2017年, 日本外科学会, Best Reviewer Award　　　　　　　　　　　　　　　
武冨 紹信

2011年, 第29回日本肝移植研究会, 優秀演題賞　　　　　　　　　　　　　　　
武冨 紹信

2006年, 第20回大学勤務医福岡県医師会長賞　　　　　　　　　　　　　　　
日本国

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年10月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月19日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年09月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年08月07日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年08月06日, ［国際誌］
英語, 研究論文（学術雑誌）

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年07月30日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年07月26日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 79回, 743, 743, (一社)日本消化器外科学会, 2024年07月
日本語

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年07月, ［国内誌］
英語, 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年07月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年07月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年07月, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 77, 6, 382, 382, (一社)日本大腸肛門病学会, 2024年06月
日本語

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年05月17日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 65, 5, 245, 245, (一社)日本肝臓学会, 2024年05月
日本語

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, 65, 5, 249, 249, (一社)日本肝臓学会, 2024年05月
日本語

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, 65, 5, 254, 255, (一社)日本肝臓学会, 2024年05月
日本語

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, 65, 5, 257, 257, (一社)日本肝臓学会, 2024年05月
日本語

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年05月, ［国際誌］
英語, 研究論文（学術雑誌）, 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 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 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年05月, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2024年05月
研究論文（学術雑誌）, 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年04月15日, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 77, 4, 240, 240, (一社)日本大腸肛門病学会, 2024年04月
日本語

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, 124回, WS, 1, (一社)日本外科学会, 2024年04月
日本語

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, 124回, WS, 2, (一社)日本外科学会, 2024年04月
日本語

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, 124回, SF, 3, (一社)日本外科学会, 2024年04月
日本語

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, 124回, SF, 4, (一社)日本外科学会, 2024年04月
日本語

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, 124回, SF, 4, (一社)日本外科学会, 2024年04月
日本語

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, 124回, SF, 5, (一社)日本外科学会, 2024年04月
日本語

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, 124回, PS, 6, (一社)日本外科学会, 2024年04月
日本語

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, 124回, PS, 4, (一社)日本外科学会, 2024年04月
日本語

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, 124回, RS, 1, (一社)日本外科学会, 2024年04月
日本語

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, 124回, RS, 4, (一社)日本外科学会, 2024年04月
日本語

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, 57, 4, 204, 211, (一社)日本消化器外科学会, 2024年04月
日本語, 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, 124回, SF, 2, (一社)日本外科学会, 2024年04月
日本語

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年04月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年04月01日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年04月, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 2024年03月23日
英語, 研究論文（学術雑誌）, 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年03月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年03月, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 85, 2, 297, 297, 日本臨床外科学会, 2024年02月
日本語

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, 85, 2, 298, 298, 日本臨床外科学会, 2024年02月
日本語

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, 44, 2, 451, 451, (一社)日本腹部救急医学会, 2024年02月
日本語

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, 44, 2, 455, 455, (一社)日本腹部救急医学会, 2024年02月
日本語

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, 44, 2, 456, 456, (一社)日本腹部救急医学会, 2024年02月
日本語

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, (一社)日本胃癌学会, 2024年02月
英語

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, Wiley, 2024年01月28日
研究論文（学術雑誌）, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月09日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年12月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2023年12月14日
研究論文（学術雑誌）, 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, 68, 2, 106, 110, 北海道外科学会, 2023年12月
日本語, 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, 58, 3, 273, 280, (一社)日本移植学会, 2023年12月
日本語, 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, Springer Science and Business Media LLC, 2023年12月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年12月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年11月09日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年11月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年11月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 76回, NCD2, 3, (一社)日本胸部外科学会, 2023年10月
日本語

【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, 87, 3, 287, 294, (株)アークメディア, 2023年09月
日本語

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, 76, 9, A93, A93, (一社)日本大腸肛門病学会, 2023年09月
日本語

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, 76, 9, A93, A93, (一社)日本大腸肛門病学会, 2023年09月
日本語

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年09月, ［国際誌］
英語, 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年09月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年08月31日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年08月21日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年07月19日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 78回, P100, 6, (一社)日本消化器外科学会, 2023年07月
日本語

【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, 85, 8, 868, 873, (株)南江堂, 2023年07月
日本語, ＜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年06月22日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年06月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

ILT2 as a biomarker of impaired natural killer cells expressing excess lipid peroxidation in patients with hepatocellular carcinoma
Toshihiro Sakata, Sachiyo Yoshio, Masaaki Mino, Shiori Yoshikawa, Taiji Yamazoe, Taizo Mori, Eiji Kakazu, Taketomi Akinobu, Tatsuya Kanto
Journal of Hepatology, 78, S444, S444, Elsevier BV, 2023年06月
研究論文（学術雑誌）

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, 27回, 105, 105, 日本がん免疫学会, 2023年06月
日本語

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年05月, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 48, 3, 424, 424, 日本外科系連合学会, 2023年05月
日本語

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, 48, 3, 318, 318, 日本外科系連合学会, 2023年05月
日本語

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, 48, 3, 427, 427, 日本外科系連合学会, 2023年05月
日本語

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, 48, 3, 436, 436, 日本外科系連合学会, 2023年05月
日本語

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年04月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年04月10日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 64, Suppl.1, A189, A189, (一社)日本肝臓学会, 2023年04月
日本語

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, 123回, DP, 4, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 6, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 5, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 2, (一社)日本外科学会, 2023年04月
日本語

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, 123回, RS, 12, (一社)日本外科学会, 2023年04月
日本語

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, 123回, RS, 1, (一社)日本外科学会, 2023年04月
日本語

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, 123回, WS, 1, (一社)日本外科学会, 2023年04月
日本語

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, 123回, SF, 7, (一社)日本外科学会, 2023年04月
日本語

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, 123回, SF, 3[Y], (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 1, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 4, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 2, (一社)日本外科学会, 2023年04月
日本語

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, 123回, DP, 7, (一社)日本外科学会, 2023年04月
日本語

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, 123回, RS, 3, (一社)日本外科学会, 2023年04月
日本語

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, 123回, RS, 3, (一社)日本外科学会, 2023年04月
日本語

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年03月20日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 64, 3, 168, 168, (一社)日本肝臓学会, 2023年03月
日本語

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, 120, 臨増総会, A339, A339, (一財)日本消化器病学会, 2023年03月
日本語

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, Wiley, 2023年02月15日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2023年02月02日, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 76, 2, 193, 193, (一社)日本大腸肛門病学会, 2023年02月
日本語

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, 76, 2, 204, 204, (一社)日本大腸肛門病学会, 2023年02月
日本語

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, 76, 2, 208, 208, (一社)日本大腸肛門病学会, 2023年02月
日本語

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, 76, 2, 226, 226, (一社)日本大腸肛門病学会, 2023年02月
日本語

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, 76, 2, 252, 252, (一社)日本大腸肛門病学会, 2023年02月
日本語

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, Wiley, 2023年01月30日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Springer Science and Business Media LLC, 2023年01月13日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月
研究論文（学術雑誌）, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 76, 1, 59, 59, (一社)日本大腸肛門病学会, 2023年01月
日本語

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, 76, 1, 77, 77, (一社)日本大腸肛門病学会, 2023年01月
日本語

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, 76, 1, 84, 84, (一社)日本大腸肛門病学会, 2023年01月
日本語

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, 76, 1, 94, 94, (一社)日本大腸肛門病学会, 2023年01月
日本語

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, 76, 1, 97, 97, (一社)日本大腸肛門病学会, 2023年01月
日本語

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, 56, 1, 20, 26, (一社)日本消化器外科学会, 2023年01月
日本語, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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年12月05日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年12月, ［国際誌］
英語, 研究論文（学術雑誌）

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, 119, 12, 1096, 1102, (一財)日本消化器病学会, 2022年12月
日本語, 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, 67, 2, 183, 184, 北海道外科学会, 2022年12月
日本語

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, 27, 7, 1341, 1341, (一社)日本内視鏡外科学会, 2022年12月
日本語

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, 27, 7, 1739, 1739, (一社)日本内視鏡外科学会, 2022年12月
日本語

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, 27, 7, 2445, 2445, (一社)日本内視鏡外科学会, 2022年12月
日本語

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, 27, 7, 2973, 2973, (一社)日本内視鏡外科学会, 2022年12月
日本語

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, 83, 12, 2121, 2121, 日本臨床外科学会, 2022年12月
日本語

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, 83, 12, 2122, 2122, 日本臨床外科学会, 2022年12月
日本語

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, 67, 2, 175, 175, 北海道外科学会, 2022年12月
日本語

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, 67, 2, 186, 186, 北海道外科学会, 2022年12月
日本語

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年11月18日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年10月11日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 83, 増刊, S170, S170, 日本臨床外科学会, 2022年10月
日本語

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, 83, 10, 1839, 1840, 日本臨床外科学会, 2022年10月
日本語

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, 83, 10, 1840, 1840, 日本臨床外科学会, 2022年10月
日本語

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, (一社)日本癌治療学会, 2022年10月
英語

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, 57, 総会臨時, 213, 213, (一社)日本移植学会, 2022年10月
日本語

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, 57, 総会臨時, 329, 329, (一社)日本移植学会, 2022年10月
日本語

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, 57, 総会臨時, 379, 379, (一社)日本移植学会, 2022年10月
日本語

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, 83, 増刊, S124, S124, 日本臨床外科学会, 2022年10月
日本語

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, 83, 増刊, S125, S125, 日本臨床外科学会, 2022年10月
日本語

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, (一社)日本癌治療学会, 2022年10月
英語

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, (一社)日本癌治療学会, 2022年10月
英語

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, (一社)日本癌治療学会, 2022年10月
英語

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, 57, 総会臨時, 379, 379, (一社)日本移植学会, 2022年10月
日本語

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年09月30日, ［国際誌］
英語, 研究論文（学術雑誌）

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年09月13日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 131回・125回, 40, 40, 日本消化器病学会-北海道支部, 2022年09月
日本語

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, (一社)日本癌学会, 2022年09月
英語

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, 131回・125回, 26, 26, 日本消化器病学会-北海道支部, 2022年09月
日本語

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, 131回・125回, 26, 26, 日本消化器病学会-北海道支部, 2022年09月
日本語

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, 75, 9, A180, A180, (一社)日本大腸肛門病学会, 2022年09月
日本語

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, 75, 9, A201, A201, (一社)日本大腸肛門病学会, 2022年09月
日本語

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, 75, 9, A223, A223, (一社)日本大腸肛門病学会, 2022年09月
日本語

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年08月12日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 47, 4, 596, 602, 日本外科系連合学会, 2022年08月
日本語, 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, SPRINGER INT PUBL AG, 2022年08月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年08月01日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年07月28日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年07月28日, ［国際誌］
英語, 研究論文（学術雑誌）

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年07月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年07月08日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 83, 7, 1325, 1330, 日本臨床外科学会, 2022年07月
日本語, 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, 77回, O8, 3, (一社)日本消化器外科学会, 2022年07月
日本語

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, 77回, P055, 1, (一社)日本消化器外科学会, 2022年07月
日本語

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, 77回, P090, 2, (一社)日本消化器外科学会, 2022年07月
日本語

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, 77回, O14, 1, (一社)日本消化器外科学会, 2022年07月
日本語

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, 77回, P138, 5, (一社)日本消化器外科学会, 2022年07月
日本語

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, Springer Science and Business Media LLC, 2022年07月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月02日, ［国際誌］
英語, 研究論文（学術雑誌）

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, 26回, 147, 147, 日本がん免疫学会, 2022年06月
日本語

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年06月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月30日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年05月24日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年05月13日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月11日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年04月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年04月08日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 122回, PD, 1, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 2, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 6, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 1, (一社)日本外科学会, 2022年04月
日本語

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, 122回, DP, 8, (一社)日本外科学会, 2022年04月
日本語

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, 122回, DP, 3, (一社)日本外科学会, 2022年04月
日本語

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, 122回, RS, 5, (一社)日本外科学会, 2022年04月
日本語

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, 122回, RS, 2, (一社)日本外科学会, 2022年04月
日本語

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, 58, 3, 410, 410, (一社)日本小児外科学会, 2022年04月
日本語

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, 122回, DP, 4, (一社)日本外科学会, 2022年04月
日本語

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, 122回, DP, 8, (一社)日本外科学会, 2022年04月
日本語

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, 122回, DP, 8, (一社)日本外科学会, 2022年04月
日本語

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, 122回, RS, 10, (一社)日本外科学会, 2022年04月
日本語

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, 122回, RS, 10, (一社)日本外科学会, 2022年04月
日本語

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, 122回, DP, 4, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 8, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 8, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 5, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 8, (一社)日本外科学会, 2022年04月
日本語

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年03月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年03月21日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 83, 3, 602, 602, 日本臨床外科学会, 2022年03月
日本語

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, 83, 3, 607, 607, 日本臨床外科学会, 2022年03月
日本語

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, 83, 3, 598, 599, 日本臨床外科学会, 2022年03月
日本語

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, 119, 臨増総会, A218, A218, (一財)日本消化器病学会, 2022年03月
日本語

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年02月09日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2022年01月22日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月21日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月05日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年01月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月03日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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年, ［国内誌］
日本語, 研究論文（学術雑誌）, 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年, ［国際誌］
英語, 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, 26, 7, MO084, 6, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 66, 2, 170, 171, 北海道外科学会, 2021年12月
日本語

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, 26, 7, PD16, 6, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, MO017, 4, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, MO141, 1, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, MO166, 6, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, MO208, 3, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, MO220, 5, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, WILEY-V C H VERLAG GMBH, 2021年12月, ［国内誌］
英語, 研究論文（学術雑誌）, 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, Springer Science and Business Media LLC, 2021年12月
研究論文（学術雑誌）, 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, Springer Science and Business Media LLC, 2021年11月16日
研究論文（学術雑誌）,

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年10月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2021年10月23日
研究論文（学術雑誌）

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, 82, 増刊, S171, S171, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S166, S166, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S195, S195, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S687, S687, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S725, S725, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S732, S732, 日本臨床外科学会, 2021年10月
日本語

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, 118, 臨増大会, A702, A702, (一財)日本消化器病学会, 2021年10月
日本語

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, 82, 増刊, S233, S233, 日本臨床外科学会, 2021年10月
日本語

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, 82, 増刊, S280, S280, 日本臨床外科学会, 2021年10月
日本語

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, (一社)日本癌治療学会, 2021年10月
英語

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年10月, ［国際誌］
英語, 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年09月10日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月05日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 56, 総会臨時, O12, 5, (一社)日本移植学会, 2021年09月
日本語

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, 56, 総会臨時, SSY7, 3, (一社)日本移植学会, 2021年09月
日本語

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], (一社)日本癌学会, 2021年09月
英語

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, 74, 9, A109, A109, (一社)日本大腸肛門病学会, 2021年09月
日本語

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, 74, 9, A117, A117, (一社)日本大腸肛門病学会, 2021年09月
日本語

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, 74, 9, A135, A135, (一社)日本大腸肛門病学会, 2021年09月
日本語

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, 74, 9, A149, A149, (一社)日本大腸肛門病学会, 2021年09月
日本語

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年08月09日, ［国内誌］
英語, 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年08月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年08月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年07月15日, ［国内誌］
英語, 研究論文（学術雑誌）, 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年07月13日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 76回, PD5, 7, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, O34, 6, (一社)日本消化器外科学会, 2021年07月
日本語

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, 56, 1, 35, 42, (一社)日本移植学会, 2021年07月
日本語, 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, 76回, P033, 4, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P061, 2, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P081, 2, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P084, 1, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P195, 4, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P256, 3, (一社)日本消化器外科学会, 2021年07月
日本語

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, 76回, P084, 1, (一社)日本消化器外科学会, 2021年07月
日本語

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, 56, 1, 35, 42, (一社)日本移植学会, 2021年07月
日本語

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, 76回, RS18, 3, (一社)日本消化器外科学会, 2021年07月
日本語

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年07月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月14日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月08日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 66, 1, 2, 12, 北海道外科学会, 2021年06月
日本語, 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, (一社)日本肝胆膵外科学会, 2021年06月
英語

【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, 66, 1, 2, 12, 北海道外科学会, 2021年06月
日本語, 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年06月, ［国際誌］
英語

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年06月, ［国内誌］
英語, 研究論文（学術雑誌）, 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年06月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月18日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月16日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月13日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 74, 5, 325, 325, (一社)日本大腸肛門病学会, 2021年05月
日本語

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, 74, 5, 344, 344, (一社)日本大腸肛門病学会, 2021年05月
日本語

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, 25回, 160, 160, 日本がん免疫学会, 2021年05月
日本語

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, 25回, 134, 134, 日本がん免疫学会, 2021年05月
日本語

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, 74, 5, 325, 325, (一社)日本大腸肛門病学会, 2021年05月
日本語

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, 74, 5, 344, 344, (一社)日本大腸肛門病学会, 2021年05月
日本語

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, 25回, 160, 160, 日本がん免疫学会, 2021年05月
日本語

【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, 83, 6, 682, 685, (株)南江堂, 2021年05月
日本語, ＜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年04月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 57, 2, 323, 323, (一社)日本小児外科学会, 2021年04月
日本語

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, 121回, SY, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 4, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, RS, 5, (一社)日本外科学会, 2021年04月
日本語

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, 121回, RS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 8, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 8, (一社)日本外科学会, 2021年04月
日本語

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, 54, 4, 253, 261, (一社)日本消化器外科学会, 2021年04月
日本語, 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, 121回, WS, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 3, (一社)日本外科学会, 2021年04月
日本語

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, 121回, WS, 5, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 3, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, WS, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 6, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 3, (一社)日本外科学会, 2021年04月
日本語

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, 62, Suppl.1, A373, A373, (一社)日本肝臓学会, 2021年04月
日本語

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, 121回, WS, 8, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 8, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 3, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 3, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 7, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 5, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 1, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 8, (一社)日本外科学会, 2021年04月
日本語

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, 121回, PS, 8, (一社)日本外科学会, 2021年04月
日本語

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, 121回, RS, 3, (一社)日本外科学会, 2021年04月
日本語

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, 121回, RS, 9, (一社)日本外科学会, 2021年04月
日本語

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, 121回, RS, 10, (一社)日本外科学会, 2021年04月
日本語

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年04月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年04月, ［査読有り］, ［国内誌］
英語, 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年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年03月23日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 74, 3, 198, 198, (一社)日本大腸肛門病学会, 2021年03月
日本語

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, (一社)日本内視鏡外科学会, 2021年03月
英語

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, 118, 臨増総会, A390, A390, (一財)日本消化器病学会, 2021年03月
日本語

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, 118, 臨増総会, A390, A390, (一財)日本消化器病学会, 2021年03月
日本語

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, 128回・122回, 57, 57, 日本消化器病学会-北海道支部, 2021年03月
日本語

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年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月26日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月25日, ［国際誌］
英語, 研究論文（学術雑誌）

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年02月22日, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月08日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 54回, 134, 134, (一社)日本臨床腎移植学会, 2021年02月
日本語

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, 74, 2, 94, 94, (一社)日本大腸肛門病学会, 2021年02月
日本語

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, 74, 2, 119, 119, (一社)日本大腸肛門病学会, 2021年02月
日本語

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, (一社)日本肝胆膵外科学会, 2021年02月
英語

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, 54回, 134, 134, (一社)日本臨床腎移植学会, 2021年02月
日本語

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年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Japanese Society of Gastroenterological Surgery, 2021年
日本語, 研究論文（学術雑誌）, 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, Japanese Society of Gastroenterological Surgery, 2021年
英語, 研究論文（学術雑誌）, 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, JAPAN SOC COLOPROCTOLOGY, 2021年
英語, 研究論文（学術雑誌）, 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年, ［国内誌］
英語, 研究論文（学術雑誌）, 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年, ［国内誌］
英語, 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, SAGE Publications, 2021年01月01日
研究論文（学術雑誌）, 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年, ［国内誌］
英語, 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年, ［国際誌］
英語, 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年01月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 75回, P224, 1, (一社)日本消化器外科学会, 2020年12月
日本語

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, 61, 12, 750, 750, (一社)日本肝臓学会, 2020年12月
日本語

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, 75回, P112, 6, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P119, 3, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P166, 3, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P178, 1, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P196, 3, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P107, 2, (一社)日本消化器外科学会, 2020年12月
日本語

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, 75回, P220, 3, (一社)日本消化器外科学会, 2020年12月
日本語

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, 65, 2, 158, 163, 北海道外科学会, 2020年12月
日本語, 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, 81, 12, 2500, 2506, 日本臨床外科学会, 2020年12月
日本語, 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年12月, ［国際誌］
英語, 研究論文（学術雑誌）, 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年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 53, Suppl.2, 235, 235, (一社)日本消化器外科学会, 2020年11月
日本語

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, 53, Suppl.2, 238, 238, (一社)日本消化器外科学会, 2020年11月
日本語

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年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, NLM (Medline), 2020年10月01日
英語, 研究論文（学術雑誌）, 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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, (一社)日本癌学会, 2020年10月
英語

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, 58回, P, 190, (一社)日本癌治療学会, 2020年10月
日本語

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年10月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年10月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

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年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月24日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 120回, PD, 5, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 4, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 3, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 7, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 3, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 5, (一社)日本外科学会, 2020年08月
日本語

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, (資)医薬出版, 2020年08月
英語

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, 120回, RS, 10, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 3, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 5, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 8, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 8, (一社)日本外科学会, 2020年08月
日本語

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, 53, 8, 617, 626, (一社)日本消化器外科学会, 2020年08月
日本語, 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, 120回, WS, 1, (一社)日本外科学会, 2020年08月
日本語

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, 120回, RS, 8, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 5, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 1, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 6, (一社)日本外科学会, 2020年08月
日本語

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, 120回, SF, 4, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 4, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 4, (一社)日本外科学会, 2020年08月
日本語

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, 120回, DP, 6, (一社)日本外科学会, 2020年08月
日本語

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年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Elsevier USA, 2020年07月01日
英語, 研究論文（学術雑誌）, 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年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月10日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Oxford University Press (OUP), 2020年06月
研究論文（学術雑誌）

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年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年06月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2020年04月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 56, 2, 227, 227, (一社)日本小児外科学会, 2020年04月
日本語

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, 54, 6, 299, 303, (一社)日本移植学会, 2020年04月
日本語, 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年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2020年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年03月31日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年03月20日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 126回, 66, 66, 日本消化器病学会-北海道支部, 2020年03月, ［査読有り］
日本語

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, 2020年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 124, 2, 250, 250, (公社)日本小児科学会, 2020年02月
日本語

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, WILEY, 2020年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2020年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月10日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2020年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Japanese Society of Gastroenterological Surgery, 2020年
日本語, 研究論文（学術雑誌）, 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, 62, 2, 464, 473, (株)じほう, 2020年01月
日本語, ＜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年, ［国際誌］
英語, 研究論文（学術雑誌）, 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年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 24, 7, WS3, 8, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, SF018, 1, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, SF021, 6, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, SF103, 4, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, MO070, 5, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, MO187, 6, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 64, 2, 212, 212, 北海道外科学会, 2019年12月, ［査読有り］
日本語

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, 2019年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年11月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年10月31日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, (一社)日本癌治療学会, 2019年10月
英語

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, (一社)日本癌治療学会, 2019年10月
英語

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, 60, Suppl.2, A683, A683, (一社)日本肝臓学会, 2019年10月, ［査読有り］
日本語

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, 2019年10月, ［査読有り］

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, 54, 総会臨時, 240, 240, (一社)日本移植学会, 2019年09月
日本語

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, 54, 総会臨時, 240, 240, (一社)日本移植学会, 2019年09月
日本語

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, 125回・119回, 45, 45, 日本消化器病学会-北海道支部, 2019年09月
日本語

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, (一社)日本癌学会, 2019年09月
英語

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, (一社)日本癌学会, 2019年09月
英語

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, (一社)日本癌学会, 2019年09月
英語

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, 2019年09月
研究論文（学術雑誌）, 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, 54, 総会臨時, 222, 222, (一社)日本移植学会, 2019年09月
日本語

【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, 124, 3, 1752, 1755, (株)南江堂, 2019年09月
日本語

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, 125回, 63, 63, 日本消化器病学会-北海道支部, 2019年09月, ［査読有り］
日本語

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, 80, 9, 1739, 1743, 日本臨床外科学会, 2019年09月, ［査読有り］
日本語, 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.
Imaizumi K, Tsukada Y, Komai Y, Nomura S, Ikeda K, Nishizawa Y, Sasaki T, Taketomi A, Ito M
International journal of colorectal disease, 34, 8, 1431, 1443, 2019年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 2019年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 64, 1, 2, 7, 北海道外科学会, 2019年06月, ［査読有り］
日本語, 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, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.
Yamaki A, Akiyama R, Murakami C, Takao S, Murakami Y, Mizuno S, Takahashi D, Kado S, Taketomi A, Shirai Y, Goto K, Sakane F
Journal of cellular biochemistry, 120, 6, 10043, 10056, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 72, 5, 278, 278, (一社)日本大腸肛門病学会, 2019年05月
日本語

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, 72, 5, 308, 308, (一社)日本大腸肛門病学会, 2019年05月
日本語

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, 72, 5, 327, 327, (一社)日本大腸肛門病学会, 2019年05月
日本語

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, 72, 5, 363, 363, (一社)日本大腸肛門病学会, 2019年05月
日本語

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, 80, 5, 1022, 1022, 日本臨床外科学会, 2019年05月
日本語

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, 80, 5, 1022, 1022, 日本臨床外科学会, 2019年05月
日本語

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, 119回, SF, 8, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 6, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 7, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 3, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 8, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 7, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 5, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 8, (一社)日本外科学会, 2019年04月
日本語

【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, 42, 5, 633, 637, (株)へるす出版, 2019年04月
日本語

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, 119回, WS, 9, (一社)日本外科学会, 2019年04月
日本語

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, 119回, RS, 1, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 7, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 1, (一社)日本外科学会, 2019年04月
日本語

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, 119回, SF, 6, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 2, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 7, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 6, (一社)日本外科学会, 2019年04月
日本語

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, 119回, PS, 5, (一社)日本外科学会, 2019年04月, ［査読有り］
日本語

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, 2019年04月, ［査読有り］, ［国内誌］
英語, 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, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2019年03月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 124回・118回, 57, 57, 日本消化器病学会-北海道支部, 2019年03月
日本語

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, 116, 臨増総会, A403, A403, (一財)日本消化器病学会, 2019年03月
日本語

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, 124回, 46, 46, 日本消化器病学会-北海道支部, 2019年03月, ［査読有り］
日本語

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年02月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年02月04日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 80, 2, 439, 439, 日本臨床外科学会, 2019年02月
日本語

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, 80, 2, 436, 436, 日本臨床外科学会, 2019年02月
日本語

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, 80, 2, 446, 446, 日本臨床外科学会, 2019年02月
日本語

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, Wolters Kluwer Medknow Publications, 2019年01月01日
英語, 研究論文（学術雑誌）, 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, 2019年
研究論文（学術雑誌）, 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, 2019年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年01月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年01月, ［査読有り］, ［国際誌］
英語, 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, 63, 2, 165, 165, 北海道外科学会, 2018年12月
日本語

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, 63, 2, 167, 167, 北海道外科学会, 2018年12月
日本語

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, 23, 7, OS20, 3, (一社)日本内視鏡外科学会, 2018年12月
日本語

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, 23, 7, OS87, 5, (一社)日本内視鏡外科学会, 2018年12月
日本語

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, 2018年12月, ［査読有り］

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, 2018年12月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2018年12月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

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, 51, Suppl.2, 165, 165, (一社)日本消化器外科学会, 2018年11月
日本語

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, 2018年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 2018年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年10月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年09月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 53, 総会臨時, 276, 276, (一社)日本移植学会, 2018年09月
日本語

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, 53, 総会臨時, 534, 534, (一社)日本移植学会, 2018年09月
日本語

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, (一社)日本癌学会, 2018年09月
英語

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, 71, 抄録号, A57, A57, (一社)日本大腸肛門病学会, 2018年09月
日本語

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, 71, 抄録号, A142, A142, (一社)日本大腸肛門病学会, 2018年09月
日本語

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, 71, 抄録号, A167, A167, (一社)日本大腸肛門病学会, 2018年09月
日本語

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, 71, 抄録号, A190, A190, (一社)日本大腸肛門病学会, 2018年09月
日本語

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, 53, 総会臨時, 255, 255, (一社)日本移植学会, 2018年09月
日本語

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, 71, 抄録号, A139, A139, (一社)日本大腸肛門病学会, 2018年09月, ［査読有り］
日本語

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, 2018年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2018年08月, ［査読有り］

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, 2018年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Wolters Kluwer Medknow Publications, 2018年07月01日
英語, 研究論文（学術雑誌）, 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, 2018年07月, ［査読有り］

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, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.
Konishi Y, Kawamata F, Nishihara H, Homma S, Kato Y, Tsuda M, Kohsaka S, Einama T, Liu C, Yoshida T, Nagatsu A, Tanino M, Tanaka S, Kawamura H, Kamiyama T, Taketomi A
Medical oncology (Northwood, London, England), 35, 7, 104, 104, 2018年06月11日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月21日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年05月, ［査読有り］

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, Springer Verlag, 2018年05月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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年04月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2018年04月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, 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, W.B. Saunders, 2018年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2018年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Spandidos Publications, 2018年03月, ［査読有り］
研究論文（学術雑誌）

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, 2018年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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年01月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, Springer Japan, 2018年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, 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, WILEY, 2018年01月, ［査読有り］
英語

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年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 2018年01月, ［査読有り］

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, 2018年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.
Kawamata F, Nishihara H, Homma S, Kato Y, Tsuda M, Konishi Y, Wang L, Kohsaka S, Liu C, Yoshida T, Tanino M, Tanaka S, Kawamura H, Kamiyama T, Taketomi A
The American journal of pathology, 188, 1, 204, 215, 2018年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 2018年01月, ［査読有り］, ［国際誌］
英語, 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年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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^™) versus linear stapler (overlap method).
Kawamura H, Ohno Y, Ichikawa N, Yoshida T, Homma S, Takahashi M, Taketomi A
Surgical endoscopy, 31, 12, 5175, 5182, SPRINGER, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2017年12月, ［査読有り］
英語, 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, SAGE PUBLICATIONS INC, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2017年12月, ［査読有り］

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, 52, 4-5, 454, 455, (一社)日本移植学会, 2017年11月
日本語

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, WILEY, 2017年11月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 50, Suppl.2, 185, 185, (一社)日本消化器外科学会, 2017年10月
日本語

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, 50, Suppl.2, 352, 352, (一社)日本消化器外科学会, 2017年10月
日本語

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, 50, Suppl.2, 513, 513, (一社)日本消化器外科学会, 2017年10月
日本語

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, 50, Suppl.2, 185, 185, (一社)日本消化器外科学会, 2017年10月
日本語

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, WILEY, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, Blackwell Publishing Ltd, 2017年10月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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, Blackwell Publishing Ltd, 2017年10月01日, ［査読有り］
英語, 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, ELSEVIER SCIENCE BV, 2017年10月, ［査読有り］
英語

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年09月, ［査読有り］
研究論文（学術雑誌）

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, SPRINGER, 2017年09月, ［査読有り］
英語, 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, WILEY, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2017年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.
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, 52, 8, 986, 991, SPRINGER JAPAN KK, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.
Nakano T, Ogasawara S, Tanaka T, Hozumi Y, Mizuno S, Satoh E, Sakane F, Okada N, Taketomi A, Honma R, Nakamura T, Saidoh N, Yanaka M, Itai S, Handa S, Chang YW, Yamada S, Kaneko MK, Kato Y, Goto K
Monoclonal antibodies in immunodiagnosis and immunotherapy, 36, 4, 181, 184, Mary Ann Liebert Inc., 2017年08月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, BIOMED CENTRAL LTD, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 72回, PL15, 3, (一社)日本消化器外科学会, 2017年07月
日本語

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, 50, 7, 535, 543, (一社)日本消化器外科学会, 2017年07月
日本語, 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年07月, ［査読有り］, ［国際誌］
英語, 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, ELSEVIER SCIENCE INC, 2017年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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-γ-carboxyprothrombin change ratio as a useful predictor of treatment response for hepatic arterial infusion chemotherapy against advanced hepatocellular carcinoma.
Tsunematsu S, Suda G, Yamasaki K, Kimura M, Takaaki I, Umemura M, Ito J, Sato F, Nakai M, Sho T, Morikawa K, Ogawa K, Kamiyama T, Taketomi A, Sakamoto N
Hepatology research : the official journal of the Japan Society of Hepatology, 47, 6, 533, 541, WILEY, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年05月, ［査読有り］

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, 117回, SF, 2, (一社)日本外科学会, 2017年04月
日本語

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, 52, 1, 60, 66, (一社)日本移植学会, 2017年04月
日本語, 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, 50, 4, 317, 325, (一社)日本消化器外科学会, 2017年04月
日本語, 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, Medknow Publications, 2017年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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年04月, ［査読有り］
研究論文（学術雑誌）

Anal canal duplication presenting with abscess formation
Shohei Honda, Masashi Minato, Hisayuki Miyagi, Hiromi Okada, Akinobu Taketomi
PEDIATRICS INTERNATIONAL, 59, 4, 500, 501, WILEY, 2017年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection.
Wakayama K, Kamiyama T, Yokoo H, Orimo T, Shimada S, Einama T, Kamachi H, Taketomi A
Journal of surgical oncology, 115, 3, 324, 329, WILEY, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 50, 2, 166, 176, (一社)日本消化器外科学会, 2017年02月
日本語, 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, SPRINGER, 2017年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2017年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, WILEY, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SOUTHEASTERN SURGICAL CONGRESS, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）

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, 49, Suppl.2, 325, 325, (一社)日本消化器外科学会, 2016年11月
日本語

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年11月, ［査読有り］
英語, 研究論文（学術雑誌）

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, 2016年11月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, 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, 77, 増刊, 409, 409, 日本臨床外科学会, 2016年10月
日本語

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, SPRINGER, 2016年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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™) for huge hepatic tumors with diaphragm invasion.
Wakayama K, Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Shimada S, Tsuruga Y, Kamachi H, Taketomi A
Surgery today, 46, 10, 1224, 1229, SPRINGER, 2016年10月, ［査読有り］
英語, 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, Medknow Publications, 2016年10月01日, ［査読有り］
英語, 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, 51, 2-3, 273, 273, (一社)日本移植学会, 2016年08月, ［査読有り］
日本語

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, SPRINGER, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2016年07月, ［査読有り］

Strong cytoplasmic expression of NF-κB/p65 correlates with a good prognosis in patients with triple-negative breast cancer.
Baba M, Takahashi M, Yamashiro K, Yokoo H, Fukai M, Sato M, Hosoda M, Kamiyama T, Taketomi A, Yamashita H
Surgery today, 46, 7, 843, 851, SPRINGER, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, BMJ PUBLISHING GROUP, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, AMER ASSOC CANCER RESEARCH, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 107, 7, 131, 135, 福岡医学会, 2016年07月, ［査読有り］
英語, 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, NATURE PUBLISHING GROUP, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER JAPAN KK, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, NATURE PUBLISHING GROUP, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER INDIA, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年05月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2016年05月, ［査読有り］
英語

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, WILEY, 2016年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, BAISHIDENG PUBLISHING GROUP INC, 2016年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2016年04月, ［査読有り］, ［国際誌］
英語, 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, SPRINGER JAPAN KK, 2016年04月, ［査読有り］
英語

Clinical trials of antiangiogenic therapy for hepatocellular carcinoma
Akinobu Taketomi
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 21, 2, 213, 218, SPRINGER JAPAN KK, 2016年04月, ［査読有り］
英語, 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, NATURE PUBLISHING GROUP, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2016年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2016年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, Springer Japan, 2016年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, 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.

99mTc-GSA SPECT/CT fusion imageによる術前肝予備能評価が有用であった巨大肝血管腫の1例
千田 圭悟, 神山 俊哉, 折茂 達也, 横尾 英樹, 菅野 宏美, 武冨 紹信
日本消化器外科学会雑誌, 49, 9, 882, 888, (一社)日本消化器外科学会, 2016年
日本語, 研究論文（学術雑誌）, 症例は34歳の女性で,嘔気と腹痛を主訴に近医を受診した.CTで肝右葉を主座とする長径20cmの腫瘤を認め,肝血管腫の診断で当科を紹介受診した.手術待機期間中に腹痛が増悪し,緊急入院となった.術前精査で肝前区域〜内側区に23×15cmの肝血管腫を認め,右肝静脈と中肝静脈は圧排され,肝右3区域にうっ血に伴う側副血行路を認めた.左肝静脈と門脈臍部は開存していた.肝右3区域切除でCT volumetryによる有効肝切除率は80%と算出されたが,Tc-99m-labeled galactosyl human serum albumin single photon emission CT/CT(99mTc-GSA SPECT/CT)fusion imageで算出した機能的肝切除率は39.2%であり,十分な残肝能を予測できたため,肝右3区域切除術を施行した.術後経過は良好で,術後14日目に退院した.(著者抄録)

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, ALL INDIA INST MEDICAL SCIENCES, 2016年01月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, BMJ Publishing Group, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, LIPPINCOTT WILLIAMS & WILKINS, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）

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, LIPPINCOTT WILLIAMS & WILKINS, 2015年11月, ［査読有り］
英語

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, WILEY-BLACKWELL, 2015年11月, ［査読有り］
英語

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, SPRINGER JAPAN KK, 2015年11月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2015年11月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, 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, 2015年11月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER JAPAN KK, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, IMPACT JOURNALS LLC, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, NATURE PUBLISHING GROUP, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER INTERNATIONAL PUBLISHING AG, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 70回, P, 4, (一社)日本消化器外科学会, 2015年07月
日本語

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, SPRINGER, 2015年07月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 27回, 626, 626, (一社)日本肝胆膵外科学会, 2015年06月
日本語

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, 2015-'16, 73, 79, (株)総合医学社, 2015年04月
日本語, 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, SPANDIDOS PUBL LTD, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 2015年03月, ［査読有り］

[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, 73, 2, 312, 316, 日本臨床社, 2015年02月, ［査読有り］
日本語

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, Elsevier Inc., 2015年01月28日, ［査読有り］
英語, 論文集(書籍)内論文

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, AMER SOC CLINICAL ONCOLOGY, 2015年01月20日, ［査読有り］
英語

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, SPRINGER, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, SPRINGER, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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].
Wakayama K, Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Tsuruga Y, Kamachi H, Soyama T, Sakuhara Y, Abo D, Taketomi A
Gan to kagaku ryoho. Cancer & chemotherapy, 41, 12, 1503, 1505, Japanese Journal of Cancer and Chemotherapy Publishers Inc., 2014年11月01日, ［査読有り］
日本語, 研究論文（学術雑誌）, 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, SPRINGER, 2014年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 47, Suppl.2, 137, 137, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 143, 143, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 175, 175, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 198, 198, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 218, 218, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 137, 137, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 143, 143, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 175, 175, (一社)日本消化器外科学会, 2014年10月
日本語

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, 47, Suppl.2, 198, 198, (一社)日本消化器外科学会, 2014年10月
日本語

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, SPRINGER, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 4, 2, 304, 304, 日本Acute Care Surgery学会, 2014年09月
日本語

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, 日本癌学会, 2014年09月
英語

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, 日本癌学会, 2014年09月
英語

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, 日本癌学会, 2014年09月, ［査読有り］
英語

Diacylglycerol kinase δ phosphorylates phosphatidylcholine-specific phospholipase C-dependent, palmitic acid-containing diacylglycerol species in response to high glucose levels.
Sakai H, Kado S, Taketomi A, Sakane F
The Journal of biological chemistry, 289, 38, 26607, 26617, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, INT COLLEGE OF SURGEONS, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, BIOMED CENTRAL LTD, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, H G E UPDATE MEDICAL PUBLISHING S A, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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, WILEY-BLACKWELL, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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年08月, ［査読有り］
研究論文（学術雑誌）

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, 2014年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, Wiley, 2014年08月, ［査読有り］
研究論文（学術雑誌）

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, 69回, RV, 1, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, O, 5, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, PD, 1, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, PD, 5, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, P, 3, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, P, 6, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, O, 2, (一社)日本消化器外科学会, 2014年07月
日本語

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, 69回, O, 1, (一社)日本消化器外科学会, 2014年07月
日本語

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, 26回, 387, 387, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 26回, 448, 448, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 26回, 484, 484, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 26回, 549, 549, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 26回, 588, 588, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 26回, 686, 686, (一社)日本肝胆膵外科学会, 2014年06月
日本語

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, 49, 3, 1669, 1669, (一社)日本癌治療学会, 2014年06月
日本語