Here we showed that SBSN expression was higher in isolated human and mouse TEC than in NEC. SBSN knockdown inhibited the migration and tube formation ability of TEC. We also showed that the AKT pathway was a downstream factor of SBSN. These findings suggest that SBSN is involved in the angiogenic potential of TEC and may be a novel TEC marker.
• Intra-arterial infusion of IA-call® combined with oral anticancer drugs for recurrent hepatocellular carcinoma after liver resection

  Kenji Wakayama, Toshiya Kamiyama, Hideki Yokoo, Tatsuhiko Kakisaka, Tatsuya Orimo, Yosuke Tsuruga, Hirofumi Kamachi, Takeshi Soyama, Yusuke Sakuhara, Daisuke Abo, Akinobu Taketomi

  Japanese Journal of Cancer and Chemotherapy 41 (12) 1503 - 1505 0385-0684 2014/11/01 [Refereed][Not invited]
   

  Continuous hepatic artery infusion chemotherapy for hepatocellular carcinoma (HCC) refractory to trans-arterial chemoembolization (TACE) sometimes adversely affects the quality of life (QOL) of patients. Herein, we report a one-shot intraarterial infusion of cisplatin powder (IA-call®) combined with oral anticancer drugs for recurrent HCC refractory to TACE after liver resection. From July 2013, 4 patients who were diagnosed with recurrent HCC refractory to TACE after liver resection were treated with IA-call® infusions at 1-2 month intervals. Encapsulated tegafur-uracil (UFT-E) or sorafenib were administered sequentially. On average, IA-call® was administered 3.6 times per patient at a mean dosage of 93 mg per treatment. UFT-E was combined with the IA-call® infusion for 3 patients, and a sorafenib combination was used for 1 patient. In terms of the therapeutic effects of these regimens, we observed complete response (CR) in 1 patient, partial response (PR) in 2 patients, and progressive disease (PD) in 1 patient (response rate: 75%). Therefore, one-shot intra-arterial infusion of IA-call® combined with oral anticancer drugs is an effective therapy for recurrent HCC while maintaining patients' QOL.
• Comparison of Single-Incision Plus One Additional Port Laparoscopy-assisted Anterior Resection with Conventional Laparoscopy-assisted Anterior Resection for Rectal Cancer

  Futoshi Kawamata, Shigenori Homma, Nozomi Minagawa, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi

  WORLD JOURNAL OF SURGERY 38 (10) 2716 - 2723 0364-2313 2014/10 [Refereed][Not invited]
   

  Reduced-port laparoscopic surgery is the latest innovation in minimally invasive surgery. We performed single-incision plus one additional port laparoscopy-assisted anterior resection (SILS + 1-AR) starting in August 2010. This study aimed at evaluating the feasibility of SILS + 1-AR and comparing it with that of conventional laparoscopy-assisted anterior resection (C-AR). Patients with preoperative clinical stage 0 to stage III rectal cancer were included. Demographic, intraoperative, and pathological examination data, as well as short-term outcome data, of 20 patients who underwent SILS + 1-AR were retrospectively compared with that of 20 patients who underwent C-AR. Invasiveness of the two procedures was also evaluated through a vital signs diary and hematological examination on postoperative days (POD) 1, 3, and 7. Operating time, mean estimated blood loss, the number of lymph nodes dissected, the number of lymph node metastases, and the mean distal resection margin length were not significantly different. However, postoperative neutrophil counts in the SILS + 1-AR group were lower than those in the C-AR group (P = 0.085). A significant difference in body temperature was observed in the SILS + 1-AR group on POD 1 (P = 0.028). No significant differences were observed in perioperative and overall morbidity between the two groups. Conversion to open surgery was required in 2 (10 %) of the 20 patients in the SILS + 1-AR group. The mean postoperative length of stay and recurrence rates were similar in the two groups. SILS + 1-AR for rectal cancer is similar to C-AR in safety, feasibility, and provision of oncological radicality.
• 腹腔鏡下残胃全摘の検討

  川村 秀樹, 柴崎 晋, 皆川 のぞみ, 本間 重紀, 高橋 典彦, 高橋 周作, 高橋 昌宏, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 137 - 137 0386-9768 2014/10
• 80歳以上高齢者胃癌に対する腹腔鏡下胃切除術の有用性についての検討

  柴崎 晋, 川村 秀樹, 皆川 のぞみ, 本間 重紀, 高橋 典彦, 高橋 周作, 高橋 昌宏, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 143 - 143 0386-9768 2014/10
• 体外式超音波検査を用いた大腸癌術前診断の試み

  深作 慶友, 本間 重紀, 柴崎 晋, 皆川 のぞみ, 川村 秀樹, 高橋 典彦, 下國 達志, 西田 睦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 175 - 175 0386-9768 2014/10
• 腸重積を伴う大腸癌に対し整復せずに待機的腹腔鏡下切除が可能であった3例

  大平 将史, 本間 重紀, 柴崎 晋, 皆川 のぞみ, 川村 秀樹, 高橋 典彦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 198 - 198 0386-9768 2014/10
• 肝細胞癌におけるFABP5発現の意義

  大畑 多嘉宣, 横尾 英樹, 神山 俊哉, 若山 顕治, 折茂 達也, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 218 - 218 0386-9768 2014/10
• 腹腔鏡下残胃全摘の検討

  川村 秀樹, 柴崎 晋, 皆川 のぞみ, 本間 重紀, 高橋 典彦, 高橋 周作, 高橋 昌宏, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 137 - 137 0386-9768 2014/10
• 80歳以上高齢者胃癌に対する腹腔鏡下胃切除術の有用性についての検討

  柴崎 晋, 川村 秀樹, 皆川 のぞみ, 本間 重紀, 高橋 典彦, 高橋 周作, 高橋 昌宏, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 143 - 143 0386-9768 2014/10
• 体外式超音波検査を用いた大腸癌術前診断の試み

  深作 慶友, 本間 重紀, 柴崎 晋, 皆川 のぞみ, 川村 秀樹, 高橋 典彦, 下國 達志, 西田 睦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 175 - 175 0386-9768 2014/10
• 腸重積を伴う大腸癌に対し整復せずに待機的腹腔鏡下切除が可能であった3例

  大平 将史, 本間 重紀, 柴崎 晋, 皆川 のぞみ, 川村 秀樹, 高橋 典彦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 47 (Suppl.2) 198 - 198 0386-9768 2014/10
• A safe combined nephrectomy and right lobectomy using the liver hanging maneuver for huge renal cell carcinoma directly invading the right lobe of the liver: report of a case

  Masanori Yoshimatsu, Ken Shirabe, Yoshihiro Nagao, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Tetsuo Ikeda, Katsunori Tatsugami, Yoshihiko Maehara

  SURGERY TODAY 44 (9) 1778 - 1782 0941-1291 2014/09 [Refereed][Not invited]
   

  We herein discuss a patient who underwent simultaneous combined right nephrectomy and right lobectomy of the liver. A 64-year-old male was diagnosed with a huge right renal cell carcinoma (RCC), 13 cm in diameter, which was invading directly into the right hepatic lobe. This type of RCC has been rarely reported, and an anterior approach using the liver hanging maneuver was extremely useful during hepatic parenchymal dissection. The liver parenchymal dissection was performed prior to mobilization of the liver, because the mobilization of the right lobe of the liver was impossible. During the hepatic parenchymal resection, the liver was suspended with the tape and transected, and thereafter, retroperitoneal dissection, nephrectomy and right lobectomy of the liver were completed. The patient was discharged from the hospital on the 12th postoperative day with an uneventful clinical course. The anterior approach using the liver hanging maneuver during hepatic parenchymal resection can be safe and feasible for huge RCC invading the right hepatic lobe.
• 巨大肝細胞癌手術症例の治療成績

  柿坂 達彦, 神山 俊哉, 横尾 英樹, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  Japanese Journal of Acute Care Surgery 日本Acute Care Surgery学会 4 (2) 304 - 304 2014/09
• 肝細胞癌におけるFatty Acid Binding Protein 5発現の臨床的意義(Clinical significance of Fatty Acid Binding Protein 5 in hepatocellular carcinoma)

  大畑 多嘉宣, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本癌学会総会記事 73回 P - 2304 0546-0476 2014/09
• 肝細胞癌におけるAPC-binding protein EB1の予後・再発予測因子としての有用性(APC-binding protein EB1 is an important predictive factor for the prognosis and recurrence in hepatocellular carcinoma)

  相山 健, 折茂 達也, 横尾 英樹, 大畑 多嘉宣, 畑中 佳奈子, 畑中 豊, 松野 吉宏, 神山 俊哉, 武冨 紹信

  日本癌学会総会記事 73回 P - 2310 0546-0476 2014/09
• CXCR7を標的とした新規血管新生阻害療法の可能性(CXCR7 as a novel target for anti-angiogenic therapy)

  山田 健司, 間石 奈湖, 秋山 廣輔, 大賀 則孝, 川本 泰輔, 進藤 正信, 高橋 典彦, 神山 俊哉, 樋田 泰浩, 武冨 紹信, 樋田 京子

  日本癌学会総会記事 73回 J - 1006 0546-0476 2014/09 [Refereed][Not invited]
  
• Diacylglycerol Kinase delta Phosphorylates Phosphatidylcholine-specific Phospholipase C-dependent, Palmitic Acid-containing Diacylglycerol Species in Response to High Glucose Levels

  Hiromichi Sakai, Sayaka Kado, Akinobu Taketomi, Fumio Sakane

  JOURNAL OF BIOLOGICAL CHEMISTRY 289 (38) 26607 - 26617 0021-9258 2014/09 [Refereed][Not invited]
   

  Decreased expression of diacylglycerol (DG) kinase (DGK) delta in skeletal muscles is closely related to the pathogenesis of type 2 diabetes. To identify DG species that are phosphorylated by DGK delta in response to high glucose stimulation, we investigated high glucose-dependent changes in phosphatidic acid (PA) molecular species in mouse C2C12 myoblasts using a newly established liquid chromatography/MS method. We found that the suppression of DGK delta 2 expression by DGK delta-specific siRNAs significantly inhibited glucose-dependent increases in 30:0-, 32:0-, and 34:0-PA and moderately attenuated 30:1-, 32:1-, and 34:1-PA. Moreover, overexpression of DGK delta 2 also enhanced the production of these PA species. MS/MS analysis revealed that these PA species commonly contain palmitic acid (16:0). D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), significantly inhibited the glucose-stimulated production of the palmitic acid-containing PA species. Moreover, PC-PLC was co-immunoprecipitated with DGK delta 2. These results strongly suggest that DGK delta preferably metabolizes palmitic acid-containing DG species supplied from the PC-PLC pathway, but not arachidonic acid (20:4)-containing DG species derived from the phosphatidylinositol turnover, in response to high glucose levels.
• Assessment of Postoperative Symptoms After Laparoscopy-Assisted Distal Gastrectomy for Stage I Gastric Cancer

  Hideki Kawamura, Norihiko Takahashi, Shigenori Homma, Nozomi Minagawa, Susumu Shibasaki, Masahiro Takahashi, Akinobu Taketomi

  INTERNATIONAL SURGERY 99 (5) 645 - 649 0020-8868 2014/09 [Refereed][Not invited]
   

  Laparoscopic gastrectomy has the advantage of early recovery at the initial phase after surgery. However, there are only few reports of mid-or long-term observations of patients' quality of life. In all, 254 Stage IA or IB [laparoscopy-assisted distal gastrectomy (LADG): 177, open distal gastrectomy (ODG): 77] patients were enrolled. Heart burn, diarrhea, abdominal pain, amount of food intake, and body weight of each patient were investigated at 1 month, 3 months, 6 months, and 1 year after surgery. Recovery of the amount of oral intake for the LADG group occurred earlier than for the ODG group; significant differences were seen at months 1 and 6 postoperatively. A significantly lower incidence of diarrhea was observed in the LADG group at months 6 and 12 postoperatively. Early recovery of the amount of food intake and fewer incidences of diarrhea were shown to have mid-term merits for postgastrectomy symptoms.
• Immunohistochemical analysis of cancer stem cell markers in pancreatic adenocarcinoma patients after neoadjuvant chemoradiotherapy

  Tatsuzo Mizukami, Hirofumi Kamachi, Tomoko Mitsuhashi, Yosuke Tsuruga, Yutaka Hatanaka, Toshiya Kamiyama, Yoshihiro Matsuno, Akinobu Taketomi

  BMC CANCER 14 687  1471-2407 2014/09 [Refereed][Not invited]
   

  Background: Cancer stem cells (CSCs) have been reported to play an important role in chemoradiation resistance. Although the association of CSC markers with clinicopathological outcomes after neoadjuvant chemoradiotherapy (NACRT) has been reported in various types of cancers, there have been no such reports for pancreatic cancer. Here we examined the sequential changes in CSC marker expressions after NACRT in patients with pancreatic adenocarcinoma (PA) and the impact of these changes on the prognosis. Methods: We used immunohistochemistry to evaluate the expressions of the CSC markers epithelial cell adhesion molecule (EpCAM), CD24, CD44, CD133, CXCR4 and Aldehyde dehydrogenase 1 (ALDH1) in resected specimens obtained from 28 PA patients, and we compared these expressions with the patients' clinicopathological parameters and survival data. Results: The expression frequencies of CD44 and ALDH1 were significantly higher in the NACRT group (n = 17) compared to the non-NACRT group (n = 11), but the CD133 expression was significantly lower in the NACRT group. In the NACRT group, the expression of CD133 was inversely correlated with that of ALDH1, and CD133 +/ALDH1-expression was associated with an unfavorable patient outcome. Conclusion: This is the first report showing that NACRT may influence the expression frequencies of CD44, CD133 and ALDH1 in PA patients. Moreover, CD133 and ALDH1 expressions may be useful predictors of prognosis in PA patients who have received NACRT.
• Minimally Invasive Image Analysis of Biliary-Pancreatic Structure for Preoperative Simulation

  Takashi Maeda, Kozo Konishi, Kazuo Tanoue, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Makoto Hashizume

  HEPATO-GASTROENTEROLOGY 61 (134) 1744 - 1747 0172-6390 2014/09 [Refereed][Not invited]
   

  For preoperative assessment of the pancreatic tumors, we developed minimally invasive method to extract the Pancreatic duct from multidetector row computed tomography (MD-CT) images and to visualize the biliary-pancreatic structures, tumor and adjacent organs simultaneously using an image workstation.
• Outcomes of living donor liver transplantation for hepatitis C virus-positive recipients in Japan: results of a nationwide survey

  Nobuhisa Akamatsu, Yasuhiko Sugawara, Norihiro Kokudo, Susumu Eguchi, Toshiyoshi Fujiwara, Hideki Ohdan, Hiroaki Nagano, Akinobu Taketomi, Yuko Kitagawa, Mitsuo Shimada, Yonson Ku, Katsuhiko Yanaga, Ken Shirabe, Toru Ikegami, Masashi Mizokami, Masahiro Takeuchi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 27 (8) 767 - 774 0934-0874 2014/08 [Refereed][Not invited]
   

  A nationwide survey of living donor liver transplantation (LDLT) for hepatitis C virus (HCV)-positive recipients was performed in Japan. A total of 514 recipients are reported and included in the study. The cumulative patient survival rate at 5 and 10 years was 72% and 63%, respectively. Of the 514 recipients, 142 patients (28%) died until the end of the observation, among which the leading cause was recurrent hepatitis C (42 cases). According to Cox regression multivariate analysis, donor age (> 40), non-right liver graft, acute rejection episode, and absence of a sustained virologic response were independent prognostic factors. Of the 514 recipients, 361 underwent antiviral treatment mainly with pegylated-interferon and ribavirin (preemptive treatment in 150 patients and treatment for confirmed recurrent hepatitis in 211). The dose reduction rate and discontinuation rate were 40% and 42%, respectively, with a sustained virologic response rate of 43%. In conclusion, patient survival of HCV-positive recipients after LDLT was good, with a 10-year survival of 63%. Right liver graft might be preferable for HCV-positive recipients in an LDLT setting.
• Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience

  Ueda Y, Ikegami T, Akamatsu N, Soyama A, Shinoda M, Goto R, Okajima H, Yoshizumi T, Taketomi A, Kitagawa Y, Eguchi S, Kokudo N, Uemoto S, Maehara Y

  Journal of Gastroenterology 2014/08 [Refereed][Not invited]
  
• Laparoscopic gastrectomy after coronary artery bypass grafting using the right gastroepiploic artery: a report of two cases.

  Kawamura H, Takahashi N, Tahara M, Takahashi M, Taketomi A

  Asian journal of endoscopic surgery 7 (3) 251 - 255 1758-5902 2014/08 [Refereed][Not invited]
   

  We successfully executed laparoscopic distal gastrectomy in two patients who had previously undergone coronary artery bypass grafting using the right gastroepiploic artery (RGEA). A laparoscopic distal gastrectomy preserving the RGEA graft with Roux-en-Y reconstruction was performed on two men, one 69 years of age and one 73 years of age. In both cases, the RGEA was used during coronary artery bypass grafting for the posterior descending branch. The laparoscopic approach helped avoid injury to the RGEA associated with laparotomy and retractor placement. In addition, the locations of ports necessary for laparoscopy were situated away from the RGEA graft and from adhesions resulting from bypass. Using typical laparoscopic settings, we were able to easily identify the grafted RGEA. Thus, laparoscopic distal gastrectomy is not only less invasive than open gastrectomy procedures, but it is also associated with a lower risk of injury to the RGEA graft.
• Hand-assisted laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen complicated by chronic disseminated intravascular coagulation: A case report

  Tatsuhiko Kakisaka, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Kenji Wakayama, Yosuke Tsuruga, Hirofumi Kamachi, Taisuke Harada, Fumi Kato, Yosuke Yamada, Tomoko Mitsuhashi, Akinobu Taketomi

  Asian Journal of Endoscopic Surgery 7 (3) 275 - 278 1758-5902 2014/08 [Refereed][Not invited]
  
• ICG蛍光法とニードルガイディングテクニックを併用した肝亜区域切除術

  折茂 達也, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 RV - 1 2014/07
• 99mTc-GSAシンチグラフィーとCTの3D fusion画像を用いた残肝機能予測

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 折茂 達也, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 O - 5 2014/07
• 肝切除術におけるリスク評価と治療成績向上に向けた対策 NCDデータに基づいた肝切除術におけるリスク評価

  武冨 紹信, 宮田 裕章, 柿坂 達彦, 横尾 英樹, 友滝 愛, 今野 弘之, 後藤 満一, 若林 剛, 森 正樹, 一般社団法人日本消化器外科学会データベース委員会

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 PD - 1 2014/07
• 肝切除術におけるリスク評価と治療成績向上に向けた対策 99mTc-GSAシンチグラフィを用いた肝障害度別換算ICGR15による肝予備能の評価

  若山 顕治, 神山 俊哉, 柿坂 達彦, 折茂 達也, 横尾 英樹, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 PD - 5 2014/07
• HBV関連肝細胞癌手術症例の術後再発に関する検討

  柿坂 達彦, 神山 俊哉, 横尾 英樹, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 P - 3 2014/07
• 肝細胞癌における門脈侵襲・予後・再発予測因子としての腫瘍マーカー AFPとPIVKA-IIの積=AP-factorの検討

  神山 俊哉, 横尾 英樹, 柿坂 達彦, 折茂 達也, 若山 顕治, 蒲池 浩文, 敦賀 陽介, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 P - 6 2014/07
• 大腸癌多発肝転移に対する外科切除のタイミング

  横尾 英樹, 神山 俊哉, 柿坂 達彦, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 O - 2 2014/07
• 血管合併切除を要する局所進行肝門部胆管癌における血管確保手技

  蒲池 浩文, 敦賀 陽介, 若山 顕示, 折茂 達也, 柿坂 達彦, 横尾 英樹, 山下 健一郎, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 69回 O - 1 2014/07
• 浸潤性膵管癌の術前治療 当科における局所進行膵癌に対する術前放射線化学療法の検討

  蒲池 浩文, 敦賀 陽介, 若山 顕治, 折茂 達也, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 387 - 387 2014/06
• 肝右葉巨大肝癌に対する、ベッセルシーリングシステムを用いた右横隔膜切除、肝右葉受動先行右系肝葉切除

  若山 顕治, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 折茂 達也, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 448 - 448 2014/06
• 99mTc-GSAシンチグラフィーとCTの3D fusion画像を用いた機能的肝切除率の算出

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 折茂 達也, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 484 - 484 2014/06
• 多発性大腸癌肝転移の治療方針

  横尾 英樹, 神山 俊哉, 柿坂 達彦, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 549 - 549 2014/06
• 人工血管を用いた肝切除症例の検討

  折茂 達也, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 588 - 588 2014/06
• 肝エキノコックス症に対する腹腔鏡下肝切除術

  柿坂 達彦, 神山 俊哉, 横尾 英樹, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 26回 686 - 686 2014/06
• 当科における肝細胞癌に対する腹腔鏡下肝切除術の成績

  柿坂 達彦, 神山 俊哉, 横尾 英樹, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本癌治療学会誌 (一社)日本癌治療学会 49 (3) 1669 - 1669 0021-4671 2014/06
• 横行結腸癌肝転移切除後断端再発に対し施行したRFA後に、biloma内再発をきたした1例

  深作 慶友, 神山 俊哉, 若山 顕治, 折茂 達也, 敦賀 陽介, 柿坂 達彦, 横尾 英樹, 蒲池 浩文, 武富 紹信

  北海道外科雑誌 北海道外科学会 59 (1) 62 - 62 0288-7509 2014/06
• 北海道大学病院陽子線治療センターの小児陽子線治療開始準備状況

  橋本 孝之, 清水 伸一, 鬼丸 力也, 大島 淳二郎, 長 祐子, 井口 晶裕, 山口 秀, 小林 浩之, 寺坂 俊介, 岡田 忠雄, 本田 昌平, 武冨 紹信, 岡村 麗香, 中村 宏治, 白土 博樹

  日本小児血液・がん学会雑誌 (NPO)日本小児血液・がん学会 51 (2) 183 - 183 2187-011X 2014/06 [Not refereed][Not invited]
  
• Percutaneous transhepatic gallbladder drainage followed by elective laparoscopic cholecystectomy in patients with moderate acute cholecystitis under antithrombotic therapy

  Susumu Shibasaki, Norihiko Takahashi, Hirofumi Toi, Ichiro Tsuda, Takahisa Nakamura, Taiji Hase, Nozomi Minagawa, Shigenori Homma, Hideki Kawamura, Akinobu Taketomi

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 21 (5) 335 - 342 1868-6974 2014/05 [Refereed][Not invited]
   

  BackgroundStandard treatment for acute cholecystitis (AC) in patients receiving antithrombotic drugs has not been established. We evaluated the safety of percutaneous transhepatic gallbladder drainage (PTGBD) followed by elective laparoscopic cholecystectomy (LC) in patients with moderate AC who were receiving antithrombotics. MethodsSeventy-five patients received PTGBD from January 2006 to March 2013 followed by elective LC for moderate AC. Patients were divided into Group A, which consisted of patients receiving antithrombotic therapy (n = 23), and Group B, which included the remaining patients (n = 52). We analyzed clinical outcomes and perioperative complications between groups. ResultsNo hemorrhagic events occurred during PTGBD insertion regardless of antithrombotic treatment. The open conversion rate was not significantly different between the two groups. Postoperative complications were found in 10 patients (13.3%). The rate of postoperative complications in Group A was slightly higher than that in Group B, but the difference was not significant (21.7% vs. 9.6%; P = 0.15). Complications associated with PTGBD occurred in six patients (8%). There were no significant differences in the incidence of these complications, operation time, intraoperative blood loss, or length of postoperative hospital stay. ConclusionsPercutaneous transhepatic gallbladder drainage followed by elective LC may be an effective therapeutic strategy for moderate AC in patients receiving antithrombotic therapy.
• 当科における脳死肝移植待機中死亡症例の検討

  青柳 武史, 杉山 昂, 後藤 了一, 大浦 哲, 渡辺 正明, 山下 健一郎, 鈴木 友己, 嶋村 剛, 太田 稔, 山本 真由美, 坂井 絢, 武冨 紹信, 藤堂 省

  移植 (一社)日本移植学会 49 (1) 68 - 68 0578-7947 2014/05
• A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.

  Nozomi Minagawa, Hideyasu Sakihama, Nozomi Kobayashi, Mito Obara, Susumu Shibasaki, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Shigenori Homma, Hideki Yokoo, Hirofumi Kamachi, Hideki Kawamura, Norihiko Takahashi, Toshiya Kamiyama, Akinobu Taketomi

  JOURNAL OF CLINICAL ONCOLOGY 32 (15) 0732-183X 2014/05 [Refereed][Not invited]
  
• Activation of IL-6/STAT3-signaling cascade induces suppression of antigen presentation by human dendritic cells

  Hidemitsu Kitamura, Yousuke Ohno, Junya Ohtake, Shun Kaneumi, Takuto Kishikawa, Satoshi Terada, Kentaro Sumida, Kazutaka Masuko, Toshiyuki Kita, Norihiko Takahashi, Akinobu Taketomi

  JOURNAL OF IMMUNOLOGY 192 0022-1767 2014/05 [Refereed][Not invited]
  
• Usefulness of artificial vascular graft for venous reconstruction in liver surgery

  Tatsuya Orimo, Toshiya Kamiyama, Hideki Yokoo, Tatsuhiko Kakisaka, Kenji Wakayama, Yosuke Tsuruga, Hirofumi Kamachi, Akinobu Taketomi

  WORLD JOURNAL OF SURGICAL ONCOLOGY 12 (1) 113  1477-7819 2014/04 [Refereed][Not invited]
   

  Background: The purpose of this study was to evaluate the results of hepatectomy with inferior vena cava or hepatic vein resection, followed by vessel reconstruction with an artificial vascular graft. Methods: From 2000 to 2011, 1,434 patients underwent several types of hepatectomy at our institution. Of these, we reviewed the cases of eight patients (0.56%) who underwent hepatectomy with inferior vena cava or hepatic vein resection and subsequent reconstruction using an expanded polytetrafluoroethylene (PTFE) graft. Results: We resected the inferior vena cava in six patients and the hepatic vein in two patients. All eight patients underwent subsequent reconstruction using an expanded PTFE graft. The median operative time was 443 minutes and the median blood loss was 2,017 mL. The median postoperative hospital stay period was 18.5 days and the in-hospital mortality rate was 0%. Complications occurred in four patients: two patients experienced bile leakage, one experienced a wound infection, and one experienced pleural effusion. The two patients who experienced bile leakage had undergone reoperation on postoperative day 1. No complication with the artificial vascular graft occurred in these eight cases. Histological invasion to the replaced inferior vena cava or hepatic vein was confirmed in four cases. All artificial vascular grafts remained patent during the observation period. Conclusions: Hepatectomy combined with inferior vena cava or hepatic vein resection, followed by reconstruction with an expanded PTFE graft can be performed safely in selected patients.
• Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients

  Yuki Ohishi, Makoto Nakamuta, Naoko Ishikawa, Ohki Saitoh, Hitomi Nakamura, Yoshihiro Aiba, Atsumasa Komori, Kiyoshi Migita, Hiroshi Yatsuhashi, Nobuyoshi Fukushima, Motoyuki Kohjima, Tsuyoshi Yoshimoto, Kunitaka Fukuizumi, Makoto Ishibashi, Takashi Nishino, Ken Shirabe, Akinobu Taketomi, Yoshihiko Maehara, Hiromi Ishibashi, Minoru Nakamura

  JOURNAL OF GASTROENTEROLOGY 49 (2) 332 - 342 0944-1174 2014/02 [Refereed][Not invited]
   

  To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes. We selected four (rs683369, rs2282143, rs622342 and rs1443844) OCT-1 single nucleotide polymorphisms (SNPs), and genotyped these SNPs using the TaqMan probe method in 275 Japanese PBC patients and 194 gender-matched, healthy volunteers as controls. The Chi-square test revealed that the rs683369 variant allele (G) was associated with insusceptibility to PBC development [P = 0.009, odds ratio (OR) 0.60, 95 % confidence interval (CI) 0.40-0.88] in an allele model, and that the rs683369 variant allele (G) was associated with jaundice-type progression in a minor allele dominant genotype model (P = 0.032, OR 3.10, 95 % CI 1.05-9.14). The OCT-1 rs2282143 variant (T) and rs622342 variant (C) were also associated with jaundice-type progression in a minor allele recessive genotype model (P = 0.0002, OR 10.58, 95 % CI 2.36-47.54, and P = 0.006, OR 7.84, 95 % CI 1.39-44.36, respectively). Furthermore, the association of OCT-1 rs683369 and rs622342 with susceptibility to jaundice-type progression was confirmed by a replication study with a distinct set of PBC patients who underwent liver transplantation. The present study is the first report on the association of OCT-1 genetic polymorphisms with the overall development and jaundice-type progression of PBC.
• Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor-B/mitogen-activated protein kinase

  Makoto Chuma, Naoya Sakamoto, Akira Nakai, Shuhei Hige, Mitsuru Nakanishi, Mitsuteru Natsuizaka, Goki Suda, Takuya Sho, Kanako Hatanaka, Yoshihiro Matsuno, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Gen Fujii, Kosuke Tashiro, Yoko Hikiba, Mitsuaki Fujimoto, Masahiro Asaka, Shin Maeda

  CARCINOGENESIS 2 35 (2) 272 - 281 0143-3334 2014/02 [Refereed][Not invited]
   

  Heat shock factor 1 (HSF1), a major transactivator of stress responses, has been implicated in carcinogenesis in various organs. However, little is known about the biological functions of HSF1 in the development of hepatocellular carcinoma (HCC). To clarify the functional role of HSF1 in HCC, we established HSF1-knockdown (HSF1 KD) KYN2 HCC cells by stably expressing either small hairpin RNA (shRNA) against HSF1 (i.e. HSF1 KD) or control shRNA (HSF1 control). Tumorigenicity was significantly reduced in orthotopic mice with HSF1 KD cells compared with those with HSF1 control cells. Reduced tumorigenesis in HSF1 KD cells appeared attributable to increased apoptosis and decreased proliferation. Tumor necrosis factor--induced apoptosis was increased in HSF1 KD cells and HSF1(/) mouse hepatocytes compared with controls. Decreased expression of IB kinase , a positive regulator of nuclear factor-B, was also observed in HSF1 KD cells and HSF1(/) mouse hepatocytes. Furthermore, expression of bcl-2-associated athanogene domain 3 (BAG3) was dramatically reduced in HSF1 KD cells and HSF1(/) mouse hepatocytes. We also found that epidermal growth factor-stimulated mitogen-activated protein kinase signaling was impaired in HSF1 KD cells. Clinicopathological analysis demonstrated frequent overexpression of HSF1 in human HCCs. Significant correlations between HSF1 and BAG3 protein levels and prognosis were also observed. In summary, these results identify a mechanistic link between HSF1 and liver tumorigenesis and may provide as a potential molecular target for the development of anti-HCC therapies.
• C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma

  Futoshi Kawamata, Shigenori Homma, Hirofumi Kamachi, Takahiro Einama, Yasutaka Kato, Masumi Tsuda, Shinya Tanaka, Masahiro Maeda, Kazunori Kajino, Okio Hino, Norihiko Takahashi, Toshiya Kamiyama, Hiroshi Nishihara, Akinobu Taketomi, Satoru Todo

  JOURNAL OF GASTROENTEROLOGY 49 (1) 81 - 92 0944-1174 2014/01 [Refereed][Not invited]
   

  Background Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Methods Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Results Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P < 0.01). Conclusion The luminal membrane expression of mesothelin was associated with unfavorable prognosis of CRC patients with lymph nodemetastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.
• High drain amylase and lipase values predict post-operative pancreatitis for choledochal cyst

  Shohei Honda, Tadao Okada, Hisayuki Miyagi, Masashi Minato, Akinobu Taketomi

  African Journal of Paediatric Surgery 11 (2) 124 - 127 0974-5998 2014 [Refereed][Not invited]
   

  Background: Post-operative pancreatitis is a severe complication after cyst excision with hepaticoenterostomy (CEHE) for choledochal cysts. The aim of this study was to examine the dynamic post-operative changes in drain amylase and lipase values after CEHE for choledochal cysts, and then compare these values with the clinical outcomes in order to identify risk factors for post-operative pancreatitis after CEHE. Patients and Methods: A total of 19 patients with choledochal cysts were retrospectively examined in the period between 2005 and 2012. The amylase and lipase values in the drainage and the serum, and the output of the effluent were measured post-operatively. The associations between their values and the clinical outcomes were evaluated. Results: Six were found to have a pancreatic leak according to an international study group definition. In two of them, who developed post-operative pancreatitis, both amylase and lipase values in drainage were markedly elevated at 1 post-operative day (1 POD). The drain amylase value seemed to elevate rather specifically dependent on the occurrence of post-operative pancreatitis, whereas the drain lipase value tended to elevate regardless of the presence/absence of post-operative pancreatitis. Conclusion: It was indicated that amylase and lipase values in drainage at 1 POD could be effective predictors of post-operative pancreatitis after CEHE.
• 人工血管による肝静脈再建を伴う肝切除術を施行した肝細胞癌の2例

  折茂 達也, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  北海道外科雑誌 北海道外科学会 58 (2) 181 - 181 0288-7509 2013/12
• 肝原発腺扁平上皮癌の1例

  宮岡 陽一, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信, 畑中 佳奈子

  北海道外科雑誌 北海道外科学会 58 (2) 182 - 183 0288-7509 2013/12
• 当科における胆管癌再発症例の検討

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 折茂 達也, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  北海道外科雑誌 北海道外科学会 58 (2) 184 - 184 0288-7509 2013/12
• RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients

  Shohei Honda, Hisayuki Miyagi, Hiromu Suzuki, Masashi Minato, Masayuki Haruta, Yasuhiko Kaneko, Kanako C. Hatanaka, Eiso Hiyama, Takehiko Kamijo, Tadao Okada, Akinobu Taketomi

  PEDIATRIC SURGERY INTERNATIONAL 29 (11) 1147 - 1152 0179-0358 2013/11 [Refereed][Not invited]
   

  The RAS association domain family protein 1 (RASSF1A) is known to be frequently inactivated by promoter hypermethylation in cancers. This study investigated the association of RASSF1A methylation with clinical outcomes in hepatoblastoma patients and whether it is correlated with the histological phenotype of hepatoblastoma tumors. Seventy-four hepatoblastoma tumors were obtained from patients enrolled in the Japanese study group for pediatric liver tumor protocol-2. From nine formalin-fixed, paraffin-embedded specimens, we extracted DNA by dissection under a light microscope. We examined the methylation status of the RASSF1A promoter region by bisulfite pyrosequencing. Twenty-five (33.8 %) hepatoblastoma tumors were classified as having methylated RASSF1A. The RASSF1A methylation was significantly associated with metastatic tumors and a poor prognosis. Despite the complete resection, five pretreatment extent of disease II tumors showed recurrence or distant metastasis postoperatively. Among these cases, four tumors were found to show RASSF1A methylation. When compared to histologically different types of cell, RASSF1A methylation values in samples of the normal liver, fetal type, and embryonal type, were significantly elevated in ascending order. We confirmed that RASSF1A methylation is a significant prognostic indicator in hepatoblastomas, and it may become a promising molecular marker to stratify patients into appropriate risk groups.
• [Long-term survival of a patient with metachronous lymph node metastasis and bile duct tumor thrombus due to hepatocellular carcinoma successfully treated with repeated surgery].

  Kakisaka T, Kamiyama T, Yokoo H, Orimo T, Wakayama K, Tsuruga Y, Kamachi H, Hatanaka K, Taketomi A

  Gan to kagaku ryoho. Cancer & chemotherapy 12 40 (12) 1831 - 1833 0385-0684 2013/11 [Refereed][Not invited]
   

  A 64-year-old man with hepatocellular carcinoma located in the left lateral lobe and segment 5 was referred to our hospital for surgical treatment. We performed left lateral sectionectomy and segmentectomy 5. The pathological diagnosis was moderately to poorly differentiated hepatocellular carcinoma, and the pathological stage was stage III. Eight months later, intrahepatic recurrence in segment 1 and lymph node metastasis in the hepatoduodenal ligament occurred. Partial resection of segment 1 was performed, and the metastatic lymph node was surgically removed. Twenty four months after the first operation, lymph node metastases along the lesser curvature and retropancreatic space were extirpated. Lymph node metastases along the common hepatic artery were removed 76 months after the first operation. The patient developed jaundice 88 months after the initial surgery, and the bile duct tumor thrombus derived from intrahepatic recurrence in segment 1 caused obstructive jaundice. After percutaneous transhepatic biliary drainage, we performed median sectionectomy and bile duct tumor thrombus removal without bile duct resection. At his 8-year follow-up visit after the primary operation, the patient was healthy and did not show any signs of recurrence. Lymph node metastasis and bile duct tumor thrombus are rare patterns of hepatocellular carcinoma recurrence, and aggressive surgery can result in long-term survival when complete resection is anticipated.
• EX-VIVO GENERATION OF HUMAN REGULATORY T CELLS BY CD80/CD86 COSTIMULATION BLOCKADE

  Nagatsu Akihisa, Yamashita Kenichiro, Zaitsu Masaaki, Emoto Shin, Asahi Yoh, Ono Hitoshi, Goto Ryoichi, Bashuda Hisashi, Taketomi Akinobu, Okumura Ko, Todo Satoru

  TRANSPLANT INTERNATIONAL 26 71 - 71 0934-0874 2013/11 [Refereed][Not invited]
  
• Surgical management of hepatocellular carcinoma with tumor thrombi in the inferior vena cava or right atrium

  Kenji Wakayama, Toshiya Kamiyama, Hideki Yokoo, Tatsuhiko Kakisaka, Hirofumi Kamachi, Yosuke Tsuruga, Kazuaki Nakanishi, Tsuyoshi Shimamura, Satoru Todo, Akinobu Taketomi

  World Journal of Surgical Oncology 11 259  1477-7819 2013/10/05 [Refereed][Not invited]
   

  Background: The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases. Methods: Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and thrombectomy. Data detailing the surgical outcome were evaluated and recurrence-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Seven patients had an IVC thrombus and six had an RA thrombus. Extra-hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures included three extended right lobectomies, three extended left lobectomies, five right lobectomies, and two sectionectomies. Right adrenal gland metastases were excised simultaneously in two patients. All IVC thrombi were removed under hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary bypass (CPB). Four patients (30.8%) experienced controllable postoperative complications, and there was no surgical mortality. The mean postoperative hospital stay for patients with IVC and RA thrombi was 23.6 ± 12.5 days and 21.2 ± 4.6 days, respectively. Curative resection was performed in 5 of 13 cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%, respectively, and the median survival duration was 15.3 months. The 1- and 3-year overall survival rates for patients who underwent curative surgical resection were 80.0% and 30.0%, respectively, with a median survival duration of 30.8 months. All patients who underwent curative resection developed postoperative recurrences, with a median recurrence-free survival duration of 3.8 months. The 1-year survival rate for patients who underwent noncurative surgery and had residual tumors was 29.2%, with a median survival duration of 10.5 months. Conclusions: Aggressive surgical resection for HCC with tumor thrombi in the IVC or RA can be performed safely and may improve the prognoses of these patients. However, early recurrence and treatment for recurrent or metastatic tumors remain unresolved issues. © 2013 Wakayama et al. licensee BioMed Central Ltd.
• 人工肛門造設予定部を利用した単孔式腹腔鏡下大腸切除術

  本間 重紀, 皆川 のぞみ, 下國 達志, 崎浜 秀康, 高橋 典彦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 228 - 228 0386-9768 2013/10
• AFPとPIVKA-IIの積=AP値の肝細胞癌切除例における術前予後・再発予測因子としての意義

  神山 俊哉, 横尾 英樹, 柿坂 達彦, 若山 顕治, 蒲池 浩文, 敦賀 陽介, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 148 - 148 0386-9768 2013/10
• vp3、4肝細胞癌の門脈腫瘍栓に対する術前放射線治療の有効性の検討

  柿坂 達彦, 神山 俊哉, 横尾 英樹, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 154 - 154 0386-9768 2013/10
• 予後向上に向けた肝内胆管癌に対する術後補助化学療法

  横尾 英樹, 神山 俊哉, 柿坂 達彦, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 154 - 154 0386-9768 2013/10
• 胆嚢癌との鑑別を要した黄色肉芽腫性胆嚢炎の3切除例

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 216 - 216 0386-9768 2013/10
• 人工肛門造設予定部を利用した単孔式腹腔鏡下大腸切除術

  本間 重紀, 皆川 のぞみ, 下國 達志, 崎浜 秀康, 高橋 典彦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 46 (Suppl.2) 228 - 228 0386-9768 2013/10
• 肝細胞癌における予後再発因子としてのFABP5の有用性(Utility of FABP5 expression as a recurrence and prognostic factor in hepatocellular carcinoma)

  大畑 多嘉宣, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本癌学会総会記事 72回 445 - 445 0546-0476 2013/10
• 腫瘍血管内皮におけるCXCR7の機能解析(The role of a chemokine receptor CXCR7 in tumor endothelial cells)

  山田 健司, 間石 奈湖, 大賀 則孝, 秋山 廣輔, 川本 泰輔, Towfik Alam Mohammad, 進藤 正信, 高橋 典彦, 神山 俊哉, 樋田 泰浩, 武冨 紹信, 樋田 京子

  日本癌学会総会記事 72回 317 - 317 0546-0476 2013/10 [Refereed][Not invited]
  
• 肝細胞癌肺転移切除後19年間無再発の一例

  相山 健, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 折茂 達也, 若山 顕治, 敦賀 陽介, 蒲池 浩文, 武富 紹信

  日本癌治療学会誌 (一社)日本癌治療学会 48 (3) 2409 - 2409 0021-4671 2013/09
• Liver Fibrosis in Prenatally Diagnosed Choledochal Cysts

  Tadao Okada, Shohei Honda, Hisayuki Miyagi, Kanako C. Kubota, Kazutoshi Cho, Akinobu Taketomi

  JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION 57 (2) E14 - E14 0277-2116 2013/08 [Refereed][Not invited]
  
• 膵島移植の成績向上を目指して イヌ自家膵島移植におけるPeroxisome proliferator-activated receptor(PPAR)-γ agonistのグラフト保護効果の検討

  旭 よう, 山下 健一郎, 渡辺 正明, 小倉 正臣, 小野 仁, 江本 慎, 長津 明久, 腰塚 靖之, 武富 紹信, 藤堂 省

  移植 (一社)日本移植学会 48 (総会臨時) 261 - 261 0578-7947 2013/08 [Refereed][Not invited]
  
• Reliability and validity of a new living liver donor quality of life scale

  Yuki Morooka, Koji Umeshita, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Mayumi Yamamoto, Tsuyoshi Shimamura, Akihiko Oshita, Keiko Kanno, Hideki Ohdan, Naoki Kawagishi, Susumu Satomi, Kaoru Ogawa, Kuniko Hagiwara, Hiroaki Nagano

  SURGERY TODAY 43 (7) 732 - 740 0941-1291 2013/07 [Refereed][Not invited]
   

  To develop a living liver donor (LLD) quality of life (QOL) scale and test its reliability and validity. We sent a draft questionnaire comprising 38 questions to 965 LLDs from five hospitals. To evaluate test-retest reliability, the questionnaire was re-sent 2 weeks later to some of the donors from one hospital. Of the 447 (54.5 %) donors who responded, 15 were excluded. Factor analysis of 26 items extracted 7 subscales; namely, damage from the operation, scarring, satisfaction, burden, after-effects, digestive symptoms, and lack of understanding of donor health. We analyzed construct validity on the basis of factor analysis and observed significant correlations among the seven subscales. Criterion-related validity was confirmed by significant correlation with the 36-item Short-Form Health Survey scores. None of the subscales showed unreasonable values. We evaluated the subscale reliability for internal consistency (alpha = 0.670-0.868, except for "digestive symptoms", alpha = 0.431) and test-retest reliability (r = 0.749-0.918). The factor "digestive symptoms" needs careful consideration because of low internal consistency. The findings of this study confirmed the reliability and validity of the LLD QOL scale, which can be used for quantitatively evaluating the QOL of LLDs.
• 肝細胞癌における予後再発因子としてのFABP5の有用性

  大畑 多嘉宣, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 68回 P - 8 2013/07
• 肝尾状葉腫瘍切除における3D画像によるシミュレーションの有用性

  若山 顕治, 神山 俊哉, 柿坂 達彦, 横尾 英樹, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 68回 O - 3 2013/07
• 左葉系切除を要する高度進行胆道癌に対するTransparenchymal glissonean approachを用いた血行再建法

  蒲池 浩文, 敦賀 陽介, 若山 顕治, 柿坂 達彦, 横尾 英樹, 山下 健一郎, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 68回 RV - 3 2013/07
• 血清中糖鎖の網羅的解析による肝細胞癌新規バイオマーカーの開発

  神山 俊哉, 柿坂 達彦, 横尾 英樹, 蒲池 浩文, 若山 顕治, 敦賀 陽介, 三浦 信明, 西村 紳一郎, 藤堂 省, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 68回 O - 5 2013/07
• Intrahepatic artery pseudoaneurysm associated with a metallic biliary stent after living donor liver transplantation: report of a case

  Noboru Harada, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Katsuhiro Asonuma, Yukihiro Inomata, Yoshihiko Maehara

  SURGERY TODAY 43 (6) 678 - 681 0941-1291 2013/06 [Refereed][Not invited]
   

  An intrahepatic artery pseudoaneurysm (IHAA) is a very rare but potentially lethal complication occurring after liver transplantation. This report presents a case of an IHAA associated with a metallic biliary stent after liver transplantation. A 40-year-old male underwent living donor liver transplantation (LDLT) using a left lobe graft. The bile duct reconstruction was performed with Roux-en-Y hepaticojejunostomy. He developed obstructive jaundice 5 years after LDLT, and had biliary stricture of the anastomosis area, therefore, the two metallic biliary stents were finally positioned at the stricture of the biliary tract. He suddenly developed hematemesis 8 years after LDLT, and computerized tomography scan showed an IHAA. Although seven interlocking detachable coils were placed at the neck of the aneurysm, hematemesis recurred 3 days after the initial embolization. Therefore, retransplantation was successfully performed 25 days after the embolization of IHAA using a right lobe graft from his son. In conclusion, metal stent insertion can lead to the fatal complication of HAA. The placement of a metallic stent could have been avoided in this case. Percutaneous metallic stent insertion for biliary stenosis after liver transplantation should therefore only be performed in carefully selected patients.
• Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

  Toshiya Kamiyama, Hideki Yokoo, Jun-Ichi Furukawa, Masaki Kurogochi, Tomoaki Togashi, Nobuaki Miura, Kazuaki Nakanishi, Hirofumi Kamachi, Tatsuhiko Kakisaka, Yosuke Tsuruga, Masato Fujiyoshi, Akinobu Taketomi, Shin-Ichiro Nishimura, Satoru Todo

  HEPATOLOGY 57 (6) 2314 - 2325 0270-9139 2013/06 [Refereed][Not invited]
   

  The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 L serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion. Conclusion: Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;)
• Treatment of Bleeding Rectal Varices With Transumbilical Venous Obliteration of the Inferior Mesenteric Vein

  Naotaka Hashimoto, Tomohiko Akahoshi, Masahiro Kamori, Morimasa Tomikawa, Daisuke Yoshida, Yoshihiro Nagao, Kazutoyo Morita, Hiroto Kayashima, Toru Ikegami, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 23 (3) E134 - E137 1530-4515 2013/06 [Refereed][Not invited]
   

  A 56-year-old male with alcohol-induced liver cirrhosis developed rectal varices. He had a prior history of treatment for esophageal varices with endoscopic variceal ligation. Despite the repeated treatment for rectal varices with endoscopic variceal ligation, endoscopic injection sclerotherapy, and surgery, the bleeding from the rectal varices could not be controlled. Multi-detector-row computed tomography and 3D-angiography revealed the hemodynamic profile of the rectal varices. We next approached the rectal varices through the umbilical vein on the abdominal wall, and successfully embolized the varices continuing from the inferior mesenteric vein using coils and a 5% solution of ethanolamine oleate with iopamidol.
• Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for patients with primary liver cancer with special reference to rare histological types, hepatocellular carcinoma with sarcomatous change and combined hepatocellular and cholangiocarcinoma

  Hideki Ijichi, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Youhei Mano, Shinichi Aishima, Koichiro Abe, Hiroshi Honda, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 43 (5) 481 - 487 1386-6346 2013/05 [Refereed][Not invited]
   

  Aim The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and staging of primary liver cancer has been demonstrated in several reports. However, no preoperative evaluations of sarcomatous hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (cHCC-CC) with FDG-PET have been reported so far. Methods Fifty-three HCC patients and three cHCC-CC patients who received liver resection or living-donor liver transplantation were enrolled in this study. All 56 patients had undergone preoperative FDG-PET, and a total of 67 HCC and three cHCC-CC were analyzed histologically. The relationship between clinicopathological features and the maximum standardized uptake value (SUVmax) of tumors were evaluated. Results The detection rate of HCC by FDG-PET was 43.3 %, and the sensitivity of FDG-PET for the detection of HCC was significantly associated with tumor differentiation, tumor size and microvascular invasion. All three cHCC-CC were detected by FDG-PET. The SUVmax values of the three sarcomatous HCC (SUVmax 14.1, 18.6 and 25.0) and the three cHCC-CC (SUVmax 9.9, 12.0 and 13.0) were higher than that of the poorly differentiated HCC (mean SUVmax 5.7 +/- 2.3). Conclusion SUVmax may be a useful diagnostic tool for the preoperative evaluation of the aggressiveness of primary liver cancers such as sarcomatous HCC and cHCC-CC.
• An intraductal papillary neoplasm of the bile duct mimicking a hemorrhagic hepatic cyst: a case report

  Tatsuhiko Kakisaka, Toshiya Kamiyama, Hideki Yokoo, Kazuaki Nakanishi, Kenji Wakayama, Yosuke Tsuruga, Hirofumi Kamachi, Tomoko Mitsuhashi, Akinobu Taketomi

  WORLD JOURNAL OF SURGICAL ONCOLOGY 11 111  1477-7819 2013/05 [Refereed][Not invited]
   

  An intraductal papillary neoplasm of the bile duct is a biliary, epithelium-lined, cystic lesion that exhibits papillary proliferation and rarely causes large hemorrhagic cystic lesions. Here, we report a case of an intraductal papillary neoplasm of the bile duct mimicking a hemorrhagic hepatic cyst in a middle-aged man with large hemorrhagic hepatic cysts who experienced abdominal pain and repeated episodes of intracystic bleeding. Following portal vein embolization, extended right hepatic lobectomy was performed, and intraoperative cholangiography revealed communication between the intracystic space and the hepatic duct. Although histological studies revealed that the large hemorrhagic lesion was not lined with epithelium, the surrounding multilocular lesions contained biliary-derived epithelial cells that presented as papillary growths without ovarian-like stroma. A diagnosis of oncocytic-type intraductal papillary neoplasm of the bile duct was made, and we hypothesized that intracystic bleeding with denudation of the lining epithelial cells might occur as the cystically dilated bile duct increased in size. Differential diagnosis between a hemorrhagic cyst and a cyst-forming intraductal papillary neoplasm of the bile duct with bleeding is difficult. However, an intraductal papillary neoplasm of the bile duct could manifest as multilocular hemorrhagic lesions; therefore, complete resection should be performed for a better prognosis.
• Comparison of circulating tumor cells (CTC) and disseminated tumor cells (DTC) in patients with colorectal carcinoma for a predictive marker for tumor recurrence.

  Hideyasu Sakihama, Nozomi Kobayashi, Nozomi Minagawa, Tatsushi Shimokuni, Shigenori Homma, Norihiko Takahashi, Toshiya Kamiyama, Akinobu Taketomi

  JOURNAL OF CLINICAL ONCOLOGY 31 (15) 0732-183X 2013/05 [Refereed][Not invited]
  
• A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.

  Nozomi Minagawa, Hideyasu Sakihama, Nozomi Kobayashi, Kenji Wakayama, Tatsuhiko Kakisaka, Yousuke Tsuruga, Tatsushi Shimokuni, Shigenori Homma, Hideki Yokoo, Hirofumi Kamachi, Norihiko Takahashi, Toshiya Kamiyama, Akinobu Taketomi

  JOURNAL OF CLINICAL ONCOLOGY 31 (15) 0732-183X 2013/05 [Refereed][Not invited]
  
• Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with extensive sarcomatous changes: report of a case.

  Mikihiro Kohno, Ken Shirabe, Yohei Mano, Jun Muto, Takashi Motomura, Kazuki Takeishi, Takeo Toshima, Masanori Yoshimatsu, Hideki Ijichi, Noboru Harada, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara

  Surgery today 43 (4) 439 - 45 1436-2813 2013/04 [Refereed][Not invited]
   

  This report describes a rare case of hepatocellular carcinoma (HCC) producing granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic hepatitis B, who presented with fever, general malaise, loss of appetite, and weight loss, had a huge liver mass in the portal region. He had marked granulocytosis and his serum level of G-CSF was elevated. Complete tumor resection was performed, and the pathological assessment of the resected specimen revealed HCC with extensive sarcomatous changes and immunohistochemical staining for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been reported, and this is the first case of G-CSF-producing HCC that also expressed G-CSF receptor.
• Spontaneous rupture of an advanced pancreatoblastoma: aberrant RASSF1A methylation and CTNNB1 mutation as molecular genetic markers.

  Shohei Honda, Tadao Okada, Hisayuki Miyagi, Masatsugu Minato, Hiromu Suzuki, Akinobu Taketomi

  Journal of pediatric surgery 48 (4) e29-32 - 32 1531-5037 2013/04 [Refereed][Not invited]
   

  Pancreatoblastoma is a rare pancreatic tumor that is most commonly encountered in infants and young children. This report describes an unusual presentation of a large pancreatic body pancreatoblastoma presenting with intraabdominal bleeding due to spontaneous rupture of the tumor in a 5-year-old boy. Subsequent molecular analysis from the resected specimen identified a mutation in CTNNB1 and aberrant methylation of the tumor suppressor RASSF1A.
• Portal vein stenosis after pancreatectomy following neoadjuvant chemoradiation therapy for pancreatic cancer

  Yosuke Tsuruga, Hirofumi Kamachi, Kenji Wakayama, Tatsuhiko Kakisaka, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi

  WORLD JOURNAL OF GASTROENTEROLOGY 19 (16) 2569 - 2573 1007-9327 2013/04 [Refereed][Not invited]
   

  Extrahepatic portal vein (PV) stenosis has various causes, such as tumor encasement, pancreatitis and as a post-surgical complication. With regard to post-pancreaticoduodenectomy, intraoperative radiation therapy with/without PV resection is reported to be associated with PV stenosis. However, there has been no report of PV stenosis after pancreatectomy following neoadjuvant chemoradiation therapy (NACRT). Here we report the cases of three patients with PV stenosis after pancreatectomy and PV resection following gemcitabine-based NACRT for pancreatic cancer and their successful treatment with stent placement. We have performed NACRT in 18 patients with borderline resectable pancreatic cancer since 2005. Of the 15 patients who completed NACRT, nine had undergone pancreatectomy. Combined portal resection was performed in eight of the nine patients. We report here three patients with PV stenosis, and thus the ratio of post-operative PV stenosis in patients with PV resection following NACRT is 37.5% in this series. We encountered no case of PV stenosis among 22 patients operated with PV resection for pancreatobiliary cancer without NACRT during the same period. A relationship between PV stenosis and NACRT is suspected, but further investigation is required to determine whether NACRT has relevance to PV stenosis. (C) 2013 Baishideng. All rights reserved.
• A rare point mutation in the Ras oncogene in hepatocellular carcinoma

  Akinobu Taketomi, Ken Shirabe, Jun Muto, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Tohru Ikegami, Tomoharu Yoshizumi, Kenji Sugio, Yoshihiko Maehara

  SURGERY TODAY 43 (3) 289 - 292 0941-1291 2013/03 [Refereed][Not invited]
   

  The Ras gene is one of the oncogenes most frequently detected in human cancers, and codes for three proteins (K-, N-, and H-Ras). The aim of this study was to examine the mutations in codons 12, 13 and 61 of the three Ras genes in cases of human hepatocellular carcinoma (HCC). Paired samples of HCC and corresponding non-malignant liver tissue were collected from 61 patients who underwent hepatectomy. A dot-blot analysis was used to analyze the products of the polymerase chain reaction (PCR) amplification of codons 12, 13, and 61 of K-, N- and H-Ras for mutations. Only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 patients. Interestingly, this patient had a medical history of surgery for both gastric cancer and right lung cancer. No mutations were found in codons 12 and 61 of K-Ras or codons 12, 13 and 61 of the N-Ras and H-Ras genes in any of the HCCs or corresponding non-malignant tissues. These findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13, and 61 does not play a major role in hepatocellular carcinogenesis.
• Clinicopathological characteristics and prognostic factors in young patients after hepatectomy for hepatocellular carcinoma

  Shingo Shimada, Toshiya Kamiyama, Hideki Yokoo, Kenji Wakayama, Yosuke Tsuruga, Tatsuhiko Kakisaka, Hirofumi Kamachi, Akinobu Taketomi

  WORLD JOURNAL OF SURGICAL ONCOLOGY 11 52  1477-7819 2013/03 [Refereed][Not invited]
   

  Background: The aim of this study was to analyze the clinicopathological characteristics and the prognostic factors for survival and recurrence of young patients who had undergone hepatectomy for hepatocellular carcinoma. Methods: Between 1990 and 2010, 31 patients aged 40 years or younger (younger patient group) among 811 consecutive patients with hepatocellular carcinoma who had undergone primary hepatectomy were analyzed with regard to patient factors, including liver function, tumor factors and operative factors. The clinicopathological characteristics of the younger patients were compared with those of patients over the age of 40 (older patient group). Then the prognostic factors of the younger patients were analyzed. Continuous variables were expressed as the means +/- standard deviation and compared using the chi(2) test for categorical variables. Overall survival and recurrence-free survival rates were determined by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis. Results: In the younger patients, the rates of HBs-antigen-positivity, high alpha-fetoprotein, portal invasion, intrahepatic metastasis, large tumors, low indocyanin green retention rate at 15 minutes, and anatomical resection were significantly higher than the same measures in the older patients. The five-year overall survival rate of the young patients was 49.6%. The prognostic factors of survival were HCV-antibody-positivity and low albumin status. Prognostic factors of recurrence were multiple tumors and the presence of portal invasion. Conclusions: In younger patients, survival appeared to be primarily affected by liver function, while recurrence was affected by tumor factors. Young patients with hepatocellular carcinoma should be aggressively treated with hepatectomy due to their good pre-surgical liver function.
• 肝細胞癌における予後再発因子としてのFABP5発現の検討

  大畑 多嘉宣, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 神山 俊哉, 武富 紹信

  日本外科学会雑誌 (一社)日本外科学会 114 (臨増2) 642 - 642 0301-4894 2013/03
• イヌ自家膵島移植モデルにおけるProliferator-activated receptor(PPAR)-γagonistによる早期グラフト傷害抑制効果の検討

  旭 よう, 山下 健一郎, 渡辺 正明, 小倉 正臣, 小野 仁, 江本 慎, 長津 明久, 吉田 雅, 腰塚 靖之, 蒲池 浩文, 武富 紹信, 藤堂 省

  日本外科学会雑誌 (一社)日本外科学会 114 (臨増2) 407 - 407 0301-4894 2013/03 [Refereed][Not invited]
  
• 大腸癌肝転移切除症例の検討

  下國達志, 高橋典彦, 中川隆公, 中野詩朗, 阿部厚憲, 濱田朋倫, 浜田弘巳, 三澤一仁, 石津寛之, 大森一吉, 小笠原和宏, 小池雅彦, 佐治裕, 湊正意, 神山俊哉, 武冨紹信

  日本臨床外科学会雑誌 74 (2) 585  1345-2843 2013/02/25 [Not refereed][Not invited]
  
• 生体肝再移植後に認めた遅発性肝静脈狭窄に対してバルーン拡張術を施行した1例

  脇坂 和貴, 青柳 武史, 巖築 慶一, 大浦 哲, 渡辺 正明, 後藤 了一, 武冨 紹信, 鈴木 友己, 嶋村 剛, 藤堂 省

  日本臨床外科学会雑誌 日本臨床外科学会 74 (2) 595 - 595 1345-2843 2013/02
• 肝エキノコッカス症と鑑別困難であったMulticystic billary hamartomaの一例

  本間 友樹, 武冨 紹信, 神山 俊哉, 蒲池 浩文, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 若山 顕治

  日本臨床外科学会雑誌 日本臨床外科学会 74 (2) 595 - 595 1345-2843 2013/02
• 第一空腸静脈切離により広範な空腸鬱血をきたした膵頭十二指腸切除の一例

  木井 修平, 蒲池 浩文, 坂本 譲, 若山 顕治, 敦賀 陽介, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 74 (2) 596 - 596 1345-2843 2013/02 [Refereed][Not invited]
  
• Clinical implications of luminal membrane expression of mesothelin in intraductal papillary mucinous neoplasms

  Takahiro Einama, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Futoshi Kawamata, Munenori Tahara, Masahiko Taniguchi, Hiroyuki Furukawa, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Satoru Todo

  JOURNAL OF CLINICAL ONCOLOGY 31 (4) 0732-183X 2013/02 [Refereed][Not invited]
  
• Tumor-Associated Macrophage Promotes Tumor Progression via STAT3 Signaling in Hepatocellular Carcinoma

  Yohei Mano, Shinichi Aishima, Nobuhiro Fujita, Yuki Tanaka, Yuichiro Kubo, Takashi Motomura, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda

  PATHOBIOLOGY 80 (3) 146 - 154 1015-2008 2013 [Refereed][Not invited]
   

  Objective: Signal transducer and activator of transcription 3 (STAT3) is activated in hepatocellular carcinoma (HCC), and tumor-associated macrophage plays an important role in tumor progression. Therefore, we examined STAT3 activation, cytokine expression and infiltration of tumor-associated macrophages in resected HCCs as well as the alteration of cell growth and migration by cytokine stimulation in HCC cell lines. Methods: Immunohistochemical staining of phosphorylated STAT3 (pSTAT3), CD163, interleukin (IL)-6, Ki-67 and Bcl-XL was performed for 101 cases of resected HCC, and correlations between pSTAT3 staining and clinicopathological findings were analyzed. In HCC cell lines (PLC/PRF/5 and Huh7), cell proliferation and migration by IL-6 stimulation and S3I-201 (STAT3 inhibitor) treatment were analyzed. Results: In HCC specimens, the pSTAT3-positive group showed high levels of alpha-fetoprotein (p = 0.0276), large tumor size (p = 0.0092), frequent intrahepatic metastasis (p = 0.0214), high Ki-67 (p = 0.0002) and Bcl-XL (p = 0.0001), poor prognosis (p = 0.0234), and high recurrence rate (p = 0.0003). CD163-positive cells were frequently observed in the pSTAT3-positive group (p = 0.0013). In two HCC cell lines, IL-6 stimulation promoted cell proliferation and migration via the STAT3 phosphorylation, and S3I-201 inhibited this activation. Conclusions: STAT3 activation was correlated with aggressive behavior of HCC and may be mediated via tumor-associated macrophage. We expect that STAT3 signaling and tumor-associated macrophages can be attractive therapeutic targets in HCC patients. Copyright (C) 2013 S. Karger AG, Basel
• Liver and biliary tract carcinoma surveillance counterpoint: Japan

  Akinobu Taketomi, Yoshihiko Maehara

  Patient Surveillance After Cancer Treatment 165 - 167 2013/01/01 [Refereed][Not invited]
  
• Anoikis Induction and Inhibition of Peritoneal Metastasis of Pancreatic Cancer Cells by a Nuclear Factor-kappa B Inhibitor, (-)-DHMEQ

  Masanori Sato, Kazuaki Nakanishi, Sanae Haga, Masato Fujiyoshi, Motoi Baba, Kazuhiro Mino, Yimin, Haruki Niwa, Hideki Yokoo, Kazuo Umezawa, Yoshihiro Ohmiya, Toshiya Kamiyama, Satoru Todo, Akinobu Taketomi, Michitaka Ozaki

  ONCOLOGY RESEARCH 21 (6) 333 - 343 0965-0407 2013 [Refereed][Not invited]
   

  The transcription factor nuclear factor-kappa B (NF-kappa B) plays a crucial role in pancreatic cancer (PC) progression. NF-kappa B is also involved in resistance to anoikis, a special type of apoptosis induced when cells are detached from the extracellular matrix or other cells. Anoikis resistance is related to the metastatic abilities of tumor cells; however, little is known about anoikis induction as it relates to inhibition of PC metastasis by NF-kappa B inhibitors. Here we used a specific NF-kappa B inhibitor, (-)-dehydroxymethylepoxyquinomicin (DHMEQ), to investigate anoikis induction and peritoneal metastasis suppression following NF-kappa B inhibition. We transduced Glue, a secretory form of luciferase, into a PC cell line, AsPC-1 (AsPC-1-Gluc), for our in vivo experiments. (-)-DHMEQ induced anoikis in AsPC-1-Gluc cells as measured by cell survival assays and flow cytometry. The DNA-binding activity of p65 was enhanced immediately after cell detachment from culture dishes in ELISA assays. Some antiapoptotic proteins such as cellular inhibitor of apoptotic protein-1 were consequently upregulated on Western blots. (-)-DHMEQ prevented this increase in p65 activity and the subsequent expressions of antiapoptotic molecules. In a murine xenograft model, anoikis-resistant PC cell lines tended to metastasize to the peritoneum more than anoikis-sensitive cells, suggesting a correlation between anoikis sensitivity and peritoneal metastasis. (-)-DHMEQ successfully inhibited peritoneal metastasis of AsPC-1-Gluc cells. We monitored metastasis inhibition by ex vivo chemiluminescent detection of Glue secreted from tumor cells into murine plasma and by in vivo imaging. Our results suggest that (-)-DHMEQ inhibited peritoneal dissemination by preventing anoikis resistance of PC cells.
• Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma: report of a case

  Naoko Iwahashi Kondo, Ken Shirabe, Yohei Mano, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Toshiro Masuda, Hiroto Kayashima, Naotaka Hashimoto, Kazutoyo Morita, Mizue Matsuo, Yoshihiko Maehara

  SURGERY TODAY 42 (12) 1210 - 1214 0941-1291 2012/12 [Refereed][Not invited]
   

  The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection.
• Impact of the VIO system in hepatic resection for patients with hepatocellular carcinoma

  Shinji Itoh, Kengo Fukuzawa, Yuki Shitomi, Masahiro Okamoto, Tadahiko Kinoshita, Akinobu Taketomi, Ken Shirabe, Kenzo Wakasugi, Yoshihiko Maehara

  SURGERY TODAY 42 (12) 1176 - 1182 0941-1291 2012/12 [Refereed][Not invited]
   

  This study aimed to evaluate a novel surgical device combination [VIO system containing a bipolar clamp (BiClamp) and the monopolar soft-coagulation (SOFT COAG)] in hepatic resection for patients with hepatocellular carcinoma (HCC). This study performed 124 hepatic resections for HCC and divided them into 2 groups: 60 patients (Conventional group) underwent liver parenchymal transection using Cavitron Ultrasonic Surgical Aspirator (CUSA) system and saline-coupled bipolar electrocautery for hemostasis; the BiClamp was used with the CUSA system for liver parenchymal transection and SOFT COAG was used with saline-coupled bipolar electrocautery for hemostasis in 64 patients (VIO group). The median blood loss in the VIO group was 345 mL, which was less than that in the Conventional group (median 548 mL, P = 0.0423). A multivariate logistic regression analysis showed that no use of the VIO system (P = 0.0172) was an independent predictor of intraoperative blood loss, respectively. In patients with liver cirrhosis, the VIO group included a significantly lower proportion of patients with liver cirrhosis that experienced more than 500 mL of intraoperative blood loss in comparison to those in the Conventional group (P = 0.0262). The VIO system was safe for hepatic resection and its use was associated with a significant decrease in intraoperative blood loss even in cirrhotic patients.
• Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer

  Futoshi Kawamata, Hirofumi Kamachi, Takahiro Einama, Shigenori Homma, Munenori Tahara, Masaya Miyazaki, Shinya Tanaka, Toshiya Kamiyama, Hiroshi Nishihara, Akinobu Taketomi, Satoru Todo

  INTERNATIONAL JOURNAL OF ONCOLOGY 41 (6) 2109 - 2118 1019-6439 2012/12 [Refereed][Not invited]
   

  Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarcinoma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal' membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EH BDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.
• Assessment of delayed gastric emptying after major hepatectomy using a C-13-acetic acid breath test

  Keishi Sugimachi, Ken Shirabe, Noriko Tokunaga, Hirotada Akiho, Akinobu Taketomi, Yuji Soejima, Tomonobu Gion, Kazuhiko Nakamura, Hidefumi Higashi, Yoshihiko Maehara

  SURGERY TODAY 42 (11) 1046 - 1050 0941-1291 2012/11 [Refereed][Not invited]
   

  Delayed gastric emptying (DGE) after hepatectomy affects the quality of life of patients, although the causes and related conditions have not been investigated. This study evaluated the relationship between hepatectomy and DGE by the objective assessment of gastric emptying (GE). Nineteen patients who underwent major hepatectomy were prospectively enrolled in the study. Their GE was studied using the C-13-acetic acid breath test before and after hepatectomy. The results of the GE analysis were correlated with the postoperative course after hepatectomy. Clinically evident DGE, which was defined as the inability to take in an appropriate amount of solid food orally by postoperative day 14, was not found in these patients, but the gastric half-emptying times before and after hepatectomy were 20.2 +/- A 9.7 and 28.6 +/- A 12.2 min, respectively (P = 0.01). The GE time was significantly delayed in patients aged a parts per thousand yen41 years, or who underwent right hemihepatectomy. Gastric emptying was significantly inhibited in patients who underwent major hepatectomy, and aging and a right-sided hemihepatectomy may be related to the development of DGE.
• Hepatic osteodystrophy complicated with bone fracture in early infants with biliary atresia.

  Tadao Okada, Shohei Honda, Hisayuki Miyagi, Masashi Minato, Akinobu Taketomi

  World journal of hepatology 4 (10) 284 - 7 1948-5182 2012/10/27 [Refereed][Not invited]
   

  Biliary atresia (BA) is one of the major hepatobiliary abnormalities in infants and one of the causes of hepatic osteodystrophy. Bone disease may be caused by the malabsorption of calcium and magnesium by vitamin D in hepatobiliary diseases in which bile flow into the intestines is deficient or absent. Bone fracture before Kasai hepatic portoenterostomy or within one month after the procedure in an infant with BA is very rare. We herein report two infants: one infant with BA who initially presented with a bone fracture before Kasai hepatic portoenterostomy, and the other at 4 wk after Kasai hepatic portoenterostomy, and also provide a review of the literature. Moreover, we conclude that clinicians should consider BA in infants with bone fracture during early infancy.
• Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis

  Hideo Uehara, Tomohiko Akahoshi, Hirohumi Kawanaka, Naotaka Hashimoto, Yoshihiro Nagao, Morimasa Tomikawa, Akinobu Taketomi, Ken Shirabe, Makoto Hashizume, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 42 (10) 1039 - 1047 1386-6346 2012/10 [Refereed][Not invited]
   

  Aim: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Methods: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied. Results: There were significant differences in PVP (17.9 +/- 0.91 vs 23.3 +/- 3.91 cmH2O; P < 0.01) and HTBF (16.6 +/- 1.72 vs 13.3 +/- 1.82 mL/min; P < 0.01) between the BDL + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL + Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation. Conclusion: ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.
• Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

  Minoru Nakamura, Nao Nishida, Minae Kawashima, Yoshihiro Aiba, Atsushi Tanaka, Michio Yasunami, Hitomi Nakamura, Atsumasai Komori, Makoto Nakamuta, Mikio Zeniya, Etsuko Hashimoto, Hiromasa Ohira, Kazuhide Yamamoto, Morikazu Onji, Shuichi Kaneko, Masao Honda, Satoshi Yamagiwa, Kazuhiko Nakao, Takafumi Ichida, Hajime Takikawa, Masataka Seike, Takeji Umemura, Yoshiyuki Ueno, Shotaro Sakisaka, Kentaro Kikuchi, Hirotoshi Ebinuma, Noriyo Yamashiki, Sumito Tamura, Yasuhiko Sugawara, Akira Mori, Shintaro Yagi, Ken Shirabe, Akinobu Taketomi, Kuniaki Arai, Kyoko Monoe, Tatsuki Ichikawa, Makiko Taniai, Yasuhiro Miyake, Teru Kumagi, Masanori Abe, Kaname Yoshizawa, Satoru Joshita, Shinji Shimoda, Koichi Honda, Hiroki Takahashi, Katsuji Hirano, Yasuaki Takeyama, Kenichi Harada, Kiyoshi Migita, Masahiro Ito, Hiroshi Yatsuhashi, Nobuyoshi Fukushima, Hajime Ota, Tatsuji Komatsu, Takeo Saoshiro, Jinya Ishida, Hirotsugu Kouno, Hirotaka Kouno, Michiyasu Yagura, Masakazu Kobayashi, Toyokichi Muro, Naohiko Masaki, Keiichi Hirata, Yukio Watanabe, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Kazuhiro Sugi, Michiaki Koga, Keisuke Ario, Eiichi Takesaki, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Hirohito Tsubouchi, Masashi Mizokami, Yasuni Nakanuma, Katsushi Tokunaga, Hiromi Ishibashi

  AMERICAN JOURNAL OF HUMAN GENETICS 91 (4) 721 - 728 0002-9297 2012/10 [Refereed][Not invited]
   

  For the identification of susceptibility loci for primary binary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 x 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 x 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 x 10(-8), 3.66 x 10(-9), and 3.04 x 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 x 10(-6) and 1.42 x 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.
• 局所進行直腸癌に対する術前化学療法

  本間 重紀, 下國 達志, 崎浜 秀康, 高橋 典彦, 片岡 昭彦, 武冨 紹信

  日本消化器外科学会雑誌 (一社)日本消化器外科学会 45 (Suppl.2) 397 - 397 0386-9768 2012/10
• Liver hanging maneuverとその応用 肝門部胆管癌におけるLiver hanging maneuverを応用した肝実質切離

  蒲池 浩文, 敦賀 陽介, 若山 顕治, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武冨 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 73 (増刊) 379 - 379 1345-2843 2012/10
• 肝尾状葉腫瘍切除における3次元画像解析システムの有用性

  若山 顕治, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 蒲池 浩文, 敦賀 陽介, 武富 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 73 (増刊) 694 - 694 1345-2843 2012/10
• 血管合併切除を伴う術前放射線化学療法施行後膵癌根治切除症例の検討

  敦賀 陽介, 蒲池 浩文, 若山 顕治, 柿坂 達彦, 横尾 英樹, 神山 俊哉, 武富 紹信

  日本臨床外科学会雑誌 日本臨床外科学会 73 (増刊) 767 - 767 1345-2843 2012/10
• Beneficial effects of preoperative lipiodolization for resectable large hepatocellular carcinoma (>= 5 cm in diameter)

  Yo-ichi Yamashita, Kazuki Takeishi, Eiji Tsuijita, Shouhei Yoshiya, Kazutoyo Morita, Hiroto Kayashima, Tomohiro Iguchi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  JOURNAL OF SURGICAL ONCOLOGY 4 106 (4) 498 - 503 0022-4790 2012/09 [Refereed][Not invited]
   

  Background The effects of preoperative lipiodolization (LPD) for large hepatocellular carcinoma (HCC) are controversial. Methods A retrospective review was undertaken for 137 patients with initial solitary resectable HCC >= 5?cm who underwent hepatic resection between 1995 and 2008. Forty-two patients underwent preoperative LPD, and clinical data and prognosis were compared to those of patients without preoperative LPD (n?=?95). Results Surgical results of the LPD group, such as surgical time, surgical blood loss, and the mortality and morbidity rate were statistically equal to those of the nonLPD group. The disease-free and overall survival of the LPD group were significantly better than those of the nonLPD group, and early tumor recurrence within 1-year of the LPD group was significantly lower than that of the nonLPD group. According to the multivariate analysis, the absence of preoperative LPD was an independent poor prognostic factor of patients with hepatic resection for HCC >= 5?cm. Conclusion Preoperative LPD suppressed early tumor recurrence and improved patient survival after hepatic resection for HCC >= 5?cm. J. Surg. Oncol. 2012; 106:498503. (c) 2012 Wiley Periodicals, Inc.
• MR prediction of liver fibrosis using a liver-specific contrast agent: Superparamagnetic iron oxide versus Gd-EOB-DTPA

  Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Tsuyoshi Tajima, Daisuke Kakihara, Tomohiro Nakayama, Yukihisa Takayama, Daisuke Okamoto, Akinobu Taketomi, Ken Shirabe, Nobuhiro Fujita, Makoto Obara, Kengo Yoshimitsu, Hiroshi Honda

  JOURNAL OF MAGNETIC RESONANCE IMAGING 36 (3) 664 - 671 1053-1807 2012/09 [Refereed][Not invited]
   

  Purpose: To examine whether the uptake of a liver-specific contrast agent in the liver parenchyma was correlated with the degree of liver fibrosis. Materials and Methods: This retrospective study included 54 and 63 patients who underwent superparamagnetic iron oxide (SPIO)- and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI before liver surgery, respectively. For each patient, we calculated ?R2* and ?R2, which represent differences in R2* and R2 values of the liver parenchyma before and after administration of SPIO; and the increase rate of liver-to-spleen signal intensity ratio (LSR) on the hepatobiliary phase compared with the precontrast image. The correlation of each MR parameter with the degree of liver fibrosis (F0 to F4) was assessed using Spearman's rank correlation test. Results: The increase rate of LSR was best correlated with the degree of liver fibrosis and significantly decreased as the liver fibrosis progressed (rho = -0.641; P < 0.0001). It showed sensitivity of 76.9% and specificity of 83.3% in differentiating F3 or greater fibrosis when 1.126 or less was set up as a cut-off value. No significant correlation was obtained between ?R2* or ?R2 and the degree of liver fibrosis. Conclusion: The uptake of Gd-EOB-DTPA in the liver parenchyma decreased as the liver fibrosis progressed. J. Magn. Reson. Imaging 2012;36:664671. (C) 2012 Wiley Periodicals, Inc.
• [A case of successful multi-venous reconstruction using recipient's jugular vein in right lobe-living donor liver transplantation].

  Mizue Matsuo, Toru Ikegami, Kazutoyo Morita, Hiroko Yano, Naotaka Hashimoto, Hiroto Kayashima, Toshirou Masuda, Naoko Kondou, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  Fukuoka igaku zasshi = Hukuoka acta medica 103 (9) 186 - 90 0016-254X 2012/09 [Refereed][Not invited]
   

  In right lobe-living donor liver transplantation (RT-LDLT), hepatic venous reconstruction of the graft is essential to prevent posttansplant graft congestion and have a good outcome. The patient was a 56-year-old man who had decompensated liver cirrhosis secondary hepatitis C with massive ascites, jaundice and hepatic encephalopathy. He underwent LDLT using his son's right lobe graft. Preoperative simulation by 3D-CT volumetry revealed that the right lobe graft needed multi-venous reconstruction for right inferior hepatic vein (RIHV) and middle hepatic venous tributaries. Preoperative CT scan revealed that the recipient had portal venous thrombus and stenosis, which meant that the recipient's explanted portal vein (EPV) was not suitable for the venous reconstruction of the right lobe graft. Therefore, the recipient's internal and external jugular veins (IJV and EJV) were procured for venous reconstruction. The multiple veins of the right lobe graft were reconstructed to have single co-orifice at the backtable, and the co-orifice was anastomosed to inferior vena cava in short time. The recipient discharged on postoperative day 22 with good venous patency. In RT-LDLT unavailable for recipient's EPV, recipient's IJV and EJV grafts are very useful for multi-venous reconstruction.
• 当科における脳死肝移植適応基準

  大浦 哲, 鈴木 友己, 嶋村 剛, 山下 健一郎, 青柳 武史, 後藤 了一, 渡辺 正明, 谷口 雅彦, 古川 博之, 武冨 紹信, 藤堂 省

  移植 (一社)日本移植学会 47 (総会臨時) 254 - 254 0578-7947 2012/09
• 多孔静脈の再建に内・外頸静脈を用いた右葉グラフト生体肝移植の一例

  松尾 瑞恵, 池上 徹, 森田 和豊, 矢野 博子, 橋本 直隆, 萱島 寛人, 増田 稔郎, 根東 順子, 吉住 朋晴, 武冨 紹信, 調 憲, 前原 喜彦

  福岡医学雑誌 福岡医学会 103 (9) 186 - 190 0016-254X 2012/09 

  56歳男。30歳時に外傷性尿道断裂に対し開腹手術、輸血の既往があり、C型肝硬変による腹水貯留のため入退院を繰り返していた。今回、高度の腹水貯留、黄疸および肝性脳症を発症し生体肝移植目的に紹介となった。腹部は大量の腹水で膨満し下腿浮腫が著明で、肝機能障害を認めた。肝腎症候群状態でNH3 160μg/dlと高値で、HCV-Ab(+)、腫瘍マーカーはAFP 3.5ng/ml、PIVKA-II 0.2nAU/mlであった。また、Child-Pugh ScoreはGrade C(13点)、MELD scoreは21点であった。腹部CTでは、肝内門脈の狭小化、門脈血栓を認め腹水が大量に貯留していた。ドナーの肝術前評価は右葉グラフトの予想グラフト重量は713g、予想グラフト・標準肝容積比は49.6%となり、右肝静脈、右下肝静脈、V5、V8と4本の肝静脈が残ることが予想された。レシピエントは全肝摘出前に静脈再建のグラフトとして予め右内頸静脈・外頸静脈を採取した。摘出肝門脈は血栓血栓のため使用不可能であった。内頸静脈・外頸静脈を用いた多孔静脈一括再建で移植を施行した。術後は良好で、術後7日目のCTで右肝静脈、右下肝静脈、V5、V8のいずれも開存を認め、術後22日に退院した。
• Nafamostat Mesilate-Induced Hepatocellular Necrosis in a Child With Pancreatitis Caused by Pancreaticobiliary Maljunction Drug-Induced Liver Injury

  Tadao Okada, Shohei Honda, Hisayuki Miyagi, Masashi Minato, Kanako C. Kubota, Akinobu Taketomi

  PANCREAS 41 (6) 981 - 983 0885-3177 2012/08 [Refereed][Not invited]
  
• Subcuticular Absorbable Suture with Subcutaneous Drainage System Prevents Incisional SSI after Hepatectomy for Hepatocellular Carcinoma

  Eiji Tsujita, Yo-ichi Yamashita, Kazuki Takeishi, Ayumi Matsuyama, Shin-ichi Tsutsui, Hiroyuki Matsuda, Akinobu Taketomi, Ken Shirabe, Teruyoshi Ishida, Yoshihiko Maehara

  WORLD JOURNAL OF SURGERY 36 (7) 1651 - 1656 0364-2313 2012/07 [Refereed][Not invited]
   

  The effectiveness of subcuticular absorbable suture with subcutaneous drainage to decrease the risk of postoperative incisional surgical site infection (SSI) in hepatocellular carcinoma (HCC) patients was evaluated. A total of 149 patients with HCC who underwent hepatectomy (Hx) were retrospectively investigated. Patients were divided into two groups: the patients with subcuticular suture combined with subcutaneous drainage (the drainage group; 61 patients) and the patients with nylon suture without subcutaneous drainage (the nylon group; 88 patients). After the operations, the complication rate of postoperative incisional SSI was analyzed and compared between the two groups. In the drainage group the rate of incisional SSI was significantly lower compared to the nylon group: 14-3 % (p = 0.033), respectively. Patients with incisional SSI needed significantly longer postoperative hospital care than the patients without incisional SSI: 28 versus 15 days (p < 0.005). Multivariate analysis revealed that subcuticular absorbable suture with subcutaneous drainage significantly reduced the occurrence of incisional SSI (odds ratio; 0.15; p = 0.034). We have demonstrated that the subcuticular suture with subcutaneous drainage is effective in preventing incisional SSI in patients undergoing Hx for HCC.
• Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway

  Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Takashi Motomura, Toru Ikegami, Tomoharu Yoshizumi, Fumio Sakane, Yoshihiko Maehara

  JOURNAL OF HEPATOLOGY 57 (1) 77 - 83 0168-8278 2012/07 [Refereed][Not invited]
   

  Background & Aims: Diacylglycerol kinases (DGKs) were recently recognized as key regulators in cell signaling pathways. We investigated whether DGK alpha is involved in human hepatocellular carcinoma (HCC) progression. Methods: We silenced or overexpressed DGK alpha in HCC cells and assessed its effect on tumor progression. DGK alpha expression in 95 surgical samples was analyzed by immunohistochemistry, and the expression status of each sample was correlated with clinicopathological features. Results: DGK alpha was detected in various HCC cell lines but at very low levels in the normal liver. Knockdown of DGK alpha significantly suppressed cell proliferation and invasion. Overexpression of wild type (WT) DGK alpha, but not its kinase-dead (KD) mutant, significantly enhanced cell proliferation. DGK alpha knockdown impaired MEK and ERK phosphorylation, but did not inhibit Ras activation in HCC cells. In a xenograft model, WT DGK alpha overexpression significantly enhanced tumor growth compared to the control, but KD DGK alpha mutant had no effect. Immunohistochemical studies showed that DGK alpha was expressed in cancerous tissue, but not in adjacent non-cancerous hepatocytes. High DGK alpha expression (>= 20%) was associated with high Ki67 expression (p < 0.05) and a high rate of HCC recurrence (p = 0.033) following surgery. In multivariate analyses, high DGK alpha expression was an independent factor for determining HCC recurrence after surgery. Conclusions: DGK alpha is involved in HCC progression by activation of the MAPK pathway. DGK alpha could be a novel target for HCC therapeutics as well as a prognostic marker. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
• Magnetic resonance differentiation between T2 and T1 gallbladder carcinoma: significance of subserosal enhancement on the delayed phase dynamic study

  Kengo Yoshimitsu, Yunosuke Nishihara, Daisuke Okamoto, Yasuhiro Ushijima, Akihiro Nishie, Koji Yamaguchi, Akinobu Taketomi, Hiroshi Honda

  MAGNETIC RESONANCE IMAGING 30 (6) 854 - 859 0730-725X 2012/07 [Refereed][Not invited]
   

  Purpose: The aim of this study is to investigate whether subserosal enhancement on the delayed-phase dynamic magnetic resonance (MR) study (SED) can differentiate T2 from T1 gallbladder carcinoma (GBC). Methods: The institutional research board approved this retrospective study. Between 1997 and 2006, there were surgically proven 11 T1 and 21 T2 GBC in 30 patients, all of whom had undergone preoperative contrast enhanced dynamic MR study, either with a 2D sequence (n=17) or 3D sequences (n=15). All images were reviewed by two radiologists for the presence of SED, and receiver operating characteristic (ROC) curve analysis was performed. Sensitivity, specificity, positive and negative predictive values were calculated by consensus. Results: The areas under the ROC curves of the two readers were 0.91 and 0.86, and the kappa value was 0.78. Of the 21 T2 GBC, 18 and 3 showed positive and negative SED, respectively. Of the 11 T1 GBC, 1 and 10 showed positive and negative SED, respectively. The sensitivity, specificity, positive and negative predictive values of SED for diagnosing T2 lesions were 86%, 88%, 91% and 77%, respectively. Conclusions: In conclusion, SED may be a useful sign to differentiate T2 from T1 GBC, which would affect the preoperative surgical planning of the patients. (C) 2012 Elsevier Inc. All rights reserved.
• Use of an Internal Jugular Vein Graft for Middle Hepatic Vein Tributary Reconstruction in Right-Lobe Living-Donor Liver Transplantation

  Hideaki Uchiyama, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara

  TRANSPLANTATION 94 (2) E17 - E18 0041-1337 2012/07 [Refereed][Not invited]
  
• 当科における胆道嚢胞性疾患症例の検討

  敦賀 陽介, 蒲池 浩文, 柿坂 達彦, 横尾 英樹, 中西 一彰, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 2 - 2 2012/07
• 予後、再発因子からみた肝内胆管癌の治療戦略

  横尾 英樹, 神山 俊哉, 中西 一彰, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 1 - 1 2012/07
• 腹腔鏡下・補助下肝切除術における肝実質切離の工夫と定型化

  神山 俊哉, 中西 一彰, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 1 - 1 2012/07
• 肝細胞癌遠隔転移切除症例の検討

  中西 一彰, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 2 - 2 2012/07
• 肝門部領域胆道系腫瘍における胆管・血管3DCT合成画像を用いた手術シミュレーション

  蒲池 浩文, 敦賀 陽介, 柿坂 達彦, 横尾 英樹, 中西 一彰, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 1 - 1 2012/07
• 超高齢者の肝細胞癌手術症例に関する検討

  柿坂 達彦, 神山 俊哉, 中西 一彰, 横尾 英樹, 蒲池 浩文, 敦賀 陽介, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 1 - 1 2012/07
• 大腸癌肝転移切除症例の検討

  下國 達志, 横尾 英樹, 高橋 典彦, 片岡 昭彦, 神山 俊哉, 武冨 紹信

  日本消化器外科学会総会 (一社)日本消化器外科学会 67回 1 - 1 2012/07
• A case of schwannoma of the small intestine resected by single incision laparoscopic surgery (SILS)

  SHIMOKUNI TATSUSHI, MINAGAWA NOZOMI, HONMA SHIGENORI, SAKIHAMA HIDEYASU, TAKAHASHI NORIHIKO, KAMIYAMA TOSHIYA, TAKETOMI AKINOBU

  北海道外科雑誌 57 (1) 57 - 60 0288-7509 2012/06/20 [Not refereed][Not invited]
  
• A case of 7cm gastric GIST in the major axis resected safely by laparoscopic surgery

  SHIMOKUNI TATSUSHI, MINAGAWA NOZOMI, HONMA SHIGENORI, SAKIHAMA HIDEYASU, TAKAHASHI NORIHIKO, KAMIYAMA TOSHIYA, TAKETOMI AKINOBU

  北海道外科雑誌 北海道外科学会 57 (1) 61 - 64 0288-7509 2012/06/20 [Not refereed][Not invited]
  
• Enhancement pattern analysis of hypervascular hepatocellular carcinoma on dynamic MR imaging with histopathological correlation: Validity of portal phase imaging for predicting tumor grade

  Daisuke Okamoto, Kengo Yoshimitsu, Akihiro Nishie, Tsuyoshi Tajima, Yoshiki Asayama, Kousei Ishigami, Masakazu Hirakawa, Yasuhiro Ushijima, Daisuke Kakihara, Tomohiro Nakayama, Yunosuke Nishihara, Shinichi Aishima, Akinobu Taketomi, Junji Kishimoto, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 81 (6) 1116 - 1121 0720-048X 2012/06 [Refereed][Not invited]
   

  Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings. Materials and methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid. Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern. Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
• Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level

  Taro Ohba, Tokujiro Yano, Tsukihisa Yoshida, Daigo Kawano, Shuichi Tsukamoto, Fumihiro Shoji, Akinobu Taketomi, Hideki Saitsu, Sadanori Takeo, Yoshihiko Maehara

  SURGERY TODAY 42 (6) 526 - 531 0941-1291 2012/06 [Refereed][Not invited]
   

  Purpose Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors. Methods This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed. Results The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5 years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19 days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP >= 500 ng/ml in comparison to those with AFP < 500 ng/ml (p < 0.05). No other factors were associated with the survival after pulmonary metastasectomy. Conclusion The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.
• Predictors for Microinvasion of Small Hepatocellular Carcinoma <= 2 cm

  Yo-ichi Yamashita, Eiji Tsuijita, Kazuki Takeishi, Megumu Fujiwara, Shinsuke Kira, Masaki Mori, Shinichi Aishima, Akinobu Taketomi, Ken Shirabe, Terutoshi Ishida, Yoshihiko Maehara

  ANNALS OF SURGICAL ONCOLOGY 6 19 (6) 2027 - 2034 1068-9265 2012/06 [Refereed][Not invited]
   

  Hepatocellular carcinoma (HCC) a parts per thousand currency sign2 cm in diameter is considered to have a low potential for malignancy. A retrospective review was undertaken of 149 patients with primary solitary HCC a parts per thousand currency sign2 cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC a parts per thousand currency sign2 cm accompanied by MI was compared to that of patients with HCC a parts per thousand currency sign2 cm without MI. Forty-three patients with HCC a parts per thousand currency sign2 cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-gamma-carboxy prothrombin (DCP) > 100 mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC a parts per thousand currency sign2 cm with MI (3 year 44%) were significantly worse than those for HCC a parts per thousand currency sign2 cm without MI (3 year 72%). This disadvantage of disease-free survival rate of patients with HCC a parts per thousand currency sign2 cm with MI could be dissolved by hepatic resection with a wide tumor margin of a parts per thousand yen5 mm ( = 0.04). Even in cases of HCC a parts per thousand currency sign2 cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (> 100 mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.
• The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation: a comparison of right and left lobe grafts

  Akinobu Taketomi, Ken Shirabe, Takeo Toshima, Kazutoyo Morita, Naotaka Hashimoto, Hiroto Kayashima, Tohru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihko Maehara

  SURGERY TODAY 42 (6) 559 - 564 0941-1291 2012/06 [Refereed][Not invited]
   

  Purpose The feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type. Methods A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed. Results The graft volume (436 +/- 74 g), as well as the graft volume-standard liver volume rate (38.3 +/- 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 +/- 82 g, 46.3 +/- 6.7%; p < 0.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (p < 0.01). The rate of severe complications (over Clavien's IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%). Conclusions The long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety.
• Acoustic radiation force impulse imaging predicts postoperative ascites resulting from curative hepatic resection for hepatocellular carcinoma

  Noboru Harada, Ken Shirabe, Hideki Ijichi, Rumi Matono, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara

  SURGERY 151 (6) 837 - 843 0039-6060 2012/06 [Refereed][Not invited]
   

  Background. Measurement of liver stiffness using Virtual Touch Tissue Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects the degree of hepatic fibrosis and reserve. This prospective study investigated how well the VTTQ value predicts the development of postoperative complications before curative hepatic resection for hepatocellular carcinoma (HCC). Methods: The study enrolled 50 consecutive patients between February 2009 and October 2010 whose preoperative VTTQ values were determined before they underwent curative hepatic resection for HCC. We assessed the relationship between postoperative complications and VTTQ values. Results. The study included 41 (82%) patients with chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was 1.60 (m/sec), which correlated with the fibrosis stage (P = .0058). The VTTQ value was the only variable correlated with postoperative ascites that did not respond to pharmacologic treatment and required invasive management. Univariate and subsequent multivariate analyses revealed that the preoperative VTTQ value was the only independent risk factor for predicting the development of postoperative ascites (cutoff 1.68 cm/sec; P = .007; odds ratio, 76.481). The area under the receiver operating characteristic curve for the diagnosis of postoperative ascites using VTTQ values was 0.90, whereas those using the aspartate transaminase-to-platelet ratio index and indocyanine green retention rate at 15 minutes values were 0.68 and 0.55, respectively. Conclusion. These data suggest that the VTTQ value is a reliable surrogate marker for predicting postoperative ascites before curative hepatic resection for HCC. (Surgery 2012;151:837-43.)
• Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma

  Toshiya Kamiyama, Kazuaki Nakanishi, Hideki Yokoo, Hirofumi Kamachi, Munenori Tahara, Tatsuhiko Kakisaka, Yosuke Tsuruga, Satoru Todo, Akinobu Taketomi

  WORLD JOURNAL OF SURGICAL ONCOLOGY 10 107  1477-7819 2012/06 [Refereed][Not invited]
   

  Background: Liver resection for hepatocellular carcinoma (HCC) has the highest local controllability among all local treatments and results in a good survival rate. However, the recurrence rates of HCC continue to remain high even after curative hepatectomy Moreover, it has been reported that some patients with HCC have an early death due to recurrence. We analyzed the preoperative risk factors for early cancer death. Methods: Between 1997 and 2009, 521 consecutive patients who underwent hepatectomy for HCC at our center were assigned to group ED (death due to HCC recurrence or progression within 1 year after hepatectomy) and group NED (alive over 1 year after hepatectomy). Risk factors for early cancer death were analyzed. Results: Group ED included 48 patients, and group NED included 473 patients. The cause of death included cancer progression (150; 78.1%), operation-related (1; 0.5%), hepatic failure (15; 7.8%), and other (26; 13.5%). Between the ED and NED groups, there were significant differences in albumin levels, Child-Pugh classifications, anatomical resections, curability, tumor numbers, tumor sizes, macroscopic vascular invasion (portal vein and hepatic vein), alpha-fetoprotein (AFP) levels, AFP-L3 levels, protein induced by vitamin K absence or antagonism factor II (PIVKA-II) levels, differentiation, microscopic portal vein invasion, microscopic hepatic vein invasion, and distant metastasis by univariate analysis. Multivariate analysis identified specific risk factors, such as AFP level > 1,000 ng/ml, tumor number >= 4, tumor size >= 5 cm, poor differentiation, and portal vein invasion. With respect to the preoperative risk factors such as AFP level, tumor number, and tumor size, 3 (1.1%) of 280 patients with no risk factors, 12 (7.8%) of 153 patients with 1 risk factor, 24 (32.9%) of 73 patients with 2 factors, and 9 (60.0%) of 15 patients with 3 risk factors died within 1 year of hepatectomy (p < 0.0001). Conclusions: Hepatectomy should be judiciously selected for patients with AFP level > 1,000 ng/ml, tumor number >= 4, and tumor size >= 5 cm, because patients with these preoperative risk factors tend to die within 1 year after hepatectomy; these patients might be better treated with other therapy.
• 生体肝移植術後の過少グラフト症候群に伴う大量腹水にPSEが著効した1例

  山田 健司, 渡辺 正明, 大浦 哲, 山下 健一郎, 鈴木 友己, 嶋村 剛, 藤堂 省, 武富 紹信

  北海道外科雑誌 北海道外科学会 57 (1) 75 - 75 0288-7509 2012/06
• 胆管空腸吻合術後の肝内結石症に対する肝切除術の検討

  敦賀 陽介, 蒲池 浩文, 柿坂 達彦, 横尾 英樹, 中西 一彰, 神山 俊哉, 武冨 紹信

  北海道外科雑誌 北海道外科学会 57 (1) 74 - 74 0288-7509 2012/06
• HBs抗原陰性・HCV抗体陰性肝細胞癌切除例の検討

  中西 一彰, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  北海道外科雑誌 北海道外科学会 57 (1) 74 - 75 0288-7509 2012/06
• 成人肝未分化肉腫の1例

  鈴木 智亮, 神山 俊哉, 中西 一彰, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 鈴木 崇史, 蒲池 浩文, 松下 通明, 武冨 紹信

  北海道外科雑誌 北海道外科学会 57 (1) 75 - 75 0288-7509 2012/06
• Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer

  T. Einama, S. Homma, H. Kamachi, F. Kawamata, K. Takahashi, N. Takahashi, M. Taniguchi, T. Kamiyama, H. Furukawa, Y. Matsuno, S. Tanaka, H. Nishihara, A. Taketomi, S. Todo

  BRITISH JOURNAL OF CANCER 107 (1) 137 - 142 0007-0920 2012/06 [Refereed][Not invited]
   

  BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric cancer, especially in terms of its association with the staining pattern. METHODS: Tissue specimens from 110 gastric cancer patients were immunohistochemically examined. The staining proportion and intensity of mesothelin expression in tumour cells were analysed, and the localisation of mesothelin was classified into luminal membrane and/or cytoplasmic expression. RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin expression was correlated with lymph-node metastasis. Furthermore, luminal membrane staining of mesothelin was identified in 16 cases, and the incidence of luminal membrane expression was also correlated with pT factor, pStage, lymphatic permeation, blood vessel permeation, recurrence, and poor patient outcome. Multivariate analysis showed that luminal membrane expression of mesothelin was an independent predictor of overall patient survival. CONCLUSION: We described that the luminal membrane expression of mesothelin was a reliable prognostic factor in gastric cancer, suggesting the functional significance of membrane-localised mesothelin in the aggressive behaviour of gastric cancer cells. British Journal of Cancer (2012) 107, 137-142. doi: 10.1038/bjc.2012.235 www.bjcancer.com Published online 29 May 2012 (C) 2012 Cancer Research UK
• Zero mortality in more than 300 hepatic resections: validity of preoperative volumetric analysis

  Shinji Itoh, Ken Shirabe, Akinobu Taketomi, Kazutoyo Morita, Norifumi Harimoto, Eiji Tsujita, Keishi Sugimachi, Yo-ichi Yamashita, Tomonobu Gion, Yoshihiko Maehara

  SURGERY TODAY 42 (5) 435 - 440 0941-1291 2012/05 [Refereed][Not invited]
   

  We reviewed a series of patients who underwent hepatic resection at our institution, to investigate the risk factors for postoperative complications after hepatic resection of liver tumors and for procurement of living donor liver transplantation (LDLT) grafts. Between April 2004 and August 2007, we performed 304 hepatic resections for liver tumors or to procure grafts for LDLT. Preoperative volumetric analysis was done using 3-dimensional computed tomography (3D-CT) prior to major hepatic resection. We compared the clinicopathological factors between patients with and without postoperative complications. There was no operative mortality. According to the 3D-CT volumetry, the mean error ratio between the actual and the estimated remnant liver volume was 13.4%. Postoperative complications developed in 96 (31.6%) patients. According to logistic regression analysis, histological liver cirrhosis and intraoperative blood loss > 850 mL were significant risk factors of postoperative complications after hepatic resection. Meticulous preoperative evaluation based on volumetric analysis, together with sophisticated surgical techniques, achieved zero mortality and minimized intraoperative blood loss, which was classified as one of the most significant predictors of postoperative complications after major hepatic resection.
• V5-Drainage-Preserved Right Lobe Grafts Improve Graft Congestion for Living Donor Liver Transplantation

  Takeo Toshima, Akinobu Taketomi, Toru Ikegami, Takasuke Fukuhara, Hiroto Kayashima, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara

  TRANSPLANTATION 93 (9) 929 - 935 0041-1337 2012/05 [Refereed][Not invited]
   

  Background. Right lobe (RL) grafts without middle hepatic vein for living donor liver transplantation (LDLT) result in congestion of recipients' livers and sometimes in unfavorable postoperative course. This study aimed to evaluate the feasibility of our new V5-drainage-preserved RL (VP-RL) graft. Methods. Based on a review of 49 donors' livers in a retrospective study using three-dimensional reconstruction-computed tomography volumetry, hepatic vein draining segment 4 (V4) anatomy was classified into three types: inferior V4 dominant (A); superior V4 dominant (B); and umbilical vein to left hepatic vein dominant (C). Differences in functional graft volume (GV) and remnant liver volume (RV) between VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a prospective study of actual 15 LDLT, the outcome of venous reconstruction and postoperative parameters with VP-RL grafts compared with M-RL grafts was analyzed. Results. In the retrospective study using three-dimensional reconstruction-computed tomography volumetry, in types B and C, functional GV of VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional RV, whereas functional RV in VP-RL was significantly decreased in type A (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B and C, size and number of venous reconstructions, and functional GV and postoperative parameters, such as postoperative serum total bilirubin levels and ascites volume, were significantly improved compared with those using M-RL (P<0.05). Conclusions. Using preoperative V4 anatomical classification, VP-RL graft procurement is a valuable strategy in RL-LDLT to improve postoperative course of both recipients and donors.
• 肝胆膵領域の外科治療 これまでの到達点、これからの課題 肝細胞癌に対する肝切除術 系統的切除か部分切除か 小型肝細胞癌に対する系統的肝切除術の術後長期成績の検討

  武冨 紹信, 神山 俊哉, 中西 一彰, 蒲池 浩文, 横尾 英樹, 柿坂 達彦, 敦賀 陽介

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 24回 195 - 195 2012/05
• 局所進行肝内胆管癌に対してR0をめざした下大静脈合併切除グラフト再建

  横尾 英樹, 神山 俊哉, 中西 一彰, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 24回 302 - 302 2012/05
• 再発形式からみた胆管癌治療戦略

  敦賀 陽介, 蒲池 浩文, 柿坂 達彦, 横尾 英樹, 中西 一彰, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 24回 420 - 420 2012/05
• 血管合併切除を伴う肝門部領域胆道系癌に対する手術アプローチ

  蒲池 浩文, 敦賀 陽介, 柿坂 達彦, 横尾 英樹, 中西 一彰, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 24回 420 - 420 2012/05
• 出血性肝嚢胞と鑑別を要した胆管内乳頭状腫瘍(IPNB)の1例

  柿坂 達彦, 中西 一彰, 横尾 英樹, 蒲池 浩文, 敦賀 陽介, 神山 俊哉, 武冨 紹信

  日本肝胆膵外科学会・学術集会プログラム・抄録集 (一社)日本肝胆膵外科学会 24回 431 - 431 2012/05
• Preoperative detection of circulating tumor cells in patients with colorectal carcinoma: Correlation with clinicopathologic variables and recurrence.

  Hideyasu Sakihama, Nozomi Kobayashi, Tohru Funakoshi, Tatsushi Shimokuni, Shigenori Homma, Norihiko Takahashi, Akihiko Kataoka, Michitaka Ozaki, Toshiya Kamiyama, Akinobu Taketomi

  JOURNAL OF CLINICAL ONCOLOGY 30 (15) 0732-183X 2012/05 [Refereed][Not invited]
  
• Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection

  Rumi Matono, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Hiroto Kayashima, Toshiro Masuda, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  HPB 14 (4) 247 - 253 1365-182X 2012/04 [Refereed][Not invited]
   

  Objectives: The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT. Methods: Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared. Results: Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364). Conclusions: Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival.
• Poor Prognostic Factors after Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma in the Modern Era

  Eiji Tsujita, Yo-Ichi Yamashita, Kazuki Takeishi, Ayumi Matsuyama, Shin-Ichi Tsutsui, Hiroyuki Matsuda, Takeo Toshima, Akinobu Taketomi, Ken Shirabe, Teruyoshi Ishida, Yoshihiko Maehara

  AMERICAN SURGEON 78 (4) 419 - 425 0003-1348 2012/04 [Refereed][Not invited]
   

  The purpose of this study was to determine the poor prognostic factors after repeat hepatectomy (Hx) in patients with recurrent hepatocellular carcinoma (HCC). Overall survival rates and clinicopathological variables in 112 patients with repeat Hx from 1992 to 2010 were compared with those in 531 patients who underwent a primary Hx. To clarify the poor prognosis factors after repeat Hx, survival data among 112 patients were univariately and multivariately analyzed. Overall survival after repeat Hx was similar for that of the patients who underwent a primary Hx. The mean age of repeat Hx group was significantly higher, and a well-preserved liver function was recognized than the primary Hx group. Multivariate analysis revealed that: 1) indocyanine green retention rate at 15 minutes; 2) disease-free interval; 3) tumor size; 4) portal vein invasion at primary Hx; 5) gender; and 6) estimated blood loss to be an independent and significant poor prognostic factors. The overall 3-year postrecurrence overall survival rates were 100, 91.3, 59.6, and 0 per cent at risk number (R) R0, R1/2, R3, R4, respectively (P < 0.05). Repeat Hx provided a good compatible prognosis with primary Hx. In our findings, five risk factors to predict poor outcomes after repeat Hx were useful. Patients with recurrent HCC do not have universally poor outcomes, and our simple scoring system using five poor prognostic factors could serve to advise the prognosis and the potential benefit for patient selection about repeat Hx.
• 血行性転移予防を念頭においた肝細胞癌術後補助化学療法の検討

  中西 一彰, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  肝臓 (一社)日本肝臓学会 53 (Suppl.1) A393 - A393 0451-4203 2012/04
• Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype

  Takashi Motomura, Erina Koga, Akinobu Taketomi, Takasuke Fukuhara, Yohei Mano, Jun Muto, Hideyuki Konishi, Takeo Toshima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 42 (3) 288 - 295 1386-6346 2012/03 [Refereed][Not invited]
   

  Aim: A genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) has been associated with pegylated-interferon/ribavirin (PEG-IFN/RBV)-induced anemia in chronic hepatitis C patients. However, correlation of the genetic variant with anemia following liver transplantation has not been determined. Methods: Sixty-three hepatitis C virus (HCV)-positive patients who underwent liver transplantation and PEG-IFN/ RBV therapy were enrolled. The rs1127354 was determined for each individual. Results: There was no relationship with anemia or RBV dosage in patients carrying the CC allele (CC group, n = 43) and those carrying the CA allele (CA group, n = 20). The incidence of hemoglobin (Hb) decline > 3 g/dL (CC: 4.7%, CA: 0%) was relatively low, whereas the incidence of Hb levels < 10 g/dL (CC: 18.6%, CA: 30.0%) was high. Univariate analysis revealed that splenectomy inversely correlated with Hb levels < 10 g/dL at 4 weeks (P = 0.04). Among the 22 patients who did not undergo splenectomy, the incidence of Hb levels < 10 g/dL tended to be lower in the seven patients carrying the CA allele (28.6%) than in the 15 patients with the CC allele (60.0%). Conclusion: The ITPA genetic polymorphism does not correlate with post-transplant PEG-IFN/RBV-induced anemia. Splenectomy is useful in preventing anemia regardless of the ITPA genotype.
• Characteristics of Extrahepatic Second Primary Malignancies after Hepatectomy for Hepatocellular Carcinoma in Japan

  Eiji Tsujita, Yo-ichi Yamashita, Kazuki Takeishi, Yasuyuki Aisaka, Shinsuke Kira, Masaki Mori, Akinobu Taketomi, Ken Shirabe, Teruyoshi Ishida, Yoshihiko Maehara

  AMERICAN SURGEON 78 (3) E129 - E131 0003-1348 2012/03 [Refereed][Not invited]
  
• 生体肝ドナーquality of life尺度の開発および信頼性と妥当性の検討

  師岡 友紀, 梅下 浩司, 武冨 紹信, 前原 喜彦, 山本 真由美, 嶋村 剛, 大下 彰彦, 菅野 啓子, 大段 秀樹, 川岸 直樹, 里見 進, 小川 馨, 萩原 邦子, 永野 浩昭

  移植 (一社)日本移植学会 47 (1) 67 - 74 0578-7947 2012/03 

  生体肝ドナーQOL尺度を開発し、実用化に向け項目の精選を図り、信頼性と妥当性を検証することを目的とし大規模調査を実施した。生体肝提供手術を受け、術後1ヵ月以上経過したドナー965例を対象とした。生体肝ドナー20例に対する半構成的インタビューの結果、および先行研究による概念枠組みをもとに独自に質問項目を作成し、QOL尺度素案を作成した。432例を分析対象とした。開発した生体肝ドナーQOL尺度は、構成概念妥当性、基準関連妥当性は十分であると考えられ、QOL評価が可能な妥当性のある尺度とみなすことができた。また、再テストによる安定性、尺度の内的整合性もまずまずで、信頼性があり使用可能な尺度であることを確認した。解釈における配慮事項はあるものの、当面の使用にあたって問題ない妥当性、信頼性が得られているため、本尺度を用いた生体肝ドナーのQOL評価は可能と考えられた。
• Oncologic emergencyとしての下大静脈・右心房浸潤肝細胞癌に対する外科治療

  中西 一彰, 神山 俊哉, 横尾 英樹, 柿坂 達彦, 敦賀 陽介, 蒲池 浩文, 武冨 紹信

  日本腹部救急医学会雑誌 (一社)日本腹部救急医学会 32 (2) 408 - 408 1340-2242 2012/02
• The impact of renal replacement therapy before or after living donor liver transplantation

  Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoshihiko Maehara

  CLINICAL TRANSPLANTATION 26 (1) 143 - 148 0902-0063 2012/01 [Refereed][Not invited]
   

  Introduction: The impact of renal replacement therapy (RRT) in living donor liver transplantation (LDLT) has not yet been investigated. Methods: Among 253 LDLT patients, RRT was started before (RRT-Pre, n = 9), or after (RRT-Post, n = 27) LDLT. The clinical outcomes were reviewed. Results: The one-yr graft survival rate was 94.1% without RRT, and 63.9% and in those with RRT (p < 0.0001). Among the RRT patients, the RRT-Pre patients exhibited acute liver failure, hepatorenal syndrome and high model for end-stage liver disease score (35 +/- 12), whereas the RRT-Post patients had sepsis as a comorbidity. The one-yr graft survival rate was 100.0% in the RRT-Pre patients vs. 51.9% in the RRT-Post patients (p < 0.01). The duration of RRT was significantly shorter in the RRT-Pre patients than that in the RRT-Post patients (5.3 +/- 2.1 vs. 17.8 +/- 14.1 d, p = 0.02). The mean duration between starting RRT and LDLT was 2.1 +/- 0.7 d in the Pre-RRT patients. Conclusion: The RRT-Pre patients had excellent outcomes because the severe condition was primarily treated by LDLT after short-term pre-transplant RRT. Post-transplant uncontrollable sepsis was the major cause of graft loss in patients who receive RRT after LDLT.
• Expanding the applications of microvascular surgical techniques to digestive surgeries: a technical review

  Hideaki Uchiyama, Ken Shirabe, Masaru Morita, Yoshihiro Kakeji, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Kazutoyo Morita, Yoshihiko Maehara

  SURGERY TODAY 42 (2) 111 - 120 0941-1291 2012/01 [Refereed][Not invited]
   

  In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries.
• Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography

  Akinobu Taketomi, Kazuki Takeishi, Yohei Mano, Takeo Toshima, Takashi Motomura, Shinichi Aishima, Hideaki Uchiyama, Tomoharu Yoshizumi, Ken Shirabe, Yoshihiko Maehara

  SURGERY TODAY 42 (1) 46 - 51 0941-1291 2012/01 [Refereed][Not invited]
   

  We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV.
• Role of tumor-associated macrophages in the progression of hepatocellular carcinoma

  Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani, Yoshihisa Sakaguchi, Yoshihiko Maehara

  SURGERY TODAY 42 (1) 1 - 7 0941-1291 2012/01 [Refereed][Not invited]
   

  Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-gamma polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs.
• Risk Factors That Increase Mortality After Living Donor Liver Transplantation

  Tomoharu Yoshizumi, Ken Shirabe, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Masanori Yoshimatsu, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara

  TRANSPLANTATION 93 (1) 93 - 98 0041-1337 2012/01 [Refereed][Not invited]
   

  Background. Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. Methods. A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. Results. The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). Conclusions. Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates.
• Switching from organ preservation to repair:Significance of mitochondrial function and intracellular Ca2＋kinetics

  Fukai Moto, Taketomi Akinobu, Todo Satoru

  Organ Biology The Japan Society for Organ Preservation and Biology 19 (1) 70 - 75 1340-5152 2012 [Not refereed][Not invited]
   

  Although organ cooling is beneficial for any kind of grafts, mainly by metabolic arrest, hypoxia and hypothermia concomitantly cause harmful reactions, such as ATP depletion, mitochondrial dysfunction, cytosolic Ca2＋ overload, intracellular acidosis, oxidative stress, cellular swelling, and cytoskeletal breakdown. To understand the optimal conditions of hypothermic oxygenated perfusion (HOPE), we reviewed the mechanisms of cold preservation injury, mainly focused on the mitochondrial function, cytosolic Ca2＋ overload, and downstream activation of proteases, phosphatases, and phospholipases. We also discussed the possibility of heavy water(deuterium water)containing buffers for the use of a perfusate in HOPE.
• Anal Gland Cancer with Pagetoid Spread in an Old Woman

  ICHIKAWA NOBUKI, HONMA SHIGENORI, KATAOKA AKIHIKO, TAKAHASHI NORIHIKO, SAKIHAMA HIDEYASU, TAKETOMI AKINOBU

  日本大腸こう門病学会雑誌 The Japan Society of Coloproctology 65 (8) 442 - 446 0047-1801 2012 [Not refereed][Not invited]
   

  A 73-year-old woman presented to our hospital with perianal skin eruption as a chief compliant. The eruptic lesion was found to be almost well-circumscribed and 1 cm in diameter, while no tumor was found in the anal canal or in the distal part of the rectum. Skin biopsy revealed pagetoid cells in the perianal skin lesion. Further radiological examinations revealed no lymph node metastases or distant metastases. She underwent abdomino-perineal resection with D2 lymph node dissection for the occult carcinoma with pagetoid spread. Pathological examination revealed continuance within the epidermis between the small primary tumor deriving from an anal gland and the pagetoid lesion. Thus, we finally diagnosed anal gland carcinoma, invading into the submucosal lesion accompanied by pagetoid spread. No adjuvant chemotherapies were introduced postoperatively. No recurrence has been found for as long as 29 months so far.
  We conclude that perianal skin lesions should be carefully examined, taking pagetoid spread into account. Furthermore, we should consider that extramucosal adenocarcinoma such as anal gland carcinoma, although rare, may cause pagetoid spread.
• Additional resection of the pancreas body prevents postoperative pancreas fistula in patients with portal annular pancreas who undergo pancreaticoduodenectomy.

  Jun Muto, Yohei Mano, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  Case reports in gastroenterology 6 (1) 131 - 4 1662-0631 2012/01 [Refereed][Not invited]
   

  Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein. Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction.
• Hepatocellular carcinoma with marginal superparamagnetic iron oxide uptake on T2*-weighted magnetic resonance imaging: Histopathologic correlation

  Kousei Ishigami, Tsuyoshi Tajima, Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Daisuke Kakihara, Tomohiro Nakayama, Daisuke Okamoto, Akinobu Taketomi, Ken Shirabe, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 80 (3) E293 - E298 0720-048X 2011/12 [Refereed][Not invited]
   

  Purpose: To evaluate the characteristics of hepatocellular carcinomas (HCCs) with marginal superparamagnetic iron oxide (SPIO) uptake on T2*-weighted MRI. Materials and methods: The study group consisted of 73 patients with 83 surgically resected HCCs. Preoperative SPIO-enhanced MRI studies were retrospectively reviewed. Marginal SPIO uptake was considered positive if a rim-like or band-like low intensity area was present on SPIO-enhanced T2*-weighted images. The prevalence of marginal SPIO uptake was evaluated. Pathological specimens with hematoxylin and eosin staining and immunohistochemical staining of CD68 were reviewed in HCCs with marginal SPIO uptake and 33 HCCs without marginal SPIO uptake (control group). Results: Ten of 83 (12%) HCCs showed marginal SPIO uptake. All HCCs were hypervascular, and only one nodule showed a nodule-in-nodule appearance on imaging findings. The pathology specimens suggested possible causes of marginal SPIO uptake, including marginal macrophage infiltration in moderately or poorly differentiated HCC (n = 4), residual normal hepatic tissue at the marginal area of confluent multinodular or single nodular with extranodular growth type HCC (n = 3), and a well-differentiated HCC component in nodule-in-nodule type HCC (n = 3). Marginal macrophage infiltration was not seen in the control group. Conclusion: SPIO-enhanced MRI may be able to demonstrate marginal macrophage infiltration in HCC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
• Factors associated with the postoperative status of donor patients for living donor liver transplantation

  Yoshufumi Wakata, Naoki Nakashima, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Akihito Hagihara

  LIVER TRANSPLANTATION 17 (12) 1412 - 1419 1527-6465 2011/12 [Refereed][Not invited]
   

  Deceased donor liver transplantation has been an established surgical procedure since the 1960s. More recently, the technique of living donor liver transplantation (LDLT) was introduced, and it is being performed with increasing frequency. However, there is a paucity of information on the clinical outcomes of donor patients. In this study, which was conducted at a single university hospital, the relationship between potentially relevant factors (eg, patient characteristics, preoperative status, and operation characteristics) and postoperative developments in donor patients was examined. We used electronic critical pathways, which are charts of medical process that include favorable states (defined as outcomes) to be achieved during the hospital stay of a patient; predefined outcomes that are not achieved are recorded as variances. With the electronic critical pathway system, objective data about the conditions of patients and relevant clinical processes could be collected readily. Using data from the electronic critical pathways for LDLT donor patients and applying multiple logistic regression analysis, we examined factors that were related to the variance of each outcome measure for postoperative developments. Among the various donor characteristics, the duration of the operation was related to variance in 5 types of health outcomes, age and blood loss volume were related to variance in 2 types of health outcomes, and other characteristics (ie, sex, body surface area, operation urgency, and volume ratio of the remnant liver) were related to variance in 1 type of health outcome. In conclusion, the findings in this study may facilitate improvements in the postoperative status of LDLT donor patients. Further studies that incorporate analogous data from other medical facilities are necessary to verify these findings. Liver Transpl, 2011. (c) 2011 AASLD.
• Pure Laparoscopic Right Hepatectomy in the Semi-Prone Position Using the Intrahepatic Glissonian Approach and a Modified Hanging Maneuver to Minimize Intraoperative Bleeding

  Tetsuo Ikeda, Yusuke Yonemura, Naoyuki Ueda, Akira Kabashima, Ken Shirabe, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yosihiro Kakeji, Masaru Morita, Shunichi Tsujitani, Yoshihiko Maehara

  SURGERY TODAY 41 (12) 1592 - 1598 0941-1291 2011/12 [Refereed][Not invited]
   

  Purpose. Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. Methods. Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). Results. The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). Conclusion. Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding.
• Roles of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase During Revascularization and Regeneration After Partial Hepatectomy in a Rat Model

  Daisuke Yoshida, Tomohiko Akahoshi, Hirofumi Kawanaka, Shohei Yamaguchi, Nao Kinjo, Akinobu Taketomi, Morimasa Tomikawa, Ken Shirabe, Yoshihiko Maehara, Makoto Hashizume

  SURGERY TODAY 41 (12) 1622 - 1629 0941-1291 2011/12 [Refereed][Not invited]
   

  Purpose. Angiogenesis is an essential process in liver regeneration. Nitric oxide (NO) and vascular endothelial growth factor (VEGF) are the main regulators of normal and pathological angiogenesis. This study aimed to determine the roles of NO derived from endothelial nitric oxide synthase (eNOS) and VEGF in sinusoidal endothelial cell (SEC) proliferation during liver regeneration. Methods. Sprague-Dawley rats underwent a 70% partial hepatectomy (PHx), and were euthanized 0, 24, 48, 72, or 168 h later. Liver regeneration and SEC proliferation were evaluated. The protein expression of VEGF and eNOS was examined by a Western blot analysis. The rats were also treated with the NO synthase inhibitor NG-nitro-l-arginine-methyl ester (L-NAME) to examine its effects on liver regeneration and SEC proliferation. Results. The proliferating cell nuclear antigen (PCNA) labeling index of hepatocytes was significantly increased at 24 h after PHx. The eNOS protein expression and NO production were significantly increased from 72 to 168 h. The expression of VEGF protein was significantly increased at 72 h. L-NAME significantly inhibited the increases in the liver mass and decreased the PCNA labeling index of hepatocytes at 24 h. L-NAME also inhibited the induction of VEGF protein at 72 h. Conclusions. Endothelial NOS and VEGF coordinately regulate SEC proliferation during liver regeneration. Sinusoidal endothelial cell proliferation is necessary and is an important step in liver regeneration.
• Diagnostic performance of apparent diffusion coefficient for predicting histological grade of hepatocellular carcinoma

  Akihiro Nishie, Tsuyoshi Tajima, Yoshiki Asayama, Kousei Ishigami, Daisuke Kakihara, Tomohiro Nakayama, Yukihisa Takayama, Daisuke Okamoto, Nobuhiro Fujita, Akinobu Taketomi, Kengo Yoshimitsu, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 80 (2) E29 - E33 0720-048X 2011/11 [Refereed][Not invited]
   

  Objective: To investigate whether the histological grade of hepatocellular carcinoma (HCC) can be predicted using the apparent diffusion coefficient (ADC). Materials and Methods: This retrospective study group consisted of 80 patients with 85 surgically resected HCCs who underwent preoperative MRI exams including diffusion-weighted imaging. The tumors were histologically classified into five groups as follows: five well (w-), 17 well to moderately (wm-), 37 moderately (m-), 16 moderately to poorly (mp-), and 10 poorly (p-) differentiated HCCs. For ADC measurement of each HCC, the largest possible region of interest was placed on the solid region on the ADC map where ADC was considered to be the lowest. The average ADCs of the five histological grades were compared using Spearman's rank correlation test and Student's t-test, and the diagnostic performance of ADC for mp- and p- HCCs was also evaluated using a receiver operating characteristic-based positive test. Results: The average ADC of p- HCC (0.76 +/- 0.10 x 10(-3) mm(2)/s) was significantly lower than those of the other four histological grades. The average ADC of mp- HCCs (0.99 +/- 0.20 x 10(-3) mm(2)/s) was significantly lower than those of w-, wm- and m- HCCs. The sensitivity, specificity, PPV, NPV, and accuracy, when an ADC of 0.972 or lower was considered an indicator of mp- and p- HCCs, were 73.1%, 72.9%, 54.3%, 86.0% and 72.9%, respectively. Conclusion: ADCs of mp- and p-HCCs were lower than those of w-, wm- and m-HCCs. ADC can contribute to radiological diagnosis of poorly differentiated components in HCCs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
• Kinetics of Anti-Blood Type Isoagglutinin Titers and B Lymphocytes in ABO-Incompatible Living Donor Liver Transplantation With Rituximab and Plasma Exchange

  Hideaki Uchiyama, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Toru Ikegami, Ken Shirabe, Yoshihiko Maehara

  TRANSPLANTATION 92 (10) 1134 - 1139 0041-1337 2011/11 [Refereed][Not invited]
   

  Background. A novel immunosuppression protocol using rituximab and plasma exchange treatment was developed for ABO-incompatible living donor liver transplantation (ABO-I LDLT). The aim of this study was to investigate the kinetics of anti-blood type isoagglutinin titers and the number of blood B lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes after ABO-I LDLT. Methods. Fifteen patients underwent ABO-I LDLT plus splenectomy with the new protocol between November 2005 and December 2010, and their data were retrospectively analyzed. Results. CD19-positive lymphocytes in the blood rapidly disappeared after rituximab treatment and began to recover approximately 6 months later. Anti-blood type isoagglutinin titers were lowered by pretransplant plasma exchange (2(3)similar to 2(12 ->)2(1)similar to 2(8)). Although the anti-donor blood type isoagglutinin titers remained consistently low after transplantation in comparison to the pretreatment levels, they persisted long after LDLT, whereas posttransplant biopsy specimens showed sustained A/B antigens on the graft livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control patients. Conclusions. Although the new protocol for ABO-I LDLT yielded great success with 100% graft survival, the acceptable anti-blood type isoagglutinin titers just before LDLT, and its application to hepatitis C-positive patients must be determined.
• Minimal Hilar Dissection Prevents Biliary Anastomotic Stricture After Living Donor Liver Transplantation

  Toru Ikegami, Ken Shirabe, Kazutoyo Morita, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Hiroto Kayashima, Naotaka Hashimoto, Yoshihiko Maehara

  TRANSPLANTATION 92 (10) 1147 - 1151 0041-1337 2011/11 [Refereed][Not invited]
   

  Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n = 135; right lobe, n = 76; posterior segment, n = 3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n = 84) and 14.6% in the Min-HD technique group (n = 130, P = 0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1- and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT.
• Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology

  Shinichi Aishima, Tomohiro Iguchi, Nobuhiro Fujita, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi, Yoshinao Oda

  HISTOPATHOLOGY 59 (5) 867 - 875 0309-0167 2011/11 [Refereed][Not invited]
   

  Aims: Hitherto, biliary intraepithelial neoplasia (BilIN) has been described in chronic biliary disease but rarely in non-biliary liver cirrhosis (LC). Intraepithelial neoplasia of the pancreas shows alterations in the expression of cell cycle and mucin core proteins. The aim of this study was to evaluate BilIN and reactive biliary lesions in biliary disease and non-biliary LC. Methods and results: BilIN was found in 51% (33 of 65) of liver tissue cases of biliary disease, and in 11% (34 of 310) of the LC group. Immunohistologically, MUC5AC, an 'early phase' protein, and Ki67, reflecting 'late phase' expression, were identified with increasing degrees of dysplasia in both groups, but that expression was significantly higher in the biliary disease group. 'Early phase' cell cycle proteins, p16 ( decrease) and p21 ( increase) altered in both biliary and LC groups with increasing degrees of dysplasia. Conclusions: We found BilIN in the large bile ducts of hepatitis B virus- and hepatitis C virus- related LC as well as in cases related to a biliary aetiology. The LC group was significantly less likely to show changes in the expression of MUC5AC and proliferative activity than the biliary group. Alterations in p16 and p21 reflected increasing degrees of dysplasia in both groups.
• Histologic classification of microscopic portal venous invasion to predict prognosis in hepatocellular carcinoma

  Nobuhiro Fujita, Shinichi Aishima, Tomohiro Iguchi, Yohei Mano, Akinobu Taketomi, Ken Shirabe, Hiroshi Honda, Masazumi Tsuneyoshi, Yoshinao Oda

  HUMAN PATHOLOGY 42 (10) 1531 - 1538 0046-8177 2011/10 [Refereed][Not invited]
   

  Portal venous invasion is one of the most important prognostic factors after surgical resection of hepatocellular carcinoma. Microscopic portal venous invasion can be evaluated histologically. We examined 280 hepatocellular carcinomas with microscopic portal venous invasion (n = 125) or without it (n = 155) for 3 characteristics: the number of invaded portal vessels, the maximum number of invading carcinoma cells, and the farthest distance from the tumor. Univariate analysis of overall and disease-free survival revealed that the number of invaded portal vessels and the number of invading carcinoma cells were poor prognostic factors. Therefore, we classified patients with microscopic portal venous invasion into 2 groups: a high microscopic portal venous invasion group, in which there were multiple invaded portal venous vessels (2) and more than 50 invading carcinoma cells (n = 57), and a low microscopic portal venous invasion group, in which microscopic portal venous invasion was observed but with invasion of only a single portal venous vessel or fewer than 50 invading carcinoma cells (n = 68). The high microscopic portal venous invasion group showed significantly higher a-fetoprotein levels, larger tumor size, and higher frequencies of poorly differentiated histology, capsule infiltration, and intrahepatic metastasis compared with the low microscopic portal venous invasion group (P = .0496, P < .0001, P = .0431, P = .0180, and P = .0012, respectively). The high microscopic portal venous invasion group showed poorer overall survival and disease-free survival rates than the low microscopic portal venous invasion group (P = .0004 and P = .0003), and the high microscopic portal venous invasion group was an independent prognostic factor for disease-free survival (P = .0259). We proposed a new definition for classifying microscopic portal venous invasion and documented the necessity of definite histologic evaluation of it. (C) 2011 Elsevier Inc. All rights reserved.
• Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan

  Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara

  LIVER INTERNATIONAL 31 (9) 1366 - 1372 1478-3223 2011/10 [Refereed][Not invited]
   

  Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). Results: AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including 13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n = 136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals.
• Outcomes of Hepatic Resection for Huge Hepatocellular Carcinoma (>= 10 cm in Diameter)

  Yo-Ichi Yamashita, Akinobu Taketomi, Ken Shirabe, Shinichi Aishima, Eiji Tsuijita, Kazutoyo Morita, Hiroto Kayashima, Yoshihiko Maehara

  JOURNAL OF SURGICAL ONCOLOGY 3 104 (3) 292 - 298 0022-4790 2011/09 [Refereed][Not invited]
   

  Background: The object of the current study was to review the outcomes of hepatic resection for hepatocellular carcinoma (HCC) >= 10 cm. Methods: Between 1995 and 2007, fifty-three patients with HCC >= 10 cm underwent hepatic resection, and clinical data were compared to those of patients with non-surgical treatment (n = 12). Surgical results for HCC >= 10 cm were compared to those of patients with HCC < 10 cm (n = 412). The independent poor prognostic factors of the patients with HCC >= 10 cm were identified. Results: Overall survival was significantly better in patients with hepatic resection for HCC >= 10 cm than in those with non-surgical treatment (P < 0.01). Survival rates of patients with hepatic resection for HCC >= 10 cm were 35% at 5 years. Morbidity and mortality rate were statistically equal. The independent poor prognostic factors of patients with hepatic resection for HCC >= 10 cm were revealed: T4 status, macroscopic tumor thrombus in portal vein (VP+), and the use of intra-operative transfusion. Conclusion: Hepatic resections for HCC >= 10 cm are safe and efficacious. Minimizing intra-operative blood loss and the establishment of an effective systemic treatment for patients with HCC >= 10 cm in T4 appear to be critical. J. Surg. Oncol. 2011;104:292-298. (C) 2011 Wiley-Liss, Inc.
• Comparative evaluation of expanded criteria for patients with hepatocellular carcinoma beyond the Milan criteria undergoing living-related donor liver transplantation

  Ken Shirabe, Akinobu Taketomi, Kazutoyo Morita, Yuji Soejima, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Takeo Toshima, Yoshihiko Maehara

  CLINICAL TRANSPLANTATION 25 (5) E491 - E498 0902-0063 2011/09 [Refereed][Not invited]
   

  Objective: To clarify the predictive impact of expanded criteria for liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) in 54 patients with HCC beyond the Milan criteria (MC) from a series of 109 consecutive living-related donor liver transplantation (LDLT) recipients with HCC. Methods: Among 54 patients with HCC exceeding the MC, the predictive values for HCC recurrence within expanded criteria comprising the UCSF, Tokyo, Kyoto, Kyushu University (based on the tumor size and des-gamma carboxy prothrombin level) and Up-to-seven criteria were compared using univariate and multivariate analyses. The histological characteristics of HCC were compared among these extended criteria. Results: All five criteria were significant predictors for recurrence-free survival after univariate analyses. The Kyushu University criteria were the most powerful predictive criteria for HCC recurrence after multivariate analyses. The incidence of microvascular invasion and poorly differentiated HCC was significantly higher in patients with HCC exceeding the Kyushu University criteria than in those with HCC within the criteria. Conclusions: Compared with the other expanded criteria, the Kyushu University criteria may be useful to eliminate LT candidates at very high risk of HCC recurrence. The Kyushu University criteria were useful to evaluate LT candidates with HCC.
• Beneficial Effects of Supplementation With Branched-Chain Amino Acids on Postoperative Bacteremia in Living Donor Liver Transplant Recipients

  Ken Shirabe, Masanori Yoshimatsu, Takashi Motomura, Kazuki Takeishi, Takeo Toshima, Jun Muto, Rumi Matono, Akinobu Taketomi, Hideaki Uchiyama, Yoshihiko Maehara

  LIVER TRANSPLANTATION 17 (9) 1073 - 1080 1527-6465 2011/09 [Refereed][Not invited]
   

  The aim of this study was to investigate the effects of preoperative oral supplementation with branched-chain amino acids (BCAAs) on postoperative bacteremia after living donor liver transplantation (LDLT) for chronic liver failure. Two hundred thirty-six patients who underwent adult-to-adult LDLT were evaluated in this retrospective study. The patients were divided into 2 groups: those who received oral supplementation with BCAAs before transplantation (the BCAA group; n = 129) and those who did not (the non-BCAA group; n = 107). Before the LDLT indication was determined, BCAA supplementation was prescribed by a hepatologist to preserve hepatic reserves. The clinical characteristics and the incidence of bacteremia were compared between the 2 groups. As for clinical characteristics, the Child-Pugh scores (P = 0.0003) and the Model for End-Stage Liver Disease scores (P = 0.0008) were significantly higher in the BCAA group versus the non-BCAA group. The incidence of bacteremia for Child-Pugh class C patients was significantly lower in the BCAA group (6/90 or 6.7%) versus the non-BCAA group (11/50 or 22.0%, P = 0.0132). In a multivariate analysis, non-BCAA supplementation was an independent risk factor for bacteremia. In conclusion, preoperative BCAA supplementation might reduce the incidence of bacteremia after LDLT. Nevertheless, this is a preliminary report, and further studies, such as randomized, prospective studies, are necessary to clarify the beneficial effects of BCAA supplementation on postoperative bacteremia after liver transplantation. Liver Transpl 17: 1073-1080, 2011. (C) 2011 AASLD.
• Three-dimensional computed tomography analysis of venous collaterals between the middle hepatic vein tributaries and the right hepatic vein in the donor remnant right lobe: Report of a case

  Hiroto Kayashima, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Mizuki Ninomiya, Nao Kinjo, Yoshihiko Maehara

  SURGERY TODAY 41 (9) 1266 - 1269 0941-1291 2011/09 [Refereed][Not invited]
   

  We report how three-dimensional computed tomography (3D-CT) showed the development of obvious venous collaterals between the middle hepatic vein (MHV) tributaries and the right hepatic vein (RHV) in the remnant right lobe of a donor liver. The donor was a healthy 34-year-old man who donated the left lobe of his liver with the MHV. The 3D-CT calculated that the total drainage of the MHV tributaries was 413 ml, corresponding to 59% of the total remnant liver. The congestion calculated by 3D-CT decreased from 286 ml on postoperative day (POD) 7 to 28 ml on POD 35, corresponding to 36% and 3% of the total remnant liver, respectively. The donor was discharged from hospital with almost normal liver function, and 3D-CT analysis on POD 35 detected obvious venous collaterals between the MHV tributaries and the RHV. These findings suggest that reconstruction of the MHV tributaries in the donor remnant right lobe may not be necessary.
• Secondary resistance of extra-gastrointestinal stromal tumors to imatinib mesylate: Report of a case

  Koji Ando, Eiji Oki, Masahiko Sugiyama, Yan Zhao, Aya Kojima, Hidetaka Yamamoto, Yoichi Yamashita, Hiroshi Saeki, Akinobu Taketomi, Masaru Morita, Yoshihiro Kakeji, Shunichi Tsujitani, Yoshihiko Maehara

  SURGERY TODAY 41 (9) 1290 - 1293 0941-1291 2011/09 [Refereed][Not invited]
   

  Extra-gastrointestinal stromal tumors (EGISTs) that do not originate in the digestive tract are rare. We report a case of multiple EGISTs, which was monitored closely by KIT gene mutation analysis and other investigations. The patient was a 52-year-old man in whom multiple tumors in the abdominal cavity were diagnosed as EGISTs. Immunohistochemical analysis revealed positive staining for c-kit; however, no mutations were found in the KIT gene. The tumors decreased in size remarkably following treatment with imatinib mesylate, but after 2 years of this treatment, multiple liver metastases and some regrowth of the abdominal masses were found simultaneously. The liver metastasis and the abdominal masses were excised, and further analysis of the KIT gene revealed the same mutation in exon 11 in the KIT gene in the metastatic tumors. We speculate that the treatment might have triggered development of the imatinib mesylate-resistant clone, which may have existed in the primary lesion as a KIT gene mutant. This report provides valuable insight into the mechanisms of recurrent GISTs after treatment with imatinib mesylate.
• NIK-333(非環式レチノイド)は自然免疫系やISG15システムを介してC型肝炎ウイルスの増殖を抑制する

  中牟田 誠, 国府島 庸之, 矢田 雅佳, 坂本 直哉, 後藤 和人, 吉本 剛志, 福嶋 伸良, 福泉 公仁隆, 河邉 顕, 水谷 孝弘, 原田 直彦, 武冨 紹信, 前原 喜彦, 遠城寺 宗近

  肝臓 (一社)日本肝臓学会 52 (Suppl.2) A587 - A587 0451-4203 2011/09 [Refereed][Not invited]
  
• C型肝炎肝における鉄代謝と治療への影響 Hepcidin発現とその制御

  国府島 庸之, 下中 靖, 後藤 和人, 吉本 剛志, 福嶋 伸良, 福泉 公仁隆, 河邉 顕, 水谷 孝弘, 原田 直彦, 矢田 雅佳, 武冨 紹信, 前原 喜彦, 遠城寺 宗近, 中牟田 誠

  肝臓 (一社)日本肝臓学会 52 (Suppl.2) A590 - A590 0451-4203 2011/09 [Refereed][Not invited]
  
• Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis

  Yoshihiro Nagao, Tomohiko Akahoshi, Masahiro Kamori, Hideo Uehara, Naotaka Hashimoto, Nao Kinjo, Ken Shirabe, Akinobu Taketomi, Morimasa Tomikawa, Makoto Hashizume, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 41 (8) 784 - 794 1386-6346 2011/08 [Refereed][Not invited]
   

  Aim: Liver cirrhosis clinically shows thrombocytopenia and hypersplenism. Although splenectomy is performed to achieve higher platelet count and better hemostasis, the effect of splenectomy for liver cirrhosis remains unclear. The aim of the present study that was focused on serotonin was to investigate the relationship between splenectomy and liver regeneration in rats with secondary biliary cirrhosis. Methods: Liver cirrhosis was induced in Sprague-Dawley rats by bile duct ligation (BDL). In addition, splenectomy and administration of ketanserin, which selectively antagonizes 5-HT2A and 2B serotonin receptors, were performed. Three weeks after the interventions, whole blood, plasma, serum, and liver specimens were obtained for the following studies: peripheral platelet counts, hemodynamics of serotonin, histopathological examination, immunostaining, and quantification of mRNA expression. Results: Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters: hepatocyte ratio to the entire liver area, Ki67-positive hepatocyte count, and expression of phosphorylated extracellular signal-regulated kinases. This enhancement of liver regeneration was negated by ketanserin. Conclusion: Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions.
• The prevalence of circumportal pancreas as shown by multidetector-row computed tomography.

  Ishigami K, Tajima T, Nishie A, Asayama Y, Kakihara D, Nakayama T, Shirabe K, Taketomi A, Nakamura M, Takahata S, Ito T, Honda H

  Insights into imaging 4 2 (4) 409 - 414 1869-4101 2011/08 [Refereed][Not invited]
   

  OBJECTIVE: To evaluate the prevalence of circumportal pancreas (CP) and any coexisting anomaly. In addition, three cases of surgically confirmed CP are presented. METHODS: The study group consisted of 317 consecutive potential liver transplant donor candidates who had undergone thin-section MDCT studies for the evaluation of vascular anatomy. MDCT images were retrospectively reviewed to assess the presence or absence of CP. If CP was present, the transverse diameter of the aberrant pancreatic tissue was measured on axial images, and the course of the main pancreatic duct (MPD) was classified into ante-portal (normal) or retro-portal. In addition, the prevalence of variant hepatic arterial anatomy was compared between cases with and without CP. RESULTS: Eight of 317 liver transplant donor candidates (2.5%) were found to have CP at CT. The transverse diameter of the aberrant pancreatic tissue ranged from 5 to 18 mm (mean ± SD: 10 ± 4 mm). One of eight (12.5%) showed the MPD to be retro-portal. A variant hepatic artery was noted in two of the of eight (25%) patients, which was similar to the finding for those without CP [72 out of 309 (23%)]. CONCLUSION: The prevalence of circumportal pancreas was 2.5%.
• 肝移植後の門脈圧亢進症 生体肝移植後における脾機能亢進症持続症例の検討

  森田 和豊, 調 憲, 池上 徹, 橋本 直隆, 萱島 寛人, 増田 稔郎, 赤星 朋比古, 吉住 朋晴, 武冨 紹信, 富川 盛雅, 前原 喜彦

  日本門脈圧亢進症学会雑誌 (一社)日本門脈圧亢進症学会 17 (3) 54 - 54 1344-8447 2011/08
• Modulation of CD4(+) T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis

  N. Hashimoto, S. Shimoda, H. Kawanaka, K. Tsuneyama, H. Uehara, T. Akahoshi, N. Kinjo, A. Taketomi, K. Shirabe, K. Akashi, A. Lleo, A. A. Ansari, M. E. Gershwin, Y. Maehara

  CLINICAL AND EXPERIMENTAL IMMUNOLOGY 2 165 (2) 243 - 250 0009-9104 2011/08 [Refereed][Not invited]
   

  Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV-related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV-related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4(+) T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4(+) T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4(+) regulatory T cells and PD-L1- and PD-L2-expressing cells than controls. Blocking of PD-1/PD-1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)-gamma to interleukin (IL)-10 and a reduction of PD-1-expressing CD4(+) T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up-regulated expression of PD-1 ligands.
• Plasma High-Mobility Group Box 1 as an Indicator of Surgical Stress

  Atsushi Osoegawa, Tokujiro Yano, Takeharu Yamanaka, Tetsuzo Tagawa, Fumihiro Shoji, Ichiro Yoshino, Akinobu Taketomi, Hiroyuki Ito, Yoshihiro Kakeji, Yoshihiko Maehara

  SURGERY TODAY 41 (7) 903 - 907 0941-1291 2011/07 [Refereed][Not invited]
   

  Purpose. High-mobility group box I (HMGB-1) is a late-phase cytokine, which is released extracellularly in response to systemic inflammation caused by infection, shock, or trauma. We examined the plasma levels of HMGB-1 to clarify its role in surgical stress. Methods. The subjects of this study were 37 patients who underwent elective general surgery. We measured plasma concentrations of HMGB-1 over time using a quantitative enzyme-linked immunosorbent assay. We then analyzed the relationships between the change in HMGB-1 concentration and perioperative factors, including postoperative complications. Statistical analyses were performed using two-way repeated-measures analysis of variance. Results. The HMGB-1 level was higher on postoperative day 3 in patients with a prolonged operative time or large intraoperative blood loss (P = 0.048 and P = 0.041, respectively). The HMGB-1 level also remained high over time in patients with postoperative complications (P = 0.037). Conclusions. These results show that the plasma HMGB-1 level is related to surgical stress such as operative time and blood loss. The level remained high over time in patients with postoperative complication, suggesting progression of the complication.
• Intraoperative Radiofrequency Ablation in an Open Thoracotomy Setting for the New Treatment of Mediastinal Liposarcoma: Report of a Case

  Fumihiro Shoji, Akinobu Taketomi, Tokujiro Yano, Yoshihiko Maehara

  SURGERY TODAY 41 (7) 992 - 994 0941-1291 2011/07 [Refereed][Not invited]
   

  This report presents the case of a patient with mediastinal liposarcoma treated by radiofrequency ablation (RFA) in an open thoracotomy setting. This procedure is safe and feasible, and it appears to be an effective option for patients with soft tissue sarcoma originating from the mediastinum, especially for patients who are not well suited to undergo a further surgical resection. This report on a new type of RFA treatment for mediastinal liposarcoma may therefore be informative for general thoracic surgeons.
• De Novo Autoimmune Hepatitis Subsequent to Switching from Type 2b to Type 2a Alpha-Pegylated Interferon Treatment for Recurrent Hepatitis C After Liver Transplantation: Report of a Case

  Kazuki Takeishi, Ken Shirabe, Takeo Toshima, Toru Ikegami, Kazutoyo Morita, Takasuke Fukuhara, Takashi Motomura, Yohei Mano, Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  SURGERY TODAY 41 (7) 1016 - 1019 0941-1291 2011/07 [Refereed][Not invited]
   

  Interferon (IFN), which is the only possible agent for recurrent hepatitis C after liver transplantation, may cause serious immune-related disorders. We report a case of de novo autoimmune hepatitis (AIH), which developed subsequent to switching from 2b pegylated interferon-alpha (peg-IFN) to 2a peg-IFN after living donor liver transplantation (LDLT). A 51-year-old man with hepatitis C-associated liver cirrhosis underwent LDLT. About 13 months after the initiation of antiviral therapy, in the form of type 2b peg-IFN with ribavirin, a negative serum hepatitis C virus (HCV)-RNA titer was confirmed. Thereafter, the 2b peg-IFN was switched to 2a peg-IFN, 3 months after which severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy showed portal and periportal inflammatory infiltrates including numerous plasma cells, indicating AIH. He was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance, but eventually died of Pneumocystis pneumonitis 4 months after the diagnosis of de novo AIH.
• Data mining reveals complex interactions of risk factors and clinical feature profiling associated with the staging of non-hepatitis B virus/non-hepatitis C virus-related hepatocellular carcinoma

  Takumi Kawaguchi, Tatsuyuki Kakuma, Hiroshi Yatsuhashi, Hiroshi Watanabe, Hideki Saitsu, Kazuhiko Nakao, Akinobu Taketomi, Satoshi Ohta, Akinari Tabaru, Kenji Takenaka, Toshihiko Mizuta, Kenji Nagata, Yasuji Komorizono, Kunitaka Fukuizumi, Masataka Seike, Shuichi Matsumoto, Tatsuji Maeshiro, Hirohito Tsubouchi, Toyokichi Muro, Osami Inoue, Motoo Akahoshi, Michio Sata

  HEPATOLOGY RESEARCH 41 (6) 564 - 571 1386-6346 2011/06 [Refereed][Not invited]
   

  Aim: Non-hepatitis B virus/non-hepatitis C virus-related hepatocellular carcinoma (NBNC-HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC-HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC using data mining techniques. Methods: A database was created from 663 patients with NBNC-HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively. Results: Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); alpha-fetoprotein (AFP); and des-gamma-carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty-nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200 ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93 IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200 ng/mL and ALT level of 20 IU/mL or more. Conclusion: Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC.
• Temporal changes in the stiffness of the remnant liver and spleen after donor hepatectomy as assessed by acoustic radiation force impulse: A preliminary study

  Mizuki Ninomiya, Ken Shirabe, Hideki Ijichi, Takeo Toshima, Noboru Harada, Hideaki Uchiyama, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 41 (6) 579 - 586 1386-6346 2011/06 [Refereed][Not invited]
   

  Aim: Virtual touch tissue quantification (VTTQ) is an implementation of ultrasound acoustic radiation force impulse imaging that provides numerical measurements of tissue stiffness. We have evaluated the temporal changes of the remnant liver and spleen after living donor hepatectomy with special reference to the differences between right and left liver donation. Methods: Nineteen living donors who received right lobectomy (small remnant liver [SRL] group; n = 7) or extended left and caudate lobectomy (large remnant liver [LRL] group; n = 12) were enrolled. They underwent measurement of liver and spleen VTTQ before and after donor surgery. Results: Virtual touch tissue quantification of the remnant liver increased postoperatively until postoperative day (POD) 3-5, and the values in the SRL group were significantly higher than those in the LRL group at POD 3-9. The values of the spleen also increased after donor surgery and the values in the SRL group were significantly higher than those in the LRL group at POD 3-14. A significant positive correlation between postoperative maximum value of VTTQ and postoperative maximum total bilirubin levels was observed. In liver transplant recipients, there was a significant positive correlation between preoperative spleen VTTQ and the corresponding actual portal venous pressure that was measured at the time of transplant surgery. Conclusion: Stiffness of the remaining liver and spleen in the smaller remnant liver group became harder than that in the larger remnant liver group. Perioperative measurement of liver and spleen VTTQ seems to be a useful means for assessing the physiology of liver regeneration.
• Gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis

  Mizuki Ninomiya, Ken Shirabe, Akinobu Taketomi, Tadahiro Nozoe, Takashi Maeda, Hideaki Nakashima, Akito Matsukuma, Takahiro Ezaki, Yoshihiko Maehara

  SURGERY TODAY 41 (6) 884 - 887 0941-1291 2011/06 [Refereed][Not invited]
   

  Surgical palliation of malignant obstructive pancreatitis poses a considerable burden to patients, especially those with extensive disease. We herein present a novel technique for performing gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis. The main pancreatic duct was punctured via the wall of the pyloric antrum. After the insertion of a guidewire, a double pigtail-type tube stent with side holes was inserted into the main pancreatic duct through the wall of the pyloric antrum. This technique was useful as a means of accomplishing less invasive palliative treatment, and has the potential to improve the quality of life for patients with malignant obstructive pancreatitis.
• A polymorphism in the integrin alpha V subunit gene affects the progression of primary biliary cirrhosis in Japanese patients

  Tatsuo Inamine, Minoru Nakamura, Ayumi Kawauchi, Yayoi Shirakawa, Hisae Hashiguchi, Yoshihiro Aiba, Akinobu Taketomi, Ken Shirabe, Makoto Nakamuta, Shigeki Hayashi, Takeo Saoshiro, Atsumasa Komori, Hiroshi Yatsuhashi, Shinji Kondo, Katsuhisa Omagari, Yoshihiko Maehara, Hiromi Ishibashi, Kazuhiro Tsukamoto

  JOURNAL OF GASTROENTEROLOGY 5 46 (5) 676 - 686 0944-1174 2011/05 [Refereed][Not invited]
   

  Accumulating evidence indicates that multiple genetic factors are involved in the pathogenesis of primary biliary cirrhosis (PBC). The aim of this study was to investigate whether polymorphisms of the integrin alpha V subunit gene (ITGAV), a component of integrin alpha V beta 6, which plays an important role in the process of fibrosis, are associated with susceptibility to the onset and/or progression of PBC. In the primary study, eight tag single nucleotide polymorphisms (SNPs) in ITGAV were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, direct DNA sequencing, or high-resolution melting curve analysis in 309 Japanese patients with PBC who were registered in the National Hospital Organization Study Group for Liver Disease in Japan (PBC cohort I) and 293 gender-matched healthy Japanese volunteers (control subjects). For the replication study, 35 PBC patients who progressed to end-stage hepatic failure and underwent liver transplantation (PBC cohort II) were also analyzed. Three tag SNPs (rs3911238, rs10174098, and rs1448427) in ITGAV were significantly associated with the severe progression of PBC, but not with susceptibility to the onset of PBC, in the primary study (PBC cohort I). Among these SNPs, rs1448427 was also significantly associated with the severe progression to end-stage hepatic failure in the replication study of PBC patients who underwent liver transplantation (PBC cohort II). ITGAV is a genetic determinant for the severe progression of PBC in Japanese patients. Genetic polymorphisms of ITGAV may be useful for identifying high-risk Japanese PBC patients, including those who will require liver transplantation, at the time of initial diagnosis.
• New method for assessing liver fibrosis based on acoustic radiation force impulse: a special reference to the difference between right and left liver

  Takeo Toshima, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  JOURNAL OF GASTROENTEROLOGY 46 (5) 705 - 711 0944-1174 2011/05 [Refereed][Not invited]
   

  Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. The VTTQ values (meters per second) in the right and left lobes were 1.61 +/- A 0.51 and 1.90 +/- A 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F a parts per thousand yen 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe.
• Clinicopathological Features and Outcomes of Young Patients with Hepatocellular Carcinoma after Hepatectomy

  Kazuki Takeishi, Ken Shirabe, Jun Muto, Takeo Toshima, Akinobu Taketomi, Yoshihiko Maehara

  WORLD JOURNAL OF SURGERY 35 (5) 1063 - 1071 0364-2313 2011/05 [Refereed][Not invited]
   

  There are few reports about hepatectomy for young patients with hepatocellular carcinoma (HCC), and the significance of resection for young patients remains unknown. The present study aimed to investigate retrospectively the clinicopathological features and outcomes after hepatectomy of young HCC patients. Among 610 patients who underwent curative hepatectomy for HCC between January 1987 and December 2007, 13 patients younger than 40 years of age were defined as the young group. Because none of the young group had hepatitis C virus antibodies (HCVAb), 246 patients aged above 40 years without HCVAb were defined as the older group. The clinicopathological findings and outcomes after hepatectomy were compared between the two groups. In the young group, 7 patients had hepatitis B surface antigen and 3 other patients had hepatitis B core antibodies. The young group had better liver function but more advanced HCC, with a large tumor size and a high incidence of portal vein invasion compared with the older group. Major hepatectomy was more frequently chosen in the young group than in the older group. There was no significant difference in the incidences of postoperative complications. The overall survival tended to be better in the young group than in the older group (p = 0.057). Hepatitis B virus-related HCC was common inthe younger group of patients reported here. Although the young patients had advanced HCC, there were no significant differences in the complication rate and the overall survival rate of the young and older groups. Aggressive hepatic resection for young patients would contribute to improved survival and should be recommended.
• Improvement of Long-Term Outcomes in Hepatitis C Virus Antibody-Positive Patients with Hepatocellular Carcinoma after Hepatectomy in the Modern Era

  Ken Shirabe, Kazuki Takeishi, Akinobu Taketomi, Hideaki Uchiyama, Hiroto Kayashima, Yoshihiko Maehara

  WORLD JOURNAL OF SURGERY 35 (5) 1072 - 1084 0364-2313 2011/05 [Refereed][Not invited]
   

  The present study was conducted to clarify the causes of recent improvement of outcomes after hepatectomy in patients with hepatitis C (HC)-related hepatocellular carcinoma (HCC). From 1990 to 2006, 323 curative liver resections for HC-HCC were performed in our department. The patients were divided into two groups: early period (1990-1999: n = 221) and the late period (2000-2006: n = 102). Prognostic factors were determined to clarify the cause of the survival improvement in the modern era. The overall survival rates for the patients in the early and late periods were 54.9 and 70.3% at 5 years, respectively (P = 0.0005). There was no difference in the recurrence-free survival rates between the two groups, although both survival without recurrence (P = 0.0003) and survival after recurrence (P = 0.0063) were significantly better in the late period than in the early period. Patients with better liver function, patients with interferon (IFN) therapy and patients with subsegmentectomy were selected more frequently, and the incidence of blood transfusion was decreased in the late period below the level recorded in the early period. For recurrent HCC, lipiodolization decreased and local ablation therapy increased in the late period. The independent prognostic factors for overall survival were preoperative serum levels of albumin and alanine aminotransferase, histological liver cirrhosis, tumor size, intrahepatic metastasis, histological grade, blood transfusion, and IFN therapy. In HC-HCC, survival was improved in the late period of the present study. Selection of patients with good liver function, no blood transfusion with reduction of blood loss, anti-hepatitis C virus therapy with IFN, and introduction of local ablation therapy for HCC recurrence may be related to the improved survival.
• Expression Profiles of Genes Associated With Viral Entry in HCV-Infected Human Liver

  M. Nakamuta, T. Fujino, R. Yada, Y. Aoyagi, K. Yasutake, M. Kohjima, K. Fukuizumi, T. Yoshimoto, N. Harada, M. Yada, M. Kato, K. Kotoh, A. Taketomi, Y. Maehara, M. Nakashima, M. Enjoji

  JOURNAL OF MEDICAL VIROLOGY 83 (5) 921 - 927 0146-6615 2011/05 [Refereed][Not invited]
   

  Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P - 0.0270 and P - 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers. J. Med. Virol. 83: 921-927, 2011. (C) 2011 Wiley-Liss, Inc.
• Evaluation of ERCC1 Expression for Cisplatin Sensitivity in Human Hepatocellular Carcinoma

  Shigeru Ueda, Ken Shirabe, Kazutoyo Morita, Kenji Umeda, Hiroto Kayashima, Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  ANNALS OF SURGICAL ONCOLOGY 18 (4) 1204 - 1211 1068-9265 2011/04 [Refereed][Not invited]
   

  Excision repair cross-complementation group 1 (ERCC1) is one of the key enzymes in DNA repair. This study was designed to investigate the correlation between ERCC1 expression and chemosensitivity to cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC). Eighty-seven HCC samples were analyzed by immunohistochemistry for ERCC1 and chemosensitivity was assessed by the succinate dehydrogenase inhibition (SDI) test for four anti-cancer agents, including CDDP. The ERCC1 expression was examined in HCC cell lines. ERCC1 siRNA was transfected to PLC/RPF/5 to investigate the correlation of ERCC1 expression and CDDP sensitivity. ERCC1 expression was observed in 33% of nuclei in immunohistochemical examination. Patients were divided into two groups as follows: ERCC1 high expression group (n = 43): more than 33% of the nuclei were stained; ERCC1 low expression group (n = 44): 33% or fewer of the nuclei were stained. Tumor size of low expression group was larger than that in the high expression group (p = 0.02). The succinic dehydrogenase (SD) activity only for CDDP was significantly higher in the high expression group than that in the low expression group (p = 0.02). An increased expression of ERCC1 was shown by immunohistochemical and Western blot analyses in PLC/RPF/5. ERCC1 expression was inhibited by ERCC1 siRNA transfection and the LC50 value (nM) of CDDP was reduced from 25.7 to 12.5 (p = 0.01). Increased ERCC1 expression is associated with CDDP resistance in HCC specimens and cell lines. Therefore, immunohistochemical analysis for resected HCC tissues may be a useful predictor for the effectiveness of adjuvant chemotherapy, using CDDP.
• Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

  Kazutoyo Morita, Akinobu Taketomi, Ken Shirabe, Kenji Umeda, Hiroto Kayashima, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Yoshihiko Maehara

  LIVER INTERNATIONAL 31 (4) 474 - 484 1478-3223 2011/04 [Refereed][Not invited]
   

  Background and aims: MicroRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on HCV in human body is unclear. Methods: Hepatic miR-122 expression was quantified using quantitative reverse-transcription polymerase chain reaction. We investigated the correlation between miR-122 expression and HCV load in liver samples from 185 patients seropositive for HCV antibody, including 151 patients seropositive for HCV RNA, and 31 patients seronegative for HCV RNA. Results: Although hepatic miR-122 expression was weakly and positively correlated with the serum HCV load (rho = 0.19, P < 0.05), it was not correlated with the hepatic HCV load (rho = -0.14, P = 0.08). The absence of a correlation between miR-122 expression and hepatic HCV load was also confirmed after stratification of histopathological liver damage (inflammatory activity grades and fibrosis stages). Furthermore, hepatic miR-122 expression in patients seronegative for HCV RNA was significantly higher than that in patients seropositive for HCV RNA (P < 0.0001). The level of hepatic miR-122 expression was inversely correlated with the severity of functional and histopathological liver damage (P < 0.0001), serum transaminase levels (P < 0.0005). Conclusions: Compared with in vitro findings, hepatic miR-122 expression is not correlated with HCV load in the human liver. Therefore, miR-122, by itself, is not a critical molecular target for HCV therapy. MiR-122 expression is inversely correlated with both functional and histopathological liver damage.
• Intracellular delivery of serum-derived hepatitis C virus

  Takasuke Fukuhara, Hideki Tani, Mai Shiokawa, Yukinori Goto, Takayuh Abe, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Yoshiharu Matsuura

  MICROBES AND INFECTION 13 (4) 405 - 412 1286-4579 2011/04 [Refereed][Not invited]
   

  A robust and reliable cell culture system for serum-derived HCV (HCVser) has not been established yet because of the presence of neutralizing antibody and tropism for infection. To overcome this obstacle, we employed a lipid-mediated protein intracellular delivery reagent (PIDR) that permits internalization of proteins into cells. Although entry of HCVcc was not enhanced by the treatment with PIDR, entry of HCVser into hepatoma cell lines (Huh7 and HepG2) and immortalized primary hepatocytes (He and HuS/E2) was significantly enhanced by the PIDR treatment. The entry of HCVser into Huh7 cells in the presence of PIDR was resistant to the neutralization by an anti-hCD81 antibody, suggesting that PIDR is capable of internalizing HCVser in a receptor-independent manner. Interestingly, the PIDR-mediated entry of HCVser and HCVcc was enhanced by the addition of sera from chronic hepatitis C patients but not from healthy donors. In addition, neutralization of HCVcc infection by anti-E2 antibody was canceled by the treatment with PIDR. In conclusion, the PIDR is a valuable tool to get over the obstacle of neutralizing antibodies to internalize HCV into cells and might be useful for the establishment of in vitro propagation HCVser. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
• Interaction Between Toll-Like Receptors and Natural Killer Cells in the Destruction of Bile Ducts in Primary Biliary Cirrhosis

  Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Ken Shirabe, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Yasuni Nakanuma, Patrick Leung, Aftab A. Ansari, M. Eric Gershwin, Koichi Akashi

  HEPATOLOGY 53 (4) 1270 - 1281 0270-9139 2011/04 [Refereed][Not invited]
   

  Primary biliary cirrhosis (PBC) is characterized by chronic nonsuppurative destructive cholangitis (CNSDC) associated with destruction of small bile ducts. Although there have been significant advances in the dissection of the adaptive immune response against the mitochondrial autoantigens, there are increasing data that suggest a contribution of innate immune mechanisms in inducing chronic biliary pathology. We have taken advantage of our ability to isolate subpopulations of liver mononuclear cells (LMC) and examined herein the role of Toll-like receptors (TLRs), their ligands, and natural killer (NK) cells in modulating cytotoxic activity against biliary epithelial cells (BECs). In particular, we demonstrate that Toll-like receptor 4 ligand (TLR4-L)-stimulated NK cells destroy autologous BECs in the presence of interferon alpha (IFN-alpha) synthesized by TLR 3 ligand (TLR3-L)-stimulated monocytes (Mo). Indeed, IFN-alpha production by hepatic Mo is significantly increased in patients with PBC compared to disease controls. There were also marked increases in the cytotoxic activity of hepatic NK cells from PBC patients compared to NK cells from controls but only when the NK cells were prepared following ligation of both TLR3-L- and TLR4-L-stimulated LMC. These functional data are supported by the immunohistochemical observation of an increased presence of CD56-positive NK cells scattered around destroyed small bile ducts more frequently in liver tissues from PBC patients than controls. Conclusion: These data highlight critical differences in the varied roles of Mo and NK cells following TLR3-L and TLR4-L stimulation. (HEPATOLOGY 2011;53:1270-1281)
• Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma: Carcinogenesis of Perihilar Type and Aggressive Behavior of Peripheral Type

  Shinichi Aishima, Nobuhiro Fujita, Yohei Mano, Yuichiro Kubo, Yuki Tanaka, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda

  AMERICAN JOURNAL OF SURGICAL PATHOLOGY 35 (4) 590 - 598 0147-5185 2011/04 [Refereed][Not invited]
   

  S100P is expressed in several kinds of malignant tumors. Intracellular S100P interacts with ezrin, and extracellular S100P activates the receptor for advanced glycation end products. However, little is known about the biological significance of S100P and related proteins in cholangiocarcinoma. Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar or perihilar cholangiocarcinoma. We examined S100P, ezrin, and the receptor for advanced glycation end product expression in 39 BilIN and 110 intrahepatic cholangiocarcinoma (ICC) cases, and analyzed its relationship with clinicopathologic factors and outcomes. S100P expression increased from reactive epithelium to low-grade BilIN to high-grade BilIN. S100P and ezrin expression rates in perihilar-type ICC were higher than those in peripheral-type ICC (P < 0.0001, P - 0.0008, respectively). S100P nuclear expression in peripheral-type ICC significantly correlated with vascular invasion (P = 0.0209), lymphatic invasion (P = 0.0003), and lymph node metastasis (P = 0.003). S100P and ezrin expression was significantly correlated. S100P-positive and ezrin-positive cases indicate shorter survival in survival analysis of the peripheral type (P = 0.001, P = 0.0728, respectively). Our results suggest that S100P-ezrin signaling has different roles of carcinogenesis of perihilar ICC and an aggressive course of peripheral ICC.
• Living Donor Liver Transplantation in Patients Who Have Received Pretransplant Treatment for Hepatocellular Carcinoma

  Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Hideaki Uchiyama, Noboru Harada, Hideki Ijichi, Yoshihiko Maehara

  TRANSPLANTATION 91 (8) E61 - E62 0041-1337 2011/04 [Refereed][Not invited]
  
• C型慢性肝炎における小胞体ストレスの検討

  中牟田 誠, 国府島 庸之, 福泉 公仁隆, 後藤 和人, 吉本 剛志, 福嶋 伸良, 武冨 紹信, 前原 喜彦, 遠城寺 宗近

  肝臓 (一社)日本肝臓学会 52 (Suppl.1) A171 - A171 0451-4203 2011/04 [Refereed][Not invited]
  
• C型肝炎肝における鉄代謝 IFN+RBV治療時における鉄の重要性

  中牟田 誠, 国府島 庸之, 下中 靖, 後藤 和人, 吉本 剛志, 福嶋 伸良, 福泉 公仁隆, 原田 直彦, 矢田 雅佳, 武冨 紹信, 前原 喜彦, 遠城寺 宗近

  肝臓 (一社)日本肝臓学会 52 (Suppl.1) A305 - A305 0451-4203 2011/04 [Refereed][Not invited]
  
• 肝細胞癌における糖・脂質代謝関連遺伝子発現の変化

  国府島 庸之, 中牟田 誠, 後藤 和人, 吉本 剛志, 福嶋 伸良, 福泉 公仁隆, 原田 直彦, 矢田 雅佳, 武冨 紹信, 前原 喜彦, 遠城寺 宗近

  肝臓 (一社)日本肝臓学会 52 (Suppl.1) A323 - A323 0451-4203 2011/04 [Refereed][Not invited]
  
• Prognostic Significance of Preoperative Imaging in Recipients of Living Donor Liver Transplantation for Hepatocellular Carcinoma

  Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomohiro Iguchi, Kazuki Takeishi, Takeo Toshima, Shinichi Aishima, Tsuyoshi Tajima, Yoshihiko Maehara

  TRANSPLANTATION 91 (5) 570 - 574 0041-1337 2011/03 [Refereed][Not invited]
   

  Background. Accurate preoperative imaging is an important aspect of patient evaluation before liver transplantation for hepatocellular carcinoma (HCC) because the size and number of tumors are indicators of posttransplant prognosis. This study aimed to evaluate the preoperative detectability of HCC and clarify the role of preoperative assessment on prognosis after living donor liver transplantation (LDLT). Methods. Eighty-one patients who underwent LDLT for HCC accompanied by liver cirrhosis were reviewed. A total of 149 nodules were pathologically diagnosed as HCCs. The pathologic findings were correlated with preoperative results from contrast-enhanced computed tomography, magnetic resonance imaging, and computed tomography with angiography. Results. The detectability of small HCCs (< 1 cm) and well-differentiated HCCs was significantly reduced. Forty-six of 81 cases were preoperatively judged to meet the Milan criteria, although 16 of these failed to meet the criteria according to postoperative pathologic examination. However, recurrence-free survival in the 16 cases was similar to that in the 30 cases who met the criteria. Conclusions. The preoperative diagnostic accuracy of radiologic imaging for small-sized, well-differentiated HCCs requires improvement. However, these undetected HCCs have little effect on prognosis after LDLT, and current imaging modalities therefore provide acceptable methods of preoperative LDLT evaluation.
• Living Donor Liver Transplantation for End-Stage Liver Disease with Severe Hepatopulmonary Syndrome: Report of a Case

  Takashi Motomura, Toru Ikegami, Yohei Mano, Shigeyuki Nagata, Keishi Sugimachi, Tomoharu Gion, Yuji Soejima, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  SURGERY TODAY 41 (3) 436 - 440 0941-1291 2011/03 [Refereed][Not invited]
   

  Hepatopulmonary syndrome (EIPS) is a serious complication of terminal liver disease, which manifests as severe hypoxia without any pulmonary anatomic or functional causes. The precise indications for liver transplantation in patients with severe HPS also remain unclear. A 49-year old woman was referred to our department for investigation and management of liver cirrhosis with severe hypoxia (PaO(2), 38 mmHg). A pulmonary perfusion scintigram showed an intrapulmonary shunt ratio of 40%, confirming a diagnosis of severe HPS. She underwent living donor liver transplantation using a right lobe graft donated by her 27-year-old daughter. Her post-transplant graft function was excellent, and her oxygenation recovered slowly but steadily. She was discharged from hospital on post-transplant day 39 with an SpO(2) of 94% under 31/min of O(2), delivered nasally. Despite the severity of the HPS, her postoperative recovery was smooth after the liver transplant.
• [Clinical experience of liver transplantation at King's College Hospital in United Kingdom].

  Nagata S, Yoshida Y, Matsuda H, Taketomi A, Shirabe K, Maehara Y

  Nihon Geka Gakkai zasshi 2 112 (2) 150 - 153 0301-4894 2011/03 [Refereed][Not invited]
  
• 最大径5cmを越える肝細胞癌に対する切除前リピオドリゼーションによる再発予防効果

  山下 洋市, 辻田 英司, 石田 照佳, 岩佐 憲臣, 小副川 敦, 吉永 敬士, 山本 学, 筒井 信一, 吉良 臣介, 相坂 康之, 植田 慶子, 光井 富貴子, 武冨 紹信, 前原 喜彦

  日本消化器病学会雑誌 (一財)日本消化器病学会 108 (臨増総会) A196 - A196 0446-6586 2011/03
• The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area

  Naota Taura, Nobuyoshi Fukushima, Hiroshi Yatsuhashi, Yuko Takami, Masataka Seike, Hiroshi Watanabe, Toshihiko Mizuta, Yutaka Sasaki, Kenji Nagata, Akinari Tabara, Yasuji Komorizono, Akinobu Taketomi, Shuichi Matsumoto, Tsutomu Tamai, Toyokichi Muro, Kazuhiko Nakao, Kunitaka Fukuizumi, Tatsuji Maeshiro, Osami Inoue, Michio Sata

  MEDICAL SCIENCE MONITOR 17 (2) PH7 - PH11 1234-1010 2011/02 [Refereed][Not invited]
   

  Background: The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu.Material/Methods: A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCV-RNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, nonBC: both of HBsAg and HCV-RNA negative.Results: B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses. Cohorts of patients with HCC were divided into six-year intervals (1996-2001 and 2002-2007). The ratio of C cases decreased from 73.1% in 1996-2001 to 64.9% in 2002-2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996-2001 to 16.2% and 17.6% in 2002-2007, respectively.Conclusions: The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients.
• Performance of radiological methods in diagnosing hepatocellular carcinoma preoperatively in a recipient of living related liver transplantation: comparison with step section histopathology

  Masakazu Hirakawa, Kengo Yoshimitsu, Hiroyuki Irie, Tsuyoshi Tajima, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Daisuke Kakihara, Akinobu Taketomi, Shin-ichi Aishima, Hiroshi Honda

  JAPANESE JOURNAL OF RADIOLOGY 29 (2) 129 - 137 1867-108X 2011/02 [Refereed][Not invited]
   

  The aim of the present study was to evaluate the performance of multidetector-row CT (MDCT) and magnetic resonance imaging (MRI) in diagnosing hepatocellular carcinoma (HCC) preoperatively in living related liver transplantation (LRLT) recipients with liver cirrhosis and HCC. A total of 25 LRLT recipients with 89 pathologically proved HCCs underwent dynamic 4-row MDCT (5 mm collimation) and MRI within 1 month before LRLT. The images were reviewed for the diagnosis of HCC on a tumor-by-tumor basis by three observers independently and randomly using explanted specimens as the gold standard. The diagnostic accuracy of these techniques in the detection of HCC was assessed with alternative free response receiver operating characteristic (ROC) analysis. The sensitivity and positive predictive values were evaluated. The average values of the area under the ROC curve (Az) of MRI images were higher than those obtained with MDCT; however, no significant difference was observed (P > 0.05). The overall sensitivity of HCC with MRI was higher than that with MDCT, especially in the case of HCCs < 20 mm. A better diagnostic performance regarding HCCs in LRLT recipients was achieved with MRI than with MDCT, although no significant difference was observed.
• Surgical Impacts of an En Bloc Resection of the Diaphragm for Hepatocellular Carcinoma with Gross Diaphragmatic Involvement

  Yo-ichi Yamahita, Kazutoyo Morita, Tomohiro Iguchi, Eiji Tsujita, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  SURGERY TODAY 41 (1) 101 - 106 0941-1291 2011/01 [Refereed][Not invited]
   

  Purpose. Diaphragmatic involvement is relatively uncommon in patients undergoing a hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the short- and long-term surgical impacts of HCC with gross diaphragmatic involvement in patients undergoing an en bloc resection of the diaphragm. Methods. Between 1990 and 2007, 911 patients with HCC underwent a hepatectomy at our institution. Twenty-seven patients (3.0%) had had gross involvement of the diaphragm. Thirteen patients (1.4%) had undergone an en bloc resection of the diaphragm, and 1.4 (1.5%) had received only a blunt dissection. The short-term surgical impacts (surgical morbidity and mortality) and long-term surgical impacts (overall and disease-free survival) were compared between the groups. Results. In patients with an en bloc resection of the diaphragm as compared with those who received a blunt dissection, the values of total bilirubin and the indocyanine green retention rate at 15 min were significantly better (P < 0.01. and P = 0.04, respectively), and the rate of positivity for the hepatitis B antigen was significantly higher (P = 0.02). The positive rates of microscopic fibrocapsular invasion (P = 0.03), microscopic vascular invasion (P = 0.04), and Ki-67 immunostaining (P = 0.04) were significantly higher in patients with an en bloc resection of the diaphragm. There were no significant differences in the short-term and long-term surgical impacts between the groups. Conclusion. An en bloc resection of the diaphragm in patients with gross diaphragmatic involvement of HCC is therefore justified, since there are no significant differences in short- or long-term surgical impacts in comparison with the patients receiving blunt dissection.
• Hypophosphatemic Osteomalacia as a Long-Term Complication After Liver Transplantation

  Hisaya Kawate, Akinobu Taketomi, Tetsuhiro Watanabe, Masatoshi Nomura, Masaki Kato, Ryuichi Sakamoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara, Ryoichi Takayanagi

  TRANSPLANTATION 91 (1) E6 - E8 0041-1337 2011/01 [Refereed][Not invited]
  
• Successful treatment for hepatic encephalopathy aggravated by portal vein thrombosis with balloon-occluded retrograde transvenous obliteration.

  Naotaka Hashimoto, Tomohiko Akahoshi, Tetsuya Shoji, Morimasa Tomikawa, Norifumi Tsutsumi, Tomoharu Yoshizumi, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  Case reports in gastroenterology 5 (2) 366 - 71 1662-0631 2011 [Refereed][Not invited]
   

  This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels.
• Cystic tumors of the liver: On the problems of diagnostic criteria

  Yohei Mano, Shinichi Aishima, Nobuhiro Fujita, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda

  PATHOLOGY RESEARCH AND PRACTICE 207 (10) 659 - 663 0344-0338 2011 [Refereed][Not invited]
   

  We report on three cases of cystic neoplasms of the liver with mucinous epithelium. Case 1 showed a low-grade cystic neoplasm with ovarian-like stroma a (OS). Case 2 showed a low-grade cystic neoplasm without OS, and case 3 showed a high-grade cystic neoplasm without OS. In all three cases, bile duct communication (BDC) was absent. Currently, pancreatic mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the pancreas (IPMN) are clearly distinguishable. However, MCN of the liver and intraductal papillary neoplasm of the bile duct (IPN-B) are not as easily distinguished. According to the latest WHO classification (2010), these conditions are classed as typical MCN of the liver, MCNs of the liver without OS, or IPN-Bs without BDC. The clinicopathological differences between MCN without OS and IPN-B without BDC are controversial. We present three cases describing these presentations and discuss the difficulties related to the diagnostic criteria used to distinguish between MCN of the liver and IPN-B. (C) 2011 Elsevier GmbH. All rights reserved.
• Bleeding ectopic varices of hepatocholangiojejunostomy following left lobe hepatectomy for cholangiocarcinoma. Report of a case

  Hashimoto N, Kawanaka H, Akahoshi T, Kinjo N, Konishi K, Yoshida D, Harada N, Soejima Y, Taketomi A, Iso Y, Maehara Y

  Japanese Journal of Portal Hypertension and Esophageal Varices The Japan Society for Portal Hypertension 17 (2) 91 - 95 1344-8447 2011 

  症例は59歳の女性で，3年前に総胆管癌に対し，肝左葉切除，胆嚢・胆管切除，右肝管空腸吻合術を施行され，術後1年目に右肝管空腸吻合部に発生した異所性静脈瘤からの出血を認めた．また，食道静脈瘤および脾機能亢進症も合併していた．右肝管空腸吻合部静脈瘤出血に対し，β-blockerの投与ならびに2回の経回結腸静脈的静脈瘤塞栓術（TIO）および，腹腔鏡下脾臓摘出術を行うも，再出血を繰り返すため上腸間膜静脈─下大静脈シャント術を行った．
• Erratum: Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: Significance for living donors (Journal of Magnetic Resonance Imaging (2008) 28 (678-684))

  Kengo Yoshimitsu, Yousuke Kuroda, Makoto Nakamuta, Akinobu Taketomi, Hiroyuki Irie, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Yasuhiro Ushijima, Tomomi Yamada, Hiroshi Honda

  Journal of Magnetic Resonance Imaging 33 (1) 255  1053-1807 2011/01 [Refereed][Not invited]
  
• Iron state in association with retinoid metabolism in non-alcoholic fatty liver disease

  Hiroyuki Tsuchiya, An Afida Ashla, Yoshiko Hoshikawa, Yoshiaki Matsumi, Keita Kanki, Munechika Enjoji, Seiya Momosaki, Makoto Nakamuta, Akinobu Taketomi, Yoshihiko Maehara, Kohei Shomori, Akihiro Kurimasa, Ichiro Hisatome, Hisao Ito, Goshi Shiota

  HEPATOLOGY RESEARCH 40 (12) 1227 - 1238 1386-6346 2010/12 [Refereed][Not invited]
   

  Aim: We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non-alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders. Methods: Thirty-six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism-related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action. Results: In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein (CRBP1), alcohol dehydrogenase 1 (ADH1) and cytochrome P450 26A1(CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively. Conclusion: The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease.
• Tumor-infiltrating lymphocytes and hepatocellular carcinoma: pathology and clinical management

  Ken Shirabe, Takashi Motomura, Jun Muto, Takeo Toshima, Rumi Matono, Yohei Mano, Kazuki Takeishi, Hideki Ijichi, Noboru Harada, Hideaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara

  INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 15 (6) 552 - 558 1341-9625 2010/12 [Refereed][Not invited]
   

  The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3(+), CD4(+), and CD8(+) T cells are often present in HCC. Some studies have reported that the percentage of CD8(+) T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field.
• Variants in IL28B in Liver Recipients and Donors Correlate With Response to Peg-Interferon and Ribavirin Therapy for Recurrent Hepatitis C

  Takasuke Fukuhara, Akinobu Taketomi, Takashi Motomura, Shinji Okano, Akinori Ninomiya, Takayuki Abe, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Yoshiharu Matsuura, Yoshihiko Maehara

  GASTROENTEROLOGY 139 (5) 1577 - + 0016-5085 2010/11 [Refereed][Not invited]
   

  BACKGROUND & AIMS: Patients with hepatitis C virus (HCV)-related liver disease frequently undergo orthotopic liver transplantation, but recurrent hepatitis C is still a major cause of morbidity. Patients are treated with peg-interferon and ribavirin (PEG-IFN/RBV), which has substantial side effects and is costly. We investigated genetic factors of host, liver donor, and virus that might predict sensitivity of patients with recurrent hepatitis C to PEG-IFN/RBV. METHODS: Liver samples were analyzed from 67 HCV-infected recipients and 41 liver donors. Liver recipient and donor DNA samples were screened for single nucleotide polymorphisms near the IL28B genes (rs12980275 and rs8099917) that affect sensitivity to PEG-IFN/RBV. HCV RNA was isolated from patients and analyzed for mutations in the core, the IFN sensitivity-determining region, and IFN/RBV resistance-determining regions in nonstructural protein 5A. RESULTS: In liver recipients and donors, the IL28B single nucleotide polymorphism rs8099917 was significantly associated with a sustained viral response (SVR; P = 0.003 and P = .025, respectively). Intrahepatic expression of IL28 messenger RNA was significantly lower in recipients and donors that carried the minor alleles (T/G or T/T) in rs8099917 (P = .010 and .009, respectively). Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83% sensitivity and 82% specificity; this was more effective than analysis of any single genetic feature. CONCLUSIONS: In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy.
• Feasibility of ABO-Incompatible Living Donor Liver Transplantation in the Rituximab Era

  Toru Ikegami, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  LIVER TRANSPLANTATION 16 (11) 1332 - 1333 1527-6465 2010/11 [Refereed][Not invited]
  
• Predictors of Extrahepatic Recurrence After Curative Hepatectomy for Hepatocellular Carcinoma

  Akinobu Taketomi, Takeo Toshima, Dai Kitagawa, Takashi Motomura, Kazuki Takeishi, Yohei Mano, Hiroto Kayashima, Keishi Sugimachi, Shinichi Aishima, Yoichi Yamashita, Toru Ikegami, Tomonobu Gion, Hideaki Uchiyama, Yuji Soejima, Takashi Maeda, Ken Shirabe, Yoshihiko Maehara

  ANNALS OF SURGICAL ONCOLOGY 17 (10) 2740 - 2746 1068-9265 2010/10 [Refereed][Not invited]
   

  Background. The aim of this study was to elucidate the predictors of extrahepatic hepatocellular carcinoma (HCC) recurrence after hepatectomy. Materials and Methods. A cohort of 252 patients with HCC who underwent hepatectomy following a recurrence were reviewed. The patients were categorized into 2 groups according to the pattern of their initial recurrence. Clinicopathological and survival data were compared between the groups. Results. Of the 252 patients, 218 had intrahepatic recurrence (IHR) (86.5%) and 34 had extrahepatic recurrence (EHR) (13.5%) as their initial recurrence. The mean duration of time until the initial recurrence after hepatectomy of the EHR and IHR groups was 1.8 and 2.2 years, respectively. The rate of recurrence within 6 months after hepatectomy of EHR and IHR groups was 35.3 and 14.2%, respectively (P = .002). The 3-, 5-, and 10-year cumulative survival rates of EHR group were 60.3, 24.0, and 6.0%, respectively, which were significantly lower than that of IHR group (74.5, 57.7, and 23.1%, P = .004). A multivariate analysis showed that blood loss during surgery and microscopic hepatic vein invasion remained as independent risk factors for increased EHR after hepatectomy for HCC. Furthermore, the combination of these 2 independent factors showed a significant association with the EHR. Conclusions. EHR of HCC was associated with early recurrence and a poor survival after a hepatectomy. The combination of 2 independent factors for EHR, the presence of microscopic hepatic vein invasion and the blood loss during surgery, may be useful for predicting the risk for occurrence of EHR during the follow-up period.
• Living Donor Hepatectomies with Procedures to Prevent Biliary Complications

  Akinobu Taketomi, Kazutoyo Morita, Takeo Toshima, Kazuki Takeishi, Hiroto Kayashima, Mizuki Ninomiya, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Yoshihko Maehara

  JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 211 (4) 456 - 464 1072-7515 2010/10 [Refereed][Not invited]
   

  BACKGROUND: Biliary complications in donor hepatectomies are still common, and occur in approximately 5% of the procedures. STUDY DESIGN: To evaluate the usefulness of the management and surgical procedures to prevent the biliary complications in donor hepatectomies, a total of 343 donors were retrospectively studied. The clinical and surgical parameters of the donors and the postoperative biliary complications were evaluated. RESULTS: Fourteen donors had biliary complication (BC) during the follow-up period (4.1%). Donors were divided into 2 groups; donors without BC (non-BC group; n = 329) and donors with BC (BC group; n = 14). Mean peak level of total bilirubin, mean duration of hospital stay after surgery, and medical cost in the BC group were significantly higher than in the non-BC group (p < 0.01). As improved procedures to prevent the BC were established at 2005, including the use of a real-time cholangiography by the C-arm, a minimized dissection of the hepatic vessels, the meticulous closure of the bile duct, and/or the use of Pringle maneuver during the parenchymal transection, the donors were divided into 2 groups before and after these establishments (the early period, n = 173; the later period, n = 170). Refinements in the management and surgical procedures reduced the occurrence of biliary complications from 6.4% during the early period to 1.8% during the later period (p < 0.01), and no biliary complications in the last 69 consecutive donors were observed. CONCLUSIONS: Technical refinements described in this study might be useful to prevent the occurrence of biliary complications in a donor hepatectomy. It is particularly important to preserve the blood supply for the biliary tract of both the graft and the remnant liver. (J Am Coll Surg 2010;211: 456-464. (C) 2010 by the American College of Surgeons)
• Early Diagnosis and Treatment Resolved Cholestatic Hepatitis C Without Fibrosis After Living Donor Liver Transplantation: Report of a Case

  Takasuke Fukuhara, Kazutoyo Morita, Kazuki Takeishi, Takeo Toshima, Kenji Umeda, Shigeyuki Nagata, Keishi Sugimachi, Toru Ikegami, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  SURGERY TODAY 40 (10) 982 - 985 0941-1291 2010/10 [Refereed][Not invited]
   

  Cholestatic hepatitis is a life-threatening recurrent pattern of hepatitis C virus (HCV) in immunosuppressed patients, for which curative treatment has not yet been established. We report the successful treatment of cholestatic hepatitis in a 59-year-old man who had undergone right lobe living donor liver transplantation (LDLT) for liver cirrhosis (LC) caused by HCV. Following uneventful surgery and an uncomplicated post-transplant clinical course, there was an abrupt increase in total bilirubin in comparison to aminotransferase on postoperative day (POD) 60 (total bilirubin 16.2 mg/dl, alanine aminotransferase 100 U/l, HCV-RNA 390 kIU/ml). The histological findings of the liver tissue showed lymphocyte infiltration in the periportal zone and severe cholestasis. Considering the clinical course, cholestatic hepatitis was strongly suspected and pegylated interferon and ribavirin therapy was started immediately, resulting in not only a viral response, but minimal progression of fibrosis. This case serves to demonstrate that early diagnosis and timely initiation of optimal antiviral therapy is essential for the resolution of cholestatic hepatitis C.
• Improved Results of a Surgical Resection for the Recurrence of Hepatocellular Carcinoma After Living Donor Liver Transplantation

  Akinobu Taketomi, Takasuke Fukuhara, Kazutoyo Morita, Hiroto Kayashima, Mizuki Ninomiya, Yoichi Yamashita, Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihko Maehara

  ANNALS OF SURGICAL ONCOLOGY 17 (9) 2283 - 2289 1068-9265 2010/09 [Refereed][Not invited]
   

  Purpose. This study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence. Methods. A total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered. Results. The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (n = 9), and nonsurgical therapy group (n = 7). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence. Conclusions. Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available.
• p62+ Hyaline Inclusions in Intrahepatic Cholangiocarcinoma Associated With Viral Hepatitis or Alcoholic Liver Disease

  Shinichi Aishima, Nobuhiro Fujita, Yohei Mano, Tomohiro Iguchi, Akinobu Taketomi, Yoshihiko Maehara, Yoshinao Oda, Masazumi Tsuneyoshi

  AMERICAN JOURNAL OF CLINICAL PATHOLOGY 134 (3) 457 - 465 0002-9173 2010/09 [Refereed][Not invited]
   

  Mallory bodies (MBs) and hyaline globules (HGs) are recognized as hepatocellular cytoplasmic inclusions in liver diseases. We reviewed 123 intrahepatic cholangiocarcinomas (ICCs) and encountered 16 cases (13.0%) in which cancer cells had MB-type inclusions and/or HG-type inclusions, both of which are positive for p62 and ubiquitin. The HG type was present in all 16 cases, and 5 cases contained the MB type. Of 16 patients, 12 had chronic liver disease that was related to alcoholic abuse in 4, hepatitis B surface antigen positive in 3, and hepatitis C virus antibody positive in 8. Viral infection and liver cirrhosis were more common in ICCs with p62+ inclusions (P = .0004 and P = .0199, respectively). Of 16 ICCs, 15 with hyaline inclusions had a peripheral tumor location (P = .0052). On ultrastructural examination, the MB type had an electron-dense fibrillar appearance, while the HG type appeared as rounded masses of granular materials. Our results suggest that intracytoplasmic hyaline bodies occasionally can be found in cholangio-carcinoma with chronic liver disease related to viral hepatitis or alcoholic intake.
• Extra-Anatomical Hepatic Artery Reconstruction in Living Donor Liver Transplantation: Can This Procedure Save Hepatic Grafts?

  Hideaki Uchiyama, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Mizuki Ninomiya, Hiroto Kayashima, Toru Ikegami, Yoshihiko Maehara

  LIVER TRANSPLANTATION 16 (9) 1054 - 1061 1527-6465 2010/09 [Refereed][Not invited]
   

  Graft hepatic arteries (HAs) are usually reconstructed with a recipient HA branch (anatomical HA reconstruction) in living donor liver transplantation (LDLT). Surgeons often encounter difficulties in reconstructing HAs, particularly when a recipient artery other than an HA branch must be used; this is known as extra-anatomical HA reconstruction. The outcomes of LDLT recipients with extra-anatomical HA reconstruction were retrospectively reviewed. Between October 1996 and October 2009, we performed primary LDLT 335 times, re-LDLT 8 times, and HA re-reconstruction 5 times for patients with HA complications. Thirty-three extra-anatomical HA reconstructions were performed in 22 patients with primary LDLT (6.6%), 4 patients with re-LDLT (50%), and 4 patients with HA re-reconstructions for HA complications (80%). In extra-anatomical HA reconstructions, we used 12 right gastroepiploic arteries, 6 right gastric arteries, 5 gastroduodenal arteries, 2 left gastric arteries, 2 splenic arteries, 2 cystic arteries, and 4 interposition grafts as recipient inflow arteries. Only 1 HA-related complication, the formation of an aneurysm, occurred after extra-anatomical HA reconstruction. The overall graft and patient survival probabilities after primary LDLT with extra-anatomical HA reconstruction were comparable to those after LDLT with anatomical HA reconstruction, although approximately half of the patients with extra-anatomical HA reconstruction suffered anastomotic biliary strictures. Therefore, extra-anatomical HA reconstruction can be safely performed through the proper selection of recipient arteries and the use of interposition grafts. These procedures can save hepatic grafts, even when recipient HAs cannot be used as inflow arteries. Liver Transpl 16:1054-1061, 2010. (C) 2010 AASLD.
• Expression profile of lipid metabolism-associated genes in hepatitis C virus-infected human liver

  Tatsuya Fujino, Makoto Nakamuta, Ryoko Yada, Yoko Aoyagi, Kenichiro Yasutake, Motoyuki Kohjima, Kunitaka Fukuizumi, Tsuyoshi Yoshimoto, Naohiko Harada, Masayoshi Yada, Masaki Kato, Kazuhiro Kotoh, Akinobu Taketomi, Yoshihiko Maehara, Manabu Nakashima, Munechika Enjoji

  HEPATOLOGY RESEARCH 40 (9) 923 - 929 1386-6346 2010/09 [Refereed][Not invited]
   

  Aim: Recent studies have shown that lipid metabolic pathways are required for the entry, replication and secretion of hepatitis C virus (HCV). Although little is known about the life cycle of HCV in humans, the activation of cholesterol and fatty acid biosynthesis may be critical for HCV proliferation. Methods: We assessed the transcription levels of genes essential for cholesterol and fatty acid biosynthesis in liver samples obtained from patients with chronic hepatitis C and determined their correlations. The serum levels of low-density lipoprotein (LDL) cholesterol and HCV core antigen were also measured. Results: The gene expression of the LDL receptor (LDLR) was suppressed, whereas that of SREBP1c, liver X receptor-alpha (LXR alpha), fatty acid synthase (FASN), and HMG-CoA reductase and synthase (HMGR and HMGS) was significantly increased, and SREBP2 transcription was comparable in HCV-infected liver compared with normal liver. Positive correlations were found for LDLR versus HMGR, HMGR versus SREBP1c, and LDLR versus SREBP2 in the HCV-infected and control liver. Although the LXR alpha-SREBP1c-FASN pathway was upregulated, proteasome activator 28 gamma (PA28 gamma) was downregulated at the transcriptional level in HCV-infected liver, and was not significantly correlated with the other genes examined. The serum LDL cholesterol level was negatively correlated with LDLR and HMGR expression. Conclusion: These results suggest that, in HCV-infected liver, the cholesterol load increases and cholesterol uptake is controlled, while de novo cholesterol synthesis is upregulated compared with the normal physiological state. The positive correlations in the expression levels of some cholesterol metabolism-associated genes indicate that not all of the metabolic pathways are dysregulated in HCV-infected liver.
• 肝移植後早期合併症 小児生体肝移植術後にreversible posterior leukoencephalopathy syndrome(RPLS)を発症した3例

  林田 真, 松浦 俊治, 水田 耕一, 佐伯 勇, 眞田 幸弘, 江上 聡, 内山 秀昭, 副島 雄二, 武富 紹信, 安田 是和, 前原 喜彦, 河原崎 秀雄, 田口 智章

  臨牀と研究 大道学館出版部 87 (9) 1308 - 1309 0021-4965 2010/09 

  症例1:7歳女児。胆道閉鎖症(BA)で父親をドナーとする生体部分肝移植術を施行したが、術後2日目より共同偏視、全身痙攣、両下肢不随意運動が出現した。頭部CTで左頭頂葉から後頭葉の低吸収域を認め、tacrolimus(TA)投与を中断してphenytoinを投与し意識清明となったが、視野欠損が残存した。術後7日目のMRIでは両側後頭葉から頭頂葉にT2延長域を認めた。術後11日目よりcycrospolin(CA)に変更したところ、症状は徐々に軽快し、画像所見も改善した。症例2:10歳男児。BAで母親をドナーとする生体肝移植術、脾臓摘出術を施行したが、術後3日目より全身痙攣が出現した。頭部CTで後頭頭頂葉の皮質、皮質下白質に低吸収域を、鞍上部に腫瘍を認めた。術後6日目より呼吸状態、意識レベルの急激な増悪を来たし、CTで低吸収域の拡大、左前頭葉皮質下の血腫、midline shift、鈎ヘルニアを認めた。脳幹反射は消失しており、術後50日目に死亡した。症例3:13歳男児。BAで母親をドナーとする生体部分肝移植術を施行したが、術後22日目に全身痙攣が出現した。頭部MRI FLAIR像で両側頭頂葉、後頭葉に皮質中心に高信号域を認め、TAをCAに変更し、carbamazepine投与を開始したところ、症状は軽快した。
• Living Donor Liver Transplantation in Patients Older Than 60 Years

  Tomoharu Yoshizumi, Ken Shirabe, Yuji Soejima, Akinobu Taketomi, Natsumi Yamashita, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara

  TRANSPLANTATION 90 (4) 433 - 437 0041-1337 2010/08 [Refereed][Not invited]
   

  Background. Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. Methods. A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. Results. Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). Conclusion. Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors.
• Imaging of cholangiolocellular carcinoma of the liver

  Yoshiki Asayama, Tsuyoshi Tajima, Daisuke Okamoto, Akihiro Nishie, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Kakihara, Shinichi Aishima, Akinobu Taketomi, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 75 (1) E120 - E125 0720-048X 2010/07 [Refereed][Not invited]
   

  Aim: Cholangiolocellular carcinoma (CoCC) is currently considered to originate from hepatic progenitor cells. The purpose of this study was to evaluate the imaging features of cholangiolocellular carcinoma of the liver. Materials and methods: Five cases of surgically resected cases of CoCC from 4 institutions were retrospectively evaluated. All of the five patients underwent contrast-enhanced dynamic CT. MRI and angio-CT including CT during arterioportography (CTAP) and CT during hepatic arteriography were performed in 3 and 2 patients, respectively. Histological evaluation was also performed and was correlated with radiographic findings. Results: On dynamic CT or MRI, the lesions presented hypervascular tumors with delayed washout in 2 cases and in the other 3 cases, the lesions showed peripheral enhancement with concentric delayed filling. On CTAP, the continued existence of portal veins or tiny spots of portal flow was identified in the tumors. Fibrous capsule or tumor necrosis was not observed. Conclusion: CoCC tumors have the dual imaging characteristics of hepatocellular carcinoma and cholangiocarcinoma. The absence of a fibrous capsule, the absence of tumor necrosis, peripheral location within the liver, and the presence of portal venous penetration within the tumor also appear to be characteristic features. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
• Clinicopathological Prognostic Factors After Hepatectomy for Patients with Mass-Forming Type Intrahepatic Cholangiocarcinoma: Relevance of the Lymphatic Invasion Index

  Ken Shirabe, Yohei Mano, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Shinichi Aishima, Hiroto Kayashima, Mizuki Ninomiya, Yoshihiko Maehara

  ANNALS OF SURGICAL ONCOLOGY 17 (7) 1816 - 1822 1068-9265 2010/07 [Refereed][Not invited]
   

  The present study was conducted to clarify the pathological factors in patients who underwent surgery for mass-forming type intrahepatic cholangiocarcinoma (IHC). From 1982 to July 2004, a total of 60 liver resections for mass-forming type IHC were performed at Kyushu University and its affiliated institutions. Portal venous, lymphatic, hepatic venous, and serosal invasion was examined by univariate and multivariate analyses for their prognostic value. The portal venous (PV) invasion index was defined as follows: PV0, portal venous invasion (-) and intrahepatic metastasis (-); PV1, portal venous invasion (+) or intrahepatic metastasis (+); PV2, portal venous invasion (+) and intrahepatic metastasis (+). The lymphatic invasion (LI) index was defined as follows: LI0, lymphatic duct invasion (-) and lymph node metastasis (-); LI1, intrahepatic lymphatic duct invasion (+) or lymph node metastasis (+); LI2, intrahepatic lymphatic duct invasion (+) and lymph node metastasis (+). In univariate analysis, statistically significant prognostic factors for poor outcome were tumor size (> 5 cm), serosal invasion (+), PV1 or PV2, LI1 or LI2, histological grade (moderate and poor), hepatic venous invasion (+) and noncurative resection. After multivariate analysis, the lymphatic invasion index and histological grade were statistically independent prognostic factors for overall survival and recurrence-free survival. In patients with mass-forming type IHC, lymphatic invasion is the most important invasion pathway, compared with serosal and portal and hepatic venous invasion. Stratification of the lymphatic invasion pathway by lymphatic invasion, including intrahepatic lymphatic duct invasion and lymph node metastasis, is a good predictor for prognosis in patients after hepatectomy for mass-forming type IHC.
• Intratumoral Neoadjuvant Immunotherapy Using IL-12 and Dendritic Cells Is an Effective Strategy To Control Recurrence of Murine Hepatocellular Carcinoma in Immunosuppressed Mice

  Hiroto Kayashima, Takeo Toshima, Shinji Okano, Akinobu Taketomi, Noboru Harada, Yo-ichi Yamashita, Yukihiro Tomita, Ken Shirabe, Yoshihiko Maehara

  JOURNAL OF IMMUNOLOGY 185 (1) 698 - 708 0022-1767 2010/07 [Refereed][Not invited]
   

  Liver transplantation is accepted as an effective therapy for hepatocellular carcinoma (HCC). However, recurrence is one of the most fatal complications. The aim of this study is to evaluate the efficacy of intratumoral immunotherapy using IL-12 gene therapy and dendritic cell injection for the purpose of effective treatment for HCC under conditions of immunosuppression. We found that the combined immunotherapy significantly induced sustained and high amounts of intratumoral IL-12 and IFN-gamma proteins and that it induced high HCC-specific CTL activity under immunosuppression as compared with each monotherapy or control. The combined immunotherapy also exerted effective antitumor effects on the immunosuppressed host, resulting in significant suppression of growth of the s.c. established tumor and complete suppression of lung and liver metastasis, without rejection of a fully allogeneic skin graft. These antitumor effects were dependent on both T cells and NK cells. Noteworthily, the combined intratumoral immunotherapy and tumor resection (that is, neoadjuvant immunotherapy) resulted in achievement of tumor-free and long-term survival of the some immunosuppressed mice, even when the mice were challenged with i.v. injection of HCC at the time of tumor resection. In contrast, all of the mice treated with neoadjuvant immunotherapy using monotherapy or control therapy suffered from lung and liver metastasis. These results suggest that intratumoral neoadjuvant immunotherapy using IL-12 gene therapy and dendritic cell therapy is a potent effective strategy to control recurrence of HCC in patients after liver transplantation for HCC and may be applicable to general cancer treatment. The Journal of Immunology, 2010, 185: 698-708.
• All-in-One Ex Vivo Self-Reconstruction Technique Using an Autologous Inferior Vena Cava for a Right Lobe Liver Graft with Multiple and Complex Venous Orifices

  Yuji Soejima, Kazuki Takeishi, Toru Ikegami, Hideaki Uchiyama, Akinobu Taketomi, Yoshihiko Maehara

  LIVER TRANSPLANTATION 16 (7) 909 - 913 1527-6465 2010/07 [Refereed][Not invited]
  
• Radiological assessment of hepatic vein invasion by hepatocellular carcinoma using combined computed tomography hepatic arteriography and computed tomography arterial portography

  Akihiro Nishie, Tsuyoshi Tajima, Yoshiki Asayama, Kousei Ishigami, Masakazu Hirakawa, Yasuhiro Ushijima, Daisuke Kakihara, Daisuke Okamoto, Nobuhiro Fujita, Akinobu Taketomi, Kengo Yoshimitsu, Hiroshi Honda

  JAPANESE JOURNAL OF RADIOLOGY 28 (6) 414 - 422 1867-108X 2010/07 [Refereed][Not invited]
   

  The aim of this study was to elucidate computed tomography hepatic arteriography (CTHA) and CT arterial portography (CTAP) findings characteristic of hepatocellular carcinoma (HCC) with large hepatic venous invasion (HVI) and then to examine whether the presence of minute HVI can be diagnosed based on each finding. Combined CTHA and CTAP of 106 HCCs were examined. Two radiologists analyzed the radiological findings of five nodules with large HVI (group vv2). The remaining 101 nodules were classified into two groups: group vv1, positive minute HVI; group vv0, negative HVI. They examined whether each finding observed in group vv2 could be detected in groups vv1 and vv0. Analysis of group vv2 identified (a) tumor thrombus, (b) early inflow of the contrast into the hepatic vein proximal to the invaded site, and (c) partially decreased portal venous flow in the peripheral parenchyma subject to the involved hepatic vein. Findings (b) and (c) were observed in 16% of group vv1. A significant difference in frequency of finding (c) was obtained between groups vv1 and vv0. The positive and negative predictive values of finding (c) were 66.7% and 77.9%, respectively. Findings (b) and (c), especially the latter, may partly contribute to the radiological diagnosis of minute HVI.
• Antineoplastic Effects of Gamma Linolenic Acid on Hepatocellular Carcinoma Cell Lines

  Shinji Itoh, Akinobu Taketomi, Norifumi Harimoto, Eiji Tsujita, Tatsuya Rikimaru, Ken Shirabe, Mitsuo Shimada, Yoshihiko Maehara

  JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 47 (1) 81 - 90 0912-0009 2010/07 [Refereed][Not invited]
   

  The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.
• Dual hepatic artery reconstruction in living donor liver transplantation using a left hepatic graft with 2 hepatic arterial stumps

  Hideaki Uchiyama, Noboru Harada, Kensaku Sanefuji, Hiroto Kayashima, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Mitsuo Shimada, Yoshihiko Maehara

  SURGERY 147 (6) 878 - 886 0039-6060 2010/06 [Refereed][Not invited]
   

  Background. A left hepatic graft in living donor liver transplantation (LDLT) often has 2 thin and short hepatic arterial stumps, which makes hepatic artery (HA) reconstructions much more difficult to perform. Consequently, some investigators regard using a lift graft as a contraindication to LDLT, whereas others report that the reconstruction. of only 1 HA is sufficient for most LDLTs. The aim of this retrospective study was to investigate whether 2 HAs on a lift hepatic graft in an LDLT can be reconstructed safely and whether the outcomes of LDLTs are affected by reconstructing both HAs (dual reconstruction). Methods. A total of 175 LDLTs using a left graft between October 1996 and April 2008 were divided into 3 groups: group (n = 104): 1 HA stump with 1 HA reconstruction; group 2 (n = 47): 2 HA stumps with dual HA reconstruction; and group 3 (n = 24): 2 HA slumps with only 1 HA reconstruction. We reconstructed HAs using microvascular surgical techniques. Results. With technical advancement, we have been able to reconstruct both HAs in most cases without any HA-related complications, despite the fact that complex HA reconstructions were needed. Group 3 patients had a significantly greater incidence of anastomotic biliary stricture, which was decreased by dual HA reconstructions to the same level as observed in group 1. Conclusion. Dual HA reconstructions can be performed safely in LDLTs with a decreased incidence of anastomotic biliary stricture. (Surgery 2010;147:878-86.)
• Down-regulation of artery in moderately differentiated hepatocellular carcinoma related to tumor development

  Nobuhiro Fujita, Shinichi Aishima, Tomohiro Iguchi, Yunosuke Nishihara, Hidetaka Yamamoto, Akinobu Taketomi, Yoshinao Oda, Hiroshi Honda, Masazumi Tsuneyoshi

  HUMAN PATHOLOGY 41 (6) 838 - 847 0046-8177 2010/06 [Refereed][Not invited]
   

  Hepatocellular carcinoma develops in a multistep process. Previous studies have revealed changes in blood supply in hepatocellular carcinoma during its carcinogenesis. However, little is known about the relationship between tumor vasculature and the biological behavior of moderately differentiated hepatocellular carcinoma which demonstrates varied degrees of biological behavior. We immunohistochemically assessed intratumoral arterial vessel density (by high-molecular-weight caldesmon and calponin) and microvessel density (by CD34) in 123 cases of moderately differentiated hepatocellular carcinomas, and compared these densities with clinicopathological findings. Arterial vessel density and microvessel density of 19 well-differentiated and 37 poorly differentiated hepatocellular carcinomas were also evaluated. The arterial vessel density of moderately differentiated hepatocellular carcinomas with capsule formation, infiltration to the capsule, portal venous invasion, and high Ki-67 labeling index was lower than that of moderately differentiated hepatocellular carcinomas without these pathological findings (high-molecular-weight caldesmon: P < .0001, P = .0074, P = .0009, P = .0244, calponin: P < .0001, P = .0695, P = .0033, and P = .0155, respectively). The low arterial vessel density group (<10) of moderately differentiated hepatocellular carcinomas tended to show poorer overall survival than the high arterial vessel density group (> 10) (high-molecular-weight caldesmon: P = .0347, calponin: P = .0404). The arterial vessel density and microvessel density of moderately differentiated hepatocellular carcinomas were significantly higher than those of well-differentiated hepatocellular carcinomas (high-molecular-weight caldesmon: P = .022, calponin: P = .027, CD34: P = .036) and poorly differentiated hepatocellular carcinomas (high-molecular-weight caldesmon, calponin and CD34: P < .0001). The moderately differentiated hepatocellular carcinomas with lower arterial vessel density had more malignant potential than those with higher arterial vessel density. The changes of arterial vessel density in moderately differentiated hepatocellular carcinomas were suggested. (C) 2010 Elsevier Inc. All rights reserved.
• The role of serum interleukin-8 in hepatic resections

  Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Hirofumi Hasegawa, Takayuki Hamatsu, Yo-ichi Yamashita, Keishi Sugimachi, Tomoharu Yoshizumi, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara

  SURGERY TODAY 40 (6) 543 - 548 0941-1291 2010/06 [Refereed][Not invited]
   

  Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38A degrees C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury.
• Genetic analysis of expression profile involved in retinoid metabolism in non-alcoholic fatty liver disease

  An Afida Ashla, Yoshiko Hoshikawa, Hiroyuki Tsuchiya, Koich Hashiguchi, Munechika Enjoji, Makoto Nakamuta, Akinobu Taketomi, Yoshihiko Maehara, Kohei Shomori, Akihiro Kurimasa, Ichiro Hisatome, Hisao Ito, Goshi Shiota

  HEPATOLOGY RESEARCH 40 (6) 594 - 604 1386-6346 2010/06 [Refereed][Not invited]
   

  Aim: The patients with non-alcoholic fatty liver disease (NAFLD) have been reported to be at greater risk for progression to chronic liver disease including liver cirrhosis (LC). To examine the mechanisms for the progression of NAFLD, a genetic analysis of hepatic expression profile in retinoid metabolism in NAFLD was performed since the loss of retinoid signaling is associated with the progression of liver disease via reactive oxygen species (ROS) generation. Methods: Fifty-one genes, which are associated with retinoid metabolism and action, were examined in thirty six subjects including 17 patients with simple steatosis, 11 with non-alcoholic steatohepatitis (NASH) and eight controls were examined by real-time reverse transcriptase polymerase chain reaction. Immunohistochemical study was also done by 3 kinds of antibodies. Results: Higher expression of CRBP1 LRAT, DGT1/2 and CES1 in NAFLD suggests that mutual conversion between retinyl ester and retinal occurs actively. Expression of ADH1/2/3, RDH5/10/11, DHRS3 and RALDH1/3 was increased in NAFLD, suggesting that oxidation process from retinol to all-trans retinoic acid (ATRA) was enhanced. Importantly, greater expression of CYP26A1 indicated that degradation of ATRA was enhanced in NAFLD. Further, expression of SOD1/2, catalase, thioredoxin and uncoupling protein 2 was also enhanced. Conclusion: Hyperdynamic state of retinoid metabolism is present in the liver tissues with NAFLD, which may be a putative mechanism by which NAFLD progresses to chronic liver disease including LC.
• Mutations in hepatitis C virus genotype 1b and the sensitivity of interferon-ribavirin therapy after liver transplantation

  Takasuke Fukuhara, Akinobu Taketomi, Shinji Okano, Toru Ikegami, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara

  JOURNAL OF HEPATOLOGY 52 (5) 672 - 680 0168-8278 2010/05 [Refereed][Not invited]
   

  Background & Aims: The results of post-transplant antiviral therapy for recurrent hepatitis C virus (HCV) are poor, and significant pre-transplant predictors for sustained viral response (SVR) have not yet been identified. Methods: Pegylated interferon/ribavirin therapy was performed for more than 48 weeks in 50 patients who underwent liver transplantation (LT) for HCV genotype 1-related liver disease. Of these, 22 patients achieved SVR. The predictive potential of the viral mutations, including amino acids (aa) 70 and 91 in the Core region, interferon sensitivity-determining region (ISDR, aa 2209-2248) and interferon/ribavirin resistance-determining region (IRRDR, aa 2334-2379) in NS5A, was evaluated. Results: In 16 patients, the sequences in the pre- and post-transplant samples were the same, except for aa 70 in the Core of 1 patient. The SVR achievement percentage was significantly lower in the Non-double wild (DW) at aa 70 and 91, the ISDR < 2 and IRRDR < 6 groups than in the DW (30% vs. 65%, p = 0.015), the ISDR >= 2 (35% vs. 69%, p = 0.035) and IRRDR >= 6 (25% vs. 78%, p<0.001) groups, respectively. Predictive scoring with these three items provides a newly established and significant predictor for SVR after LT (p = 0.015). Conclusion: DW, ISDR >= 2 and IRRDR >= 6 were found to be significant predictors for SVR after LT. In addition, it is possible that the establishment of a new scoring system consisting of these three factors may be a useful marker to predict interferon sensitivity for recurrent HCV after LT. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
• Acute biliary obstruction due to a large intracholedochal hematoma after living-donor liver transplantation: Report of a case

  Shigeyuki Nagata, Toru Ikegami, Kazuki Takeishi, Takeo Toshima, Keishi Sugimachi, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  SURGERY TODAY 40 (5) 474 - 476 0941-1291 2010/05 [Refereed][Not invited]
   

  This report presents a rare case of an acute biliary obstruction caused by the postoperative development of an intracholedochal hematoma in a 57-year-old female patient who underwent living-donor liver transplantation for end-stage liver disease of cryptogenic origin. This is the first report to describe the development of an intracholedochal hematoma after livingdonor liver transplantation.
• Successful Curative Extracorporeal Hepatic Resection for Far-Advanced Hepatocellular Carcinoma in an Adolescent Patient

  Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yo-Ichi Yamashita, Kenji Umeda, Kazutoyo Morita, Yoshihiko Maehara

  LIVER TRANSPLANTATION 16 (5) 685 - 687 1527-6465 2010/05 [Refereed][Not invited]
  
• Impact of preoperative serum sodium concentration in living donor liver transplantation

  Takasuke Fukuhara, Toru Ikegami, Kazutoyo Morita, Kenji Umeda, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 25 (5) 978 - 984 0815-9319 2010/05 [Refereed][Not invited]
   

  Background and Aims: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. Methods: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na < 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. Results: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). Conclusion: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT.
• 生体肝移植後神経合併症としてreversible posterior leukoencephalopathy syndrome(RPLS)を発症した三例

  林田 真, 松浦 俊治, 水田 耕一, 佐伯 勇, 眞田 幸弘, 江上 聡, 内山 秀昭, 副島 雄二, 武冨 紹信, 安田 是和, 前原 喜彦, 河原崎 秀雄, 田口 智章

  日本小児外科学会雑誌 (一社)日本小児外科学会 46 (3) 608 - 608 0288-609X 2010/05
• New prediction factors of small-for-size syndrome in living donor adult liver transplantation for chronic liver disease

  Kensaku Sanefuji, Tomohiro Iguchi, Shigeru Ueda, Shigeyuki Nagata, Keishi Sugimachi, Toru Ikegami, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 23 (4) 350 - 357 0934-0874 2010/04 [Refereed][Not invited]
   

  P>Small-for-size syndrome (SFSS), which is characterized by synthetic dysfunction and prolonged cholestasis, is a major cause of worse short-term prognoses after living donor adult liver transplantation (LDALT). However, the risks of SFSS remain unclear. The aim of this study was to clarify the risks of SFSS, which were analysed in 172 patients who underwent LDALT for chronic liver disease. Graft types included left lobe with caudate lobe graft (n = 110) and right lobe graft (n = 62). Thirty-four cases (24 with left lobe grafts and 10 with right lobe grafts) were determined as SFSS. SFSS developed even if the actual graft-to-recipient standard liver volume ratio was > 40%. Logistic regression analysis revealed three independent factors associated with SFSS development in left and right lobe grafts: donor age, actual graft-to-recipient native liver volume ratio, and Child's score. Donor age and actual graft-to-recipient native liver volume ratio may become predictive factors for SFSS development in left and right lobe grafts in patients undergoing LDALT.
• Use of Recipient's Left Hepatic Artery for Artery Reconstruction in Right Lobe Living Donor Liver Transplantation With Duct-to-Duct Anastomosis

  Hideaki Uchiyama, Toru Ikegami, Yuji Soejima, Mizuki Ninomiya, Hiroto Kayashima, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  TRANSPLANTATION 89 (8) 1016 - 1021 0041-1337 2010/04 [Refereed][Not invited]
   

  Background. The hepatic arteries (HAs) in a hepatic graft are usually reconstructed using the recipient's left or right HAs in living donor liver transplantation (LDLT). There have been no apparent selection criteria concerning which of the recipient's HAs should be used. This study retrospectively investigated whether the selection of left or right HA for HA reconstruction affects the outcomes of right lobe LDLT (RL-LDLT). Methods. Ninety-nine RL-LDLT were performed between July 1998 and March 2009. After excluding 10 cases of RL-LDLT with complex HA reconstruction(s), 89 cases of RL-LDLT were divided into four groups: RL-LDLT with duct-to-duct biliary anastomosis with an HA reconstruction using the recipient's left HA (DD-L-group; n=41), the recipient's right HA (DD-R-group; n=27), RL-LDLT with hepaticojejunostomy with an HA reconstruction using the recipient's left HA (HJ-L-group; n=11), and the recipient's right HA (HJ-R-group; n=10). The outcomes of RL-LDLT were compared among these four groups. Results. Septic complications occurred more frequently in the DD-R-group than in the DD-L-group (2.4% vs. 22.2%, P=0.013). Furthermore, 39% of the patients in the DD-R-group suffered anastomotic biliary stricture within 2 years after transplantation, in comparison with 8.1% in the DD-L-group (P=0.003). The selection of the recipient's left or right HA did not influence patient outcomes in the case of a hepaticojejunostomy. Conclusions. The DD-L-group patients experienced favorable outcomes in comparison with the DD-R-group patients. Therefore, recipient's left HAs should be selected for HA reconstruction in RL-LDLT when biliary reconstruction is performed by duct-to-duct anastomosis.
• Sclerosed hemangioma of the liver: possible diagnostic value of diffusion-weighted magnetic resonance imaging

  Tomoyuki Hida, Akihiro Nishie, Tsuyoshi Tajima, Akinobu Taketomi, Shin-ichi Aishima, Hiroshi Honda

  JAPANESE JOURNAL OF RADIOLOGY 28 (3) 235 - 238 1867-108X 2010/04 [Refereed][Not invited]
   

  We present a case of a sclerosed hemangioma (SH) of the liver that showed a high apparent diffusion coefficient (ADC) value. The patient was undergoing preoperative evaluation for a metastatic breast cancer lesion when a liver mass with a diameter of 3 cm was found. It was described as a heterogeneously hyperechoic mass on ultrasonography and as a well-defined, lobulated mass with early peripheral enhancement and internal heterogeneous enhancement in the delayed phase on computed tomography. The fat-suppressed T2-weighted images demonstrated a heterogeneously hyperintense mass, which showed an ADC value of 2.01 x 10(-3) mm(2)/s. Liver metastasis and cholangiocellular carcinoma could not be excluded based on the imaging findings. After surgery, a definite diagnosis of SH was obtained. Microscopically, many hyalinized portions with poor cellular and fibrous components were observed in the tumor, and this hyalinization accompanied with liquiform degeneration, which may have been one of the causes of the high ADC value. We discuss the diagnostic value of diffusion-weighted imaging for SH of the liver.
• A case of hepatic sclerosing hemangioma mimicking a malignant liver tumor

  吉田 月久, 杉町 圭史, 祇園 智信, 副島 雄二, 相島 慎一, 武冨 紹信, 前原 喜彦

  臨床外科 株式会社医学書院 65 (3) 451 - 455 0386-9857 2010/03/20
• Extracorporeal hepatic resection for advanced liver cancer

  Keishi Sugimachi, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Mizuki Ninomiya, Hiroto Kayashima, Dai Kitagawa, Hidefumi Higashi, Yoshihiko Maehara

  Japanese Journal of Cancer and Chemotherapy 37 (3) 399 - 401 0385-0684 2010/03/06 [Refereed][Not invited]
   

  Hepatic resection is the most curative treatment for the patient with hepatocellular carcinoma (HCC) which occurs in the non-cirrhotic liver. It is not common, but extracorporeal hepatic resection (EHR) is sometimes considered as the treatment of otherwise unresectable tumors due to the location, size, and vascular invasion of the tumor. In the EHR, the liver is completely removed and perfused with the preservation solution. Bloodless transection of hepatic parenchyma is done, and reimplanted in the patient. Preoperative assessment of the vascular anatomy and liver volume, advanced surgical technique of hepatic resection and transplantation, and experienced postoperative care are essential to the accomplishment of EHR. In this issue, we give an outline of the indication, procedures, and the problems of EHR.
• Impact of amino acid substitutions in the core region of HCV on multistep hepatocarcinogenesis

  Takasuke Fukuhara, Kazuki Takeishi, Takeo Toshima, Kazutoyo Morita, Shigeru Ueda, Tomohiro Iguchi, Shigeyuki Nagata, Keishi Sugimachi, Toru Ikegami, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  HEPATOLOGY RESEARCH 40 (2) 171 - 178 1386-6346 2010/02 [Refereed][Not invited]
   

  Aim: The core protein of hepatitis C virus (HCV) has multiple functions for not only viral replication but also hepatocellular carcinogenesis. A significant association of the substitutions in the core region with hepatocarcinogenesis has recently been reported. In this report, we evaluated the association of the substitutions in the core region with multistep hepatocarcinogenesis. Methods: Sixty-nine non-cancerous and cancerous liver tissues were obtained from the patients with primary developed hepatocellular carcinoma (HCC) due to HCV and 17 cirrhotic liver tissues were obtained from the patients without HCC. A sequence analysis of the core protein of HCV was performed and the association between the substitution rates in the core gene and the degree of fibrosis or steatosis during the primary development of HCC and tumor differentiation was analyzed. Results: The substitution rates of amino acid 70, 75, 91 and 147 exceeded 25% (amino acid 70, 51%; 75, 45%; 91, 36%; 147, 30%). All substitution rates were comparable among cancerous and non-cancerous region of patients with HCC and non-cancerous region without HCC. The substitution rates of these four amino acids were not associated with the degree of fibrosis, steatosis or tumor differentiation during the primary development of HCC. In addition, the substitution rates were comparable between the patients with or without HCC. The cumulative substitution numbers in the core region were also not associated with the degree of fibrosis and steatosis. Conclusions: It is possible that the substitutions in the core region are not associated with HCV-related multistep hepatocarcinogenesis.
• CX3CL1 (Fractalkine): A Signpost for Biliary Inflammation in Primary Biliary Cirrhosis

  Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Kentaro Kikuchi, Yasuni Nakanuma, Ian R. Mackay, M. Eric Gershwin, Koichi Akashi

  HEPATOLOGY 51 (2) 567 - 575 0270-9139 2010/02 [Refereed][Not invited]
   

  Improvements in the treatment of primary biliary cirrhosis (PBC) may depend upon dissection of mechanisms that determine recruitment of mononuclear cells to intralobular bile ducts, including the role of the chemokine-adhesion molecule CX3CL1 (fractalkine). We submit that there are unique interactions between intrahepatic biliary epithelial cells (BECs), endothelial cells (ECs), liver sinusoidal. endothetial cells (LSECs), and liver-infiltrating mononuclear cells (ILMCs), and that such interactions will in part dictate the biliary specific inflammatory response. To address this, we studied fresh explanted livers from pretransplantation patients with PBC and with inflammatory liver disease due to viral infection (disease controls) and biopsy material from patients with a discrete liver tumor (normal controls). Using this clinical material, we isolated and stimulated BECs, ECs, LSECs, and LMCs with a panel of Toll-like receptor ligands. We also studied the interactions of these cell populations with LMCs with respect to adhesion capability and production of tumor necrosis factor alpha (TNF-alpha). Finally, we used fresh biopsy samples to evaluate mononuclear cells around intrahepatic biliary ductules using monoclonal antibodies specific to CD68 or CD154, markers for monocytes/macrophagcs, and activated T cells, respectively. Conclusion: There are common properties of ECs, LSECs, and BECs, whether derived from PBC or viral hepatitis, but there are also significant differences, particularly in the potential in PBC for LMCs to adhere to ECs and BECs and to produce TNF-alpha; such properties were associated with augmented CX3CL1 production by BEC from PBC liver. The processes defined herein suggest potential novel biotherapies for biliary specific inflammation. (HEPATOLOGY 2010;51:567-575.)
• Detection of Hepatocellular Carcinoma (HCC) Using Super Paramagnetic Iron Oxide (SPIO)-Enhanced MRI: Added Value of Diffusion-Weighted Imaging (DWI)

  Akihiro Nishie, Tsuyoshi Tajima, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Okamoto, Masakazu Hirakawa, Yunosuke Nishihara, Akinobu Taketomi, Masamitsu Hatakenaka, Hiroyuki Irie, Kengo Yoshimitsu, Hiroshi Honda

  JOURNAL OF MAGNETIC RESONANCE IMAGING 31 (2) 373 - 382 1053-1807 2010/02 [Refereed][Not invited]
   

  Purpose: To evaluate whether diffusion-weighted imaging (DWI) improves the detection of hepatocellular carcinoma (HCC) on super paramagnetic iron oxide (SPIO)-enhanced MRI. Materials and Methods: This retrospective study group consisted of 30 patients with 50 HCC nodules who underwent MRI at 1.5 Tesla. Two combined MR sequence sets were compared for detecting HCC: SPIO-enhanced MRI (axial T2-weighted fast spin-echo (FSE) and T1-/T2*-weighted fast field echo (FFE) scanned before and after administration of ferucarbotran) and SPIO-enhanced MRI + DWI (SPIO-enhanced MRI With axial DWI scanned before and after administration of ferucarbotran). Three blinded readers independently reviewed for the presence of HCC on a segment-by-segment basis using a four-point confidence scale. The performance of the two combined MR sequence sets was evaluated using receiver operating characteristic (ROC) analysis. Results: The average area under the ROC curve (Az) of the three readers for the SPIO-enhanced MRI + DWI set (0.870 +/- 0.046) was significantly higher that that for the SPIO-enhanced MRI set (0.820 +/- 0.055) (P = .025). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of HCC were 66.0%, 98.0%, 90.0%, and 91.4%, respectively, for the SPIO-enhanced MRI set, and 70.0%, 98.6%, 92.9%, and 92.4%, respectively, for the SPIO-enhanced MRI + DWI set. Conclusion: The SPIO-enhanced MRI + DWI set outperformed the SPIO-enhanced MRI set for depicting HCC.
• Phase I/II study of the lipiodolization using DDP-H (CDDP powder; IA-call(A (R))) in patients with unresectable hepatocellular carcinoma

  Yo-ichi Yamashita, Akinobu Taketomi, Shinji Itoh, Norifumi Harimoto, Kazutoyo Morita, Takasuke Fukuhara, Shigeru Ueda, Kensaku Sanefuji, Keishi Sugimachi, Tsuyoshi Tajima, Yoshihiko Maehara

  CANCER CHEMOTHERAPY AND PHARMACOLOGY 2 65 (2) 301 - 307 0344-5704 2010/01 [Refereed][Not invited]
   

  Lipiodol Ultra-Fluid (Lipiodol(A (R))), an oily contrast medium, is selectively retained in hepatocellular carcinoma (HCC) through hepatic arterial infusion. DDP-H (IA-call(A (R))) developed as a CDDP powder, and may be a possible chemotherapeutic agent with lipiodol. We carried out a phase I/II study of the lipiodolization using DPP-H in patients with unresectable HCC. Phase I and pharmacokinetic study: The dose-limiting toxicity (DLT), the maximum tolerance dose (MTD), and the recommended dose (RD) were determined using a modified Fibonacci scheme. The concentration-time profile of total platinum in plasma was analyzed. Phase II study: Thirty-five patients with unresectable HCC received lipiodolization using DDP-H under RD, and the efficacy and safety were assessed. DLT was grade 3 vomiting at 40 mg/m(2). Therefore, MTD and RD were 35 mg/m(2). The peak of total platinum in plasma was over 1.0 mu g/ml at 40 mg/m(2) at 30 min after infusion. Of the 35 patients, 16 (45.7%) demonstrated complete responses, and 4 (11.4%) demonstrated partial responses with an additional 9 patients (25.7%) having stable diseases, as assessed by RECIST. Grade 3 thrombocytopenia was found in 1 patient (2.9%), grade 2 hyperbilirubinemia was found in 2 patients (5.7%), and grade 2 vomiting was found in 4 patients (11.4%). Lipiodolization using DDP-H at 35 mg/m(2) is effective and well tolerated in patients with unresectable HCC.
• Phase II Trial of Gemcitabine Combined with 5-fluorouracil and Cisplatin (GFP) Chemotherapy in Patients with Advanced Biliary Tree Cancers

  Yo-ichi Yamashita, Akinobu Taketomi, Shinji Itoh, Norifumi Harimoto, Eiji Tsujita, Keishi Sugimachi, Tomonobu Gion, Yoshihiko Maehara

  JAPANESE JOURNAL OF CLINICAL ONCOLOGY 40 (1) 24 - 28 0368-2811 2010/01 [Refereed][Not invited]
   

  Advanced biliary tree cancers are often diagnosed at an advanced or metastatic stage and have poor prognoses. We reported the promising anti-tumor activity of gemcitabine/5-fluorouracil (5-FU)/cisplatin (CDDP) therapy, called 'GFP chemotherapy' in a pilot study. Twenty-one patients with advanced or metastatic biliary tree cancers with no prior chemotherapy were enrolled in this Phase II trial. Patients were treated on 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m(2) on days 1, 8 and 15, and 5-FU at 150 mg/m(2) and CDDP at 3 mg/m(2) on days 1-5, 8-12 and 15-19. After two cycles, a 4-week outpatient treatment of gemcitabine (1000 mg/m(2)) on days 1 and 15 combined with 5-FU (500 mg/m(2)) and CDDP (7 mg/m(2)) on days 1 and 15 was commenced. Treatment was repeated until tumor progression or remission allowing curative operation, or unacceptable toxicity occurred. Of these 21 patients, no complete responses were observed, but 7 patients (33.3%) demonstrated partial responses (PRs) with an additional 12 patients (57.2%) having stable diseases, as assessed by RECIST. Three patients with PRs were treated by curative operation after GFP chemotherapy, and all of them survived with no recurrence for over 3 years. The median overall survival time was 18.8 months, and median time to progression was 13.4 months. Grade 3 side effects such as leukopenia, thrombocytopenia and anemia were found in six patients (28.6%), but no patients dropped out because of toxicity. This GFP chemotherapy has promising anti-tumor activity and is well tolerated in patients with advanced biliary tree cancers.
• Solitary asymptomatic thyroid metastasis from hepatocellular carcinoma detected by FDG-PET/CT

  Takeo Toshima, Akinobu Taketomi, Ken Shirabe, Kazuki Takeishi, Takashi Motomura, Youhei Mano, Kazutoyo Morita, Takasuke Fukuhara, Keishi Sugimachi, Yasuhiro Maruoka, Koichiro Abe, Tsuyoshi Tajima, Yoshihiko Maehara

  Case Reports in Gastroenterology 4 (2) 279 - 285 1662-0631 2010 [Refereed][Not invited]
   

  Thyroid metastases from hepatocellular carcinoma (HCC) seldom occur and are often difficult to diagnose because of their asymptomatic clinical course. We evaluated a very rare case of solitary thyroid metastasis from HCC that showed high uptake of fluorine-18 fluorodeoxyglucose (FDG), when imaged using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The patient was a 74-year-old man and presented with a remarkably elevated des-gamma-carboxy prothrombin level of 1,157 mAU/ml 22 months after hepatic lobectomy. FDG-PET/CT imaging revealed a hypodense tumor with high FDG uptake, with a maximum standardized uptake value of 5.2 in the thyroid left lobe. Solitary thyroid metastasis from HCC was suspected and subsequent fine needle aspiration did indeed reveal HCC. The patient received left thyroidectomy with left regional lymph node dissection. Two months after left thyroidectomy, contrast-enhanced computed tomography showed local recurrence, and the patient received ongoing radiotherapy treatment. To our knowledge, the present study is the first to demonstrate the feasibility of FDG-PET/CT in the diagnosis and management of clinically diagnosed, asymptomatic, solitary thyroid metastasis from HCC. © 2010 S. Karger AG, Basel.
• Activation of Morphine Glucuronidation by Fatty Acyl-CoAs and Its Plasticity: A Comparative Study in Humans and Rodents Including Chimeric Mice Carrying Human Liver

  Arief Nurrochmad, Yuji Ishii, Hitomi Nakanoh, Tae Inoue, Toru Horie, Kazumi Sugihara, Shigeru Ohta, Akinobu Taketomi, Yoshihiko Maehara, Hideyuki Yamada

  DRUG METABOLISM AND PHARMACOKINETICS 25 (3) 262 - 273 1347-4367 2010 [Refereed][Not invited]
   

  The formation of morphine-3-glucuronide (M-3-G, pharmacologically inactive) and morphine-6-glucuronide (M-6-G, active metabolite) by liver microsomes from humans and rodents, including chimeric mice carrying human liver, was evaluated in the presence of fatty acyl-CoAs. Medium-to long-chain fatty acyl-CoAs, including oleoyl-CoAs, at a physiologic level (around 15 mM) markedly enhanced M-3-G formation catalyzed by rat liver microsomes. A separate experiment indicated that 15 mM oleoyl-CoA enhanced C-14-UDP-glucuronic acid (UDPGA) uptake by microsomes. The activation by acyl-CoAs disappeared or was greatly reduced by either pre-treating microsomes with detergent or freezing/thawing the rat liver before preparation. Many of the microsomes prepared from frozen human livers (N = 14) resisted oleoyl-CoA-mediated activation of UDP-glucuronosyltransferase (UGT) activity, including M-6-G formation, which is highly specific to humans. In sharp contrast, the activity of M-6-G and M-3-G formation in freshly-prepared hepatic microsomes from chimeric mice with humanized liver was potently activated by oleoyl-CoA. Thus, acyl-CoAs activate morphine glucuronidation mediated by human as well as rat UGTs. This activation is assumed to be due to the acyl-CoA-facilitated transportation of UDPGA, and microsomes need to maintain the intact conditions required for the activation. The function of UGT appears to be dynamically changed depending on the cellular acyl-CoA level in many species.
• The Significance of Fibroblast Growth Factor Receptor 2 Expression in Differentiation of Hepatocellular Carcinoma

  Norifumi Harimoto, Kenichi Taguchi, Ken Shirabe, Eisuke Adachi, Yoshihisa Sakaguchi, Yasushi Toh, Takeshi Okamura, Hiroto Kayashima, Akinobu Taketomi, Yoshihiko Maehara

  ONCOLOGY 78 (5-6) 361 - 368 0030-2414 2010 [Refereed][Not invited]
   

  Fibroblast growth factor receptors (FGFRs) have been reported to be involved in the progression of many cancers. The aim of this study is to clarify the significance of FGFR2 expression in the differentiation of hepatocellular carcinoma (HCC). One nodule-in-nodule HCC sample was obtained from a patient to analyze the different expression in well-to moderately differentiated HCC and poorly differentiated HCC using microarray technique. The expression of FGFR2 in 46 patients with surgically resected HCC was immunohistochemically examined and analyzed in relation to their clinicopathological factors. Fgfr2 was 4.7 times up-regulated in poorly differentiated HCC from a nodule-in-nodule sample. The high expression group was 16 cases and the low expression group was 30 cases. The high FGFR2 expression correlated significantly with a poor histological differentiation, a higher incidence of portal vein and a high level of alpha-fetoprotein. The overall survival rates and the disease-free survival rates in high expression were significantly worse than those in low. In conclusion, a high FGFR2 expression plays an important role in poor differentiation, portal vein invasion, high alpha-fetoprotein production, and poor prognosis. These data suggest that FGFR2 may be a potentially useful biological marker of tumor invasiveness in HCC as well as a novel molecular target for HCC. Copyright (C) 2010 S. Karger AG, Basel
• Immunohistochemical examination of a resected advanced hilar cholangiocarcinoma arising in a 29-year-old male without primary sclerosing cholangitis

  Taketoshi Suehiro, Takashi Matsumata, Tomohiro Iguchi, Kensaku Sanefuji, Ken-Ichi Nomoto, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara

  Case Reports in Gastroenterology 4 (2) 144 - 152 1662-0631 2010 [Refereed][Not invited]
   

  A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9) level was elevated to 939 IU/l, and the pathological findings revealed moderately differentiated tubular adenocarcinoma which involved almost the entire thickness of the hepatic duct and the adjacent liver tissue (T3) and which was associated with lymph node metastasis (N1). It was a stage IIB (T3N1M0) tubular adenocarcinoma according to UICC pathological staging. Immunohistochemical examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3-3σ and p27 were negative. The pathological and immunohistochemical findings indicated high malignant potential indicating poor prognosis. We administrated the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient is alive without recurrence and doing well two years after surgery. We also review other reports of cholangiocarcinoma patients aged less than 30 years. © 2010 S. Karger AG, Basel.
• Survival benefits of chemotherapy for unresectable biliary tract cancer - A multicenter retrospective analysis

  Akihiro Funakoshi, Hikoyuki Horiuchi, Terufumi Sakai, Toshihiko Miyahara, Toru Muranaka, Masashi Nakamura, Kazuhiro Mizumoto, Toshiharu Ueki, Akinobu Taketomi, Hiroya Yamaguchi, Toshihiko Sumii, Tetsuhide Ito

  Japanese Journal of Cancer and Chemotherapy 37 (13) 2875 - 2879 0385-0684 2010 [Refereed][Not invited]
   

  There is no agreement on the standard chemotherapeutic regimen for biliary tract cancer (BTC), although multi-drug regimens such as gemcitabine and/or S-1 have been tested in clinical trials. This study retrospectively reviewed data from patients with BTC who were seen at hospitals in the Kitakyushu and Fukuoka areas between 2005 and 2006, and examined the effect of systemic chemotherapy regimen on survival benefits in patients with unresectable BTC. Chemotherapy may benefit patients with BTC any age group, regardless of the primary site.
• Significance of DNA Polymerase Delta Catalytic Subunit p125 Induced by Mutant p53 in the Invasive Potential of Human Hepatocellular Carcinoma

  Kensaku Sanefuji, Akinobu Taketomi, Tomohiro Iguchi, Keishi Sugimachi, Toru Ikegami, Yo-ichi Yamashita, Tomonobu Gion, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara

  ONCOLOGY 79 (3-4) 229 - 237 0030-2414 2010 [Refereed][Not invited]
   

  Objective: To clarify the role of DNA polymerase delta in tumor progression, we examined the expression of its main catalytic subunit p125 encoded by POLD1 in hepatocellular carcinoma (HCC) and human HCC cell lines. Methods: We examined the expression of p53 and p125 in HCC by using immunohistochemistry and Western blotting. Characteristic changes observed in human HCC cell lines after transfection were examined. Results: Immunohistochemical examination revealed positive staining of p125 in HCC cell nuclei, but few positively stained cells were observed in noncancerous tissues (p < 0.0001). p125 expression in specimens significantly correlated with cellular differentiation (p = 0.0048) and the degree of vascular invasion (p = 0.0401). It also significantly correlated with abnormal p53 expression. In vivo studies showed that p125 was upregulated in mutant p53-transfected HepG2 cells, which had more invasive potential than did control cells. Furthermore, the expression and invasive potential were reduced by the silencer sequence for POLD1. Conclusions: These findings suggest that the DNA polymerase delta catalytic subunit p125 induced by mutant type p53 plays an important role in tumor invasion, which leads to a poorer prognosis in HCC. Copyright (C) 2011 S. Karger AG, Basel
• Living donor liver transplantation for acute liver failure caused by acute fatty liver of pregnancy

  Masayuki Miyazaki, Nobito Higuchi, Masatake Tanaka, Akihiro Ueda, Shigeyuki Nagata, Toru Ikegami, Masaki Kato, Yuji Soejima, Akinobu Taketomi, Ryoichi Takayanagi

  American Journal of Case Reports 11 126 - 129 1941-5923 2010 

  Background: Acute fatty liver of pregnancy (AFLP) is a rare but serious maternal disease that occurs in the third trimester of pregnancy. Generally, prompt delivery can improve hepatic function, while delayed diagnosis and treatment of patients with AFLP could allow progression to acute liver failure. Case Report: A previously healthy 37-year-old woman presented to the clinic at 38 weeks gestation because of appetite loss and lower abdominal pain. Because her blood tests showed liver enzyme elevation, she was admitted to our hospital. She was diagnosed as having AFLP on the basis of clinical symptoms and laboratory data. She underwent an emergency caesarean section. Even after delivery, her condition worsened despite supportive care including plasma exchange and abdominal computed tomography (CT) showed atrophy of the liver. She underwent living donor liver transplantation on postpartum day 4. Histopathological findings were consistent with acute fatty liver of pregnancy. Conclusions: A small number of the patients with AFLP progress to fatal liver failure despite delivery of the fetus and aggressive supportive care. Liver transplantation is one treatment for acute liver failure caused by AFLP, and quantification of hepatic volume might be useful in prognostic prediction of the disease. © The American Journal of Case Reports.
• Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPAR alpha-MDR3 pathway

  M. Nakamuta, T. Fujino, R. Yada, K. Yasutake, T. Yoshimoto, N. Harada, M. Yada, N. Higuchi, M. Kato, M. Kohjima, A. Taketomi, Y. Maehara, T. Nishinakagawa, K. Machida, K. Matsunaga, M. Nakashima, K. Kotoh, M. Enjoji

  INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 48 (1) 22 - 28 0946-1965 2010/01 [Not refereed][Not invited]
   

  Objective: Bezafibrate (BF) has been used to treat biliary damage, particularly in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has been demonstrated. The mechanism of action is thought to involve activation of the PPAR alpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this hypothesis in patients with hepatobiliary disease. Methods: The levels of serum gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile components were examined before and after BF administration in patients with obstructive jaundice undergoing percutaneous transhepatic biliary drainage (PTBD). Hepatic expression of PPAR alpha and MDR3 was quantified by real-time PCR in patients with PBC or non-alcoholic fatty liver disease (NAFLD). Results: In patients with obstructive jaundice, BF decreased the scrum levels of biliary enzymes and increased the bile concentration of PL. In patients with PBC or NAFLD, the expression levels of MDR3 were already up-regulated before starting the BF treatment. Although BF treatment did not further up-regulate MDR3 expression in NAFLD patients, PPAR alpha expression was significantly increased. Conclusions: BF enhanced the secretion of PL into bile in cholestatic patients undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent cholesterol overload, MDR3 was already expressed at a high level to compensate for bile acids overproduction, and its expression was hardly affected by BF. In patients with chronic liver diseases such as PBC, BF may induce clinical effects via mechanisms independent of PL secretion.
• Fascin Expression in Progression and Prognosis of Hepatocellular Carcinoma

  Tomohiro Iguchi, Shinichi Aishima, Kenji Umeda, Kensaku Sanefuji, Nobuhiro Fujita, Keishi Sugimachi, Tomonobu Gion, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  JOURNAL OF SURGICAL ONCOLOGY 100 (7) 575 - 579 0022-4790 2009/12 [Refereed][Not invited]
   

  Background and Objectives: Fascin is an actin-bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry. Methods: A total of 137 patients with HCC were stained with anti-fascin antibody. The tumor cells having unequivocal cytoplasmic and/or membranous fascin immunoreactivity were defined as fascin-positive. Results: Immunohistochemically, 23 (16.8%) HCCs having unequivocal fascin immunoreactivity were found. Tumors showing fascin expression were larger and less differentiated than those showing no fascin expression (P = 0.0239 and 0.0018, respectively). Portal venous invasion, bile duct invasion, and intrahepatic metastasis were detected significantly more frequently in fascin-positive group (P = 0.0029, 0.0333, and 0.0403, respectively). In addition, high alpha-fetoprotein (AFP) levels were significantly associated with the fascin expression in HCC (P = 0.0116). Fascin-positive group had significantly poorer outcomes than fascin-negative group and was an independent prognostic factor for disease-free survival. Conclusions: Fascin might become a novel marker of progression in HCC and a significant indicator of a poor prognosis for patients with HCC. J. Surg. Oncol. 2009;100:575-579. (C) 2009 Wiley-Liss, Inc.
• Long-Term Results of Hepatic Resection Combined with Intraoperative Local Ablation Therapy for Patients with Multinodular Hepatocellular Carcinomas

  Shinji Itoh, Kazutoyo Morita, Shigeru Ueda, Keishi Sugimachi, Yo-ichi Yamashita, Tomonobu Gion, Kengo Fukuzawa, Kenzo Wakasugi, Akinobu Taketomi, Yoshihiko Maehara

  ANNALS OF SURGICAL ONCOLOGY 16 (12) 3299 - 3307 1068-9265 2009/12 [Refereed][Not invited]
   

  Recently, local ablation therapy has been widely used for treatment of small hepatocellular carcinoma (HCC). The present study assessed the outcome of hepatic resection combined with intraoperative local ablation therapy in patients with multinodular HCCs. Forty-one patients with initial and multinodular HCCs underwent hepatic resection combined with intraoperative local ablation therapy. The mean maximum diameter of all tumors was 3.8 cm (range 2.1-16.0 cm), and the mean number of nodules was 3.2 (range 2-11). We evaluated the survival rates and assessed the prognostic factors associated with overall survival rates using Cox proportional hazard models. Intraoperative local ablation therapy was completed in all patients with no evidence of residual viable tumor on the first postoperative computed tomography (CT) scan. The 3-, 5- and 7-year overall survival rates were 84.3%, 61.2%, and 61.2%, respectively. Patients with preoperative des-gamma carboxyprothrombin (DCP) level > 300 mAU/ml showed significantly worse overall survival than those with DCP level a parts per thousand currency sign300 mAU/ml (P < 0.01). Hepatic resection combined with intraoperative local ablation therapy is effective for multinodular HCCs. DCP > 300 mAU/ml was a significant prognostic factor of long-term overall survival.
• Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: A novel target for therapy?

  Makoto Nakamuta, Ryoko Yada, Tatsuya Fujino, Masayoshi Yada, Nobito Higuchi, Masatake Tanaka, Masayuki Miyazaki, Motoyuki Kohjima, Masaki Kato, Tsuyoshi Yoshimoto, Naohiko Harada, Akinobu Taketomi, Yoshihiko Maehara, Momoko Koga, Takuya Nishinakagawa, Manabu Nakashima, Kazuhiro Kotoh, Munechika Enjoji

  INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 24 (6) 825 - 828 1107-3756 2009/12 [Refereed][Not invited]
   

  Recent investigations indicate that hepatitis C virus (HCV) infection is closely associated with hepatocytic lipid metabolism and induces hepatic steatosis. However, the actual lipid metabolism in HCV-infected liver has not been extensively investigated in humans. In this Study, we evaluated the expression of lipid metabolism-associated genes in patients with HCV infection by real-time PCR. Sterol regulatory element-binding protein (SREBP)-2 expression was unchanged and low density lipoprotein receptor expression was markedly reduced by 90% in HCV-infected liver. The expression of apolipoprotein B100, microsomal triglyceride transfer ptotein and ATP-binding cassette G5 was significantly increased. Up-regulation of cholesterol synthesis-associated genes, including HMG-CoA reductase, HMG-CoA synthase, farnesyl-diphosphate synthase and squalene synthase, confirmed enhanced de novo cholesterol synthesis. The expression of cholesterol 7 alpha-hydroxylase and farnesoid X receptor was enhanced, while bile salt export pump expression was unchanged. Fatty acid synthase expression was increased which was accompanied by increased expression of liver X receptor a and SREBP-1c. In summary, the regulation of lipid metabolism was impaired and cholesterol and fatty acid synthesis continued to increase without negative feedback in HCV-infected liver. These changes may be beneficial for HCV replication.
• Multiple Pulmonary Mucosa-Associated Lymphoid Tissue Lymphomas After Living Donor Liver Transplantation

  Fumihiro Shoji, Tokujiro Yano, Yuji Soejima, Akinobu Taketomi, Masafumi Takeshita, Katsuo Sueishi, Yoshihiko Maehara

  LIVER TRANSPLANTATION 15 (12) 1891 - 1893 1527-6465 2009/12 [Refereed][Not invited]
  
• The Feasibility and Effectiveness of a Hand-assisted Laparoscopic Splenectomy for Hypersplenism in Patients After Living-donor Liver Transplantation

  Hideo Uehara, Hirofumi Kawanaka, Tomohiko Akahoshi, Morimasa Tomikawa, Nao Kinjo, Naotaka Hashimoto, Toru Ikegami, Yuuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 19 (6) 484 - 487 1530-4515 2009/12 [Refereed][Not invited]
   

  Background: A laparoscopic splenectomy in patients who previously underwent living-donor liver transplantation (LDLT) is thought to be technically difficult because of the presence of severe adhesions and splenomegaly. This report documents the efficacy and safety of a hand-assisted laparoscopic splenectomy (HALS) for hypersplenism in patients after LDLT. Methods: Five patients underwent HALS for hypersplenism after LDLT between 1999 and 2007. The medical records of those patients were retrospectively evaluated. Results: The mean operative time was 237 +/- 12 minutes. The mean blood loss was 229 +/- 100mL and mean weight of excised spleen was 461 +/- 46 g. There was no to open surgery. The number of platelets and leukocytes were significantly increased after surgery. No major complications were observed except for a patient with paralytic ileus postoperatively. The mean hospital stay after the operation was 16.7 +/- 2.5 days. Conclusions: HALS for patients after LDLT is a feasible and safe procedure. This technique can thus become a standard procedure after LDLT.
• The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C

  T. Ikegami, A. Taketomi, Y. Soejima, T. Yoshizumi, T. Fukuhara, K. Kotoh, S. Shimoda, M. Kato, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 41 (10) 4246 - 4252 0041-1345 2009/12 [Refereed][Not invited]
   

  Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). Methods. Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. Results. In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group 1, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). Conclusion. IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR.
• De Novo Hepatocellular Carcinoma in a Liver Graft with Sustained Hepatitis C Virus Clearance After Living Donor Liver Transplantation

  Kazutoyo Morita, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Takasuke Fukuhara, Tomohiro Iguchi, Shigeyuki Nagata, Keishi Sugimachi, Tomonobu Gion, Ken Shirabe, Yoshihiko Maehara

  LIVER TRANSPLANTATION 15 (11) 1412 - 1416 1527-6465 2009/11 [Refereed][Not invited]
   

  The occurrence of de novo hepatocellular carcinoma (HCC) after liver transplantation (LT) for advanced HCCs has been extremely limited. In this article, a case of de novo HCC in a liver graft with sustained hepatitis C virus clearance after living donor liver transplantation (LDLT) for multiple HCCs and hepatitis C cirrhosis is reported. The recipient was a 58-year-old female, and the left lobe living donor was the 30-year-old healthy daughter of the recipient. Three years after LDLT, the patient received 48 weeks of interferon treatment for recurrent hepatitis C with advanced fibrosis. The patient has shown successful viral clearance since then. However, an HCC was recognized in the liver graft during a follow-up computed tomography scan performed 6 years after LDLT, and it was surgically resected. To analyze its origin [either from the patient (metastatic) or from the living donor (de novo)], genotyping by microsatellite analysis of tissue and blood samples from the donor and recipient was performed, and it revealed that the HCC originated from the donor. To the best of our knowledge, this is the first report of de novo HCC in a liver graft with sustained hepatitis C virus clearance after LT for advanced HCCs and hepatitis C cirrhosis. Liver Transpl 15:1412-1416, 2009. (C) 2009 AASLD.
• Diacylglycerol Kinase eta Augments C-Raf Activity and B-Raf/C-Raf Heterodimerization

  Satoshi Yasuda, Masahiro Kai, Shin-ichi Imai, Kazuki Takeishi, Akinobu Taketomi, Minoru Toyota, Hideo Kanoh, Fumio Sakane

  JOURNAL OF BIOLOGICAL CHEMISTRY 284 (43) 29559 - 29570 0021-9258 2009/10 [Refereed][Not invited]
   

  The Ras/B-Raf/C-Raf/MEK/ERK signaling cascade is critical for the control of many fundamental cellular processes, including proliferation, survival, and differentiation. This study demonstrated that small interfering RNA-dependent knockdown of diacylglycerol kinase eta (DGK eta) impaired the Ras/B-Raf/C-Raf/MEK/ERK pathway activated by epidermal growth factor (EGF) in HeLa cells. Conversely, the overexpression of DGK eta 1 could activate the Ras/B-Raf/C-Raf/MEK/ERK pathway in a DGK activity-independent manner, suggesting that DGK eta serves as a scaffold/adaptor protein. By determining the activity of all the components of the pathway in DGK eta-silenced HeLa cells, this study revealed that DGK eta activated C-Raf but not B-Raf. Moreover, this study demonstrated that DGK eta enhanced EGF-induced heterodimerization of C-Raf with B-Raf, which transmits the signal to C-Raf. DGK eta physically interacted with B-Raf and C-Raf, regulating EGF-induced recruitment of B-Raf and C-Raf from the cytosol to membranes. The DGK eta-dependent activation of C-Raf occurred downstream or independently of the already known C-Raf modifications, such as dephosphorylation at Ser-259, phosphorylation at Ser-338, and interaction with 14-3-3 protein. Taken together, the results obtained strongly support that DGK eta acts as a novel critical regulatory component of the Ras/B-Raf/C-Raf/MEK/ERK signaling cascade via a previously unidentified mechanism.
• CD10+fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma

  Yunosuke Nishihara, Shinichi Aishima, Akifumi Hayashi, Tomohiro Iguchi, Nobuhiro Fujita, Akinobu Taketomi, Hiroshi Honda, Masazumi Tsuneyoshi

  HISTOPATHOLOGY 55 (4) 423 - 431 0309-0167 2009/10 [Refereed][Not invited]
   

  Aims: To identify the role of CD10 expression of tumour-associated fibroblastic cells in the progression of cholangiocarcinoma (CC). Methods and results: The CD10 expression of fibroblastic cells was investigated immunohistochemically in 167 cases of intrahepatic and extrahepatic CC and 29 cases of biliary dysplasia, comparing the clinicopathological parameters. CD10 expression of fibroblastic cells was observed in 5.7% (4/70) of peripheral intrahepatic CC, 29.2% (14/48) of hilar intrahepatic CC, and 57.1% (28/49) of extrahepatic CC. As for biliary dysplasia, CD10 expression of fibroblastic cells was observed in 4.3% (1/23) in the hepatic hilum and 20% (3/15) in the extrahepatic bile duct. CD10 expression had a strong relationship with the anatomical location of CC, and was more frequently detected in the periductal infiltrating type of hilar intrahepatic CC (P < 0.0001) and in less differentiated cases in extrahepatic CC (P = 0.0151). CD10 expression was observed more frequently in CC than in biliary dysplasia of hepatic hilum (P = 0.0365) and extrahepatic bile duct (P = 0.0262). CD10 expression was not a prognostic indicator in CC. Conclusions: We suggest that CD10+ fibroblasts are more involved in the progression of hilar and extrahepatic CC than of peripheral intrahepatic CC.
• Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: A Histological Assessment of 365 Patients in Japan

  Tomohiro Iguchi, Shinichi Aishima, Kensaku Sanefuji, Nobuhiro Fujita, Keishi Sugimachi, Tomonobu Gion, Akinobu Taketomi, Ken Shirabe, Yoshihiko Maehara, Masazumi Tsuneyoshi

  ANNALS OF SURGICAL ONCOLOGY 16 (9) 2539 - 2546 1068-9265 2009/09 [Refereed][Not invited]
   

  Background. A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. Methods. A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type ( n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type ( n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. Results. The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). Conclusions. Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.
• Surgical complications after living donor liver transplantation in patients with biliary atresia: a relatively high incidence of portal vein complications

  Yukiko Takahashi, Yuko Nishimoto, Toshiharu Matsuura, Makoto Hayashida, Tatsuro Tajiri, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Tomoaki Taguchi

  PEDIATRIC SURGERY INTERNATIONAL 25 (9) 745 - 751 0179-0358 2009/09 [Refereed][Not invited]
   

  The aim of this study is to present the surgical complications in living donor liver transplantation (LDLT) for biliary atresia (BA) as a treatment for end stage liver disease. Twenty-nine LDLTs were performed in patients with BA between October 1996 and April 2008 in Department of Pediatric Surgery at Kyushu University Hospital. The initial immunosuppression was a combination of tacrolimus and steroids. Twenty-eight of 29 cases with BA, who previously underwent Kasai's operation and LDLT was performed at a median age of 9.1 years (range 7 months to 28 years). Only one case was performed primary LDLT. Post-transplant complications included portal vein complications (n = 5), three of which successfully treated by Rex-shunt or ballooning. Others were bile leakage (n = 4), intestinal perforation (n = 4), and so on. The overall survival rate was 86.2% (25/29). One patient died of chronic rejection, surgical complications after LDLT in BA while others died of sepsis, multi-organ failure, and brain hemorrhage. The incidence of portal vein complications and intestinal perforations was relatively high in LDLT for BA, possibly due to inflammation of the hepatoduodenal ligament and colonic adhesion to the liver. It is important to make an accurate diagnosis at an early stage and provide appropriate treatment.
• The state of cholesterol metabolism in the liver of patients with primary biliary cirrhosis: the role of MDR3 expression

  Munechika Enjoji, Ryoko Yada, Tatsuya Fujino, Tsuyoshi Yoshimoto, Masayoshi Yada, Naohiko Harada, Nobito Higuchi, Masaki Kato, Motoyuki Kohjima, Akinobu Taketomi, Yoshihiko Maehara, Manabu Nakashima, Kazuhiro Kotoh, Makoto Nakamuta

  HEPATOLOGY INTERNATIONAL 3 (3) 490 - 496 1936-0533 2009/09 [Refereed][Not invited]
   

  Because dyslipidemia, such as hypercholesterolemia, is a characteristic of primary biliary cirrhosis (PBC), hepatic lipid metabolism may be disturbed in PBC patients. We examined the expression of lipid metabolism-associated genes in PBC liver. All of the patients examined were in stage I or II PBC and without medication. RNA was isolated from liver specimens by needle biopsies of PBC patients and controls. The expression levels of various genes were measured by real-time RT-PCR. Multidrug resistance 3 (MDR3) expression was examined immunohistochemically. Statistical correlations between the gene expression levels and indices of blood testing were calculated. The expression levels of sterol regulatory element-binding protein (SREBP) 2 and LDL receptor were significantly lower, and those of apolipoprotein B, microsomal triglyceride transfer protein, ATP-binding cassette G5, and liver X receptor alpha (LXR alpha) were significantly higher in the PBC liver than in the normal control liver. The expression levels of bile acid synthesis- and excretion-associated genes did not change, and those of farnesoid X receptor, peroxisome proliferator-activated receptor alpha, and SREBP-1c were similar between the PBC and normal liver. MDR3 gene expression levels in the PBC liver were more than 4-fold higher than those in the control liver. Immunohistochemically, strong canalicular staining for MDR3 was observed in the PBC liver. LXR alpha expression was positively correlated with MDR3 levels. Serum levels of gamma-glutamyl transpeptidase (GGT) and IgM were negatively correlated with MDR3 levels. Hepatocellular cholesterol metabolism was at least partially disturbed, even in the early stage of PBC. The most characteristic finding was a distinct elevation of MDR3 expression, and the MDR3 levels were negatively correlated with GGT and IgM levels.
• Congestion of the donor remnant right liver after extended left lobe donation

  Takasuke Fukuhara, Kenji Umeda, Takeo Toshima, Kazuki Takeishi, Kazutoyo Morita, Shigeyuki Nagata, Keishi Sugimachi, Toru Ikegami, Tomonobu Gion, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 22 (8) 837 - 844 0934-0874 2009/08 [Refereed][Not invited]
   

  P>The clinical importance of congestion of the remnant right lobe has not yet been fully elucidated in donors who donate their left lobe with the middle hepatic vein. The impact of congestion on clinical course and liver regeneration in 52 donor remnant livers were evaluated. The donors were divided into three groups according to the degree of the congestion: the mild [congestion ratio (CR) < 10%], moderate (CR ranged from 10% to 25%) and severe congestion groups (CR > 25%). The regeneration ratio of the graft at postoperative day 7 (7 POD) was 22.0 +/- 14.3% and inversely correlated with the CR in the remnant right lobe (P = 0.003). Aspartate aminotransferase and alanine aminotransferase at 7 POD were significantly higher in the severe CR group in comparison to the mild CR group (P = 0.003 and 0.019, respectively), but those of the three groups were comparable at 30 POD. The hospital stays were significantly longer in the severe CR group (P = 0.010). In conclusion, the congestion of the donors' remnant right liver can lead the transient liver dysfunction and poor regeneration. Therefore, the conversion of the graft from the left to right lobe might be appropriate according to the degree of the congestion.
• The use of autologous vena cava patch graft for reconstructing multiple outflow orifices in right hemiliver living donor graft

  Toru Ikegami, Yuji Soejima, Shigeyuki Nagata, Akinobu Taketomi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 22 (8) 853 - 855 0934-0874 2009/08 [Refereed][Not invited]
  
• Human VAP-C Negatively Regulates Hepatitis C Virus Propagation

  Hiroshi Kukihara, Kohji Moriishi, Shuhei Taguwa, Hideki Tani, Takayuki Abe, Yoshio Mori, Tetsuro Suzuki, Takasuke Fukuhara, Akinobu Taketomi, Yoshihiko Maehara, Yoshiharu Matsuura

  JOURNAL OF VIROLOGY 83 (16) 7959 - 7969 0022-538X 2009/08 [Refereed][Not invited]
   

  Human vesicle-associated membrane protein-associated protein (VAP) subtype A (VAP-A) and subtype B (VAP-B) are involved in the regulation of membrane trafficking, lipid transport and metabolism, and the unfolded protein response. VAP-A and VAP-B consist of the major sperm protein (MSP) domain, the coiled-coil motif, and the C-terminal transmembrane anchor and form homo- and heterodimers through the transmembrane domain. VAP-A and VAP-B interact with NS5B and NS5A of hepatitis C virus (HCV) through the MSP domain and the coiled-coil motif, respectively, and participate in the replication of HCV. VAP-C is a splicing variant of VAP-B consisting of the N-terminal half of the MSP domain of VAP-B followed by the subtype-specific frameshift sequences, and its biological function has not been well characterized. In this study, we have examined the biological functions of VAP-C in the propagation of HCV. VAP-C interacted with NS5B but not with VAP-A, VAP-B, or NS5A in immunoprecipitation analyses, and the expression of VAP-C inhibited the interaction of NS5B with VAP-A or VAP-B. Overexpression of VAP-C impaired the RNA replication of the HCV replicon and the propagation of the HCV JFH1 strain, whereas overexpression of VAP-A and VAP-B enhanced the replication. Furthermore, the expression of VAP-C was observed in various tissues, whereas it was barely detected in the liver. These results suggest that VAP-C acts as a negative regulator of HCV propagation and that the expression of VAP-C may participate in the determination of tissue tropism of HCV propagation.
• Rituximab, IVIG, and Plasma Exchange Without Graft Local Infusion Treatment: A New Protocol in ABO Incompatible Living Donor Liver Transplantation

  Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Tomohiro Iguchi, Naotaka Hashimoto, Yoshihiko Maehara

  TRANSPLANTATION 88 (3) 303 - 307 0041-1337 2009/08 [Refereed][Not invited]
   

  Background. Although graft local infusion (GLI) treatment via the portal vein or the hepatic artery has been the pivotal strategy in ABO incompatible (ABOi) living donor liver transplantation (LDLT) in Japan, the procedure is associated with a high rate of catheter-associated complications. Methods. A new ABOi-LDLT protocol has been implemented using rituximab, intravenous immune globulin (IVIG), plasma exchange (PE), and splenectomy, without using GLI, on four patients, since 2007. Three other patients, treated before 2007, received GLI. Results. Three of the four patients with liver cirrhosis received rituximab over 3 weeks before LDLT, followed by PEs and post-LDLT IVIG, resulting in no rebound elevation of the isoagglutinin titers. The remaining patient, with fulminant hepatitis, received rituximab 3 days before the LDLT, resulting in antibody-mediated rejection, successfully treated by IVIG and PE. All four patients that were treated with the new protocol are alive, 26, 8, 6, and 5 months after ABOi-LDLT with normal liver function. Two of the three other patients with GLI, before 2007, had catheter-associated complications, including one graft loss. Conclusion. The new ABOi-LDLT protocol using rituximab, IVIG, and PE, without the use of GLI, therefore seems to be a safe and an effective treatment modality.
• Chronological Improvement of Portal Flow in the Remnant Right Lobe Liver of a Left Lobe Living Donor

  Keishi Sugimachi, Takeo Toshima, Akinobu Taketomi, Yuji Soejima, Tomonobu Gion, Toru Ikegami, Shigeyuki Nagata, Kazuki Takeishi, Yoshihiko Maehara

  TRANSPLANTATION 88 (4) 598 - 600 0041-1337 2009/08 [Refereed][Not invited]
  
• Surgical Resection of Pulmonary Malignant Tumors After Living Donor Liver Transplantation

  Fumihiro Shoji, Daigo Kawano, Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tokujiro Yano, Yoshihiko Maehara

  ANNALS OF THORACIC SURGERY 88 (1) 206 - 211 0003-4975 2009/07 [Refereed][Not invited]
   

  Background. The aim of this study is to report on patients who developed tumor recurrence of the lung or de novo pulmonary malignancies after living donor liver transplantation (LDLT) and to show the benefit of a surgical resection for these pulmonary malignant tumors. Methods. A total 246 patients who underwent LDLT were investigated. Results. Pulmonary malignant tumors after LDLT were observed in 12 (4.9%) of 246 patients studied. These patients included 9 tumor recurrences and 3 de novo malignancies. The frequency of pulmonary recurrence was 9.4% (9 of 96 patients) and that of pulmonary de novo malignancies including 2 primary lung cancer and 1 mucosa-associated lymphoid tissue (MALT) lymphoma, was 1.2% (3 of 246 patients). Four of 9 recurrent patients could undergo surgical resections and the survival range in patients who received surgery was 17 to 56 months with a mean of 36 months after LDLT; on the other hand, the survival range in patients that could not undergo a surgical resection was 4 to 26 months with a mean of 18 months. Among the de novo malignancies, only the MALT lymphoma patient could undergo a surgical resection. Repeated surgical resections of pulmonary malignant tumors could be performed in 3 patients and all these patients have been long-term survivors. Conclusions. These results suggest a surgical resection of pulmonary malignancies including tumor recurrences or de novo malignancies after LDLT is a feasible procedure and may prolong survival in selected patients, even under immunosuppressive conditions. (Ann Thorac Surg 2009;88:206-11) (C) 2009 by The Society of Thoracic Surgeons
• Recurrent Familial Hypobetalipoproteinemia-Induced Nonalcoholic Fatty Liver Disease After Living Donor Liver Transplantation

  Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Toshiharu Saibara, Takashi Nishizaki, Yoshihiko Maehara

  LIVER TRANSPLANTATION 15 (7) 806 - 809 1527-6465 2009/07 [Refereed][Not invited]
   

  Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Low albuminemia and refractory ascites persisted after transplantation. A biopsy specimen obtained 11 months after liver transplantation revealed severe steatosis and fibrosis, and recurrent NASH was diagnosed on the basis of pathological findings. Both the patient's and donor's laboratory tests demonstrated low LDL cholesterol and apolipoprotein levels. Because mutations in messenger RNAs of microsomal triglyceride transfer protein and apolipoprotein B genes were excluded neither in the recipient nor in the donor, both were clinically diagnosed as being heterozygous for FHBL. We successfully treated the recipient with heterozygous FHBL-induced recurrent NASH after liver transplantation using our diet and exercise programs. Liver Transpl 15.806-809, 2009. (C) 2009 AASLD.
• Potential Risk in Using Hepatic Veins of a Native Liver for Reconstructing Accessory Veins in Right Lobe Living Donor Graft

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shigeyuki Nagata, Yoshihiko Maehara

  TRANSPLANTATION 88 (1) 143 - 144 0041-1337 2009/07 [Refereed][Not invited]
  
• Surgical Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: An Endoscopic or Open Approach

  Shinji Tanaka, Mitsuo Shimada, Ken Shirabe, Ahinobu Taketomi, Shin-ichiro Maehara, Eiji Tsujita, Shinji Ito, Dai Kitagawa, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 56 (93) 1169 - 1173 0172-6390 2009/07 [Refereed][Not invited]
   

  Radiofrequency ablation (RFA) is widely used for the treatment of unresectable hepatocellular carcinoma (HCC) with cirrhosis, however, unexpected injuries to the adjacent organs remains the most critical problem after endoscopic radiofrequency ablation (RFA) using a percutaneous approach. The endoscopic RFA is a minimally invasive treatment for HCC with difficultly in the location due to limited percutaneous access. In this study, it was used an endoscopic approach or an open surgical approach for the treatment of 46 patients with unresectable HCC. There was difficulty in ablating the lesions due to limited percutaneous access. The endoscopic approach was assessed for 26 patients with primary HCC, and the open approach was used for 18 patients of recurrent HCC after surgical resection as well as the other 2 patients with multiple HCCs. The endoscopic RFA was performed using a laparoscopic approach for 20 cases and a thoracoscopic approach for 6 cases. The endoscopic RFA had significantly less intraoperative blood loss compared to the open RFA (56 g vs. 277 g; p<0.001) as well as a reduced postoperative hospital stay (13 days vs. 16 days; p<0.05). The occurrence of postoperative complications did not different between the two groups; 5 of 26 cases of the endoscopic RFA, and in 3 of 20 cases of the open RFA. The local recurrence of HCC occurred in only 1 case for each group, and the patient survival did not differ significantly between the groups. Endoscopic RFA is a feasible and reliable therapy for unresectable primary HCCs in the patients with cirrhosis.
• Radiological detectability of minute hepatic venous invasion in hepatocellular carcinoma

  Akihiro Nishie, Kengo Yoshimitsu, Hiroyuki Irie, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Okamoto, Yunosuke Nishihara, Akinobu Taketomi, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 70 (3) 517 - 524 0720-048X 2009/06 [Refereed][Not invited]
   

  Objective: To determine if minute hepatic venous invasion in hepatocellular carcinoma (HCC) can be diagnosed radiologically. Materials and methods: CT hepatic arteriography (CTHA) and CT arterioportography (CTAP) of 95 cases with HCCs were examined. Histopathology after surgery has been the gold standard in all patients. Based on the presence of microscopic portal venous invasion (MPVI) and microscopic hepatic venous invasion (MHVI), the cases were classified into four groups as follows: Group vp0vv0, negative MPVI and MHVI; Group vp1vv0, positive MPVI and negative MHVI; Group vp0vv1, negative MPVI and positive MHVI; Group vp1vv1, positive MPVI and MHVI. An area showing low attenuation on CTAP and high attenuation on CTHA around the tumor was defined as an area of peritumoral hemodynamic change (APTHC). The shape and size of APTHC were compared between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0. The ratio of APTHC volume to tumor volume (RAT) was employed as an indicator of APTHC size. Each comparison was also made independently when tumor diameter was limited to either less than 3 cm or 3 cm or more. Results: Three types of APTHC were identified: wedge-shaped, belt-shaped or irregular, and linear. No significant difference in the frequency of each type of APTHC was observed between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0. There was no significant difference in RAT between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0, unrelated to tumor size. Conclusions: The presence of minute hepatic venous invasion in HCC is difficult to determine even on combined CTHA and CTAP. (C) 2008 Published by Elsevier Ireland Ltd.
• Rapid Normalization of Portopulmonary Hypertension After Living Donor Liver Transplantation

  K. Sugimachi, Y. Soejima, K. Morita, S. Ueda, T. Fukuhara, S. Nagata, T. Ikegami, A. Taketomi, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 41 (5) 1976 - 1978 0041-1345 2009/06 [Refereed][Not invited]
   

  Portopulmonary hypertension (PPHTN) is a relatively rare complication of end-stage liver disease, and a serious problem in the context of liver transplantation. Herein we have reported a case of decompensated liver cirrhosis with PPHTN, which rapidly resolved after adult-to-adult living donor liver transplantation (LDLT). A 54-year-old man was referred to our hospital with end-stage liver cirrhosis owing to chronic hepatitis C. Preoperative mean pulmonary artery pressure (mPAP), as assessed by right heart catheterization, was 38 mm Hg. Continuous infusion of epoprostenol decreased the mPAP to 24 mm Hg over 44 days. He underwent LDLT using a right hepatic lobe graft donated by his son. The postoperative course was uneventful, epoprostenol was weaned by postoperative day (POD) 21, and the mPAP normalized to 21 mm Hg on POD 28. The patient was discharged on POD 31 without any vasodilators. Our case revealed that liver transplantation can rapidly resolve PPTHN.
• Tumor ablation therapy of liver cancers with an open magnetic resonance imaging-based navigation system

  Takashi Maeda, Jaesung Hong, Kozo Konishi, Takanori Nakatsuji, Takefumi Yasunaga, Yo-ichi Yamashita, Akinobu Taketomi, Kazuhiro Kotoh, Munechika Enjoji, Hideaki Nakashima, Kazuo Tanoue, Yoshihiko Maehara, Makoto Hashizume

  SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES 23 (5) 1048 - 1053 0930-2794 2009/05 [Refereed][Not invited]
   

  As minimally invasive treatments for liver cancers, percutaneous ablation therapies represent a valid alternative to liver resections, especially in patients with poor liver function. Recently, image-guided surgical and interventional procedures using open magnetic resonance imaging (MRI) have been introduced. We performed percutaneous ablation therapy for 51 nodules of liver cancer in 34 patients using a navigation system based on open MRI. During the ablation therapy, the ultrasonography (US) probe, needle, and tumor were displayed on the MR image. Immediately after the procedure, the therapeutic effect was evaluated by open MRI. In all cases, percutaneous puncture into the tumors was successful, even in the case of tumor undetectable by US. Mean fiducial registration error was approximately 3 mm. MR images captured after the procedure clearly demonstrated the ablated area. No mortality or major complications occurred, except for mild hemorrhage, pyrexia, and ascites. We developed a novel navigation system integrating US and MR images using open MRI for percutaneous ablation therapy of liver cancers. The presented system allows a safe and accurate approach to liver cancers, especially certain tumors that cannot be adequately visualized by US, and an evaluation of therapeutic results immediately after the procedures.
• Impact of cholesterol metabolism and the LXR alpha-SREBP-1c pathway on nonalcoholic fatty liver disease

  Makoto Nakamuta, Tatsuya Fujino, Ryoko Yada, Masayoshi Yada, Kenichiro Yasutake, Tsuyoshi Yoshimoto, Naohiko Harada, Nobito Higuchi, Masaki Kato, Motoyuki Kohjima, Akinobu Taketomi, Yoshihiko Maehara, Manabu Nakashima, Kazuhiro Kotoh, Munechika Enjoji

  INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 23 (5) 603 - 608 1107-3756 2009/05 [Refereed][Not invited]
   

  We previously studied fatty acid metabolism in the liver of nonalcoholic fatty liver disease (NAFLD) and reported the activation of the LXR alpha-SREBP-1c pathway in hepatocytes. LXR alpha regulates cholesterol metabolism as well as fatty acid metabolism, and its agonistic ligands are oxysterols. Moreover, there is some evidence that excess cholesterol intake is involved in the onset of NAFLD. Therefore, in this study, we examined the expression of cholesterol metabolism-associated genes in the NAFLD liver by real-time PCR. Expression of LXR alpha and ACAT1 was up-regulated in NAFLD and this was more noticeable in non-obese rather than in obese patients. Although the expression of the LDL receptor, which acts on cholesterol uptake, and of SREBP-2, a positive key regulator of cholesterol, was suppressed, the expression of enzymes that promote cholesterol synthesis was uniformly increased in NAFLD. Gene expression of apoB100 and microsomal triglyceride transfer protein, which are associated with VLDL secretion, and ABCG5, which is involved in cholesterol excretion, was significantly elevated in NAFLD. Because cholesterol accumulates in hepatocytes in NAFLD liver, cholesterol uptake and synthesis should be physiologically down-regulated. However, cholesterol synthesis was activated in NAFLD liver, meaning that cholesterol metabolism is dysregulated in NAFLD. Overproduction of cholesterol may lead to an increased level of oxysterols, activation of LXR alpha and SREBP-1c, and enhanced fatty acid synthesis.
• Hypersplenism after Living Donor Liver Transplantation

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hirofumi Kawanaka, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 56 (91-92) 778 - 782 0172-6390 2009/05 [Refereed][Not invited]
   

  Background/Aims: It has not determined whether post-transplant persistent hypersplenism (PTPH) occurs after living donor liver transplantation (LDLT). Methodology: One hundred and ninety-four patients who survived more than 6 months after LDLTs were examined for the evaluation to determine the incidence of PTPH (leukocyte counts <3,500/mu L and/or platelet counts <7.5x10(4)/mu L). In addition, 154 patients without a splenectomy were evaluated for the risk factors for PTPH. Results: The incidence of PTPH was 20.1% (n=31/154), and the occurrence ranged between 1.1 and 9.9 years after the LDLT, with the mean follow-up periods of 3.3 +/- 2.5 years. Multivariate analysis showed that portal pressure >30mmHg at the time of the laparotomy (p<0.01) and post-LDLT small for size syndrome (p<0.01) are risk factors for PTPH. For those with severe portal hypertension (>30 mmHg at laparotomy), the splenectomy tended to give better survival rate (p=0.09) without increasing the rate of septic complications. Conclusions: Hypersplenism did persist in a proportion of patients after LDLT. A high-risk for PTPH, especially severe portal hypertension, may be an indication for a splenectomy during LDLT in order to achieve uncomplicated post-transplant recovery.
• Decreased intratumoral arteries reflect portal tract destruction and aggressive characteristics in intrahepatic cholangiocarcinoma

  Shinichi Aishima, Tomohiro Iguchi, Yunosuke Nishihara, Nobuhiro Fujita, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HISTOPATHOLOGY 54 (4) 452 - 461 0309-0167 2009/03 [Refereed][Not invited]
   

  To assess the relationship between arterial blood supply and the progression of intrahepatic cholangiocarcinoma (ICC). The intratumoral arterial vessel density (AVD) was assessed in 76 cases of mass-forming type of ICC using anti-h-caldesmon antibody, a marker of smooth muscle cells, and AVD compared with pathological findings. AVD was directly correlated with the presence of intratumoral portal tracts (P < 0.0001) and inversely correlated with the grade of tumour necrosis (P = 0.0013). AVD was inversely correlated with vascular invasion and lymph node metastasis (P = 0.0159 and P = 0.0023, respectively). The hilar type of ICC had lower AVD regardless of tumour size, whereas the peripheral type with high AVD showed branching ductular formation composed of cuboidal cells with mild nuclear atypia. AVD was found to be an independent prognostic factor on multivariate survival analysis (P = 0.0013). This study demonstrates that intratumoral arterial vessels reflect engulfed portal tracts in ICC and decreased arterial vessels indicate aggressive tumour behaviour. Our results could contribute to clinical tumour staging and more effective therapy.
• Erratum: Extracapsular penetration is a new prognostic factor in human hepatocellular carcinoma (American Journal of Surgical Pathology (2008) 32 (1675-1682))

  T. Iguchi, S. Aishima, A. Taketomi

  American Journal of Surgical Pathology 33 (3) 485  0147-5185 2009/03
• Fascin overexpression is involved in carcinogenesis and prognosis of human intrahepatic cholangiocarcinoma: immunohistochemical and molecular analysis

  Tomohiro Iguchi, Shinichi Aishima, Akinobu Taketomi, Yunosuke Nishihara, Nobuhiro Fujita, Kensaku Sanefuji, Keishi Sugimachi, Yo-ichi Yamashita, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HUMAN PATHOLOGY 40 (2) 174 - 180 0046-8177 2009/02 [Refereed][Not invited]
   

  Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been associated with progression or prognosis in various neoplasms; however, its role in intrahepatic cholangiocarcinoma is unknown. Tumor sections from 84 patients with intrahepatic cholangiocarcinoma and 16 patients with intrahepatic biliary dysplasia were stained with antifascin antibody. Fascin mRNA expression, measured by real-time reverse transcription-polymerase chain reaction in 20 frozen samples, was compared with the immunohistochemical results. Furthermore, the expression of cyclin D1 was compared with that of fascin. Immunohistochemically, fascin expression was absent or sporadic in normal biliary epithelium, whereas high expression (>70% of tumor cells) was found in 2 (12.5%) dysplasias and 30 (35.7%) intrahepatic cholangiocarcinomas. The difference between the fascin mRNA concentrations in the high-expression and low-expression groups was significant (P = .0082). Tumors showing high expression were poorly differentiated (P = .0019), and among poorly differentiated intrahepatic cholangiocarcinoma, larger tumors (>5 cm) were more likely than smaller lesions to have high fascin expression (P = .0205). A significant correlation was observed between fascin and cyclin D1 immunoreactivity (P = .0289). Patients whose tumors expressed fascin abundantly had a poorer outcome (P = .0085), and fascin overexpression was an independent prognostic factor (P = .0477). Fascin is expressed early in biliary carcinogenesis and might contribute to poor differentiation and to growth of intrahepatic cholangiocarcinoma. It is a significant indicator of a poor prognosis for patients with intrahepatic cholangiocarcinoma. (C) 2009 Elsevier Inc. All rights reserved.
• Hepatocellular Carcinoma with a Pseudocapsule on Gadolinium-enhanced MR Images: Correlation with Histopathologic Findings

  Kousei Ishigami, Kengo Yoshimitsu, Yunosuke Nishihara, Hiroyuki Irie, Yoshiki Asayama, Tsuyoshi Tajima, Akihiro Nishie, Masakazu Hirakawa, Yasuhiro Ushijima, Daisuke Okamoto, Akinobu Taketomi, Hiroshi Honda

  RADIOLOGY 250 (2) 435 - 443 0033-8419 2009/02 [Refereed][Not invited]
   

  Purpose: To evaluate the characteristics of hepatocellular carcinoma (HCC) with a pseudocapsule on dynamic magnetic resonance (MR) images. Materials and Methods: The institutional review board approval was obtained, and the requirements for informed consent were waived for this retrospective study. Dynamic MR studies of surgically resected 106 HCCs in 93 patients were retrospectively reviewed. A false-positive fibrous capsule (FC) on dynamic MR images was considered to be a pseudocapsule. Pathologic specimens of HCCs with a pseudocapsule were reviewed. The differences in size, tumor grade, the degree of liver fibrosis and background liver diseases, and the incidence of vascular invasion were compared between HCCs with a pseudocapsule on MR images and those with FC at histologic examination by using Student t, Kruskal-Wallis, and chi(2) tests. Results: The sensitivity, specificity, and accuracy of dynamic MR in the diagnosis of histologic FC were 94.0% (47 of 50), 73.2% (41 of 56), and 83.0% (88 of 106), respectively. There were 15 (14.2%) HCCs with a pseudocapsule. The pathologic specimens suggested possible causes of the pseudocapsule that included prominent sinusoids (n = 6), peritumoral fibrosis mimicking bridging fibrosis (n = 3), and both (n = 5). In one case, the capsulated HCC was surrounded by a well-differentiated HCC component. The mean size of a HCC with a pseudocapsule tended to be smaller than that with histologic FC, although it was not significant (mean +/- standard deviation: 2.8 cm +/- 1.0 vs 3.5 cm +/- 2.0, P = .09). Liver cirrhosis was less frequent in HCCs with a pseudocapsule than in those with a histologic FC (one of 14 [7.1%] vs 20 of 49 [40.8%], P < .05). The tumor grades were not significantly different, and the incidence of vascular invasion after standardizing the tumor size (<= 4 cm) was similar (five of 14 [35.7%] vs 12 of 37 [32.4%]). Conclusion: Dynamic MR imaging is accurate in depicting FC in HCCs. HCC with a pseudocapsule at MR possibly consists of peritumoral sinusoids and/or fibrosis. The pseudocapsule may be similar to histologic FC in terms of tumor invasiveness. (C) RSNA, 2008
• Donor Risk in Adult-to-Adult Living Donor Liver Transplantation: Impact of Left Lobe Graft

  Akinobu Taketomi, Hiroto Kayashima, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara

  TRANSPLANTATION 87 (3) 445 - 450 0041-1337 2009/02 [Refereed][Not invited]
   

  Background. To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Methods. Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Results. Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. Conclusions. LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation.
• Bloodless splenectomy during liver transplantation for terminal liver diseases with portal hypertension.

  Toru Ikegami, Takeo Toshima, Kazuki Takeishi, Yuji Soejima, Hirofumi Kawanaka, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara

  Journal of the American College of Surgeons 208 (2) e1-4 - 4 1072-7515 2009/02 [Refereed][Not invited]
  
• Impact of Des-Gamma-Carboxy Prothrombin and Tumor Size on the Recurrence of Hepatocellular Carcinoma After Living Donor Liver Transplantation

  Akinobu Taketomi, Kensaku Sanefuji, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uhciyama, Toru Ikegami, Noboru Harada, Yoichi Yamashita, Keishi Sugimachi, Hiroto Kayashima, Tomohiro Iguchi, Yoshihko Maehara

  TRANSPLANTATION 87 (4) 531 - 537 0041-1337 2009/02 [Refereed][Not invited]
   

  Backgrounds. Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. Methods and Results. A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free Survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within I year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free Survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). Conclusions. A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC.
• Diagnostic value of the delayed phase image for iso-attenuating pancreatic carcinomas in the pancreatic parenchymal phase on multidetector computed tomography

  Kousei Ishigami, Kengo Yoshimitsu, Hiroyuki Irie, Tsuyoshi Tajima, Yoshiki Asayama, Akihiro Nishie, Masakazu Hirakawa, Yasuhiro Ushijima, Daisuke Okamoto, Shigenori Nagata, Yunosuke Nishihara, Koji Yamaguchi, Akinobu Taketomi, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 69 (1) 139 - 146 0720-048X 2009/01 [Refereed][Not invited]
   

  Purpose: To assess the value of the delayed phase (DP) in pancreatic carcinomas which appear iso-attenuating in the pancreatic parenchymal phase (PPP). Materials and methods: Fifty-seven preoperative MDCT studies of pancreatic carcinomas were retrospectively reviewed. The size of the tumors, and the Hounsfield unit (HU) of the tumors and pancreatic parenchyma were measured. The tumor-to-pancreas contrast (TPC: vertical bar HU [tumor] - HU [normal pancreas]vertical bar) was calculated. Results: Eight cases (14.0%) showed iso-attenuation and 49 showed hypo-attenuation in the PPP. The DP images revealed seven of eight (87.5%) iso-attenuating tumors to be hyper-attenuating. The size of iso-attenuating tumors was smaller than that of hypo-attenuating tumors (mean +/- S.D.: 12.4 +/- 4.8 mm vs. 30.3 +/- 9.0 mm, p < 0.0001). In hypo-attenuating tumors, TPC in the PPP (60.2 +/- 24.6 HU) was higher than those in the portal venous phase (PVP, 40.5 +/- 23.0 HU, p < 0.0001) and DP (18.3 +/- 11.8 HU, in p < 0.0001). In contrast, in iso-attenuating tumors, TPC in the DP (26.0 +/- 14.9 HU) was higher than those in the PPP (9.2 +/- 3.7 HU, p = 0.0003) and PVP (7.1 +/- 4.7 HU, p = 0.001) phases. Conclusion: The DP image is helpful in depicting small iso-attenuating pancreatic carcinomas as slightly hyper-attenuating tumors. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
• Characterization of Hepatocellular Carcinoma Developed After Achieving Sustained Virological Response to Interferon Therapy for Hepatitis C

  Kensaku Sanefuji, Hiroto Kayashima, Tomohiro Iguchi, Keishi Sugimachi, Yo-Ichi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Takashi Nishizaki, Akinobu Taketomi, Yoshihiko Maehara

  JOURNAL OF SURGICAL ONCOLOGY 99 (1) 32 - 37 0022-4790 2009/01 [Refereed][Not invited]
   

  Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients.
• Feasibility of Adult-to-Adult Living Donor Liver Transplantation for Acute Liver Failure

  Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Yoshihiko Maehara

  LIVER TRANSPLANTATION 15 (1) 117 - 118 1527-6465 2009/01 [Refereed][Not invited]
  
• Proctocolectomy for colon cancer associated with ulcerative colitis a few months after living donor liver transplantation for primary sclerosing cholangitis: Report of a case

  Takasuke Fukuhara, Akinori Egashira, Masakazu Imamura, Toru Ikegami, Eiji Oki, Yuji Soejima, Noriaki Sadanaga, Akinobu Taketomi, Takashi Yao, Masaru Morita, Yoshihiro Kakeji, Masazumi Tsuneyoshi, Yoshihiko Maehara

  SURGERY TODAY 39 (1) 59 - 63 0941-1291 2009/01 [Refereed][Not invited]
   

  Colorectal cancer (CRC) frequently develops in patients with ulcerative colitis (UC). We report a case of CRC treated successfully by proctocolectomy 8 months after living donor liver transplantation (LDLT) for primary sclerosing cholangitis (PSC). The lesion was detected early, probably as a result of colonoscopic surveillance after LDLT. Thus, patients with a long history of UC, who undergo LDLT for PSC, should be followed up with regular surveillance colonoscopy. Moreover, surgery, such as radical resection of the colon and rectum should be performed without delay, even shortly after LDLT. To our knowledge, this is the first report of a patient undergoing proctocolectomy after LDLT.
• A Comprehensive Analysis of Immunohistochemical Studies in Intrahepatic Cholangiocarcinoma Using the Survival Tree Model

  Tomohiro Iguchi, Natsumi Yamashita, Shinichi Aishima, Yousuke Kuroda, Takahiro Terashi, Keishi Sugimachi, Ken-ichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  ONCOLOGY 76 (4) 293 - 300 0030-2414 2009 [Refereed][Not invited]
   

  Objective: Various immunohistochemical studies have been performed regarding intrahepatic cholangiocarcinoma (ICC), including the cell cycle-related proteins (p27, cyclin D1, 14-3-3 sigma, p53, cyclin B1 and Ki-67), the proto-oncogenes (c-erbB-2 and c-Met), the extracellular matrix proteins (tenascin and laminin) and others (beta-catenin, epidermal growth factor receptor, osteopontin, aquaporin 1, MUC5AC and fascin). Nevertheless, none of these have been proven to be a predictive power of the prognosis with high specificity and sensitivity for ICC. Methods: Sixty-one patients with ICC were selected and ICC specimens were immunohistochemically stained with the above 16 markers, as previously reported. Results: The immunoreactivity of osteopontin, tenascin and Ki-67 divided the patients with ICC into 4 subgroups by the survival tree model. There was a significant relationship between the location of the tumor, TNM classification, histological differentiation, tumor size, lymphatic permeation, perineural invasion, lymph node metastasis, intrahepatic metastasis and viral infection among the 4 subgroups. In addition, there was a significant difference in survival among the 4 subgroups. Conclusion: In this study, the subgrouping by the survival tree model might be helpful for predicting the patients' prognosis in ICC. Copyright (C) 2009 S. Karger AG, Basel
• Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization

  Yunosuke Nishihara, Shinichi Aishima, Yousuke Kuroda, Tomohiro Iguchi, Kenichi Taguchi, Yoshiki Asayama, Akinobu Taketomi, Naoko Kinukawa, Hiroshi Honda, Masazumi Tsuneyoshi

  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 23 (12) 1860 - 1868 0815-9319 2008/12 [Refereed][Not invited]
   

  Transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for non-curative hepatocellular carcinoma (HCC), and hoped to have chemotherapeutic and ischemic effects; however, the histopathological changes of HCC caused by TACE have not been sufficiently discussed so far. We aimed to assess the morphological and immunohistochemical features of HCC treated with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to correlate these data with observed clinicopathological characteristics. Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of HCC resected without TACE as a control were analyzed. The incidences of intrahepatic metastasis, poorly differentiated histology, multinucleated giant cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were significantly higher than those in the non-TACE group. The TACE group showed reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in 23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the TACE group was significantly higher than in the non-TACE group (P = 0.0423). There was no correlation between immunoreactivity and the number of times TACE was carried out, but the expression of CK19 and vimentin in the massive necrotic group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229, respectively). Only TACE was an independent determinant of CK19 expression in all cases by multivariate analysis. These results suggest that preoperative TACE may have an impact on the biliary phenotype of HCC. Some post-therapeutic HCC patients might develop HCC with a biliary phenotype indicating more aggressive malignancies.
• Extracapsular Penetration is a New Prognostic Factor in Human Hepatocellular Carcinoma

  Tomohiro Iguchi, Shinichi Aishima, Akinobu Taketomi, Yunosuke Nishihara, Nobuhiro Fujita, Kensaku Sanefuji, Yoshihiko Maehara, Masazumi Tsuneyoshi

  AMERICAN JOURNAL OF SURGICAL PATHOLOGY 32 (11) 1675 - 1682 0147-5185 2008/11 [Refereed][Not invited]
   

  The fibrous capsule is a unique characteristic of hepatocellular carcinoma (HCC) and acts as a barricade preventing the spread of cancer cells. Infiltration to the capsule (fc-inf) is the invasive feature in HCC; however, there are no reports of a detailed investigation regarding fc-inf. We selected 88 HCCs of <= 5 cm in diameter, when considered together with both the single nodular and the single nodular with extranodular growth types. We classified the infiltrating pattern into 2 types: extracapsular (EC) infiltrating type (n = 38), in which cancer cells infiltrated outside the capsule and touched the existing liver parenchyma, and intracapsular (IQ infiltrating type (n = 50), in which the infiltrating cancer cells stayed inside the capsule. The distance of infiltration and the capsular thickness were measured and the ratio of capsular infiltration (Cl index) was calculated. There were no clinicopathologic differences between the 2 types, but the capsular thickness of IC type was greater than that of EC type (P < 0.0001). EC type showed a poorer outcome for the overall survival and the disease-free survival (P = 0.0210 and P = 0.0115, respectively) and EC type was an independent prognostic factor for a disease-free survival (P = 0.0158). However, Cl index did not correlate with any clinicopathologic factors or the patient prognosis in IC type. We propose a new definition of fc-inf as a histologic feature of cancer cells penetrating to the liver parenchyma through the fibrous capsule. It may be closely related to the patient prognosis and may therefore, become a new and useful pathologic factor.
• The significance of differences in fatty acid metabolism between obese and non-obese patients with non-alcoholic fatty liver disease

  Makoto Nakamuta, Motoyuki Kohjima, Nobito Higuchi, Masaki Kato, Kazuhiro Kotoh, Tsuyoshi Yoshimoto, Masayoshi Yada, Ryoko Yada, Ryosuke Takemoto, Kunitaka Fukuizumi, Naohiko Harada, Akinobu Taketomi, Yoshihiko Maehara, Manabu Nakashima, Munechika Enjoji

  INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22 (5) 663 - 667 1107-3756 2008/11 [Refereed][Not invited]
   

  Non-alcoholic fatty liver disease (NAFLD) is considered to be associated with metabolic syndrome; however, a number of NAFLD patients are not obese. To explore any differences in lipid metabolism between obese and non-obese patients, we determined the expression of fatty acid metabolism-related genes. Expression levels of target genes were quantified by real-time PCR using liver biopsy samples from NAFLD patients and normal controls. Serum adipocytokine levels were also determined. The expression of genes related to fatty acid synthesis and uptake was generally up-regulated in NAFLD patients; however, no significant difference was seen between obese and non-obese groups. Most of the genes tested related to fatty acid and reactive oxygen species (ROS) elimination, were overexpressed in NAFLD and the levels were significantly higher in non-obese patients. As an exception, peroxisome proliferator-activated receptor a expression was suppressed in NAFLD and the levels were lower in the obese group. Triglyceride synthesis-related genes were up-regulated and lipolytic enzymes were decreased in NAFLD, but there was no significant difference between the obese and non-obese groups. In NAFLD, increased de novo synthesis and uptake of fatty acids led to further hepatocyte accumulation of fatty acids. The upregulation of fatty acid oxidation and the antioxidant pathway and the suppression of lipolysis seemed to be involved in this process. Expression of genes related to fatty acid oxidation and ROS elimination were higher in the non-obese group than in the obese group, which contributes to the trend of more severe liver injury, insulin resistance and steatosis in obese patients.
• A Simple Hilar Dissection Technique Preserving Maximum Blood Supply to the Bile Duct in Living Donor Liver Transplantation

  Yuji Soejima, Takasuke Fukuhara, Kazutoyo Morita, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara

  TRANSPLANTATION 86 (10) 1468 - 1469 0041-1337 2008/11 [Refereed][Not invited]
   

  Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipient's bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT.
• The Risks of HBV Infection after Liver Transplantation from HBc Antibody Positive Donor to HBs Antibody Positive Recipient

  Toru Ikegami, Akinobu Taketomi, Ryuji Ohta, Yuji Soejima, Tomoharu Yoshizumi, Noboru Harada, Mitsuo Shimada, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (88) 2162 - 2165 0172-6390 2008/11 [Refereed][Not invited]
   

  The rate of de novo hepatitis B infection, after liver transplantation from a hepatitis B core antibody (HBcAb) (+) donor to a surface antibody (HBsAb) (+) recipient has not yet elucidated.. Four recipients with HBsAb (+) and HBcAb (+), who received living donor grafts from HBcAb (+) donors were herein reviewed. They received lamivudine monotherapy: three patients with HBsAb titer > 10 IU/L did not demonstrate the onset of HBsAg, whereas one patient with HBsAb titer <10 IU/L developed hepatitis B antigen (HBsAg) 4 years after transplantation. An HBsAb (+) patient with a titer of >10 IU/L is therefore considered not to require combination therapy when receiving an HBcAb W liver graft. However, a great deal of caution is necessary in patients with negative or low HBsAb titers <10 IU/L.
• Sequential pancreaticoduodenectomy after living donor liver transplantation for cholagiocacinoma

  Y. Soejima, S. Ueda, K. Sanefuji, H. Kayashima, T. Yoshizumi, T. Ikegami, Y. Yamashita, K. Sugimachi, T. Iguchi, A. Taketomi, Y. Maehara

  AMERICAN JOURNAL OF TRANSPLANTATION 8 (10) 2158 - 2162 1600-6135 2008/10 [Refereed][Not invited]
   

  Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC) is often contraindicated due to concomitant occurrence of cholangiocarcinoma (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been sporadically reported; however, the applicability of such an invasive procedure to patients with CC has not been validated. We report here a case of sequential PD performed 44 days after a successful living donor liver transplantation (LDLT) using a left lobe graft. Although a clear pancreatic juice leakage through the drain persisted for days after surgery, the patient recovered from the complication and was discharged 32 days after the procedure. Currently, 1 year after LDLT, the patient is doing well with no evidence of recurrence. In conclusion, a sequential PD following LDLT is a safe and feasible option to treat CC complicating PSC. Long-term follow-up and accumulation of cases are necessary to evaluate the effectiveness of this procedure for this complicated disease.
• The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft

  Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Toru Ikegami, Hideaki Uchiyama, Hiroto Kayashima, Noboru Harada, Yo-ichi Yamashita, Hirofumi Kawanaka, Takashi Nishizak, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 21 (9) 833 - 842 0934-0874 2008/09 [Refereed][Not invited]
   

  Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n = 69), in which splenectomy was not performed, and the Sp (+) group (n = 44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n = 50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio < 40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P = 0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less.
• Accuracy of an age-adjusted formula in assessing the graft volume in living donor liver transplantation

  Hiroto Kayashima, Akinobu Taketomi, Yusuke Yonemura, Hideki Ijichi, Noboru Harada, Tomoharu Yoshizumi, Yuji Soejima, Kengo Yoshimitsu, Yoshihiko Maehara

  LIVER TRANSPLANTATION 14 (9) 1366 - 1371 1527-6465 2008/09 [Refereed][Not invited]
   

  In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age-adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age-adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age-adjusted formula and 3-dimensional computed tomography (3D-CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age-adjusted formula was created as follows: age-adjusted GV = 70.767 + (0.703 X GV estimated with 3D-CT volumetry) + (1.298 X donor age). The mean error ratio for the age-adjusted formula (9.6%) was significantly lower than that from 3D-CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age-adjusted formula is very useful in reducing the error in estimating GV.
• Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: Significance for living donors

  Kengo Yoshimitsu, Yousuke Kuroda, Makoto Nakamuta, Akinobu Taketomi, Hiroyuki Irie, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Yasuhiro Ushijima, Tomomi Yamada, Hiroshi Honda

  JOURNAL OF MAGNETIC RESONANCE IMAGING 28 (3) 678 - 684 1053-1807 2008/09 [Refereed][Not invited]
   

  Purpose: To compare plain computed tomography (CT) and chemical-shift MR imaging (CSI) for establishing a non-invasive method to estimate the degree of steatosis. Materials and Methods: A total of 58 patients who had histological proof of liver tissue and underwent CT and/or CSI within two weeks. were studied. They consisted of 38 living donor candidates and 20 liver surgery patients without hepatitis or cirrhosis. The CT index (CTI) and MR index (MRI) were defined and correlated to histological grades of steatosis. Correlation was also performed exclusively for mild steatosis (grades 0-2). Results: Both plain CT (p = 0.74, P < 0.0001) and CSI (p = 0.83. P < 0.0001) had good correlation with histological grades of steatosis. showing no significant difference between them. For mild steatosis. CSI (p = 0.77. P < 0.0001) had better correlation than CT (p = 0.49. P = 0.001) (P = 0.049). Accuracy in differentiation between grade 0-1 vs. grade 2-4 steatosis was 85% using a CTI >6, and 91% using an MRI <0.03 as criteria. That between grade 0-2 and grade 3-4 was 91% using a CTI >-8 and 88% using an MRI <0.25 as criteria. Conclusion: Both plain CT and CSI were useful in estimating the degree of steatosis but CSI was superior to CT in differentiating mild steatosis. These indices may at least partially replace percutaneous biopsy in evaluating grades of steatosis for living donors.
• 中分化肝細胞癌における成熟型動脈性血管の検討(Evaluation of mature arterial vessels in moderately differentiated hepatocellular carcinoma)

  藤田 展宏, 相島 慎一, 井口 友宏, 山元 英崇, 武冨 紹信, 本田 浩, 恒吉 正澄

  日本癌学会総会記事 67回 211 - 211 0546-0476 2008/09
• Liver metastasis with intraductal invasion originating from rectal cancer: Report of a case

  Hiroto Kayashima, Akinobu Taketomi, Yo-Ichi Yamashita, Yousuke Kuroda, Dai Kitagawa, Norifumi Harimoto, Eiji Tsujita, Yoshihiko Maehara

  SURGERY TODAY 38 (8) 765 - 768 0941-1291 2008/08 [Refereed][Not invited]
   

  We report a case of liver metastasis with intraductal invasion from colorectal cancer. The patient underwent abdominoperineal resection of the rectum for rectal cancer, and a computed tomography (CT) scan, done 4 years later, revealed a low-density lobular mass in the left lobe of the liver, with a tumor embolus in the second branch of the left bile duct (B2). Because the preoperative imaging findings showed an intraductal growth pattern, we performed a left lobectomy of the liver for intrahepatic cholangiocarcinoma (IHCC). Immunohistochemically, the carcinoma cells, including the intraductal growth, were focally positive for Cytokeratin (CK) 20, but negative for CK 7. This CK staining pattern suggested that the liver tumor was a metastasis from the previously resected rectal cancer. Thus, metastases from colorectal cancer can involve intraductal growth.
• Retroperitoneal well-differentiated inflammatory liposarcoma: a diagnostic dilemma

  Rinsaku Kawano, Akihiro Nishie, Kengo Yoshimitsu, Hiroyuki Irie, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Yasuhiro Ushijima, Daisuke Okamoto, Hidetake Yabuuchi, Akinobu Taketomi, Yunosuke Nishihara, Nobuhiro Fujita, Hiroshi Honda

  RADIATION MEDICINE 26 (7) 450 - 453 1862-5274 2008/08 [Refereed][Not invited]
   

  We present a case of retroperitoneal well-differentiated inflammatory liposarcoma that was extremely difficult to diagnose preoperatively. Computed tomography and magnetic resonance images showed a 5-cm homogeneous soft-tissue mass with a decreased apparent diffusion coefficient and without fat component in the retroperitoneum. Minimal fat stranding was detected around the mass. The preoperative working diagnosis was malignant lymphoma or inflammatory pseudotumor, whereas the final diagnosis after surgery was well-differentiated inflammatory liposarcoma. As a result, only a large component of lymphoid infiltration was recognized as a tumor preoperatively, and minimal fat stranding represented a component of lipoma-like liposarcoma. In this entity, a lipomatous component could easily be missed on radiologic imaging because of the conspicuity of lymphoid infiltration. We should consider the possibility of this variant when we evaluate a retroperitoneal tumor.
• Graft size, donor age, and patient status are the indicators of early graft function after living donor liver transplantation

  Tomoharu Yoshizumi, Akinobu Taketomi, Hideaki Uchiyama, Noboru Harada, Hiroto Kayashima, Yo-Ichi Yamashita, Yuji Soejima, Mitsuo Shimada, Yoshihiko Maehara

  LIVER TRANSPLANTATION 14 (7) 1007 - 1013 1527-6465 2008/07 [Refereed][Not invited]
   

  No reliable model for predicting early graft function and patient survival after living donor liver transplantation (LDLT) exists. The aim of this study was to establish a new formula for predicting early graft function and prognosis using technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy. The ratio of the hepatic uptake ratio of Tc-GSA to the clearance index of Tc-GSA (LHL/HH) was determined 7 days after LDLT. There were 22 patients with a ratio greater than 1.3 and 6 patients with a ratio less than 1.3. Graft function on the 14th postoperative day (POD) was compared between the 2 groups. A new formula to predict the LHL/HH score was established as follows: LHL/HH (predictive score) = 0.011 x graft weight (%) 0.016 x donor age - 0.008 x Model for End-Stage Liver Disease score - 0.15 X shunt (if present) + 1.757 (r(2) = 0.497, P < 0.01). This predicted LHL/HH ratio was compared to the graft function on POD 14 for 110 LDLT patients. The total bilirubin (TB) and prothrombin time international normalized ratio (PT-INR) in the group with an LHL/HH score >= 1.3 were lower than those in the group with an LHL/HH score < 1.3. The TB, PT-INR, and volume of ascites in the group with a predictive score >= 1.3 (n = 86) were lower than those in the group with a score < 1.3 (n = 24). The 6-month survival probability was improved in the group with a predictive score >= 1.3. In conclusion, this preoperative calculated LHL/HH score is correlated with graft function and short-term prognosis. Thus, this predictive model may allow transplant surgeons to use a living donor left lobe graft with greater confidence.
• The impact of surgical treatment and poor prognostic factors for patients with intrahepatic cholangiocarcinoma: Retrospective analysis of 60 patients

  Yo-Ichi Yamashita, Akinobu Taketomi, Kazutoyo Morita, Takasuke Fukuhara, Shigeru Ueda, Kensaku Sanefuji, Tomohiro Iguchi, Hiroto Kayashima, Keishi Sugimachi, Yoshihiko Maehara

  ANTICANCER RESEARCH 28 (4C) 2353 - 2359 0250-7005 2008/07 [Refereed][Not invited]
   

  Background: Intrahepatic cholangiocarcinoma (ICC) is a primary adenocarcinoma of the liver arising from the intrahepatic bile duct. Hepatectomy with extensive lymph node dissection is the standard treatment for ICC. Patients and Methods: Sixty patients with ICC who underwent hepatectomy in our institution between 1986 and 2005 were investigated to determine prognostic factors and to evaluate the impact of surgical treatment for ICC using univariate and multivariate analyses. Results: The overall survival rate of the RO resection group (n=43) was significantly higher than that of the RI/2 group (n=17). However, in patients with lymph node metastasis (n=24), RO resection had no survival impact. According to multivariate analysis, the independent factors of poor prognosis were: the presence of lymph node metastasis, lymphatic invasion, poor differentiation and RI/2 resection. Conclusion: RO resection can provide prolonged survival for patients with ICC. Patients with lymph node metastasis, lymphatic invasion, or poorly differentiated ICC have poor prognosis after operation and additional treatment, such as adjuvant chemotherapy, is recommended.
• Living donar live transplantation for hepatitis B associated liver diseases: A 10-year experience in a single center

  Toru Ikegami, Yuji Soejima, Ryuji Ohta, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (85) 1445 - 1449 0172-6390 2008/07 [Refereed][Not invited]
   

  Background/Aims: Hepatic failure associated with hepatitis B virus (HBV) is one of the main indications for living donor liver transplantation (LDLT). Methodology: Twenty-nine LDLTs, including liver cirrhosis due to HBV (LC-B) (n=17) and fulminant hepatitis B (FH-B) (n=12) were reviewed. Prophylaxis for reinfection was performed with a combination of lamivudine, or hepatitis B Immune globulin (HBIG) or adefovir, depending on the viral status. The changes in serological markers, recurrence and survival rate were examined. Results: There were 3 patients with re-emergencies of HBV surface antigen (HBsAg): suspension of HBIG for giving vaccination for HBV (n=1.), HBsAg positive donor (n=1) and non-compliance for HBIG (n=1). All patients with. YMDD mutants (n=9), except the case with HBsAg positive donor (n=1), were successfully protected by the triple therapy of lamivudine, adefovir and HBIG. No graft loss was due to the recurrence of HBV. Conclusion: The basic strategy using a combination of HBIG and antiviral agents gave acceptable long-term outcomes for LDLT for HBV associated liver diseases. The close monitoring of HBV viral after transplantation still crucial in managing these patients.
• Appraisal of hepatic resection in the treatment of hepatocellular carcinoma with severe thrombocytopenia

  Keishi Sugimachi, Yasuharu Ikeda, Morimasa Tomikawa, Akinobu Taketomi, Shuichi Tsukamoto, Katsumi Kawasaki, Shinji Yamamura, Daisuke Korenaga, Yoshihiko Maehara, Kenji Takenaka

  WORLD JOURNAL OF SURGERY 32 (6) 1077 - 1081 0364-2313 2008/06 [Refereed][Not invited]
   

  Background Hepatic resection for hepatocellular carcinoma (HCC) patients with liver cirrhosis and severe hypersplenic thrombocytopenia is risky and controversial. Methods From 1989 to 2005, 341 patients underwent hepatic resection for HCC in our hospital. Of these, 15 patients were concomitant with severe thrombocytopenia (platelet count, <= 5 x 10(4)/mm(3)), and their clinical outcomes were retrospectively reviewed. Results Among the 15 patients, 11 underwent hepatectomy alone and 4 underwent concomitant splenectomy. The mean preoperative platelet count was 4.2 +/- 0.8 x 10(4)/mm(3) (range, 1.9-5 x 10(4)/mm(3)). The surgical procedures performed were partial resection in five patients, subsegmentectomy in three, and segmentectomy in seven. A blood transfusion was required for 11 of 15 patients, and 8 of these received a platelet-rich plasma transfusion. With the exception of one patient who suffered from postoperative liver failure, all the patients had an uneventful postoperative course. The 3-year cumulative survival rate of these patients was comparable to those without thrombocytopenia. Conclusions Severe thrombocytopenia alone is not a contraindication for hepatectomy in patients with HCC associated with liver cirrhosis. For these patients, hepatic resection-hepatectomy alone or concomitant splenectomy-should be considered as a treatment option.
• Biliary neoplasia with extensive intraductal spread associated with liver cirrhosis: a hitherto unreported variant of biliary intraepithelial neoplasia

  Shinichi Aishima, Yunosuke Nishihara, Eiji Tsujita, Kenichi Taguchi, Yuji Soejima, Akinobu Taketomi, Yasuharu Ikeda, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HUMAN PATHOLOGY 39 (6) 939 - 947 0046-8177 2008/06 [Refereed][Not invited]
   

  We describe the histopathologic features of 2 cases of biliary neoplasia, with extensive intraductal spread arising in liver cirrhosis. The prevalence of this type of biliary neoplasia may be 0.4% from the review of 468 cases of cirrhotic liver. Histologic analysis revealed that the micropapillary proliferation of the atypical biliary epithelium composed of columnar cells with enlarged nuclei diffusely extended superficially from the septal intrahepatic bile duct to the reactive ductules associated with liver cirrhosis. Both cases exhibited prominent fibrous or sclerotic stroma near the biliary lesion. Immunohistochemical analysis revealed a characteristic cytokeratin and mucin expression pattern (CK7++, CK19++, CK20+, MUC1+/-, MUC2-, MUC5AC+, MUC6-). The tumor cytoplasm was focally positive for laminin gamma 2 together with linear staining of the basement membrane. Proliferative activity confirmed by Ki67 staining was relatively high. Both patients were disease-free for 3 years after the operation. We believe that the possibility of biliary neoplasia, with extensive intraductal spread should be considered to be a variant of biliary intraepithelial neoplasia. (C) 2008 Published by Elsevier Inc.
• Small-intestinal volvulus around the superior mesenteric artery as an extremely rare positioning-associated complication after percutaneous liver biopsy

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Noboru Harada, Hideo Uehara, Yo-ichi Yamashita, Yoshihiko Maehara

  SURGERY TODAY 38 (6) 576 - 577 0941-1291 2008/06 [Refereed][Not invited]
   

  Small-bowel volvulus around the superior mesenteric artery is a very unusual cause of small-intestinal obstruction, which may result in intestinal ischemia and necrosis. A 45-year-old woman, who had received a living-donor liver transplant with a right lobe graft for fulminant hepatic failure 5 years earlier, underwent a liver biopsy and was placed in the right decubitus position. Abdominal pain, high fever, tachycardia, and altered mental status developed quickly, suggesting abdominal sepsis. Computed tomography (CT) showed a "target sign," representing a counter-clockwise rotation of the mesenteric pedicle. However, without laparotomy, the symptoms subsided completely within 12 It by her lying strictly in the left decubitus position. A second CT scan showed an orthotopic untwisted jejunum. Although many complications associated with percutaneous liver biopsy have been described, to our knowledge this is the first report of positioning-associated intestinal volvulus after a liver biopsy.
• Donor age in living donor liver transplantation

  T. Ikegami, A. Taketomi, R. Ohta, Y. Soejima, T. Yoshizumi, M. Shimada, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 40 (5) 1471 - 1475 0041-1345 2008/06 [Refereed][Not invited]
   

  Background. We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Methods. Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age <= 50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age <= 50, n = 61). We compared post-LDLT graft functions. Results. Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group 0 and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Conclusion. Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT.
• Estimation of standard liver volume for Japanese adults

  T. Yoshizumi, A. Taketomi, H. Kayashima, Y. Yonemura, N. Harada, H. Ijichi, Y. Soejima, T. Nishizaki, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 40 (5) 1456 - 1460 0041-1345 2008/06 [Refereed][Not invited]
   

  Introduction. Accurate pretransplant estimation of the recipient's standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. Methods. We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 X body surface area [BSA] - 220), Urata (LV = 706.2 X BSA + 2.4), Noda (LV = 50.12 X BW0.78), Heinemann (LV = 1072.8 X BSA - 345.7), Vauthey (LV = 18.51 X BW + 191.8) and Yoshizumi (LV = 772 X BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. Results. Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P <.01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P <.05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the 3 CTV was greater than 1600 cm. When the Yoshizumi formula was applied, the number of donors with an acceptable difference (15%) between CTV and estimated LV was 55 (78.6%). Conclusions. The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates.
• One-step venous reconstruction for a right lobe graft with multiple venous orifices in living donor liver transplantation

  Yuji Soejima, Naoyuki Ueda, Takasuke Fukuhara, Tomoharu Yoshizumi, Toru Ikegami, Yoichi Yamashita, Keishi Sugimachi, Akinobu Taketomi, Yoshihiko Maehara

  LIVER TRANSPLANTATION 14 (5) 706 - 708 1527-6465 2008/05 [Refereed][Not invited]
  
• Characteristics of biliary reconstruction using a T-tube as compared with other methods in left-lobe adult living-donor liver transplantation

  Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuo Shimada, Yoshihiko Maehara

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 15 (3) 346 - 347 0944-1166 2008/05 [Refereed][Not invited]
  
• Living donor liver transplantation in a patient with giant hepatic hemangioma complicated by Kasabach-Merritt syndrome: Report of a case

  Makoto Meguro, Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Yo-Ichi Yamashita, Noboru Harada, Shinji Itoh, Koichi Hirata, Yoshihiko Maehara

  SURGERY TODAY 38 (5) 463 - 468 0941-1291 2008/05 [Refereed][Not invited]
   

  We herein present a case of unresectable giant hepatic hemangiomas with Kasabach-Merritt syndrome which was successfully treated by living donor liver transplantation using a left lobe graft. The patient was a 45-year-old woman who complained of abdominal distension. Two sessions of transarterial embolization were performed, but failed to reduce the size of the tumor. The hepatic tumors were thus judged untreatable and the only option for a cure was to offer living donor liver transplantation, because of the tumor size, its location, and the association with Kasabach-Merritt syndrome. A left lobe graft with the middle hepatic vein donated by her 47-year-old brother was transplanted under venovenous bypass. The postoperative course of the recipient was complicated by small-for-size graft syndrome, which developed after episodes of acute cellular rejection on postoperative day 8 and sepsis on day 31. The patient successfully recovered from the complications and was discharged on day 72, and she remains well at 10 months after transplantation. In conclusion, living donor liver transplantation was found to be an effective option for the treatment of a patient with unresectable giant hepatic hemangiomas complicated by Kasabach-Merritt syndrome.
• Stenotrophomonas maltophilia bacteremia after living donor liver transplantation: Report of a case

  Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara

  SURGERY TODAY 38 (5) 469 - 472 0941-1291 2008/05 [Refereed][Not invited]
   

  Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, nonfermentive, Gram-negative bacillus that is widespread in the environment. It is considered to be an organism with a limited pathogenic potential, which is rarely capable of causing diseases in humans other than in those who are in an immunocompromised state. In this study, we outline the case of a patient with Stenotrophomonas maltophilia bacteremia after living donor liver transplantation, which showed the clinical signs of severe sepsis and was resistant to almost all antibiotics. However, we successfully treated the patient with the antibiotics trimethoprim-sulfamethoxazole (TMP/SMX) and minocycline hydrochloride (MINO), and performed endotoxin-absorbing therapy using polymyxin B (PMX) to remove the endotoxin from Gram-negative bacillus as well as continuous hemodiafiltration (CHDF) to remove inflammatory cytokines. To the best of our knowledge, this is the first report on the treatment of Stenotrophomonas maltophilia bacteremia after living donor liver transplantation.
• Recurrence of intrahepatic cholangiocarcinoma nine years after surgical resection

  Dai Kitagawa, Akinobu Taketomi, Shinichi Aishima, Yosuke Kuroda, Tomonobu Gion, Ken Shirabe, Mitsuo Shimada, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (84) 1085 - 1088 0172-6390 2008/05 [Refereed][Not invited]
   

  This paper reports a rare case of intrahepatic cholangiocarcinoma (ICC) which recurred nine years after surgical resection. The patient underwent right hepatic trisegmentectomy with lymph node dissection and biliary tract reconstruction for a tumor in the right lobe of the liver. The patient was diagnosed with ICC, intraductal growth (IG) type. Nine years after the operation a rise of tumor markers and a recurrent lesion in the remnant liver were recognized and the patient underwent S2 subsegmentectomy with tumor thrombectomy and biliary tract reconstruction. The resected specimen showed well differentiated adenocarcinoma, which consisted of chiefly intraductal growth component. The patient is still alive 26 months after the second operation without recurrence. It is important to observe the patient carefully cosidering that it is possible for an IG type cholangiocarcinoma to recur a long time after surgical treatment, and surgical treatment for the recurrent tumor should be tried for long survival.
• [Liver transplantation for hepatocellular carcinoma: status quo and experience in Kyushu University].

  Yuji Soejima, Akinobu Taketomi, Toru Ikegami, Tomoharu Yoshizumi, Hideaki Uchiyama, Tomonobu Gion, Keishi Sugimachi, Shigeyuki Nagata, Yoshihiko Maehara

  Fukuoka igaku zasshi = Hukuoka acta medica 99 (5) 95 - 101 0016-254X 2008/05 [Refereed][Not invited]
  
• Left lobe living donor liver transplantation in an adult patient with situs inversus: technical considerations

  Yuji Soejima, Makoto Meguro, Akinobu Taketomi, Toru Ikegami, Yoichi Yamashita, Noboru Harada, Shinji Ito, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 21 (4) 384 - 389 0934-0874 2008/04 [Refereed][Not invited]
   

  Situs inversus (SI) is a rare congenital disorder involving a complete mirror image of the thoracic and abdominal organs. Living donor liver transplantation (LDLT) in SI cases poses particular challenges on account of its technical complexity, and only a few cases have been reported. Here, we present an adult with SI who was managed successfully by LDLT using a left lobe graft. Some technical modifications, including triangulated anastomosis of the hepatic vein, were required but no vascular graft was necessary. Graft function and vascular integrity were excellent throughout the postoperative course, although sepsis secondary to wound infection with methicillin -resistant Staphylococcus aureus developed. In conclusion, LDLT using a left lobe graft is a feasible procedure for patients with SI, even for adults. Therefore, this condition, while rare, should not be a contraindication for LDLT. Meticulous preoperative simulation and planning of the vascular reconstruction are important steps in LDLT for this rare anomaly.
• 免疫抑制療法抵抗性の拒絶反応における抗ドナー抗体の関与に関する検討

  永田 茂行, 岡野 慎士, 皆川 亮介, 内山 秀昭, 吉住 朋晴, 副島 雄二, 武冨 紹信, 居石 克夫, 前原 喜彦

  日本外科学会雑誌 (一社)日本外科学会 109 (臨増2) 473 - 473 0301-4894 2008/04
• Living donor liver transplantation using dual grafts from two donors: A feasible option to overcome small-for-size graft problems?

  Y. Soejima, A. Taketomi, T. Ikegami, T. Yoshizumi, H. Uchiyama, Y. Yamashita, M. Meguro, N. Harada, M. Shimada, Y. Maehara

  AMERICAN JOURNAL OF TRANSPLANTATION 8 (4) 887 - 892 1600-6135 2008/04 [Refereed][Not invited]
   

  Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks.
• Living donor liver transplantation for fulminant hepatic failure from ABO-incompatible donors

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 21 (3) 284 - 285 0934-0874 2008/03 [Refereed][Not invited]
  
• Extended hemi-hepatectomy with portal vein reconstruction in a patient with situs ambiguous.

  Sugimachi K, Ikeda Y, Taketomi A, Tomikawa M, Kawasaki K, Korenaga D, Maehara Y, Takenaka K

  Case reports in gastroenterology 1 2 (1) 76 - 82 2008/03 [Refereed][Not invited]
  
• Defective endothelial nitric oxide synthase signaling is mediated by rho-kinase activation in rats with secondary biliary cirrhosis

  Go Anegawa, Hirofumi Kawanaka, Daisuke Yoshida, Kozo Konishi, Shohei Yamaguchi, Nao Kinjo, Akinobu Taketomi, Makoto Hashizume, Hiroaki Shimokanva, Yoshihiko Maehara

  HEPATOLOGY 47 (3) 966 - 977 0270-9139 2008/03 [Refereed][Not invited]
   

  In liver cirrhosis, down-regulation of endothelial nitric oxide synthase (eNOS) has been implicated as a cause of increased intrahepatic resistance. We investigated whether Rho-kinase activation is one of the molecular mechanisms involved in defective eNOS signaling in secondary biliary cirrhosis. Liver cirrhosis was induced by bile duct ligation (BDL). We measured mean arterial pressure (MAP), portal venous pressure (PVP), and hepatic tissue blood flow (HTBF) during intravenous infusion of saline (control), 0.3, 1, or 2 mg/kg/hour fasudil for 60 minutes. In BDL rats, I and 2 mg/kg/hour fasudil significantly reduced PVP by 20% compared with controls but had no effect on HTBF. MAP was significantly reduced in response to 2 mg/kg/hour fasudil. In the livers of BDL rats, I and 2 mg/kg/hour fasudil significantly suppressed Rho-kinase activity and significantly increased eNOS phosphorylation, compared with controls. Fasudil significantly reduced the binding of serine/threonine Akt/PKB (Akt) to Rho-kinase and increased the binding of Akt to eNOS. These results show in secondary biliary cirrhosis that (1) Rho-kinase activation with resultant eNOS down-regulation is substantially involved in the pathogenesis of portal hypertension and (2) Rho-kinase might interact with Akt and subsequently inhibit the binding of Akt to eNOS.
• Biliary epithelial cells and primary biliary cirrhosis: The role of liver-infiltrating mononuclear cells

  Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Yasunj Nakanuma, Hiromi Ishibashi, Carlo Selmi, M. Eric Gershwin

  HEPATOLOGY 47 (3) 958 - 965 0270-9139 2008/03 [Refereed][Not invited]
   

  Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DR alpha (HLA-DR alpha) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DR alpha. Conclusion: We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC.
• Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

  Shinichi Aishima, Yunosuke Nishihara, Tomohiro Iguchi, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  MODERN PATHOLOGY 21 (3) 256 - 264 0893-3952 2008/03 [Refereed][Not invited]
   

  Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P = 0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P = 0.0315 and P = 0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/ 38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P = 0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P = 0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P = 0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.
• Living donor liver transplantation for acute liver failure: A 10-year experience in a single center

  Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Kensaku Sanefuji, Hiroto Kayashima, Mitsuo Shimada, Yoshihiko Maehara

  JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 206 (3) 412 - 418 1072-7515 2008/03 [Refereed][Not invited]
   

  BACKGROUND: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. STUDY DESIGN: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. RESULTS: Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilson's disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2 +/- 9.2% in left lobe grafts and 50.5 +/- 3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/- 18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. CONCLUSIONS: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated.
• Liver transplantation for hepatocellular carcinoma

  Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yo-Ichi Yamashita, Yoshihiko Maehara

  JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 15 (2) 124 - 130 0944-1166 2008/03 [Refereed][Not invited]
   

  The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC.
• Successful treatment for a patient with hemophagocytic syndrome after a small-for-size graft liver transplantation

  Tomoharu Yoshizumi, Akinobu Taketomi, Hiroto Kayashima, Noboru Harada, Hideaki Uchiyama, Yo-ichi Yamashita, Toru Ikegami, Yuji Soejima, Takashi Nishizaki, Mitsuo Shimada, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (82-83) 359 - 362 0172-6390 2008/03 [Refereed][Not invited]
   

  Hemophagocytic syndrome (HPS) is a hematological disorder caused by activated T lymphocytes, which leads to the proliferation of stimulated macrophages that phagocytose and destroy circulating blood elements and their precursors within bone marrow, and lead to the further production of inflammatory cytokines. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports concerning HPS after LDLT; however, its prognosis is disappointingly poor. In particular, there is no report of treated HPS developed after LDLT using small-for-size left lobe grafts. We herein report a case of HPS in a 63-year old woman who underwent LDLT using left lobe graft weighing only 330g. The HPS was diagnosed on postoperative day 13, and was successfully treated using a combination of intravenous immunoglobulin, granulocyte colony stimulating factor, conversion of calcineurin inhibitor and steroid pulse. The trigger of HPS may not only be systemic infection, but also hypercytokinemia caused by various factors. HPS is a fatal complication in immunologically compromised patients; however, early and accurate diagnosis could lead to an adequate treatment and improve the outcome.
• Living donor liver transplantation with extra-small graft; Inflow modulation using splenectomy and temporary portocaval shunt

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Kensaku Sanefuji, Hiroto Kayashima, Noboru Harada, Yo-ichi Yamashita, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (82-83) 670 - 672 0172-6390 2008/03 [Refereed][Not invited]
   

  In living donor liver transplantation in adults, a strategy to manage unexpected small graft is essential. The patient was a 47-year-old female with end-stage liver disease secondary to hepatitis C with hepatocellular carcinoma, and the donor was a 20-years-old female. Although the estimated left lobe graft volume was 379g and 35.8% of the standard liver volume of the recipient, the actual volume was just 250g, representing only 23% of the standard liver volume. After implantation of this graft, a splenectomy followed by end-to-side portocaval shut was done, both for modulating excessive portal inflow to the small graft. Despite the excellent mitial graft function with hepatopetal portal flow and an excellent gold-colored bile from the graft, the graft portal flow decreased with liver regeneration 4 days after transplantation. So the closure of the portocaval shunt was carried out. Since then there was a good postoperative course without any sign of small graft syndrome. She was discharged from the hospital at 21 days after transplantation. This type of inflow modulation may allow us to manage such an extra-small graft. However, careful post-transplant monitoring of the portal flow is essential for gaining an acceptable outcome.
• Transient Elastography for the prediction of oxaliplatin-associated liver injury in colon cancer patients: A preliminary analysis

  Eiji Oki, Yoshihiro Kakeji, Akinobu Taketomi, Yoichi Yamashita, Kippei Ohgaki, Noboru Harada, Tomohiro Iguchi, Kotaro Shibahara, Noriaki Sadanaga, Masaru Morita, Yoshihiko Maehara

  Journal of Gastrointestinal Cancer 39 (1-4) 82 - 85 1941-6628 2008/03 [Refereed][Not invited]
   

  Objective: The prognosis of advanced colon cancer has improved significantly over the last decade since new chemotherapy regimens including oxaliplatin have been developed. However, oxaliplatin-induced liver injury and characterized hepatic hemostatic status can occur after chemotherapy. The assessment of this type of liver injury is often difficult. Methods: Elastography (Fibroscan™) was used to evaluate liver injury in five cases before and after 5-FU, leucovorin, and oxaliplatin combination (FOLFOX) treatment. Results: A clear change was observed in the stiffness of liver after chemotherapy within 48 h, and the hepatic stiffness was normalized in most cases after 2 weeks. Among the five patients, one patient showed aberrant elevation after a FOLFOX treatment, and the patient showed liver injury pathologically. Conclusion: Elastography is a good tool for evaluating hepatic injury after FOLFOX treatment. © 2009 Humana Press Inc.
• Impact of donor age and recipient status on left-lobe graft for living donor adult liver transplantation

  Tomoharu Yoshizumi, Akinobu Taketomi, Yuji Soejima, Hideaki Uchiyama, Toru Ikegami, Noboru Harada, Hiroto Kayashima, Yo-Ichi Yamashita, Mitsuo Shimada, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 21 (1) 81 - 88 0934-0874 2008/01 [Refereed][Not invited]
   

  Donor safety is the priority when performing a living donor adult liver transplantation (LDALT). We herein present our findings using left-lobe graft in LDALT. Data on 119 recipients who underwent the LDALT, and on 119 donors who underwent extended left lobectomy were reviewed. The recipients were divided into groups above (n = 19) and below (n = 100) 50 years of donor age, into groups above (n = 63) and below (n = 56) 40% of graft size (graft volume/standard liver volume, GV/SLV), and above (n = 25) and below (n = 94) 20 of pre-operative model for end-stage liver disease (MELD). Total bilirubin (TB), volume of ascites, prothrombin time international normalized ratio on postoperative day 14 or survival rates were compared. TB (mg/dl) or volume of ascites (ml) of the group in donor age < 50 years was better than that of the group in donor age >= 50 years (7.4 vs. 14.7 or 788 vs. 1379, P < 0.001 or P < 0.005, respectively). The graft and patient survival rates of the lower MELD group tended to be better than that of the higher MELD group. LDALT can be safely performed using a left-lobe graft. However, when using the graft from the donor >= 50 years, especially for the recipients with the MELD >= 20, the indications should be carefully discussed.
• Meso-systemic shunt for middle hepatic vein reconstruction in right lobe living donor liver transplantation

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Yoshihiko Maehara

  TRANSPLANT INTERNATIONAL 21 (1) 94 - 95 0934-0874 2008/01 [Refereed][Not invited]
  
• Arterial blood supply of hepatocellular carcinoma and histologic grading: radiologic-pathologic correlation.

  Asayama Y, Yoshimitsu K, Nishihara Y, Irie H, Aishima S, Taketomi A, Honda H

  AJR. American journal of roentgenology 1 190 (1) 28 - 34 1546-3141 2008/01 [Refereed][Not invited]
  
• Radiologic detectability of minute portal venous invasion in hepatocellular carcinoma

  Akihiro Nishie, Kengo Yoshimitsu, Yoshiki Asayama, Hiroyuki Irie, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Tomohiro Nakayama, Daisuke Kakihara, Yunosuke Nishihara, Akinobu Taketomi, Hiroshi Honda

  AMERICAN JOURNAL OF ROENTGENOLOGY 190 (1) 81 - 87 0361-803X 2008/01 [Refereed][Not invited]
   

  OBJECTIVE. The objective of this study was to evaluate whether minute portal venous invasion in hepatocellular carcinoma (HCC) can be diagnosed radiologically. MATERIALS AND METHODS. CT hepatic arteriography and CT with arterioportography ( CTAP) of 15 patients with minute portal venous invasion ( group 1) and 30 patients without it ( group 0) were evaluated. An area showing low attenuation on CTAP and high attenuation on CT hepatic arteriography around the tumor was defined as an area of peritumoral hemodynamic change. The shape and size of the area were compared between the two groups. The ratio of the area of peritumoral hemodynamic change volume to tumor volume ( area volume-tumor volume ratio) was used as an indicator of the size of the area of peritumoral hemodynamic change and was categorized as one of three grades: grade I, 10% or less; grade II, between 10% and 30%; and grade III, 30% or more. The detectability of minute portal invasion was assessed when grade III was considered as an indicator. Each comparison was also made independently when the tumor diameter either was limited to less than 3 cm or was 3 cm or more. RESULTS. Three types of area of peritumoral hemodynamic change were identified: wedge-shaped, belt-shaped or irregular, and linear. No significant difference in the frequency of each type of area of peritumoral hemodynamic change was observed between the two groups. The area volume-tumor volume ratio in group 1 was larger than that in group 0, with statistical significance when the tumor diameter was less than 3 cm ( p = 0.046). Positive and negative predictive values were 71.4% and 75.0%, respectively, when the tumor diameter was less than 3 cm. CONCLUSION. The area of peritumoral hemodynamic change in HCC patients with minute portal invasion ( group 1) may be larger than in those without it ( group 0), especially when tumors are small.
• Extracorporeal hepatic resection for unresectable giant hepatic hemangiomas

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Hiroto Kayashima, Kensaku Sanefuji, Tomoharu Yoshizumi, Noboru Harada, Yo-Ichi Yamashita, Yoshihiko Maehara

  LIVER TRANSPLANTATION 14 (1) 115 - 117 1527-6465 2008/01 [Refereed][Not invited]
  
• Successful management of chylous ascites after living donor liver transplantation with somatostatin

  Hideki Ijichi, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yusuke Yonemura, Yoshihiko Maehara

  LIVER INTERNATIONAL 28 (1) 143 - 145 1478-3223 2008/01 [Refereed][Not invited]
   

  Chylous ascites is a rare complication following liver transplantation. A variety of treatment options have been proposed for the management of chylous ascites; however, their effectiveness following a liver transplant is unknown. A 40-year-old woman who underwent living donor liver transplantation for primary biliary cirrhosis developed chylous ascites 21 days after the transplant. A conventional treatment consisting of a low-fat diet with total parenteral nutrition failed to treat the complication for 104 days. However, the use of somatostatin in combination with total parenteral nutrition resulted in a rapid falloff in chyle output without any adverse effects. Somatostatin and total parenteral nutrition are an effective option for the treatment of chylous ascites after living donor liver transplantation.
• Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation

  Noboru Harada, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Toru Ikegami, Yo-ichi Yamashita, Shinji Itoh, Yosuke Kuroda, Yoshihiko Maehara

  TRANSPLANTATION 85 (1) 69 - 74 0041-1337 2008/01 [Refereed][Not invited]
   

  Background. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. Methods. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who under-went both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness m easured by the transient elastography. Results. The fibrosis grades were as follows: F0, n=22; F1, n = 13; F2, n = 9; F3, n= 7; and F4, n= 5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F >= 1, 9.9 kPa for F > 2, 15.4 kPa for F >= 3, and 26.5 kPa for F >= 4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F >= 2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. Conclusions. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation.
• Living donor liver transplantation for acute liver failure using left lobe grafts

  Toru Ikegami, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Machara

  TRANSPLANTATION 85 (1) 160 - 161 0041-1337 2008/01 [Refereed][Not invited]
  
• Hilar anatomical variations in living-donor liver transplantation using right-lobe grafts

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hiroto Kayashima, Shinji Itoh, Yo-ichi Yamashita, Yoshihiko Maehara

  DIGESTIVE SURGERY 25 (2) 117 - 123 0253-4886 2008 [Refereed][Not invited]
   

  Background: Living-donor liver transplantation using a right-lobe graft has increased the frequency of hilar anatomical variations despite its advantage of a larger graft volume. Methods: Sixty-seven living-donor liver transplantations using right-lobe grafts are reviewed, regarding the surgical anatomy of hilar vascular and biliary systems. Results: The portal anatomy was classified into four types. The incidence of double portal vein was 6.0% (n = 4), and for such cases a unified orifice (n = 1) or a Y-graft (n = 3) was used for reconstruction. The arterial system was classified into five types. The incidence of arterial complications was 6.0% (n = 4), all of which occurred in cases where the graft artery was connected to the recipient's right hepatic artery. The biliary system was classified into four types. The incidence of a double bile duct was 7.5% (n = 5), and that of a unified one was 29.8% (n = 20). Hepaticojejunostomy was more prone to biliary sepsis (25.0%) and bile leakage (18.8%) than duct-to-duct connection (0 and 2%, respectively). Conclusion: Hilar anatomi-cal variations in right-lobe living-donor liver transplantation could be managed after preoperative detailed evaluation of the graft and intraoperative appropriate surgical decision and techniques. Copyright (c) 2008 S. Karger AG, Basel.
• B-RTO for ectopic variceal bleeding after living donor liver transplantation

  Nao Kinjo, Hirofumi Kawanaka, Morimasa Tomikawa, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Shohei Yamaguchi, Daisuke Yoshida, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 55 (81) 241 - 243 0172-6390 2008/01 [Refereed][Not invited]
   

  Gastrointestinal bleeding (GIB) is a serious gas-troenterological complication after orthotropic liver transplantation, as well as living donor liver transplantation (LDLT). Although ectopic varices are rare causes of GIB, they may lead to life-threatening bleeding and it is difficult to diagnose them. We herein report a rare case of a jejunal variceal bleeding in a recipient five years after LDLT for primary sclerosing cholangitis with successful result by balloon-occluded retrograde transvenous obliteration (B-RTO).
• 35. 生体肝移植術時に門脈血流確保が困難であった胆道閉鎖症の1例(一般演題,第34回日本胆道閉鎖症研究会)

  高橋 由紀子, 西本 祐子, 林田 真, 佐伯 勇, 田尻 達郎, 田口 智章, 吉住 朋晴, 副島 雄二, 武冨 紹信, 前原 喜彦

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 44 (2) 206 - 207 2008
• 34.一次的肝移植を施行した胆道閉鎖症の1例(一般演題,第34回日本胆道閉鎖症研究会)

  西本 祐子, 高橋 由紀子, 松浦 俊治, 林田 真, 佐伯 勇, 田尻 達郎, 田口 智章, 副島 雄二, 武富 紹信, 前原 喜彦, 松尾 進

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 44 (2) 206 - 206 2008
• P008.一次的肝移植を施行した胆道閉鎖症の1例(第45回日本小児外科学会九州地方会)

  松浦 俊治, 西本 祐子, 高橋 由紀子, 林田 真, 佐伯 勇, 田口 智章, 副島 雄二, 武富 紹信, 前原 喜彦, 松尾 進

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 44 (6) 851 - 851 2008
• A case of hepatocellular carcinoma resected after improvement of liver function by balloon-occluded retrograde transvenous obliteration

  Kazutoyo Morita, Akinobu Taketomi, Yo-Ichi Yamashita, Takasuke Fukuhara, Hiroto Kayashima, Yousuke Kuroda, Shinji Itoh, Kouzou Konishi, Hirofumi Kawanaka, Yoshihiko Maehara

  Japanese Journal of Gastroenterological Surgery 41 (4) 418 - 423 1348-9372 2008 [Refereed][Not invited]
   

  Hepatocellular carcinoma with liver cirrhosis is often unresectable due to liver dysfunction. A 82-year-old man had two hepatocellular carcinomas measuring 2.5cm at S6 and 1cm at S8 of the liver. Despite transcatheter arterial chemoembolization (TACE) for these carcinomas, local recurrence was seen at S6, TACE repeated, and local recurrence seen again. He had severe liver dysfunction (Child-Pugh 8 Grade B, and liver damage C) and a huge gastro-renal shunt. Balloon-occluded retrograde transvenous obliteration (B-RTO) was conducted to increase portal flow to the liver and improve liver function. After B-RTO, liver function improved to Child-Pugh 6 Grade A, and liver damage B. Partial hepatic resection (S6) was successful and the man was discharged on postoperative day 14 without postoperative complications. The obliteration of portosystemic shunt using B-RTO makes it possible to conduct hepatic resection for hepatocellular carcinoma in patients with severe liver dysfunction. This strategy is especially useful in the treatment of TACE resistant carcinoma. ©2008 The Japanese Society of Gastroenterological Surgery.
• HCV陽性肝移植の現状と展望

  高田 泰次, 上田 佳秀, 武冨 紹信, 丸橋 繁

  今日の移植 (株)日本医学館 21 (1) 69 - 88 0916-0094 2008/01 [Refereed][Not invited]
  
• Arterial blood supply of hepatocellular carcinoma and histologic grading: Radiologic-pathologic correlation

  Yoshiki Asayama, Kengo Yoshimitsu, Yunosuke Nishihara, Hiroyuki Irie, Shinichi Aishima, Akinobu Taketomi, Hiroshi Honda

  AMERICAN JOURNAL OF ROENTGENOLOGY 190 (1) W28 - W34 0361-803X 2008/01 [Refereed][Not invited]
   

  OBJECTIVE. The objective of our study was to clarify the sequential changes of arterial blood supply during the development of hepatocellular carcinoma (HCC) with an emphasis on its late stage. MATERIALS AND METHODS. Sixty HCC nodules were confirmed at pathology in 59 patients who had undergone CT hepatic arteriography and CT during arterioportography (CTAP). Lesions were classified into one of the four groups: group 1, nodules that appeared to show preserved portal perfusion on CTAP and showed hypo- or isoattenuation on CT hepatic arteriography; group 2, very hyperattenuating on CT hepatic arteriography; group 3, hyperattenuating on CT hepatic arteriography; and group 4, hypo- or isoattenuating on CT hepatic arteriography. Groups 2, 3, and 4 showed the portal perfusion defect on CTAP. These hemodynamic patterns were compared among different histologic grades. We also examined the number of unpaired arteries and the Ki-67 labeling index of the tumor pathologically. RESULTS. The numbers of lesions in each group were as follows for groups 1, 2, 3, and 4, respectively: 17, one, two, and 0 well-differentiated HCCs; 0, 10, nine, and one moderately differentiated HCC; and 0, three, 12, and five poorly differentiated HCCs. The lesions showed significantly different hemodynamic patterns among different histologic grades (Cramer's V = 0.6919, p < 0.0001). The number of unpaired arteries showed a strong correlation with Ki-67 labeling index in well-differentiated HCC and moderately differentiated HCC (rho = 0.673, p < 0.0001) and a moderate inverse correlation with Ki-67 labeling index in poorly differentiated HCC (rho = - 0.540, p = 0.0185). CONCLUSION. In the late stage of HCC development, the arterial blood supply significantly decreases as the histologic grade progresses.
• Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression

  Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Tornohiro Iguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HUMAN PATHOLOGY 38 (12) 1819 - 1825 0046-8177 2007/12 [Refereed][Not invited]
   

  Aquaporin-1 (AQP-1) has been found to be important in bile formation across cell membranes of the biliary epithelium, and thus it has been suggested that AQP-1 is involved it) the pathogenesis of hepatobiliary disease. To clarify the role of AQP-1 in the development of intrahepatic cholangiocarcinoma, we determined AQP-1 expression in the normal bile duct, 21 cases of biliary dysplasia, and in 112 cases of intrahepatic cholangiocarcinoma by immunohistochemical analysis. Mucus core protein 5AC expression, a poor prognostic marker of intrahepatic cholangiocarcinoma, was also assessed in intrahepatic cholangiocarcinoma, cases. High (> 50%) expression of AQP-1 was detected in 16% (9/58) of the normal large bile ducts examined, and in 48% (10/21) of the biliary dysplasia samples originating from large bile ducts. High (> 50%), low (<= 50%), and negative AQP-1 expression was observed in 46 (41%),20 (19%), and 46 (41%) cases of intrahepatic cholangiocarcinoma, respectively. Large tumor size (> 40 mm) and poorly differentiated histology were significantly more prevalent in the negative AQP-1 group than in the high AQP-1 group. Low or negative AQP-1 expression was associated with positive lymph node metastasis (P = .0001). AQP-1 expression was found to inversely correlate with that of mucus core protein 5AC, and their distributions tended to be complementary. The low and negative AQP-1 expression was an independent prognostic factor by multivariate survival analysis. We concluded that AQP-1 is up-regulated in biliary dysplasia, as compared with in the normal large bile duct, and down-regulation of AQP-1 is associated with mucin production and aggressive progression of intrahepatic cholangiocarcinoma. (c) 2007 Elsevier Inc. All rights reserved.
• Clinical usefulness of biliary scope for Pringle's maneuver in laparoscopic hepatectomy

  Shin-Ichiro Maehara, Eisuke Adachi, Mitsuo Shimada, Akinobu Taketomi, Ken Shirabe, Shinji Tanaka, Takashi Maeda, Keisuke Ikeda, Hidefurni Higashi, Yoshihiko Maehara

  JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 205 (6) 816 - 818 1072-7515 2007/12 [Refereed][Not invited]
  
• Successful ABO incompatible living donor liver transplantation in a patient with high isoagglutinin titer using high-dose intravenous immunoglobulin

  T. Ikegami, A. Taketomi, Y. Soejima, T. Iguchi, K. Sanefuji, H. Kayashima, T. Yoshizumi, N. Harada, Y. Maehara

  TRANSPLANTATION PROCEEDINGS 39 (10) 3491 - 3494 0041-1345 2007/12 [Refereed][Not invited]
   

  The optimal management in living donor liver transplantation using an ABO incompatible donor with a high isoagglutinin titer is still uncertain. Our patient was a 20-year-old woman with fulminant hepatitis. The only available donor was her 54-year-old father-in-law of an incompatible blood type. The initial isoagglutinin titer was 2048X. She received 375 mg/m(2) of anti-CD20 antibody 3 days before the living donor liver transplantation with concomitant splenectomy. Despite daily plasma exchanges after transplantation, the isoagglutinin titer started to shoot up to its maximum value of 2048X, with a sudden decline in the bile output. High-dose intravenous immunoglobulin (0.6 g/kg) was given after the plasma exchanges; thereafter, her liver function tests stabilized without a further increase in the isoagglutinin titer. We showed the effectiveness of high-dose intravenous immunoglobulin for the management of the rebound elevation of isoagglutinin titer. The combination of anti-CD20 antibody and daily plasma exchanges seemed ineffective for such a situation. This strategy might be another management option for ABO incompatible liver transplantation.
• Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor

  Yuji Soejima, Mitsuo Shimada, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Makoto Nakamuta, Yoshihiko Maehara

  LIVER INTERNATIONAL 27 (9) 1282 - 1286 1478-3223 2007/11 [Refereed][Not invited]
   

  Background/Aims: Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). Method: Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. Results: To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. Conclusions: Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis.
• Explanted portal vein grafts for middle hepatic vein tributaries in living-donor liver transplantation

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara

  TRANSPLANTATION 84 (7) 836 - 841 0041-1337 2007/10 [Refereed][Not invited]
   

  Background. The availability of a venous graft is limited in the setting of living donor liver transplantation (LDLT), and the management of the middle hepatic vein middle hepatic vein tributaries in right lobe LDLT still remains controversial. Methods. Twenty-three right lobe LDLT grafts, with the reconstruction of middle hepatic vein tributaries using the explanted portal veins from the explanted livers, were evaluated for the patency, postLDLT liver function tests, and graft survival. Results. The methods of outflow reconstruction were classified into three types: the interposition of the graft to the middle/left hepatic vein (n=12), to the vena cava (n=9), and to the vena cava as a co-orifice with the graft right hepatic vein (n=2). The 1- and 3-year patency rates were 76.7% and 76.7% respectively, with the graft occlusion in five cases. The occluded cases (n=5) had significantly higher aspartate aminotransferase and alanine transaminase levels as compared with those of patent cases (n=18) at 4 weeks after transplantation (P < 0.01). However, there was no significant difference in the total bilirubin and prothrombin time in either group during the observation periods. The 1- and 3-year graft survival rates were 91.1% and 91.1%, respectively. In addition, there was no graft loss due to occlusion. Conclusion. The use of the recipient's explanted full-length hilar portal vein for the reconstruction of the middle hepatic vein tributaries is thus considered to be a feasible and valuable strategy in the setting of a right lobe LDLT, where appropriate vascular grafts are not always available.
• One orifice vein reconstruction in left liver plus caudate lobe grafts

  Toru Ikegami, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara

  TRANSPLANTATION 84 (8) 1065 - 1065 0041-1337 2007/10 [Refereed][Not invited]
  
• Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child

  Makoto Hayashida, Keiko Ogita, Toshiharu Matsuura, Yukiko Takahashi, Yuko Nishimotol, Shouichi Ohga, Toshiro Hara, Yuji Soejima, Akinobu Taketorni, Yoshihiko Maehara, Kenichi Kohash, Masazumi Tsuneyosh, Tornoaki Taguchi

  PEDIATRIC TRANSPLANTATION 11 (6) 671 - 675 1397-3142 2007/09 [Refereed][Not invited]
   

  PTLD is a serious complication of immunosuppression in solid organ transplant recipients. The incidence of PTLD is significantly higher in pediatric recipients than in adult because children are often EBV-seronegative and they may develop primary EBV infection after transplantation. We herein describe a case of GI-PTLD who achieved a complete remission by prolonged rituximab, a chimeric monoclonal antibody against CD20, mono-therapy. A one-yr-old female underwent a LDLT for liver failure after having previously undergone the Kasai procedure for billary atresia. At sixty days following the transplantation. GI-PTLD developed. Withdrawal of immunosuppression and a Surgical resection were thus performed. A histopathological examination of tumor revealed atypical medium to large cell lymphoid proliferation with strong CD20 immunopositivity indicating their B-cell origin. Polymorphic PTLD was diagnosed. Rituximab was administered at a dose of 375 mg/m(2) once a week, and the monotherapy resulted in a complete remission after 34 administrations. Based on this case, rituximab appears to be beneficial as a first-line therapy for PTLD.
• Hepatitis B vaccination after living donor liver transplantation

  Yuji Soejima, Toru Ikegami, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Noboru Harada, Yoichi Yamashita, Yoshihiko Maehara

  LIVER INTERNATIONAL 27 (7) 977 - 982 1478-3223 2007/09 [Refereed][Not invited]
   

  Background: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown. Method: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed. Results: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non- responders (44.4 years, P < 0.05). None had side effects or hepatitis B infection during the study period. Conclusions: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.
• Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis

  Akira Kawano, Shinji Shimoda, Takashi Kamihira, Fumihiko Ishikawa, Hiroaki Niiro, Yuji Soejima, Akinobu Taketomi, Yoshihiko Maehara, Minoru Nakamura, Atsumasa Komori, Kiyoshi Migita, Hiromi Lshibashi, Miyuki Azuma, M. Eric Gershwin, Mine Harada

  JOURNAL OF IMMUNOLOGY 179 (5) 3315 - 3324 0022-1767 2007/09 [Refereed][Not invited]
   

  Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2(163-176-) We studied the ability of eight T cell clones (TCC) specific for PDC-E2(163-176) to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2,(163-176), an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDCE2(34-47)), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2(163-176), E. coli OGDC-E2(34-47)) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation-dependent responses to OGDGE2 become anergic to PDGE2 when preincubated with mimic, even if costimulation is independent for PDGE2(163-176), Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2(163-176-)pulsed L-DR53 but became anergic using L-DR53 pulsed with PDGE2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBCspecific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen.may restore rather than break peripheral tolerance.
• Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

  Yo-Ichi Yamashita, Kengo Fukuzawa, Akinobu Taketomi, Shinichi Aishima, Tomoharu Yoshizumi, Hideaki Uchiyama, Eiji Tsujita, Norifumi Harimoto, Noboru Harada, Kenzo Wakasugi, Yoshihiko Maehara

  World journal of surgical oncology 5 98 - 98 1477-7819 2007/08/28 [Refereed][Not invited]
   

  BACKGROUND: Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established. CASE PRESENTATION: We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. CONCLUSION: It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct.
• Usefulness of the long-axis and short-axis reformatted images of multidetector-row CT in evaluating T-factor of the surgically resected pancreaticobiliary malignancies

  Daisuke Kakihara, Kengo Yoshimitsu, Hiroyuki Irie, Tsuyoshi Tajima, Yoshiki Asayama, Masakazu Hirakawa, Kousei Ishigami, Koji Yamaguchi, Akinobu Taketomi, Yunosuke Nishihara, Hiroshi Honda

  EUROPEAN JOURNAL OF RADIOLOGY 63 (1) 96 - 104 0720-048X 2007/07 [Refereed][Not invited]
   

  Purpose: To evaluate the diagnostic efficacy of curved planar reformations along the duct (long-axis CPR) and series of reformations perpendicular to the duct (short-axis MPR) in evaluating T-factors of pancreaticobiliary malignancy. Materials and methods: Twenty-five patients with surgically proven pancreaticobiliary malignancy (12 bile duct cancers and 13 pancreas cancers) were evaluated. A dynamic study was performed with multidetector-row CT with four detectors, and reconstructed with 1 mm thickness and intervals. Tracing the center of the duct system on axial images, long-axis CPR images and serial short-axis MPR images were obtained. Two radiologists interpreted the T factor of the diseases three times: session (1), axial images only; session (2), axial, coronal and sagittal multiplanar reformation images; and session (3), axial, long-axis CPR, and short-axis MPR images. Receiver operating characteristic curves were analyzed. Results: In evaluations of bile duct cancer, Az values of (3) (0.95, 0.92) were higher than those of (1) (0.89, 0.88) and (2) (0.92, 0.89), with some significant differences. In evaluations of pancreas cancer, Az values of all interpretations were almost equal. Conclusion: Long-axis CPR and short-axis MPR images were suggested to be useful as additional images to the original axial images in evaluating the local extension of bile duct carcinomas. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
• 14-3-3 sigma negatively regulates the cell cycle, and its down-regulation is associated with poor outcome in intrahepatic cholangiocarcinoma

  Yousuke Kuroda, Shinichi Aishima, Akinobu Taketomi, Yunosuke Nishihara, Tomohiro Iguchi, Kenichi Taguchi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HUMAN PATHOLOGY 38 (7) 1014 - 1022 0046-8177 2007/07 [Refereed][Not invited]
   

  The 14-3-3 sigma gene has been implicated in G2/M cell cycle arrest by p53, and the loss of 14-3-3 sigma protein expression has been reported in diverse human cancers. However, the role of 14-3-3 sigma in the signaling pathway of the cell cycle in the progression of intrahepatic cholangiocarcinoma has not been well understood. To clarify the role of 14-3-3 sigma, we examined the protein expressions of 14-3-3 sigma, cyclin B1, and p53 in 93 cases of intrahepatic cholangiocarcinoma by immunohistochemical staining. We also examined the correlation between these expressions and survival rate and clinicopathologic factors such as sex, age, tumor grade (ie, pathologic differentiation, tumor size, lymphatic permeation, vascular invasion, perineural invasion, lymph node metastasis), and tumor stage. Positive 14-3-3 sigma protein expression (> 30% of tumor cells) was observed in 67.7% (63/93) of cases of intrahepatic cholangiocarcinoma and was inversely correlated with cyclin B 1 expression. No correlation was found between 14-3-3 sigma expression and p53 expression or clinicopathologic factors; however, decreased 14-3-3 sigma expression was an independent prognostic factor by multivariate survival analysis (P =.0282). Extensive methylation of 14-3-3 sigma was found by methylation-specific polymerase chain reaction and sequence; however, no significant correlation was detected between methylation states and protein expression. These results indicate that depressed 14-3-3 sigma protein is involved in the uncontrolled cell cycle in intrahepatic cholangiocarcinoma and that the decreased expression of 14-3-3 sigma protein is a significant indicator of poor prognosis for patients with intrahepatic cholangiocarcinoma. (c) 2007 Elsevier Inc. All rights reserved.
• Proposal of progression model for intrahepatic cholangiocarcinoma: Clinicopathologic differences between hilar type and peripheral type

  Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Tomohiro Iguchi, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  AMERICAN JOURNAL OF SURGICAL PATHOLOGY 31 (7) 1059 - 1067 0147-5185 2007/07 [Refereed][Not invited]
   

  It is important to clarify the histologic progression of intrahepatic cholangiocarcinorna (ICC) in consideration of its origin from the intrahepatic large or small biliary ducts. On the basis of the gross and histologic assessment, we classified 87 cases of ICC smaller than 5cm in diameter into hilar type (H-ICC, n = 38) or peripheral type (P-ICC, n = 49) to compare their clinical and histologic features. Biliary dysplasia was observed in 65.8% (25/38) of H-ICC cases, whereas hepatitis virus infection and liver cirrhosis were associated with 46.7% (21/45) and 28.6% (14/49) of P-ICC, respectively. The frequency of perineural invasion, lymph node metastasis, and extrahepatic recurrence of H-ICC was significantly higher than that of P-ICC (P < 0.0001, 0.0106, and 0.0279, respectively). H-ICC cases showed frequent vascular invasion and intrahepatic metastasis even with small tumor size, compared with P-ICC cases. H-ICC showed large duct involvement within the tumor, and in the cases of large tumor size, intraductal spread was detected in the tumor periphery. P-ICC of small size contained preserved architecture of the portal tracts. The survival of patients with H-ICC was worse than that of patients with P-ICC (P = 0.0121). The independent and best prognostic factor by multivariate analysis was intrahepatic metastasis for H-FCC and lymph node metastasis for P-ICC. Our results suggest that ICCs derived from a different level of biliary ducts were related to different premalignant conditions and different tumor progression. Some ICCs arising from the large biliary duct are likely to exhibit an aggressive course even in cases of small tumor size. The recognition of the above events induces the proper therapy.
• Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma: 20 years of experience

  Yo-ichi Yamashita, Akinobu Taketomi, Shinji Itoh, Dai Kitagawa, Hiroto Kayashima, Norifumi Harimoto, Eiji Tsujita, Yosuke Kuroda, Yoshihiko Maehara

  JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 205 (1) 19 - 26 1072-7515 2007/07 [Refereed][Not invited]
   

  Background: Recently, anatomic resection has been, in theory, considered preferable for eradicating portal venous tumor extension and intrahepatic metastasis in hepatocellular carcinoma (HCC). We have reported the effectiveness of limited hepatic resection for cirrhotic patients with HCC. Study Design: A retrospective study was carried out in 321 patients who underwent curative hepatic resection (anatomic resection, n=201; limited resection, n=120) as the initial treatment for solitary HCC<5 cm in our institution in the period 1985 to 2004 (median followup period 5.1 years). Results: Anatomic resection did not influence overall and recurrence-free survival rates after hepatic resection. In the liver damage A group (n=215), both 5-year overall and recurrence-free Survival rates in the anatomic resection group were considerably better than those in the limited resection group (87% versus 76%, p=0.02, and 63% versus 35%, p<0.01, respectively). In the liver damage B group (n=106), both 5-year overall and recurrence-free survival rates in the anatomic resection group were substantially worse than those in the limited resection group (48% versus 72%, p<0.01, and 28% versus 43%, p=0.01, respectively). The results of multivariate analysis revealed that anatomic resection was a notably poor factor in promoting recurrence-free survival in patients with liver damage B. Conclusions: Anatomic resection should be recommended for noncirrhotic patients (liver damage A) with HCC. Longterm results of limited hepatic resection proved its validity for cirrhotic patients (liver damage 13) with HCC.
• Role of growth factor receptor-bound protein 7 in hepatocellular carcinoma

  Shinji Itoh, Akinobu Taketomi, Shinji Tanaka, Norifumi Harimoto, Yo-ichi Yamashita, Shin-ichi Aishima, Takashi Maeda, Ken Shirabe, Mitsuo Shimada, Yoshihiko Maehara

  MOLECULAR CANCER RESEARCH 5 (7) 667 - 673 1541-7786 2007/07 [Refereed][Not invited]
   

  The human growth factor receptor-bound protein 7 (Grb7) is an adaptor molecule and is related to cell invasion. In this present study, we investigated the clinical and biological significance of Grb7 expression in human hepatocellular carcinoma (HCC). We reviewed 64 consecutive patients who had undergone liver resection for HCC, and we investigated the correlation between Grb7 expression and clinical outcome. To analyze the biological behavior of Grb7 in vitro and in vivo, we established Grb7 stable knockdown HCC cells using RNA interference technology. The positive staining of Grb7 protein was correlated with portal venous invasion (P < 0.01), hepatic venous invasion (P < 0.01), and intrahepatic metastasis (P < 0.05). Positive expression of Grb7 was significantly correlated with focal adhesion kinase (FAK) protein levels in HCC (P < 0.01). The Grb7- and FAK-positive group showed a significantly poorer prognosis as compared with the Grb7- and FAK-negative group (P < 0.05). Grb7 knockdown HCC cells exhibited significantly lower levels of invasion potential (P < 0.05) and motility (P < 0.05) than the control cells in vitro; moreover, Grb7 knockdown HCC cells showed delayed onset of the tumors compared with the control cells in vivo. Grb7 expression can modulate the invasive phenotype of HCC. Grb7 plays an important role in HCC progression and is strongly associated with expression of FAK. Grb7 could be a therapeutic target in HCC.
• [Estimation of indication for living donor liver transplantation in patients with HCV and/or HBV infection].

  Sawako Inoue, Shusuke Morizono, Shinsaku Yamashita, Yuki Horikawa, Motoyuki Kohjima, Yuzuru Miyagi, Tsuyosi Yoshimoto, Kazuhiro Kotoh, Munechika Enjoji, Ryoichi Takayanagi, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Yoshihiko Maehara, Makoto Nakamuta

  Fukuoka igaku zasshi = Hukuoka acta medica 98 (7) 295 - 300 0016-254X 2007/07 [Refereed][Not invited]
   

  We evaluated 78 patients with chronic viral hepatitis for liver transplantation. 51 patients met our original criteria for liver transplantation, and 35 patients of them suffered from hepatocellular carcinoma (HCC). Patients with HCC were significantly older and showed higher prothrombin activity than those without HCC. Eighteen of 35 patients with HCC did not meet the Milan criteria, and they showed lower levels of total bilirubin, Child-Pugh score, and MELD score than those who met the criteria. Theses results indicate that acceptability for transplantation should be evaluated soon after the patients have become candidates for liver transplantation. In Japan, decompensated liver cirrhosis is a necessary condition for the application of public health insurance against liver transplantarion and, in cases with HCC, it is necessary to meet the Milan criteria. Application to liver transplantation should also be considered based on HCC stage such as the UNOS scoring system.
• Histologic characteristics and prognostic significance in small hepatocellular carcinoma with biliary differentiation - Subdivision and comparison with ordinary hepatocellular carcinoma

  Shinichi Aishima, Yunosuke Nishihara, Yousuke Kuroda, Kenichi Taguchi, Tomohiro Iguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  AMERICAN JOURNAL OF SURGICAL PATHOLOGY 31 (5) 783 - 791 0147-5185 2007/05 [Refereed][Not invited]
   

  The morphologic characteristics and biologic behavior of small liver cancers with hepatic and biliary differentiation, and their histogenesis, remain unclear. In this study, 35 cases of hepatocellular carcinoma (HCC) smaller than 3 cm in diameter with biliary differentiation were divided into 3 groups, group 1 [cytokeratin (CK) 19-negative/mucin-negative], group 2 (CK 19-positive/mucin-negative), and group 3 (CK 19-positive/mucinpositive). Sixty-one HCCs without biliary differentiation were used as controls. We compared the histologic features of these tumors and the postoperative outcomes. Three morphologic features of HCCs with biliary differentiation were respectively observed in 40% (14/35), 60% (21/35), and 42.9% (15/35) as follows: (1) cancer cells with intermediate morphology, (2) prominent inflammatory cell infiltrate, (3) desmoplastic stroma; neural cell adhesion molecule and c-kit expression were noted in 25.7%(9/35) and 8.6%(3/35), respectively. Extrahepatic tumor recurrence after surgery occurred in 0% (0/16) of group 1, 33.3% (3/9) of group 2, 40.0% (4/10) of group 3, and 8.2% (5/61) of the ordinary HCCs. The tumor-related survival of group 3 patients was worse than that of patients with ordinary HCCs, but there were no differences between the survival of group 1, or group 2 patients and those with ordinary HCCs. Our results suggest that the biliary differentiation does occur even in small HCC, and a mucin-producing cancer cells indicates aggressive tumor behavior. The combination of intermediate cancer cells, inflammatory cell infiltrate, and desmoplastic stroma is likely to be related to the biliary differentiation of HCC.
• Risk factors for and management of delayed intraperitoneal hemorrhage after pancreatic and biliary surgery

  Yo-ichi Yamashita, Akinobu Taketomi, Kengo Fukuzawa, Eiji Tsujita, Norifumi Harimoto, Dai Kitagawa, Yosuke Kuroda, Hiroto Kayashima, Kenzo Wakasugi, Yoshihiko Maehara

  AMERICAN JOURNAL OF SURGERY 193 (4) 454 - 459 0002-9610 2007/04 [Refereed][Not invited]
   

  Background: Delayed intraperitoneal hemorrhage (DIH) is still an important cause of postoperative mortality in pancreatic and biliary surgery. Methods: Sixty-nine patients who underwent pancreatic and biliary surgery with skeletonization for lymphadenectomy of the hepatoduodenal ligament between April 2002 and March 2005 were included in this study. Statistical analyses of the risk factors for DIH were performed using both univariate and multivariate modalities. Results: DIH occurred in 4 patients (5.8%) within a median time of 15 days after surgery. Stepwise logistic regression analysis identified intra-abdominal abscess formation as the independent predictor of DIH. All 4 patients had a sentinel bleed before the onset of DIH. Three patients were treated by transarterial embolization and I patient was treated by surgical intervention. Three patients had liver abscess after hemostasis of DIH, but all 4 patients recovered and were discharged from the hospital. Conclusions: A computed tomography angiography should be performed on patients with intra-abdominal abscess formation and sentinel bleed after pancreatic and biliary surgery to check if a pseudoaneurysm has formed. (c) 2007 Excerpta Medica Inc. All rights reserved.
• Trends in morbidity and mortality after hepatic resection for hepatocellular carcinoma: An institute's experience with 625 patients

  Akinobu Taketomi, Dai Kitagawa, Shinji Itoh, Norifumi Harimoto, Yo-ichi Yamashita, Tomonobu Gion, Ken Shirabe, Mitsuo Shimada, Yoshihiko Maehara

  JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 204 (4) 580 - 587 1072-7515 2007/04 [Refereed][Not invited]
   

  BACKGROUND: Despite recent developments in surgery and patient management during the perioperative period, critical complications still developed in a few patients who had hepatic resection for hepatocellular carcinoma (HCC). STUDY DESIGN: Six hundred twenty-five consecutive patients who had hepatic resection for HCC were reviewed and operative morbidity and mortality rates assessed. RESULTS: There were progressive decreases in the surgical blood loss and the rate of blood transfusion (p = 0.0001). Occurrence of ascites and other complications dramatically decreased in the study series (p = 0.0001). Hospital death rate and incidence of postoperative liver failure also decreased from 2.5%, 1.9% (1985 to 1990), 4.4%, 3.2% (1991 to 1996) to 1.9%, 1.4% (1997 to 2002), respectively. Using multiple logistic regression, independent risk factors associated with postoperative complications were found to be the period of operation (odds ratio [OR] = 0.408; p < 0.0001) and alanine aminotransferase >= 70 IU/L (OR = 2.020; p = 0.0009) over the entire period of this study (1985 to 2002), or the platelet count of < 100 X 10(3)/mm(3) (OR = 4.654; p = 0.0072) and the presence of blood transfusion during operation (OR = 8.249; p = 0.0230) in 1997 to 2002. CONCLUSIONS: In this series, there has been a decline in surgical blood loss and rate of blood transfusion and in the number of patients with major complications. These results are largely attributable to the adequate selection of surgical candidate and factors aimed at reducing surgical blood loss. (J Am Coll Surg 2007;204:580-587. (C) 2007 by the American College of Surgeons).
• Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma

  Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Shinich Aishima, Takahiro Terashi, Mitsuo Shimada, Yoshihiko Maehara

  TRANSPLANTATION 83 (7) 893 - 899 0041-1337 2007/04 [Refereed][Not invited]
   

  Background. Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. Methods. A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. Results. Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter > 5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value > 300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. Conclusions. LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors < 5 cm.
• Successful pylorus-preserving pancreaticoduodenectomy for a patient with carcinoma of the papilla Vater two years after living donor liver transplantation

  Tomoharu Yoshizumi, Mitsuo Shimada, Yuji Soejima, Takahiro Terashi, Akinobu Taketomi, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 54 (75) 941 - 943 0172-6390 2007/04 [Refereed][Not invited]
   

  Liver transplantation has been recognized as the treatment for various kinds of end-stage liver diseases. Standardized surgical technique, potent immunosuppressive agents and diligent postoperative care have made it possible for patients to survive for a longer period. For this reason, recurrent primary disease and/or de novo malignancy regarded as chronic immunosuppressant have been paid a great deal of attention. Even pancreas cancer after liver transplantation is extremely rare and has never been successfully treated. Furthermore, cancer of the papilla Vater, which is less frequent than pancreas cancer after liver transplantation has not been reported as yet. In this paper we, discuss the first case of cancer of the papilla Vater, which was successfully treated by pylorus-preserving pancreaticoduodenectomy two years after a living related liver transplantation using a left lobe. In addition, we discuss the type of malignancy after liver transplantation.
• The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma - With special reference to the serum levels of des-gamma-carboxy prothrombin

  Ken Shirabe, Shinji Itoh, Tomoharu Yoshizumi, Yuji Soejima, Akinobu Taketomi, Shin-Ichi Aishima, Yoshihiko Maehara

  JOURNAL OF SURGICAL ONCOLOGY 95 (3) 235 - 240 0022-4790 2007/03 [Refereed][Not invited]
   

  The microvascular invasion of cancer cells (mvi) is a good prognostic factor after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The aim of this study is to predict mvi in patients with HCC who were candidates for OLT. We studied 218 patients with HCC resections who had HCC without any extrahepatic metastases and vascular invasion detected during preoperative evaluation. We analyzed the clinico-pathological data of these patients to predict the mvi presence. The mvi prediction scoring system was made and the accuracy of this system was examined using independent clinico-pathologic factors. The size and histological grade of the tumor were significantly correlated with the mvi. The des-gamma-carboxy prothrombin (DCP) is a mvi predictor. The sensitivity of our mvi prediction system was 75% and the specificity was 85% in 32 patients who underwent living-donor liver transplantations for HCC. Our study shows that besides the tumor size and histological grade, a measurement of the serum DCP levels could be a good predictor for mvi. A tumor biopsy and a preoperative measurement of DCP could improve the selection of patients with HCC for OLT. Our scoring system for mvi provides us a precise prediction of the presence of mvi.
• Poorly versus moderately differentiated hepatocellular carcinoma: Vascularity assessment by computed tomographic hepatic angiography in correlation with histologically counted number of unpaired arteries

  Yoshiki Asayama, Kengo Yoshimitsu, Hiroyuki Irie, Yunosuke Nishihara, Shinichi Aishima, Tsuyoshi Tajima, Masakazu Hirakawa, Kousei Ishigami, Daisuke Kakihara, Akinobu Taketomi, Hiroshi Honda

  JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 31 (2) 188 - 192 0363-8715 2007/03 [Refereed][Not invited]
   

  Purpose: To determine the vascularity of moderately and poorly differentiated hepatocellular carcinoma (mHCC and pHCC, respectively) as observed on and depicted by computed tomography during hepatic angiography and to perform pathological correlation. Materials and Methods: Eighty-seven consecutive patients with 89 hepatocellular carcinomas (61 mHCCs and 28 pHCCs) were surgically resected in our hospital. The degree of contrast enhancement on computed tomography during hepatic angiography of the tumors was classified into high attenuation (H), isoattenuation (I), and low attenuation (Q. We also examined hepatocellular carcinomas measuring less than 4 cm in diameter. Pathologically, the number of impaired arteries in the tumors was determined (x 200 magnification). Results: The number of mHCC and pHCC in each degree of enhancement (H/I/L) was 59:1:1 and 19:63, respectively. The number of mHCC and pHCC measuring less than 4 cm without portal invasion was 48 and 15, respectively; the number of these tumors in each degree of enhancement (H/I/L) was 47:1:0 and 11:3:1, respectively. The mean number of unpaired arteries was 8.9 +/- 4.4 in mHCC and 5.2 +/- 4.3 in pHCC, respectively. All results were statistically significant (P < 0.01). Conclusions: Our results indicated that the arterial blood supply of pHCC was lower than that of mHCC.
• Selective hepatic vascular exclusion for the hepatic resection of HCC

  Eiji Tsujita, Akinobu Taketomi, Dai Kitagawa, Shinji Itoh, Norifumi Harimoto, Tomonobu Gion, Shunji Kohnoe, Yoshihiko Maehara

  HEPATO-GASTROENTEROLOGY 54 (74) 527 - 530 0172-6390 2007/03 [Refereed][Not invited]
   

  Background/Aims: Selective hepatic vascular exclusion (SHVE) is an effective technique for the control of bleeding in major hepatic resections. Outcomes of the procedures of the SHVE group were compared with the non-SHVE group. Methodology: A retrospective study was carried out of 312 hepatic resections performed over a period of 10 years. The cases in this study were limited to Child's classification A, because of the rate of Child A in the SHVE group (n=82) was significantly higher than that within the non-SHVE group (n= 158) (93% vs. 71%; p < 0.001). Preoperative factors, like age, gender, tumor size, intraoperative blood loss, operation time, and the postoperative course of the two groups were compared for both groups. Results: The SHVE group showed significantly less blood loss, necessary blood transfusion, and a significant rate of severe postoperative complications. The rate of segmentectomy and subsegmentectomy in the SHVE group was higher than in the non-SHVE group, and the rate of partial hepatectomy and lobectomy in the non-SHVE group was higher than that in the SHVE group. Although the more difficult operations were performed in the SHVE group than in the non-SHVE group, there was no significant difference in the postoperative hospital stays in both groups. Conclusions: The SHVE technique is effective for bleeding control in major liver resections.
• Hepatic artery aneurysm arising from an interposition vein graft four years after auxiliary partial orthotopic liver transplantation

  Hideaki Uchiyama, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Noboru Harada, Hideki Ijichi

  TRANSPLANT INTERNATIONAL 20 (2) 197 - 200 0934-0874 2007/02 [Refereed][Not invited]
  
• Clinical significance of histone deacetylase 1 expression in patients with hepatocellular carcinoma

  Tatsuya Rikimaru, Akinobu Taketomi, Yo-Ichi Yamashita, Ken Shirabe, Takayuki Hamatsu, Mitsuo Shimada, Yoshihiko Maehara

  ONCOLOGY 72 (1-2) 69 - 74 0030-2414 2007 [Refereed][Not invited]
   

  Objective: Histone deacetylases (HDACs) play an important role in chromatin remodeling, gene repression and regulating cell cycle progression and differentiation. This study was designed to clarify the role of HDAC1 expression in hepatocellular carcinoma (HCC). Method: The expression of HDAC1 in 47 patients with surgically resected HCC was immunohistochemically examined and analyzed in relation to their clinicopathological factors. The patients were divided into two groups according to the expression status of HDAC1: a high HDAC1 group (n = 25) with more than 20% of positively stained cells and a low HDAC1 group (n = 22) with 20% or fewer positively stained cells. Results: A high HDAC1 expression indicated a higher incidence of cancer cell invasion into the portal vein, a poorer histological differentiation, and a more advanced TNM stage. The survival rates after a surgical resection in low and high HDAC1 patients at 1, 3, 5 and 10 years were 100, 95.5, 81.8 and 60.8% and 88.0, 60.0, 40.0 and 32.0%, respectively (p = 0.008). A multivariate analysis using the Cox regression analysis showed that a high HDAC1 expression was an independent prognostic factor of HCC in patients after hepatic resection (relative risk: 10.1, p = 0.0018). Conclusions: High HDAC1 expression might have an important role in the aggressiveness and cell dedifferentiation, and its expression status may be a useful biomarker for predicting the outcome of the patients with HCC. Copyright (c) 2007 S. Karger AG, Basel.
• Expression of platelet-activating factor receptor: A novel prognosticator in patients with hepatocellular carcinoma following hepatectomy

  Dai Kitagawa, Akinobu Taketomi, Hiroto Kayashima, Yosuke Kuroda, Shinji Itoh, Yo-ichi Yamashita, Yoshihiko Maehara

  ONCOLOGY 72 (5-6) 381 - 387 0030-2414 2007 [Refereed][Not invited]
   

  Backgrounds and Aims: Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator and acts by binding to a specific G-protein-coupled receptor. Though various functions of PAF have been associated with tumor activities, the mechanism of PAF-PAF receptor signaling in the development of hepatocellular carcinoma (HCC) remains to be elucidated. Methods: In this study, PAF receptor (PAFR) expression was examined in hepatoma cell lines (Huh7, PLC/PRF/5 and HepG2) and clinical samples of HCC (n = 60) using immunohistochemical staining. The relationships between the expression of PAFR and clinicopathological parameters were also investigated. Results: An immunohistochemical study showed that 24 HCC cases (40%) showed a lower PAFR expression than non-cancerous hepatocytes. The patients were divided into two groups according to the degree of PAFR expression: the high (n = 36) and low PAFR groups (n = 24). Lower expression of PAFR was correlated with poor differentiation, portal vein invasion, high levels of serum alpha-fetoprotein and poor prognosis after surgery. In the low PAFR group, multiple recurrences and distant metastases were more often observed than in the high PAFR group. Multivariate analysis revealed that lower PAFR expression in addition to portal vein invasion is significantly related to survival after hepatectomy. Conclusions: A lower expression of PAFR correlated with poor differentiation and a poor prognosis, and may therefore be used as a prognostic marker in HCC after hepatectomy. Copyright (C) 2008 S. Karger AG, Basel.
• PD-028 Post-transplantation complication and outcome after living donor liver transplantation for patients with biliary atresia(Organ transplantation : Liver transplantation -Problems of long-term results, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons)

  Takahashi Yukiko

  Journal of the Japanese Society of Pediatric Surgeons 特定非営利活動法人 日本小児外科学会 43 (3) 346 - 346 2007
• PD-042 Efficacy of liver transplantation in pediatric patients with fulminant hepatitis(Organ transplantation : Fulminant hepatic failure in children, the 44th Annual Meeting of Japanese Society of Pediatric Surgeons)

  Nishimoto Yuko

  Journal of the Japanese Society of Pediatric Surgeons 特定非営利活動法人 日本小児外科学会 43 (3) 353 - 353 2007
• S3-4.胆道閉鎖症に対する一次的肝移植の検討(シンポジウム3「胆道閉鎖症の長期予後・移植時期」,第23回日本小児外科学会秋季シンポジウム)

  西本 祐子, 高橋 由紀子, 林田 真, 佐伯 勇, 田尻 達郎, 田口 智章, 副島 雄二, 武富 紹信, 前原 喜彦, 松尾 進

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 43 (6) 738 - 739 2007
• S3-5.胆道閉鎖症に対する生体肝移植術における門脈血流確保についての検討(シンポジウム3「胆道閉鎖症の長期予後・移植時期」,第23回日本小児外科学会秋季シンポジウム)

  高橋 由紀子, 西本 祐子, 林田 真, 佐伯 勇, 田尻 達郎, 田口 智章, 吉住 朋晴, 副島 雄二, 武冨 紹信, 前原 喜彦

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 43 (6) 739 - 739 2007
• ウイルス肝炎，特に肝細胞癌合併症例に対する生体肝移植適応評価の現況

  井上佐和子, 森園周祐, 山下晋作, 堀川ゆき, 国府島庸之, 宮城譲, 吉本剛志, 古藤和浩, 遠城寺宗近, 高柳涼一, 副島雄二, 武冨紹信, 吉住朋晴, 前原喜彦, 中牟田誠

  福岡医学雑誌 福岡医学会 98 (7) 295 - 300 0016-254X 2007 [Refereed][Not invited]
   

  We evaluated 78 patients with chronic viral hepatitis for liver transplantation. 51 patients met our original criteria for liver transplantation,and 35 patients of them suffered from hepatocellular carcinoma (HCC). Patients with HCC were significantly older and showed higher prothrombin activity than those without HCC. Eighteen of 35 patients with HCC did not meet the Milan criteria, and they showed lower levels of total bilirubin, Child-Pugh score, and MELD score than those who met the criteria. Theses results indicate that acceptability for transplantation should be evaluated soon after the patients have become candidates for liver transplantation. In Japan, decompensated liver cirrhosis is a necessary condition for the application of public health insurance against liver transplantation and,in cases with HCC,it is necessary to meet the Milan criteria.Application to liver transplantation should also be considered based on HCC stage such as the UNOS scoring system.
• Characteristic differences according to the cirrhotic pattern of advanced primary biliary cirrhosis: Macronodular cirrhosis indicates slow progression

  Shinichi Aishima, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Tomoharu Yoshizumi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

  HEPATOLOGY RESEARCH 36 (3) 188 - 194 1386-6346 2006/11 [Refereed][Not invited]
   

  It is important to evaluate advanced primary biliary cirrhosis (PBC) clinicopathologically to clarify its progressive mechanism. According to the cirrhotic pattern, 26 cases of explanted PBC were classified into non-cirrhotic (n = 4), macronodular (n = 4), mixed nodular (n = 6), and micronodular cirrhosis (n = 12), to compare their clinical and morphological features. In addition, the degree of preserved intrahepatic bile ducts and other histologic features were analyzed. Patients at living donor liver transplantation (LDLT) in the macronodular cirrhosis were significantly older than those in the micronodular cirrhosis. The mean duration between clinical presentation and LDLT in the macronodular cirrhosis was significantly longer than in the micronodular cirrhosis. The non-cirrhotic group showed a short duration between clinical presentation and LDLT. The ratio of explanted liver volume to standard liver volume (ELV/SLV) indicates that macronodular cirrhosis revealed more atrophic change than that in the other three types. The density of remnant intrahepatic bile ducts of less than 50 mu m per group in cases of macronodular cirrhosis was significantly higher than that in cases of micronodular cirrhosis. Therefore, different cirrhotic patterns of advanced PBC were correlated with the disease progression and the degree of bile duct disappearance. The macronodular cirrhotic patients were older, had a longer disease course, yet had less bile duct loss. We suggest that macronodular cirrhosis and micronodular cirrhosis of PBC are different type of PBC. (C) 2006 Published by Elsevier Ireland Ltd.
• High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma

  Shinichi Aishima, Yuji Basaki, Yoshinao Oda, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Fumihito Hosoi, Yuichiro Maruyama, Abbas Fotovati, Shinji Oie, Mayumi Ono, Takato Ueno, Michio Sata, Hirohisa Yano, Masamichi Kojiro, Michihiko Kuwano, Masazumi Tsuneyoshi

  CANCER SCIENCE 97 (11) 1182 - 1190 1347-9032 2006/11 [Refereed][Not invited]
   

  Insulin-like growth factor binding protein-3 (IGFBP-3) modulates cell proliferation of various cancer cell types. However, it remains unclear how IGF-IGFBP-3-signaling is involved in growth and progression of hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP-3 in HCC. Type 1 receptor for IGF (IGF-1R) was expressed at various levels in the seven lines examined, but IGF-2R was not expressed. Of the seven lines, the growth of HAK-1B, KIM-1, KYN-2 and HepG2 cells was stimulated in a dose-dependent manner by the exogenous addition of IGF-I or IGF-II, but the HAK-1A, KYN-1 and KYN-3 cell lines showed no growth. Exogenous addition of IGFBP-3 markedly blocked IGF-I and IGF-II-stimulated cell growth of KYN-2 and HepG2 cells, and moderately stimulated that of KIM-1 and HAK-1B cells, but no growth of the KYN-1, KYN-3 and HAK-1A cell lines was observed. IGF-I enhanced the phosphorylation of IGF-1R, Akt and Erk1/2 in KYN-2 cells, and coadministration of IGFBP-3 blocked all types of activation by IGF-I investigated here. In contrast, no such activation by IGF-I was detected in KYN-3 cells. IGFBP-3 also suppressed IGF-I-induced cell invasion by KYN-2 cells. Moreover, we were able to observe the apparent expression of IGFBP-3 in KYN-3 cells, but not in the other six cell lines. Furthermore reduced expression of IGFBP-3, but not that of IGF-1R, was significantly correlated with tumor size, histological differentiation, capsular invasion and portal venous invasion. Low expression of IGFBP-3 was independently associated with poor survival. IGFBP-3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC.
• Diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling

  Tracy Crotty, Jinjin Cai, Fumio Sakane, Akinobu Taketomi, Stephen M. Prescott, Matthew K. Topham

  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 103 (42) 15485 - 15490 0027-8424 2006/10 [Refereed][Not invited]
   

  Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate its signaling. To study DGK delta, we disrupted its gene in mice and found that DGK delta deficiency reduced EGF receptor (EGFR) protein expression and activity. Similar to EGFR knockout mice, DGK delta-deficient pups were born with open eyelids and died shortly after birth. PKCs are activated by DAG and phosphorylate EGFR to reduce its expression and activity. We found DAG accumulation, increased threonine phosphorylation of EGFR, enhanced phosphorylation of other PKC substrates, and increased PKC autophosphorylation in DGK delta knockout cells, indicating that DGK delta regulates EGFR by modulating PKC signaling.
• Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation

  Noriaki Kawano, Kazuya Shimoda, Fumihiko Ishikawa, Akinobu Taketomi, Tomoharu Yoshizumi, Shinji Shimoda, Shuro Yoshida, Koji Uozumi, Shinsuke Suzuki, Yoshihiko Maehara, Mine Harada

  TRANSPLANTATION 82 (6) 840 - 843 0041-1337 2006/09 [Refereed][Not invited]
   

  Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-1) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-1 carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier.
• Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy

  H Ijichi, A Taketomi, T Yoshizumi, H Uchiyama, Y Yonemura, Y Soejima, M Shimada, Y Maehara

  JOURNAL OF HEPATOLOGY 45 (1) 28 - 34 0168-8278 2006/07 [Refereed][Not invited]
   

  Background/Aims: The aim of this study was to investigate the effect and the mechanism of hyperbaric oxygen treatment on regenerating rat liver after partial hepatectomy (PH). Methods: Wistar rats underwent a 70% PH, followed by treatment with hyperbaric oxygen starting 8 h after PH. The regenerated liver weight and serum parameters were compared. Proliferation of both hepatocytes and sinusoidal endothelial cell (SEC) was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, the hepatic adenosine triphosphate levels and vascular endothelial growth factor (VEGF) protein expression were analyzed at different times. Results: Hyperbaric oxygen treatment significantly reduced the serum alanine aminotransferase levels at 24 h, total bilirubin and total bile acid levels at 48 and 72 h, respectively. No significant differences in the hepatic adenosine triphosphate levels, the restitution of liver weight, or PCNA positive hepatocytes were observed between the two groups. The PCNA positive SEC, in contrast, was significantly increased in the hyperbaric oxygen group at 48 h, furthermore, the hyperbaric oxygen treatment significantly increased the expression of VEGF protein in the regenerating liver at 24 and 48 h. Conclusions: Hyperbaric oxygen treatment can be considered as a therapeutic modality after massive PH. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
• Gastric mucin phenotype defines tumour progression and prognosis of intrahepatic cholangiocarcinoma: gastric foveolar type is associated with aggressive tumour behaviour

  S Aishima, Y Kuroda, Y Nishihara, K Taguchi, A Taketomi, Y Maehara, M Tsuneyoshi

  HISTOPATHOLOGY 49 (1) 35 - 44 0309-0167 2006/07 [Refereed][Not invited]
   

  Aims: To identify the role of mucus core protein (MUC) in intrahepatic cholangiocarcinoma (ICC). Methods and results: We examined the expression profile of MUC2, MUC5AC and MUC6 by immunohistochemical staining in 100 ICCs and compared the clinicopathological factors and the immunohistochemical results. The expression frequency was: MUC2, 9%; MUC5AC, 40%; and MUC6, 21%. According to the gastric mucin expression profile, ICCs were classified into the following groups: null type (n = 43), gastric foveolar type (n = 36), pyloric gland type (n = 11) and gastric combined type (n = 10). Half of the gastric foveolar type and the gastric combined type were located in the hilar region, but the other types were predominant at the periphery (P = 0.0004). Well-differentiated components were more often detected in the gastric combined type and the pyloric gland type (P = 0.0281). The gastric foveolar type was associated with a higher incidence of lymph node metastasis (P < 0.0001). The pyloric gland type was associated with better survival and the gastric foveolar type was associated with worse survival. The gastric mucin phenotype was an independent prognostic factor by multivariate survival analysis. Conclusion: The gastric foveolar type of ICC was more often associated with aggressive tumour development, whereas the pyloric gland type exhibited less aggressive behaviour.
• Biliary strictures in living donor liver transplantation: Incidence, management, and technical evolution

  Y Soejima, A Taketomi, T Yoshizumi, H Uchiyama, N Harada, H Ijichi, Y Yonemura, T Ikeda, M Shimada, Y Maehara

  LIVER TRANSPLANTATION 12 (6) 979 - 986 1527-6465 2006/06 [Refereed][Not invited]
   

  Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct-to-duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux-en-Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1- and 3-year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P = not significant). The left-lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either precutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS.
• Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein

  Y Soejima, T Taguchi, K Ogita, A Taketomi, T Yoshizumi, H Uchiyama, T Ohno, M Shimada, Y Maehara

  LIVER TRANSPLANTATION 12 (5) 845 - 849 1527-6465 2006/05 [Refereed][Not invited]
   

  Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary.
• New concept of cholecystectomy combined resection of the gallbladder bed for chronic cholecystitis

  T Ezaki, T Ikegami, A Taketomi, M Hashizume, Y Maehara

  HEPATO-GASTROENTEROLOGY 53 (69) 335 - 337 0172-6390 2006/05 [Refereed][Not invited]
   

  Cholecystectomy is sometimes the most difficult operation to perform. When the atrophic gallbladder with severe inflammation falls into the spongy soft liver, it is not easy to perform a standard cholecystectomy without causing bleeding and serious injury around the hilar structures. Some selected patients with chronic cholecystitis under some particular circumstances might be better suited to undergo a cholecystectomy combined resection with the gallbladder bed rather than the ordinary standard cholecystectomy. Herein, we showed a partial hepatic resection of the gallbladder bed with the gallbladder using an intermittent hepatic inflow occlusion.
• Feasibility of left lobe living donor liver transplantation between adults: An 8-year, single-center experience of 107 cases

  Y Soejima, A Taketomi, T Yoshizumi, H Uchiyama, N Harada, H Ijichi, Y Yonemura, M Shimada, Y Maehara

  AMERICAN JOURNAL OF TRANSPLANTATION 6 (5) 1004 - 1011 1600-6135 2006/05 [Refereed][Not invited]
   

  Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of ILL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.
• Effect of hyperbaric oxygen on cold storage of the liver in rats

  H Ijichi, A Taketomi, Y Soejima, T Yoshizumi, H Uchiyama, M Shimada, Y Maehara

  LIVER INTERNATIONAL 26 (2) 248 - 253 1478-3223 2006/03 [Refereed][Not invited]
   

  Background: The depletion of biochemical energy stores during prolonged cold storage is one of the most critical events of cold ischemia-reperfusion (CI/R) injury. The aim of this study was to evaluate the effect of hyperbaric oxygen (HBO) treatment on CI/R injury. Methods: Livers were harvested from male Wistar rats and stored for 24 h at 4 degrees C in University of Wisconsin solution (Group 1). Others were additionally treated with HBO during the preservation period (Group 2). At the end of the 24 h cold preservation, the concentrations of hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic adenosine triphosphate (ATP) levels were measured. After preservation, the livers were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. Results: In group 2, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and LPO into the effluent at the end of preservation were decreased and the depletion of ATP was prevented (P < 0.05). After reperfusion, the portal flow was significantly improved in group 2 (P < 0.05). The time-dependent increase of alanine aminotransferase levels (ALT) observed in group 1 was suppressed significantly in group 2, and total bile production during 90 min of reperfusion was significantly greater in group 2 (P < 0.05). The structure of the livers in group 2 was significantly well maintained, and the liver weight change ratio was significantly greater in group 1 (P < 0.05). Conclusions: HBO treatment during cold storage seems to prevent hepatic ischemic injury and have protective effects against CI/R injury by attenuating the depletion of energy stores.
• Successful adult-to-adult living donor liver transplantation in a patient with moderate to severe portopulmonary hypertension

  H Uchiyama, Y Soejima, A Taketomi, T Yoshizumi, N Harada, H Ijichi, Y Yonemura, Y Maehara

  LIVER TRANSPLANTATION 12 (3) 481 - 484 1527-6465 2006/03 [Refereed][Not invited]
   

  Portopulmonary hypertension (PPHTN) is one of the most devastating consequences of end-stage liver cirrhosis. When a patient has moderate to severe PPHTN, his or her candidature for liver transplantation is denied. Here we report a successful adult-to-adult living donor liver transplantation (LDLT) in a patient with moderate to severe PPHTN. The patient was a 58-yr-old female who was diagnosed with end-stage liver cirrhosis due to chronic hepatitis C. Preoperative evaluation revealed that the patient had moderate to severe PPHTN. Her mean pulmonary artery pressure (mPAP) was 35-47 mmHg without treatment. Continuous epoprostenol therapy was introduced to lower the mPAP. She underwent LDLT using an extended right hepatic lobe graft which was donated by her daughter. Prolonged artificial ventilation was necessary until postoperative day (POD) 25, after which her general condition gradually improved. By POD 72, she was in good condition and was allowed to leave the hospital. Currently, 1 yr after the operation, she visits the outpatient clinic regularly and enjoys a normal life. It should be noted, however, that the PPHTN markedly improved but did not completely resolve, as assessed by right heart catheterization 1 yr after successful LDLT.
• Prognostic impact of cholangiocellular and sarcomatous components in combined hepatocellular and cholangiocarcinoma

  S Aishima, Y Kuroda, Y Asayama, K Taguchi, Y Nishihara, A Taketomi, M Tsuneyoshi

  HUMAN PATHOLOGY 37 (3) 283 - 291 0046-8177 2006/03 [Refereed][Not invited]
   

  Combined hepatocellular and cholangiocarcinoma (cHC-CC) is a rare type of liver cancer. P displaying both hepatocellular and cholangiocellular components. The cholangiocellular carcinoma (CC) in these tumors ranges from focal to prominent. Those cHC-CCs with sarcomatous features are reported to have a poor prognosis. To clarify whether the CC and sarcomatous component affects the prognosis, we classified 40 patients with cHC-CCs into 4 groups according to the presence of a sarcomatous component and the extent of the CC component. Seven (17.5%) tumors showed areas with a sarcomatous component. The remaining tumors were divided into a low-CC group (CC occupying < 30% of the tumor, n = 12), a middle-CC group (30%-60%, n = 15), and a high-CC group (> 60%, n = 6). Vascular invasion was more frequently present in the high-CC and sarcomatous group than in the other groups (P = .0007). No lymph node metastasis occurred in either the low- or the middle-CC groups, but it was detected in 3 (50%) cases of the high-CC group and in 2 (29%) cases of the sarcomatous group (P < .0001). There was a tendency for tumor size to increase from the low- to the middle- to the high-CC group. The Ki-67 labeling index values for the hepatocellular carcinoma, CC, and sarcomatous components were 11.4% +/- 12.9%. 25.4% +/- 18.3%, and 46.0% +/- 23.6%, respectively. The overall Survival of patients in the high-CC and sarcomatous group was significantly poorer than that of patients in the low- and middle-CC groups (P = .0048). By multivariate analysis of overall survival, lymph node metastasis. histological subgroup, and vascular invasion were significant independent prognostic factors. A cHC-CC with a large CC component is as aggressive as cHC-CC with sarcomatous features. (c) 2006 Elsevier Inc. All rights reserved.
• [Development of a molecular target therapy on the basis of global gene analyses of gastrointestinal carcinoma].

  Maehara Y, Oki E, Tokunaga E, Maehara S, Tsujita E, Yamashita Y, Egashira A, Taketomi A, Yoshihiro K

  Fukuoka igaku zasshi = Hukuoka acta medica 2 97 (2) 30 - 36 0016-254X 2006/02 [Refereed][Not invited]
   

  癌の治療には,手術療法のみならず,化学療法,放射線療法などの補助療法を加えた集学的な治療が必要である.しかし,化学療法,放射線療法はすべての患者へ効果が一定しているわけではなく,実際の治療,特に化学療法には副作用が生じることがある.そこで,症例毎に応じたレジメンの決定や,薬剤の選択,新しい分子標的の探索を目的とした,いわゆる個別化医療の必要性が提唱されるようになってきた.当教室では,2003年から2年間にわたり,九州大学のP&P(九州大学教育研究プログラム・研究拠点形成プロジェクト)より研究支援を頂き,「消化器癌の網羅的遺伝子解析に基づいた分子標的治療の開発」に関する研究を行なった.この研究では,まず,DNAマイクロアレイを用いて,網羅的な遺伝子解析を行ない,抗癌剤に耐性な細胞において,どのような遺伝子が高発現しているのか,また,転移しやすい細胞においてどのような遺伝子が高発現しているのかについて検討した.それにより,膵臓癌細胞株におけるゲムシタビン耐性に関わる遺伝子や,胆管癌細胞株における腹膜播種に関わる遺伝子なども同定された.その他にも,新しい分子標的を集約的に探索するため,抗癌剤によるシグナル伝達機構や,抗癌剤とDNAミスマッチ修復機構についての研究も行なった.例えば,新しい分子標的治療薬の標的分子としても米国などで注目を集めているシグナル伝達分子AKTが,抗癌剤による細胞死の抑制に重要な役割を果たしていること,また胃癌や乳癌では,そのシグナル伝達経路が持続的に活性化していることも明らかにした.
• Delayed-phase dynamic CT enhancement as a prognostic factor for mass-forming intrahepatic cholangiocarcinoma

  Y Asayama, K Yoshimitsu, H Irie, T Tajima, A Nishie, M Hirakawa, T Nakayama, D Kakihara, A Taketomi, S Aishima, H Honda

  RADIOLOGY 238 (1) 150 - 155 0033-8419 2006/01 [Refereed][Not invited]
   

  Purpose: To retrospectively determine whether the degree of contrast material enhancement at delayed-phase dynamic computed tomography (CT) for intrahepatic cholangiocarcinoma (ICC) is related to the patient's prognosis after surgery. Materials and Methods: Neither institutional review board approval nor informed consent was required for this retrospective evaluation. Thirty-two patients ( 22 men, 10 women; mean age, 60.8 years; range, 33-80 years) with mass-forming ICC underwent dynamic CT. Delayed CT images obtained 4-6 minutes after the injection of contrast material were evaluated by two radiologists. Patients were classified in consensus into one of two groups: Group 1 included those in whom more than two-thirds of the tumor showed enhancement on delayed-phase scans. Group 2 included those in whom less than two-thirds of the tumor showed enhancement on delayed-phase scans. The imaging findings were correlated with pathologic findings. Survival curves were drawn by using the Kaplan-Meier method, and the differences between the groups were compared with the log-rank test. Multivariate analysis was performed to clarify prognostic factors. Results: There were 13 patients in group 1 and 19 in group 2. The degree of enhancement on the delayed-phase images showed statistically significant correlation with the amount of fibrous stroma (P=.001) and the frequency of perineural invasion (P=.01). The survival rate in group 1 was significantly lower than that in group 2 (P=.016). Multivariate analysis revealed that enhancement of more than two-thirds of the ICC was a significant and independent prognostic factor. Conclusion: The degree of enhancement on delayed-phase CT scans is a useful indicator for prediction of the prognosis of patients with mass-forming ICC. (c) RSNA, 2005.
• Gemcitabine combined with 5-fluorouracil and cisplatin (GFP) in patients with advanced biliary tree cancers: A pilot study

  YI Yamashita, A Taketomi, K Fukuzawa, T Yoshizumi, H Uchiyama, M Simada, K Shirabe, K Wakasugi, Y Maehara

  ANTICANCER RESEARCH 26 (1B) 771 - 775 0250-7005 2006/01 [Refereed][Not invited]
   

  Background: Advanced biliary tree cancers have poor prognosis and chemotherapy has been shown to have little impact To date, no standard chemotherapy regimens have been established. A pilot study, to evaluate gemcitabine/5-Fluorouracil(5-FU)/cisplatin(CDDP) (GFP) chemotherapy in patients with advanced biliary tree cancers was performed. Patients and Methods: Eight patients with advanced intrahepatic cholangiocarcinoma and gallbladder carcinoma with no prior chemotherapy were treated with a 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m(2) on days 1, 8, and 15, and of 5-FU at 250 mg/patient and CDDP at 5 mg/patient on days 1 to 5, 8 to 12 and 22 to 26 Results: Of these 8 patients, no complete responses (CR) were observed, but 3 patients (375%) demonstrated partial responses (PR) with an additional 3 patients (37.5%) having stable diseases (SD), as assessed by RECIST Two patients with PR and 1 patient with SD were treated by curative operation after GFP chemotherapy and all of them survived with no recurrence. The median overall survival time was 23.5 months, and median time to progression was 14.5 months. Grade 314 side-effects, such as leukopenia, thrombocytepenia and anemia were found in 4 patients (50%), but no patients dropped out because of toxicity. Conclusion: This GFP chemotherapy has promising antitumor activity and is well tolerated in patients with advanced biliary tree cancers. This regimen warrants further evaluation in a phase II study, including larger numbers of patients.
• Reduced expression of focal adhesion kinase in intrahepatic cholangiocarcinoma is associated with poor tumor differentiation

  Ryuji Ohta, Yo-ichi Yamashita, Akinobu Taketomi, Dai Kitagawa, Yosuke Kuroda, Shinji Itoh, Shin-ichi Aishima, Yoshihiko Maehara

  ONCOLOGY 71 (5-6) 417 - 422 0030-2414 2006 [Refereed][Not invited]
   

  Objective: Focal adhesion kinase ( FAK) expression has been linked to tumor cell invasion and metastasis, but its role in intrahepatic cholangiocarcinoma ( ICC) has not been addressed. The goal of this study was to investigate FAK expression in ICC and to assess whether its expression is correlated with clinicopathological factors or prognosis in patients with ICC. Methods: FAK expression was examined using immunohistochemistry with sections from 56 resected ICC specimens. The correlations between FAK expression and clinical outcome were assessed. Results: The patients were divided into two groups according to the degree of FAK expression: high FAK group ( n = 16) and low FAK group ( n = 40). A lower expression of FAK was correlated with tumor size, poor differentiation, lymph node metastasis, vascular invasion, and intrahepatic metastasis. In the low FAK expression group, multiple recurrence and distant metastases were more prevalent than in the high FAK expression group. The overall and disease- free survival analysis indicated worse outcomes of the low FAK expression group ( p < 0.01). Conclusions: A low expression of FAK in ICC is associated with a poor outcome after a surgical resection. Copyright (C) 2006 S. Karger AG, Basel.
• P-27 門脈欠損・低形成を伴う先天性門脈体循環シャントに対する生体肝移植(示説7 移植2・内視鏡,第43回 日本小児外科学会総会)

  荻田 桂子, 松浦 俊治, 林田 真, 西本 祐子, 副島 雄二, 武冨 紹信, 前原 喜彦, 大野 拓郎, 原 寿郎, 田口 智章

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 42 (3) 433 - 433 2006
• P-26 小児肝移植後リンパ増殖性疾患(PTLD)の治療経験(示説6 移植1,第43回 日本小児外科学会総会)

  林田 真, 荻田 桂子, 松浦 俊治, 西本 祐子, 吉住 朋晴, 副島 雄二, 武富 紹信, 前原 喜彦, 田口 智章

  日本小児外科学会雑誌 特定非営利活動法人 日本小児外科学会 42 (3) 432 - 432 2006
• Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography

  Y Yonemura, A Taketomi, Y Soejima, T Yoshizumi, H Uchiyama, T Gion, N Harada, H Ijichi, K Yoshimitsu, Y Maehara

  LIVER TRANSPLANTATION 11 (12) 1556 - 1562 1527-6465 2005/12 [Refereed][Not invited]
   

  Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right-lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MRV tributaries by volumetry using 3-dimensional computed tomography (3D-CT). Between November 2003 and January 2005, 42 donor livers (right-lobe graft, n = 25; left-lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right-lobe grafts, CV/(right liver volume [RLV]) and (GV - CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV:5 20%, n = 4). The mean CV/RLV ratio was 32.3 +/- 17.1% M, 15.2 +/- 9.9%; V8, 9.2 +/- 4.1%; and IRHV, 8.5 +/- 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV - CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 +/- 12.8% and 55.4 +/- 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day I compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D-CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right-lobe LDLT.
• Liver metastasis with apparent intratumoral superparamagnetic iron oxide uptake

  K Tsushima, A Nishie, K Yoshimitsu, A Taketomi, H Honda

  EUROPEAN RADIOLOGY 15 (10) 2203 - 2204 0938-7994 2005/10 [Refereed][Not invited]
  
• Surgical outcome of patients with hepatocellular carcinoma originating in the caudate lobe

  S Tanaka, M Shimada, K Shirabe, S Maehara, E Tsujita, A Taketomi, Y Maehara

  AMERICAN JOURNAL OF SURGERY 190 (3) 451 - 455 0002-9610 2005/09 [Refereed][Not invited]
   

  Background: Hepatocellular carcinoma (HCC) originating in the caudate lobe is rare, and the treatment for this type of carcinoma is difficult because of its unique anatomic location. Methods: This retrospective study assessed the surgical outcome of patients with caudate lobe HCC. There were 20 cases of HCC originating in the caudate lobe among 435 patients with primary HCC who underwent hepatic resection in our department from 1990 to 2002. The caudate tumors were located in the Spiegel lobe in 3 patients, the paracaval portion in,15 patients, and the caudate process in 2 patients. Surgical procedures consisted of limited resection of the caudate lobe in 6 patients and extended caudate lobectomy in 14 patients. Recurrence was recognized in 12 patients, including 8 patients with multiple intrahepatic recurrences, 1 with peritoneal dissemination, and I with lymph node metastasis. Results: There was no significant difference in postoperative survival rate between patients who underwent limited resection of the caudate lobe and those who underwent extended caudate lobectomy. Compared with 415 patients with HCC originating in other locations, the 20 patients with caudate lobe HCC showed significantly more intraoperative blood loss (P < .05), longer operation time (P < .000 1), and more postoperative complications (P < .005). Intrahepatic recurrence was more frequent in the caudate lobe HCC compared with HCC originating in other locations (40% vs 17.6%; P < .05). There was a significantly poor survival rate in the postoperative patients with caudate HCC (25.9% vs 54.1% for five-year survival; P = .01). Intrahepatic multiple recurrences were frequently recognized in the patients with caudate lobe HCC, indicating no significance for extended caudate lobectomy. Conclusions: Because of the relatively poor prognosis in patients with caudate lobe HCC, adjuvant therapy combined with surgical operation should be considered. (c) 2005 Excerpta Medica Inc. All rights reserved.
• Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation

  M Nakamuta, S Morizono, Y Soejima, T Yoshizumi, S Aishima, S Takasugi, K Yoshimitsu, M Enjoji, K Kotoh, A Taketomi, H Uchiyama, M Shimada, H Nawata, Y Maehara

  TRANSPLANTATION 80 (5) 608 - 612 0041-1337 2005/09 [Refereed][Not invited]
   

  Background. The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for I I living-donor liver transplantation (LDLT) candidates with steatosis. Methods. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. Results. The treatment significantly improved macrovesicular steatosis (30 +/- 4% vs. 12 +/- 12% [mean +/- SEM], P= 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P=0.0033, 26.4 +/- 0.7 kg/m(2)vs. 24.1 +/- 0.8 kg/m(2), P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steotosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. Conclusions. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.
• The newly established human hepatocyte cell line: application for the bioartificial liver

  N Harimoto, A Taketomi, D Kitagawa, Y Kuroda, S Itoh, T Gion, S Tanaka, K Shirabe, M Shimada, Y Maehara

  JOURNAL OF HEPATOLOGY 42 (4) 557 - 564 0168-8278 2005/04 [Refereed][Not invited]
   

  Background/Aims: Human hepatocyte cell lines are reported to lose many of their biochemical functions in a hybrid artificial liver support system (HALSS). Differentiation therapy is useful to up-regulate liver function. Methods: The human hepatoblastoma cell line HepG2 was transfected with HSV/tk gene. Albumin synthesis and ammonia removal activity were evaluated when HepG2/tk was cultured with histone deacetylase inhibitor (FR228) and peroxisome proliferator activated receptor-gamma ligand (pioglitazone). To investigate the function of HepG2/tk in vivo, cell transplantation for 90% hepatectonized rats was conducted. Results: We established stable cell lines which expressed HSV/tk and were sensitive to gancyclovir in vitro and in vivo. Both albumin synthesis rate and ammonia removal rate improved for HepG2/tk incubated with FR228 and pioglitazone for 3 days, which induced nuclear transport of p21. Rats with intrasplenic injection of HepG2/tk precultured for 3 days with FR228 and pioglitazone survived significantly longer than the control rats. The ammonia and total bilirubin concentrations were significantly lower in the test group than in the control group. The injection of gancyclovir inhibited the prolonged survival of the rats with precultured HepG2/tk. Conclusions: HepG2/tk is safe as well as enhancing high levels of liver function. It will be a potential cell source for HALLS in the future. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
• Suppressed MKP-1 is an independent predictor of outcome in patients with hepatocellular carcinoma

  E Tsujita, A Taketomi, T Gion, Y Kuroda, K Endo, A Watanabe, H Nakashima, S Aishima, S Kohnoe, Y Maehara

  ONCOLOGY 69 (4) 342 - 347 0030-2414 2005 [Refereed][Not invited]
   

  Objective: An increase in the activity of mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vivo. This study was designed to clarify the expression of MKP-1 in surgically resected hepatocellular carcinoma (HCC). Methods: We reviewed the cases of 77 patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on paraffin-embedded tissues. The correlation between MKP-1 expression and clinical outcome was investigated. Results: Tumor cells were immunohistochemically stained for MKP-1 expression, and the same levels as in normal hepatocytes were detected in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1 expression significantly correlated with serum alpha-fetoprotein levels and tumor size ( p < 0.05). The disease-free survival rates in MKP-1-negative and - positive patients were 0 and 31.0% at 5 years, respectively ( p < 0.01). The survival rates after a surgical resection in MKP-1-negative and - positive patients were 18.2 and 65.5% at 5 years, respectively ( p < 0.01). Conclusions: The MKP-1 expression in HCC was an independent prognostic factor for outcome in HCC patients. In the future, it will be useful to explore whether the phosphatase expression might account for the response to HCC treatments targeting at MAPK activation. Copyright (C) 2005 S. Karger AG, Basel.
• Preoperative imaging workup for laparoscopic abdominal surgeries; the liver, the gallbladder, and the pancreas

  Kengo Yoshimitsu, D. Kakihara, H. Irie, T. Tajima, Y. Asayama, M. Hirakawa, Y. Ishigami, T. Nakayama, H. Honda, S. Shimizu, A. Taketomi

  Japanese Journal of Clinical Radiology 50 (6) 721 - 730 0009-9252 2005 

  Current status of the preoperative radiological workup for laparoscopic cholecystectomy, hepatectomy, and pancreatic surgery are described. For gallbladder surgery, MRC and/or DICCT can provide useful information regarding the presence of common bile duct stones and the anatomy of the biliary system. For liver surgery, CTA/CTAP may be necessary for the detailed intrahepatic vascular anatomy. For pancreas surgery, thin-sliced MDCT with various reconstructed images may provide sufficient information. Although preoperative imaging technique specifically tailored for laparoscopic surgery is not established, continuous communication between radiologists and surgeons may be important to make it more useful for the surgeons, and also to improve the outcome of the patients.
• 生体肝移植術後C型肝炎再発に対する抗ウイルス療法の成績

  原田 昇, 武冨 紹信, 副島 雄二, 吉住 朋晴, 内山 秀昭, 岡野 慎士, 祇園 智信, 塩谷 聡子, 伊地知 秀樹, 米村 祐輔, 前原 喜彦, 島田 光生

  臨牀と研究 大道学館出版部 82 (1) 154 - 155 0021-4965 2005/01
• Augmented reality navigation system for endoscopic surgery based on three-dimensional ultrasound and computed tomography: Application to 20 clinical cases

  K Konishi, M Hashizume, M Nakamoto, Y Kakeji, Yoshino, I, A Taketomi, Y Sato, S Tamura, Y Maehara

  CARS 2005: Computer Assisted Radiology and Surgery 1281 537 - 542 0531-5131 2005 [Refereed][Not invited]
   

  In the endoscopic Surgical fields, more information which could be used intraoperatively is strongly demanded. Three-dimensional reconstructed images are useful imaging modalities to assist the surgeon in endoscopic surgery. We expected a new magneto-optic hybrid 3-D sensor configuration, and have developed an augmented reality navigation system using an accurate three-dimensional sensory system that can be utilized in endoscopic Surgery. The system has accommodated oblique endoscope, real-time distortion correction of magnetic fields. We have preliminary established 'combined' navigation system. The complete system consists of a laparoscope, two (magnetic and optic) 3D digitizers, ultrasonographic device, a laparoscopic US probe, and a workstation with a volume rendering accelerator. Augmented reality (AR) visualization, which superimposed the visualized 3D-US images and segmented and rendered CT-based images on captured laparoscopic live images, was achieved. We applied Our system to various clinical cases. The system provides us real-time anatomical information which cannot be visualized without navigation system. 3D-US as an imaging modality has the advantage that real-time imaging is acquirable, regardless of organ shift or distortion. (c) 2005 CARS & Elsevier B.V All rights reserved.
• [Living donor liver transplantation for the patient with hepatocellular carcinoma].

  Akinobu Taketomi, Yuuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Yoshihiko Maehara

  Gan to kagaku ryoho. Cancer & chemotherapy 31 (13) 2118 - 21 0385-0684 2004/12 [Refereed][Not invited]
   

  Since 1989, over 3,000 living donor liver transplantation (LDLTx) were performed in Japan. Among them, LDLTx for advanced hepatocellular carcinoma (HCC) with severe liver cirrhosis have recently increased. LDLTx for HCC has been offered only when liver function was severely impaired, or HCC became uncontrollable by other modalities such as hepatic resection or ablation therapies, which often exceeded the Milan criteria. One-and 3-year survivals were 84.6% and 73.3%, respectively. When exceeding the Milan criteria, tumor size over 5 cm, vascular invasion, grade of histologic differentiation of HCC, and high PIVKA-II over 300 mAU/ml were independent risk factors for HCC recurrence. Prevention of HCC or hepatitis C recurrence after transplantation should be resolved to improve graft and patient survival.
• [Evaluation of acute hepatic failure treated at the Department of Medicine III, Kyushu University Hospital: indications for living-donor liver transplantation].

  Shusuke Morizono, Makoto Nakamura, Motoyuki Kohjima, Izuru Miyagi, Tsuyoshi Yoshimoto, Eiichirou Arimaura, Kazuhiro Kotoh, Munechika Enjoji, Yuji Soejima, Akinobu Taketomi, Tomoharu Yoshizumi, Hideaki Uchiyama, Mitsuo Shimada, Yoshihiko Maehara, Hajime Nawata

  Fukuoka igaku zasshi = Hukuoka acta medica 95 (12) 321 - 31 0016-254X 2004/12 [Refereed][Not invited]
   

  To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36%) improved with conservative treatment (conservative treatment group), and the other 16 patients (64%) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82% (9/11); two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters: ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below: p(%) = 1/(1+exp (-(-36.2375 + ALP x 0.0251 + gamma-GTP x 0.0102 + PT x 0.2558 + Volume 21.2158))) x 100. This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure.
• [Current status and future prospects for liver transplantation: Kyushu University Hospital experience].

  Akinobu Taketomi, Yuji Soejima, Tomonobu Gion, Noboru Harada, Norifumi Harimoto, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshihiko Maehara

  Fukuoka igaku zasshi = Hukuoka acta medica 95 (10) 269 - 73 0016-254X 2004/10 [Refereed][Not invited]
  
• Serous surface papillary carcinoma of the peritoneum: Clinical, radiologic, and pathologic findings in 11 patients

  H Morita, J Aoki, A Taketomi, N Sato, K Endo

  AMERICAN JOURNAL OF ROENTGENOLOGY 183 (4) 923 - 928 0361-803X 2004/10 [Refereed][Not invited]
   

  OBJECTIVE. The purpose of our study was to describe the clinical, radiologic, and pathologic findings of serous surface papillary carcinoma of the peritoneum in 11 patients. CONCLUSION. Serous surface papillary carcinoma of the peritoneum should be included in the differential diagnosis when ascites, omental caking, and peritoneal nodules or enhancement are observed in a postmenopausal woman with or without ovarian enlargement.
• The role of heat shock protein 27 expression in hepatocellular carcinoma in Japan: special reference to the difference between hepatitis B and C

  N Harimoto, M Shimada, S Aishima, D Kitagawa, S Itoh, E Tsujita, S Maehara, A Taketomi, S Tanaka, K Shirabe, Y Maehara

  LIVER INTERNATIONAL 24 (4) 316 - 321 1478-3223 2004/08 [Refereed][Not invited]
   

  Background: A recent report showed that heat shock protein (HSP)-27 expression was related to histological grade and survival of patients with hepatocellular carcinoma (HCC). Aims: The aim of this study was to examine the effect of expression of HSP-27 on clinicopathological variables in Japanese patients with HCC. Methods: An immunohistochemical study for HSP-27 was performed on 60 HCC cases using a monoclonal anti-HSP-27 antibody. We divided 60 patients into two groups, patients with a low expression of HSP-27 (n=34) and those with a high expression of HSP-27 (n=26). Forty patients tested positive for the hepatitis C virus (HCV) antibody and 20 tested positive for the hepatitis B surface antigen. Results: There appeared to be no relationship between HSP expression and clinicopathologic factors and no differences were observed between the high expression group and the low expression group. In the hepatitis B virus (HBV) group (n=20), HSP-27 expression correlated significantly with prognosis, disease-free survival (DFS) and overall survival. High expression was significantly associated with poor prognosis in the HBV group. In contrast, patients with a high expression tended to have a good prognosis in the HCV group (n=40): DFS and overall survival. Conclusions: This study showed the possibility that HSP-27 plays different roles in HBV- and HCV-associated HCCs.
• 肝移植後再発肝癌に対するIL-12遺伝子治療に関する実験的研究

  原田 昇, 武冨 紹信, 副島 雄二, 吉住 朋晴, 岡野 慎士, 内山 秀昭, 伊地知 秀樹, 米村 祐輔, 前原 喜彦

  移植 (一社)日本移植学会 39 (総会臨時) 218 - 218 0578-7947 2004/07
• The effects of frequency-encoding gradient upon detectability of the margins and height measurements of normal adult pituitary glands

  A Taketomi, N Sato, J Aoki, K Endo

  NEURORADIOLOGY 46 (1) 60 - 64 0028-3940 2004/01 [Refereed][Not invited]
   

  We investigated the effects of frequency-encoding gradient (FEG) upon detectability and height measurements of the normal adult pituitary gland. We obtained two sets of T1-weighted sagittal images of the pituitary gland from 70 adult subjects without known pituitary dysfunction using 1.5 tesla imagers; one with an inferior-superior FEG, and one with an anterior-posterior FEG. We classified the subjects into three types according to the distribution of fatty marrow in the clivus. Each set of images was assessed for pituitary height on midline sagittal images, and detectability of pituitary margins. Height measurements and detectability scores were evaluated for significant difference between the two FEGs. In subjects with fatty marrow in the clivus, there was significant difference between pituitary height measurements (P<0.005) and pituitary margin detectability (P<0.001). Care should be taken to image the pituitary gland using an anterior-posterior FEG.
• 九州大学病院第三内科における急性肝不全の治療：生体肝移植への適応検討

  森園周祐, 中牟田誠, 国府島庸之, 宮城譲, 吉本剛志, 有村英一郎, 古藤和浩, 遠城寺宗近, 副島雄二, 武冨紹信, 吉住朋晴, 内山秀昭, 島田光生, 前原喜彦, 名和田新

  福岡医学雑誌 95 321 - 331 2004 [Refereed][Not invited]
  
• The combination of multi-voxel MR spectroscopy with MR imaging improve the diagnostic accuracy for localization of prostate cancer

  M Hasumi, K Suzuki, A Taketomi, H Matsui, T Yamamoto, K Ito, K Kurokawa, J Aoki, K Endo, H Yamanaka

  ANTICANCER RESEARCH 23 (5B) 4223 - 4227 0250-7005 2003/09 [Refereed][Not invited]
   

  Background: We assessed the usefulness of combined multi-voxel magnetic resonance spectroscopy (MRS) and MR imaging (MR[) in the diagnosis of prostate cancer localization. Patients and Methods: MRS and MRI were performed in 21 patients with prostate cancer. On T2-weighted images, tumor localization was based on low signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed when the ratio of choline plus creatine to citrate was greater than 0.86 The results were analyzed with reference to pathological confirmation of prostate cancer at bilateral or unilateral lobe. Results: Six out of I I patients with unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9 of 10 patients with bilateral positive biopsy specimens were diagnosed as bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and MRS. The accuracy of MRI alone was 71.4%, while that of combined MR[ and MRS was 81.0%. Conclusion: Combined MRI and MRS improved the diagnostic accuracy for localization of prostate cancer.
• Diacylglycerol kinase epsilon regulates seizure susceptibility and long-term potentiation through arachidonoylinositol lipid signaling

  EBR de Turco, W Tang, MK Topham, F Sakane, VL Marcheselli, C Chen, A Taketomi, SM Prescott, NC Bazan

  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 98 (8) 4740 - 4745 0027-8424 2001/04 [Refereed][Not invited]
   

  Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from phosphatidylinositol 4,5-bisphosphate and generated by stimulation of glutamate metabotropic receptors linked to C proteins and activation of phospholipase C. 20:4-DAG signaling is terminated by its phosphorylation to phosphatidic acid, catalyzed by diacylglycerol kinase (DGK). We have cloned the murine DGK epsilon gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGKe in synaptic function was investigated in mice with targeted disruption of the DGK epsilon. DCK epsilon (-/-) mice showed a higher resistance to eletroconvulsive shock with shorter tonic seizures and faster recovery than DGK epsilon (+/+) mice. The phosphatidylinositol 4,5-bisphosphate-signaling pathway in cerebral cortex was greatly affected, leading to lower accumulation of 20:4-DAG and free 20:4. Also, long-term potentiation was attenuated in perforant path-dentate granular cell synapses. We propose that DGK epsilon contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.
• Renin-producing hepatoblastoma

  Hiroshi Moritake, Akinobu Taketomi, Sachiyo Kamimura, Yoshiko Ikuno, Yousuke Seo, Toshirou Fukuda, Haruo Iguchi, Jun Okamura

  American Journal of Pediatric Hematology/Oncology 22 (1) 78 - 80 0192-8562 2000 [Refereed][Not invited]
   

  Renin-producing tumors of extrarenal origin are rare in children. An 8-year-old boy with hepatoblastoma and hypertension associated with a high plasma renin level is reported. After chemotherapy, the plasma renin level normalized and the hypertension spontaneously resolved. The patient underwent surgery, and a right trisegmentectomy of the liver and a partial resection of the second and third segments were performed. The tumor was as shown the source of renin by immunohistochemical study and reverse transcriptase-polymerase chain reaction. 2000 Lippincott Williams & Wilkins, Inc. © 2000 Lippincott Williams & Wilkins, Inc.
• Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism

  Hisanobu Oda, Akinobu Taketomi, Riichiroh Maruyama, Riyoko Itoh, Kenichi Nishioka, Hiroyuki Yakushiji, Tomokazu Suzuki, Mutsuo Sekiguchi, Yusaku Nakabeppu

  Nucleic Acids Research 27 (22) 4335 - 4343 0305-1048 1999/11/15 [Refereed][Not invited]
   

  The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase, produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs in their 5' regions. We report here that these transcripts produce three forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation reactions. Three polypeptides were also detected in extracts of human cells, using western blotting. B-type mRNAs with a polymorphic alteration (GU→GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream, produced an additional polypeptide (p26) in vitro. Substitution of each AUG abolished the production of each corresponding polypeptide. Cell lines from individuals with the GC allele contain more B-type mRNAs than do those of GT homozygotes, and the former produce all of four polypeptides but the latter lack p26. Amounts of each polypeptide reflected copy number of the GC allele in each cell line. There is an apparent linkage disequilibrium between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at codon 83 for p18.
• Diffuse bone metastasis with hematologic disorders from gastric cancer: Clinicopathological features and prognosis

  T Etoh, H Baba, A Taketomi, H Nakashima, S Kohnoe, Y Seo, T Fukuda, H Tomoda

  ONCOLOGY REPORTS 6 (3) 601 - 605 1021-335X 1999/05 [Refereed][Not invited]
   

  Bone metastases diffusely invading the bone marrow from gastric cancer often manifest a rapid clinical course and the prognosis is very poor due to hematologic disorders such as DIC (disseminated intravascular coagulation) and/or MAHA (microangiopathic hemolytic anemia). The objective of this study was to clarify the clinicopathological features and prognosis of patients with gastric cancer in whom diffuse bone metastasis associated with hematologic disorders were evident. Thirty-eight patients with bone metastasis from a primary gastric cancer were thus selected and placed into 2 groups consisting of 15 with diffuse bone metastasis with DIC and/or MAMA, and 23 patients who had bone metastasis without hematological disorders. We compared the clinicopathological features and prognosis between the two groups. The clinicopathological features in patients with diffuse bone metastasis accompanied by hematologic disorders were significantly related to undifferentiated adenocarcinoma, a relatively younger age, elevated levels of serum ALP-BI and LDH, and a lower frequency of extraosseous metastasis. The median survival time after manifestation was 2 and 11 months for the patients with or without hematologic disorders, respectively. The prognosis was significantly worse in cases of DIC with the median survival being only one month. Since: prognosis of diffuse bone metastasis from gastric cancer is significantly poor, close attention should be directed to the specific clinicopathologic features related to diffuse bone metastasis plus hematologic disorders. Regarding high risk patients, a regular follow-up of the serum chemistry levels and a bone scan will aid in the early detection of the disease.
• Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma

  M Morita, H Kuwano, H Baba, A Taketomi, S Kohnoe, H Tomoda, K Araki, H Saeki, K Kitamura, K Sugimachi

  CANCER 83 (7) 1307 - 1311 0008-543X 1998/10 [Refereed][Not invited]
   

  BACKGROUND. Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS, The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS. The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with greater than or equal to 2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS. In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized. Cancer 1998; 83:1307-11. (C) 1998 American Cancer Society.
• A case of biliary cystadenoma with obstructive jaundice

  A Taketomi, R Tamada, K Takenaka, R Kawano, T Maeda, K Sugimachi

  ONCOLOGY REPORTS 5 (4) 833 - 835 1021-335X 1998/07 [Refereed][Not invited]
   

  Biliary cystadenoma is a rare cause of obstructive jaundice. We report a case of a 78-year-old Japanese man with biliary cystadenoma presenting repetitive abdominal pain and jaundice. Ultrasound sonography revealed a hyperechoic mass in the left lateral lobe of the liver. Histological examination revealed a biliary cystadenoma. Intracystic. hemorrhage was assumed to be the cause of obstruction of the bile ducts.
• Family aggregation of carcinoma of the hypopharynx and cervical esophagus: Special reference to multiplicity of cancer in upper aerodigestive tract

  M Morita, H Kuwano, T Nakashima, A Taketomi, H Baba, T Saito, H Tomoda, A Egashira, H Kawaguchi, K Kitamura, K Sugimachi

  INTERNATIONAL JOURNAL OF CANCER 76 (4) 468 - 471 0020-7136 1998/05 [Refereed][Not invited]
   

  The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer. (C) 1998 Wiley-Liss, Inc.
• Sequential methotrexate and 5-fluorouracil therapy for diffuse bone metastasis from gastric cancer

  T Etoh, H Baba, A Taketomi, H Nakashima, S Kohnoe, Y Seo, T Saito, H Tomoda

  ANTICANCER RESEARCH 18 (3B) 2085 - 2088 0250-7005 1998/05 [Refereed][Not invited]
   

  We herein present a case of diffuse bone metastasis from early gastric cancer with disseminated intravascular coagulation (DIC) in a 40-year old man, who had undergone a curative gastrectomy and had no evidence of recurrence for five yeats after surgery. The patient was treated with an intravenous administration of sequential methothrexate (MTX) and 5-fluorouracil (5-FU), and demonstrated a favorable clinical course without any severe pain. Despite the fact that the presence of diffuse bone metastasis from gastric cancer plus hematologic disorders tends to indicate a significantly poor prognosis, the patient survived for a relatively long period (11 months) following chemotherapy. We thus conclude that MTX/5-FU sequential therapy seems to be a clinically useful regimen to improve both the symptoms and survival for cases of diffuse bone metastasis from gastric cancer.
• Submucosal gastric cancer with lymph node metastasis

  M Morita, H Baba, T Fukuda, A Taketomi, S Kohnoe, Y Seo, T Saito, H Tomoda, K Sugimachi

  JOURNAL OF SURGICAL ONCOLOGY 68 (1) 5 - 10 0022-4790 1998/05 [Refereed][Not invited]
   

  Background and Objectives: The intraoperative assessment of lymph node metastasis of gastric cancer remains difficult and the characteristics of recurrence after gastrectomy are not well known regarding submucosal cancer. Methods: We examined 452 patients with submucosal gastric cancer and compared the clinicopathologic features as well as recurrence patterns between the 71 cases with lymph node metastasis (group I) and the 381 without it (group II). Results: The mean tumor sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I, which were significantly higher than those in group II (36.7 and 14.2%, 140/381 and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452) experienced recurrence after undergoing a gastrectomy and hematogenic recurrence was the most frequent type of recurrence (2.0%, 9/452). However, in group I, lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II, respectively (P < 0.05). Conclusions: The submucosal cancer with larger size, lymphatic invasion, and vascular invasion has high risks for lymph node metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic recurrence is important fur the patients with node positive submucosal cancer, especially within 5 years after operation. (C) 1998 Wiley-Liss, Inc.
• The clinicopathological characteristics and outcome of patients with right colon cancer

  H Tomoda, A Taketomi, H Baba, S Kohnoe, Y Seo, T Saito

  ONCOLOGY REPORTS 5 (2) 481 - 483 1021-335X 1998/03 [Refereed][Not invited]
   

  We compared the characteristics between the 281 cases with right colon cancer (RCC) and 438 cases with left colon cancer (LCC) who underwent a resection for the disease at our hospital between 1972 and 1995. The mean patient age was significantly higher for RCC than for LCC (62.5 years vs 60.4 years). The mean tumor size was also significantly larger in RCC than in LCC (6.1 cm vs 4.8 cm). The type of recurrence or survival was similar between RCC and LCC. Elderly patients were also found to be more likely to develop RCC than younger patients. This cancer often grows to a large size before being diagnosed. These findings, therefore, suggest the need for targeted examinations for the early detection of RCC, especially in the elderly.
• Second primary extracolonic cancers in Japanese hereditary nonpolyposis colorectal cancer

  H Tomoda, H Baba, A Taketomi, S Kohnoe, Y Seo, T Saito

  ONCOLOGY REPORTS 5 (1) 143 - 145 1021-335X 1998/01 [Refereed][Not invited]
   

  We examined the occurrence of second primary extracolonic cancers in 1,170 patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1994. Such cancers occurred more often in cases with hereditary nonpolyposis colorectal cancer (HNPCC) than in those without (11.1% vs. 3.6%, P=0.0286). Five HNPCC cases developed 6 cancers in the stomach, endometrium, ovary, and ureter. The mean interval between the first and second operation was 66 months (range: 18-153). These findings thus indicate the importance of targetted surveillance for any second primary cancers in the upper gastrointestinal, female genital, or upper urologic tract, especially in HNPCC patients.
• Multiple primary colorectal and gastric carcinoma in Japan

  H Tomoda, A Taketomi, H Baba, S Kohnoe, Y Seo, T Saito

  ONCOLOGY REPORTS 5 (1) 147 - 149 1021-335X 1998/01 [Refereed][Not invited]
   

  We investigated the occurrence of multiple primary colorectal and gastric cancer (MPCGC) in 1277 colorectal cancer patients between 1972 and 1996. MPCGC was found in 65 (5.1%). In the 28 synchronous cases, gastric or colorectal cancer was accidentally detected by pre-, intra-, or postoperative examinations. In 23 of the 37 metachronous cases, colorectal cancer developed on average 83 months after the operation for gastric cancer. In the other 14 cases, gastric cancer developed on average 70 months after the operation for colorectal cancer. Therefore, careful pre-, intra-, or postoperative examinations are strongly called for in order to not overlook the presence of colorectal or gastric lesions in MPCGC cases.
• Changing site distribution of Japanese colorectal cancer

  H Tomoda, H Baba, A Taketomi, S Kohnoe, Y Seo, T Saito

  ONCOLOGY REPORTS 4 (5) 1011 - 1013 1021-335X 1997/09 [Refereed][Not invited]
   

  To clarify the time trends in the characteristics of colorectal cancer, we investigated 1,286 Japanese patients with colorectal cancer who underwent a resection of the disease between 1972 and 1995 at our hospital. Based on our findings, this carcinoma tended to shift to the more proximal colon in the second 11-year period in comparison to the first 11-year period (P=0.0001). This tendency was also found in elderly patients (P=0.0001), but not in young ones. These findings thus suggest the need for targeted examinations for the early detection of the proximal colon cancer, especially in the elderly.
• Inguinal lymph node recurrence of mucosal cancer of the stomach

  M Morita, H Baba, A Taketomi, S Kohnoe, H Tomoda, T Fukuda, K Sugimachi

  ONCOLOGY REPORTS 4 (4) 713 - 715 1021-335X 1997/07 [Refereed][Not invited]
   

  Metastasis to the inguinal lymph node from early gastric cancer is rare. We report a case of 63-year-old Japanese male with gastric mucosal cancer which metastasized to the left inguinal lymph nodes 4 years after a curative gastrectomy. The importance of routine examination of inguinal lymph nodes for cases with gastric cancer is suggested.
• Pyrimidine nucleoside phosphorylase activity, 5-fluorouracil concentration and thymidylate synthase inhibition rate in colorectal cancer after oral administration of 5'-doxifluridine

  H. Tomoda, M. Morita, H. Matsuoka, H. Baba, A. Taketomi, S. Kohnoe, Y. Seo, T. Saito

  Japanese Journal of Cancer and Chemotherapy 24 (8) 971 - 974 0385-0684 1997 [Refereed][Not invited]
   

  To assess the mechanism of the anticancer effect of doxifluridine (5'- DFUR), a clinico-pharmacological study was performed. So far, no comparative study has been reported between the thymidylate synthase (TS) inhibition rate and the 5-FU concentration in colorectal cancer after oral administration of 5'-DFUR. In 37 patients with colorectal cancer, 5'-DFUR was administered orally/preoperatively (800 mg/day x more than 4 days before operation and 300mg on the day of operation). The mean total dosage was 6.9g. Specimens of tumor and normal intestinal tissue were obtained 4.4 hours on average after final administration. The TS inhibition rate as well as the 5-FU concentration and the activity of pyrimidine nucleoside phosphorylase (PyNPase) were analyzed in both tissues. The PyNPase activity was significantly higher in the tumor tissue than in the normal tissue (137.9±10.8 vs. 31.0±4.7 μ g FU/mg protein/hr, p< 0.0001). The 5-FU concentration was also significantly higher in the tumor tissue than in the normal tissue (101.3±30.6 vs. 23.2±5.5 ng/g, p=0.024). The TS inhibition rate correlated with the 5-FU concentration in the tumor tissue (r=0.527, p=0.047). These findings suggest that the TS inhibition rate may be an index of the anticancer effect of 5'-DFUR in colorectal cancer.
• Renal function after elective hepatic resection

  T Matsumata, A Taketomi, Y Fujiwara, M Shimada, K Takenaka, K Sugimachi

  HEPATO-GASTROENTEROLOGY 43 (9) 602 - 607 0172-6390 1996/05 [Refereed][Not invited]
   

  Background/Aims: Although morbidity and mortality associated with liver surgery has declined, in particular operative death from river failure, accumulation of fluid in the peritoneal or pleural cavities after hepatic resection is still the most common post-operative complication and it often decreases the patient's quality of life. The purpose of this retrospective review is to discuss the effect of renal dysfunction following hepatic resection on ascites formation in patients who underwent hepatic resection. Materials and Methods: The patients who underwent hepatectomy were assigned to two groups; Group A patients (n=119) had some form of ascites or pleural effusion, either intractable or easily controlled, while Group B patients (n=178) had neither ascites nor pleural effusion. We compared the clinical and laboratory data, operative risk factors, and the postoperative renal us well as hepatic functions of the two groups. Results: In addition to ordinary risk factors associated with ascites formation such as decreased plasma oncotic pressure due to hypoalbuminemia along with increased hydrostatic pressure in the portal circulation, renal dysfunction after hepatic resection might be the primary cause of fluid accumulation in the peritoneal cavity. Conclusion: As one of the mechanisms of ascites formation following hepatic resection, toe must consider the presence of renal dysfunction and protect against ascites formation and treat refractory ascites after hepatic resection not only by such traditional methods such as water and salt restriction, the use of diuretics, and the infusion of albumin products, but also by preserving the renal function after hepatectomy.
• Requirement for two conserved cysteine residues in the Ada protein of Escherichia coli for transactivation of the ada promoter

  A. Taketomi, Y. Nakabeppu, K. Ihara, D. J. Hart, M. Furuichi, M. Sekiguchi

  Molecular and General Genetics 250 (5) 523 - 532 0026-8925 1996/03/20 [Refereed][Not invited]
   

  Cysteine residue 69 of the Escherichia coli Ada transcription factor, which accepts a methyl group from methylphosphotriester in methylated DNA, was substituted by each of 19 other amino acids. Only the mutant Ada (C69H), carrying a histidine substitution of Cys69, exhibited a limited degree of transactivating potential for the ada promoter in E. coli cells although the mutant protein was completely devoid of methylphosphotriester-DNA methyltransferase activity. Using a multicopy plasmid system for the expression of Ada protein, we have shown that Ada C69H has a transactivating capacity equivalent to that of wild-type Ada protein in the absence of an alkylating agent. This indicates that the zinc-binding capacity of histidine at residue 69 is likely to be sufficient for Ada to recognize and bind to the ada promoter. Furthermore, transactivation of the ada promoter by Ada C69H was enhanced up to 6-fold by treatment with methylating agents. An additional substitution was made with alanine in Ada C69H, replacing Cys321, the site for acceptance of a methyl group from O6-methylguanine and O4-methylthymine residues in DNA, with alanine. This renders the protein completely inactive as a methyltransferase but this derivative is constitutively active as a transactivator for the ada promoter. Therefore, acquisition of a methyl group at Cys321 apparently enhances the transactivating capacity of Ada protein on the ada promoter. We propose that the transcription-regulating function of Ada protein is under dual control by methylation of cysteine residues at positions 69 and 321 the former enhances DNA binding, while the latter enhances the transactivating capacity of the protein.
• Mutations in the repair system of neuroblastoma

  T Tajiri, S Suita, Y Zaizen, S Okuzono, K Shono, Y Fujii, Y Nakabeppu, K Nishioka, A Taketomi, M Sekiguchi

  XXX WORLD CONGRESS OF THE INTERNATIONAL COLLEGE OF SURGEONS, VOLS 1-2 1225 - 1228 1996 [Refereed][Not invited]
   

  MTH1 protein is the repair enzyme, which degrades 8-oxodGTP into the monophosphate. We investigated the mutation of the MTH1 gene in neuroblastoma cell lines and frozen samples. The mutations of the MTH1 gene were examined using the PCR/SSCP method. One polymorphism of exon4 was detected in 1 of 3 cell lines and 10 (17.9%) of 56 frozen samples of neuroblastoma. Direct sequencing revealed that this polymorphism resulted in a change of the amino acid. Five of these 10 samples were tumors from the patients with stage IV. But this polymorphism was also found in 35 (17.5%) of 200 samples of blood cells in a normal human group. We are presently continuing to evaluate the biological significance of this polymorphism.
• Simplified inflow control using stapling devices for major hepatic resection

  Katsuhiko Yanaga, Takashi Nishizaki, Kazuharu Yamamoto, Akinobu Taketomi, Takashi Matsumata, Kenji Takenaka, Keizo Sugimachi

  Archives of Surgery 131 (1) 104 - 106 0004-0010 1996 [Refereed][Not invited]
   

  We describe the efficacy of a new technique for hepatic inflow division using stapling devices in major hepatic resections. We studied 28 consecutive patients who underwent major hepatic resection at a tertiary referral center by en masse inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow control with stapling devices. Although stapling devices were used for larger tumors (mean±SD, 12.2±8.6 vs 5.7±5.0 cm P=.02), the operation time (261±57 vs 301±143 minutes), operative blood loss (2071±1318 vs 4792±6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]), and hospital stay (16.0±2.6 vs 20.6±7.4 days) were favorable for resections with staplers vs resections without staplers the overall incidences of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10% [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling devices allow simple, quick, and safe en masse inflow control in major hepatic resections.
• Continuous hepatic arterial infusion chemotherapy with low dose CDDP plus 5-FU for liver metastases from colorectal carcinoma

  S. Kohnoe, A. Taketomi, M. Morita, H. Baba, H. Matsuoka, Y. Seo, T. Saito, H. Tomoda

  Japanese Journal of Cancer and Chemotherapy 23 (11) 1429 - 1432 0385-0684 1996 [Refereed][Not invited]
   

  Seven patients with unresectable liver metastases from colorectal carcinoma were treated with low dose CDDP plus 5-FU continuous hepatic arterial infusion chemotherapy. A hepatic artery catheter was placed into the gastroduodenal artery at laparotomy or percutaneously placed into the proper hepatic artery via left subclavian artery. Through an injection port placed beneath the skin, 5-FU (300 mg/m2/day) was continuously infused for 5 days CDDP (6 mg/m2/day) was infused for 5 successive days a week. One cycle consisted of 4 weeks. The response rate was 71% (1 CR, 4 PR, 2 NC). The CEA level decreased in all cases. The median survival was 17 months. Major toxicities were abdominal pain and appetite loss due to extrahepatic perfusion of the drugs. Failure in maintaining the catheter was a problem in most cases. The pharmacokinetic study demonstrated high hepatic extraction of CDDP and 5-FU (40% and 90%, respectively). These results suggest that continuous hepatic arterial infusion chemotherapy with low dose CDDP plus 5- FU is effective for patients with unresectable liver metastases from colorectal carcinoma.
• Influence of blood transfusion on postoperative long-term liver function in patients with hepatocellular carcinoma

  H Itasaka, K Yamamoto, A Taketomi, H Higashi, T Kamakura, T Matsumata

  HEPATO-GASTROENTEROLOGY 42 (5) 465 - 468 0172-6390 1995/09 [Refereed][Not invited]
   

  Background/Aims: To research for possible adverse effects of blood transfusion on Liver function at a relatively long term after hepatic resection, Liver function tests at one and two years after the surgery were studied in patients with hepatocellular carcinoma. Materials and Methods: Seventy-one patients with no evidence of cancer recurrence during two years after the surgery were selected for this retrospective analysis. Patients were divided into two groups depending on perioperative blood transfusion: those who received blood transfusion (BT(+), n=38), and those without blood transfusion (BT(-), n=33). Results: There were no statistical differences in the preoperative clinical features including fiver function tests except decreased prothrombin time index (P<0.01) and larger amount of intraoperative blood loss (P<0.01) in BT(+) group. Platelet counts at 2 years after the surgery were significantly higher in the BT(-) group (P<0.05). Two-way ANOVA showed no significant difference in liver function tests between the two groups. In multiple regression analysis, blood transfusion significantly correlated with serum total bilirubin at 2 year, but did not at 2 years after the surgery. Conclusions: The influence of blood transfusion in, the patients with hepatocellular carcinoma was considered to be minimum within 2 years after hepatectomy.
• DES-GAMMA-CARBOXY PROTHROMBIN AND PROLIFERATIVE ACTIVITY OF HEPATOCELLULAR-CARCINOMA

  T SUEHIRO, T MATSUMATA, H ITASAKA, A TAKETOMI, K YAMAMOTO, K SUGIMACHI

  SURGERY 117 (6) 682 - 691 0039-6060 1995/06 [Refereed][Not invited]
   

  Background. Des-gamma-carboxy prothrombin (DCP) is a useful marker for the prognosis of hepatocellular carcinoma (HCC). In this report we investigated the relationship between the positivity of DCP and proliferative activity of HCC and discuss the cause of poor prognosis of DCP-positive HCC. Methods. Immunohistochemical and clinicopathologic study was done in 114 patients with resected HCC measuring less than 6 cm in diameter by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). Results. PCNA labeling index (PCNA-LI) was significantly higher in the patients with DCP-positive HCC than in those with DCP-negative HCC; also a positive correlation was noted between the PCNA-LI and the DCP level. We divided patients into two groups according to the PCNA-LI. In the high PCNA-LI group the patients with DCP-positive HCC exhibited a higher PCNA-LI than did the patients with DCP-negative HCC. As for pathologic prognostic factors, the DCP-positive high PCNA-LI group showed the highest incidence of tuner thrombus of the portal vein and intrahepatic metastasis while also exhibiting the lowest recurrence-freedom rate. From multivariate analysis we find that DCP, as well as PCNA-LI, is one of the risk factors for recurrence of HCC after hepatectomy. Conclusions. Our results thus suggest that DCP-positive HCC showed high PCNA-LI, and this might be the main cause for early intrahepatic spread and poor prognosis of DCP-positive HCC.
• THROMBOMODULIN INHIBITS INTRAHEPATIC SPREAD IN HUMAN HEPATOCELLULAR-CARCINOMA

  T SUEHIRO, M SHIMADA, T MATSUMATA, A TAKETOMI, K YAMAMOTO, K SUGIMACHI

  HEPATOLOGY 21 (5) 1285 - 1290 0270-9139 1995/05 [Refereed][Not invited]
   

  Thrombomodulin (TM) converts thrombin from procoagulant into anticoagulant protein to activate protein C. Thrombin also plays an important role in the metastatic process of cancer cells. We performed an immunohistochemical and clinicopathological study of TM in 141 cases with resected hepatocellular carcinoma (HCC) measuring less than 6 cm in diameter. Twenty-five specimens (17.73%) stained positive for TM. TM was found in the cytoplasm and surface of cancer cells. The clinicopathological findings according to the positive of TM are examined in HCC. The preoperative plasma TM level of the patients with tissue that stained positive for TM was significantly higher than that of the patients with negative results; for the postoperative TM level, there were no differences between them, In addition, the frequencies of intrahepatic metastasis, tumor thrombus in the portal vein, and capsular infiltration were significantly lower in patients whose tissue stained positive for TM ban in patients whose tissue stained negative for TM. The recurrence freedom rate was significantly higher in patients whose tissue stained positive for TM than patients whose tissue stained negative for TM. Thus, TM-producing HCC shows a slow intrahepatic spread. Therefore, these findings suggest that TM may inhibit the adhesion of tumor cells to the portal vein because of anticoagulant activity and thus prevent the spread of intrahepatic metastasis.
• Generation and Elimination of 8-Oxo-7, 8-Dihydro-2'-Deoxyguanosine 5'-Triphosphate, A Mutagenic Substrate for DNA Synthesis, in Human Cells

  Hiroshi Hayakawa, Michihiko Kuwano, Akinobu Taketomi, Kunihiko Sakumi, Mutsuo Sekiguchi

  Biochemistry 34 (1) 89 - 95 1520-4995 1995 [Refereed][Not invited]
   

  8-Oxo-7, 8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a potent mutagenic substrate for DNA synthesis. The present study deals with generation and degradation of 8-oxo-dGTP in the nucleotide pool of human cells. (1) 8-Oxo-dGTP can be generated not only by direct oxidation of dGTP but also by phosphorylation of 8-oxo-dGDP by nucleoside diphosphate kinase. (2) 8-Oxo-dGTP is rapidly degraded to 8-oxo-dGMP by cellular 8-oxo-dGTPase activity. 8-Oxo-dGMP thus produced cannot be rephosphorylated guanylate kinase, which phosphorylates both GMP and dGMP to the corresponding nucleoside diphosphates, is totally inactive for 8-oxo-dGMP. (3) 8-Oxo-dGMP is further degraded to 8-oxo-deoxyguanosine by a nucleotidase. The enzyme was partially purified from an extract of human Jurkat cells, and the mode of action was elucidated. 8-Oxo-dGMP is the most preferred substrate of the enzyme, and other nucleoside monophosphates are cleaved at significantly lower rates: Km for 8-oxo-dGMP is 10 times lower than that for dGMP, the second best substrate for the enzyme. The enzyme appears to convert 8-oxo-dGMP, which accumulates in the cellular nucleotide pool, to a form readily excretable to the cell exterior. © 1995, American Chemical Society. All rights reserved.
• Levels of Amino Acids in Human Hepatocellular Carcinoma and Adjacent Liver Tissue

  Takashi Nishizaki, Takashi Matsumata, Akinobu Taketomi, Kazuharu Yamamoto, Keizo Sugimachi

  Nutrition and Cancer 23 (1) 85 - 90 1532-7914 1995/01/01 [Refereed][Not invited]
   

  Total parenteral nutrition can be used to overcome amino acid imbalance in cancer patients. Because there is little documentation of treatment for amino acid imbalance in patients with hepatocellular carcinoma (HCC), we designed a study 1) to compare tissue levels of amino acids between HCC and the adjacent liver and 2) to determine which serum amino acids correlate to tumor volume. A significant elevation of methionine and a significant decrease of glycine and cystine were observed in HCC compared with adjacent liver tissue, and a significant correlation was found between tumor volume and serum methionine levels (r = -0.636, p 0.01). Thus the tumor tissue competes successfully with host tissue for nitrogen substrates, particularly methionine, and an accelerated protein synthesis in HCC consumes large amounts of these amino acids. The possibility of methionine-depleted treatment could be considered for patients with HCC. © 1995, Taylor & Francis Group, LLC. All right reserved.
• Outpatient follow-up system using a personal computer for patients with hepatocellular carcinoma after surgery

  Hidetoshi Itasaka, Takashi Matsumata, Akinobu Taketomi, Kazuharu Yamamoto, Katsuhiko Yanaga, Kenji Takenaka, Kouhei Akazawa, Keizo Sugimachi

  Journal of Medical Systems 18 (6) 329 - 333 0148-5598 1994/12 [Refereed][Not invited]
   

  A simple outpatient follow-up system was developed with a laptop personal computer to assist management of patients with hepatocellular carcinoma after hepatic resections. Since it is based on a non-relational database program and the graphical user interface of Macintosh operating system, those who are not a specialist of the computer operation can use it. It is helpful to promptly recognize current status and problems of the patients, to diagnose recurrences of the disease and to prevent lost from follow-up cases. A portability of the computer also facilitates utilization of these data everywhere, such as in clinical conferences and laboratories. © 1994 Plenum Publishing Corporation.
• DETECTION OF HEPATITIS-C VIRUS-RNA IN THE ULTRASONIC DISSECTOR IRRIGATING SOLUTION USED IN LIVER SURGERY

  H HIGASHI, T MATSUMATA, J HAYASHI, K YANAGA, M SHIMADA, K SHIRABE, A TAKETOMI, S KASHIWAGI, K SUGIMACHI

  BRITISH JOURNAL OF SURGERY 81 (9) 1346 - 1347 0007-1323 1994/09 [Refereed][Not invited]
   

  Hepatitis C virus (HCV) was detected in the irrigating solution aspirated by the ultrasonic dissector system used in liver surgery with reverse transcription polymerase chain reaction technique and was then compared with HCV RNA in the serum to clarify the risk of viral transmission to hospital personnel. The positivity of HCV RNA in the aspirated irrigating solution was approximately equal in all patients whose serum was positive for HCV RNA. However, viral RNA was not detected in the aspirated irrigating solution of any patient who seronegative for HCV RNA. These results indicate that it is necessary to be cautious regarding the transmission of HCV during liver surgery when using the ultrasonic dissector in HCV RNA seropositive patients, the irrigating solution aspirated by this device appears to be highly infectious.
• BENEFICIAL OR ADVERSE-EFFECTS OF HEPATECTOMY VS ETHANOL INJECTION THERAPY IN RBT-1 CARCINOMA OF THE RAT-LIVER

  Y IKEDA, T MATSUMATA, H HAYASHI, A TAKETOMI, K YAMAMOTO, K SUGIMACHI

  HEPATOLOGY 20 (1) 166 - 169 0270-9139 1994/07 [Refereed][Not invited]
   

  In an attempt to ascertain the possible beneficial or adverse effects of ethanol injection into a hepatic malignant tumor, we carried out a series of experiments using the RBT-1 carcinoma. Ten days after the inoculation of RBT-1 carcinoma into the rat livers, the animals were separated into four groups: group A received a sham operation, group B had ethanol injections directly into the hepatic tumor, group C underwent tumor removal and group D underwent tumor removal 20 min after ethanol injection. When a comparison was made with all groups, survival time was significantly longer in group B than in A (p < 0.01), group C than A (p < 0.01) and group C than B (p < 0.01). The incidence of vascular permeation of liver tumor cells into the hepatic vein was significantly higher in group D than C (p < 0.05). Twenty days after initial injection of RBT-1 tumor, 10 rats in each group were killed, and their lungs were assessed for evidence of metastatic spread of tumor. The number of metastatic nodules in the lungs was significantly increased in those rats that had undergone intrahepatic ethanol injection vs. those that had not (group B vs. A [p < 0.05] and group D vs. C [p < 0.05]). The number of metastatic nodules in the lungs differed significantly in those rats that had undergone hepatectomy vs. those that had not. These results are taken to mean that hepatectomy and ethanol injection into a tumor was an effective therapy. However, we believe ethanol injection into hepatic tumors may increase the risk of metastasis and should not, at present, be recommended in those patients who have operable liver cancer.
• REPEAT HEPATECTOMY FOR RECURRENT HEPATOCELLULAR-CARCINOMA

  M SHIMADA, T MATSUMATA, A TAKETOMI, K YAMAMOTO, H ITASAKA, K SUGIMACHI

  SURGERY 115 (6) 703 - 706 0039-6060 1994/06 [Refereed][Not invited]
   

  Background. The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. Methods. The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. Results. Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7%+/-8.7%) was significantly higher than that in the first hepatectomy (14.7%+/-5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patietns survival and disease-free survival afte a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. Conclusions. A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma.
• CHARACTERISTICS OF HEPATOCELLULAR-CARCINOMA ORIGINATING IN THE CAUDATE LOBE

  M SHIMADA, T MATSUMATA, T MAEDA, K YANAGA, A TAKETOMI, K SUGIMACHI

  HEPATOLOGY 19 (4) 911 - 915 0270-9139 1994/04 [Refereed][Not invited]
   

  Nine patients with hepatocellular carcinoma originating in the caudate lobe who underwent hepatic resection were studied. The caudate lobe was divided into three parts, according to the criteria of Kumon, including the Spiegel lobe, the paracaval portion and the caudate process. The tumors were located in the Spiegel lobe in four, the paracaval portion in four and the caudate process in one. Surgical procedures consisted of right hepatic lobectomy in one, central bisegmentectomy in one and caudate lobectomy in seven. The mean surgical time was 379 +/- 129 min; the mean estimated blood loss was 2,994 +/- 2,303 ml. The above-mentioned surgical risks were more clearly recognized in the paracaval portion than in the Spiegel lobe. In addition, most patients experienced significant postoperative complications. Six of eight patients with 6 mo or longer follow-up had recurrences, and two of six patients died. The characteristics of hepatocellular carcinoma in the caudate lobe were as follows: (a) a higher surgical risk, and more definite risk in the paracaval portion; and (b) a higher rate of early recurrence. A left lobectomy for the Spiegel lobe, a right or left trisegmentectomy for the paracaval portion and a right lobectomy for the caudate process would be ideal from the point of view of the portal supply of the caudate lobe. However, in cirrhotic patients either a caudate lobectomy or partial resection might be preferable because longer survival can be expected.
• Protein induced by vitamin K absence or antagonist II as a prognostic marker in hepatocellular carcinoma. Comparison with alpha‐fetoprotein

  Taketoshi Suehiro, Keizo Sugimachi, Takashi Matsumata, Hidetoshi Itasaka, Akinobu Taketomi, Takashi Maeda

  Cancer 73 (10) 2464 - 2471 1097-0142 1994 [Refereed][Not invited]
   

  Background. Protein induced by vitamin K absence or antagonist II (PIVKA‐II) was widely used as a diagnostic marker for hepatocellular carcinoma (HCC), however, its prognostic value is unclear. The authors evaluated PIVKA‐II clinicopathologically as a prognostic marker for HCC. Methods. The relationship between pathologic prognostic factors and plasma PIVKA‐II and alpha‐fetoprotein (AFP) was investigated in 72 patients with resectable HCC measuring less than 6 cm in greatest dimension. Results. PIVKA‐II shows significantly lower sensitivity, but higher specificity than AFP, and the use of these two complementary markers appears to be useful in the diagnosis of HCC. The frequencies of intrahepatic metastasis, portal vein tumor thrombus, hepatic vein tumor thrombus, and capsular infiltration were significantly higher in patients with positive PIVKA‐II than in those with negative‐PIVKA‐II, and the recurrence‐free rate was significantly lower in patients with positive rather than with negative PIVKA‐II. However, there were no significant differences between the patients who were AFP positive and those who were AFP negative in pathologic prognostic factors and the recurrence‐free rate. From univariate and multivariate analyses, the authors find that PIVKA‐II is one of the risk factors for recurrence of HCC after hepatectomy. Conclusions. PIVKA‐II may be a useful marker for the prediction of intrahepatic spread and for the prognosis of HCC. In addition, PIVKA‐II‐positive patients, thus, need aggressive postoperative adjuvant therapy for undetectable residual tumors and careful postoperative monitoring to enable the early recognition of recurrence. Copyright © 1994 American Cancer Society
• Influence of viral hepatitis status on operative morbidity and mortality in patients with primary hepatocellular carcinoma

  H. Higashi, T. Matsumata, E. Adachi, A. Taketomi, S. Kashiwagi, K. Sugimachi

  British Journal of Surgery 81 (9) 1342 - 1345 1365-2168 1994 [Refereed][Not invited]
   

  The influence of associated viral hepatitis status on 119 patients with primary hepatocellular carcinoma (HCC) undergoing hepatic resection was investigated. Operative morbidity and mortality were examined in three patient groups: 31 patients (group B) positive for hepatitis B surface antigen (HBsAg), 14 (group Be) positive for both HBsAg and hepatitis B e antigen, and 74 (group C) positive for hepatitis C virus antibody (HCVAb). Preoperative liver function in groups Be and C was similar and more impaired than that of patients in group B combined active hepatitis was seen most frequently in group C (68 per cent). The tumour size in group B was significantly greater than that in groups Be and C. Postoperative complications occurred more frequently in group C (39 per cent) and early postoperative deaths, other than those from cancer, were seen in nine patients positive for HCVAb, of whom three developed postoperative liver failure. Patients with HCC and hepatitis B without seroconversion as well as hepatitis C frequently have active hepatitis, which may impair liver function and play an important role in operative morbidity and mortality. Copyright © 1994 British Journal of Surgery Society Ltd.
• INITIATION OF A FIBRINOLYTIC SYSTEM IN HEPATIC RESECTION - THE ROLES OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR-1

  M SHIMADA, T MATSUMATA, K YAMAMOTO, H ITASAKA, A TAKETOMI, K SUGIMACHI

  SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 24 (9) 780 - 784 0941-1291 1994 [Refereed][Not invited]
   

  The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the alpha2-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values Of alpha2-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress.
• The association between transfusion and cancer‐free survival after curative resection for hepatocellular carcinoma

  Takashi Matsumata, Yasuharu Ikeda, Hiroshi Hayashi, Tatsuro Kamakura, Akinobu Taketomi, Keizo Sugimachi

  Cancer 72 (6) 1866 - 1871 1097-0142 1993 [Refereed][Not invited]
   

  Background. In cases of surgery for hepatocellular carcinoma (HCC), postoperative intrahepatic recurrence is the main obstacle to long‐term survival of patients. The association between perioperative transfusion and recurrence‐free survival was studied in 126 patients with HCC who underwent hepatic resection between 1985 and 1990 and in whom complete follow‐up information was available until 1992. Methods. Patients who received neither whole blood nor packed erythrocytes during hospitalization formed the no transfusion group (n = 72), and the remaining patients who were given either whole blood or packed erythrocytes during hospitalization constituted the transfusion group (n = 54). Results. The 1‐year, 3‐year, and 5‐year recurrence‐free survival rates of the nontransfused versus transfused groups were 80.6% versus 74.1%, 50.9% versus 33.4%, and 37.1% versus 26.2%, respectively (P = 0.1590). After adjustment for other covariates, the serum albumin level and histological intrahepatic metastasis (im) remained as significant variables for recurrence‐free survival. Although there was no association between the erythrocyte transfusion and the recurrence‐free survival of the patients with serum albumin levels either more than 3.5 g/dl or less than or equal to 3.5 g/dl, the 1‐year, 3‐year, and 5‐year recurrence‐free survival rates of the nontransfused versus transfused groups of the patients with im‐negative HCC were 92.2% versus 80.0%, 62.6% versus 36.3%, and 47.4% versus 27.1%, respectively (P = 0.0254). Conclusions. The association between erythrocyte transfusion and the recurrence‐free survival was recognized only in patients with im‐negative HCC. Copyright © 1993 American Cancer Society