Papers

• Postoperative Cholangitis After Biliary Reconstruction: Risk Factors, Timing of Occurrence, and Validity of Tokyo Guidelines.
  Kimitaka Tanaka, Shintaro Takeuchi, Masataka Wada, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toru Nakamura, Satoshi Hirano
  World journal of surgery, 49, 5, 1306, 1316, May 2025, [International Magazine]
  English, Scientific journal, BACKGROUND: Postoperative cholangitis (POC) is a major late complication of biliary reconstruction. This study aimed to investigate the risk factors and timing of POC occurrence and the validity of the Tokyo Guidelines 18 (TG18) for POC diagnosis in patients who underwent biliary reconstruction. METHODS: A retrospective review was conducted on 635 patients who underwent biliary reconstruction between January 2010 and December 2020. The incidence of first-occurrence POC requiring hospitalization was determined. Risk factors were identified using logistic regression analysis. The validity of the original and modified TG18 criteria for POC diagnosis was examined. RESULTS: The incidence of first-occurrence POC was 8.2% in the first year and 13.5% in the second year. No difference was observed in incidence between the surgical procedures. Male sex (OR, 2.22; 95% CI: 1.29-3.82) and preoperative alkaline phosphatase level ≤ 296 IU/L (OR, 1.79; 95% CI: 1.10-2.92) were independent risk factors for POC. The definite diagnosis rate of POC using the original TG18 criteria was low (48.7%) and increased to 66.7% using the modified TG18 criteria, which included transient hepatic attenuation difference and pneumobilia as additional diagnostic imaging findings. No association was observed between positive blood cultures and POC severity using TG18. CONCLUSION: Male sex and preoperative alkaline phosphatase level ≤ 296 IU/L were independent risk factors for POC. The original TG18 score was unsuitable for diagnosing POC after biliary reconstruction, while the modified TG18 score showed improved sensitivity. However, the diagnostic accuracy of the modified TG18 score requires further verification in prospective studies.
• Survivin as a Therapeutic Target for Neuroendocrine Neoplasms.
  Yuma Hane, Takahiro Tsuchikawa, Toru Nakamura, Kanako C Hatanaka, Katsunori Sasaki, Noriko Kawai, Shintaro Takeuchi, Kimitaka Tanaka, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toshiaki Shichinohe, Yutaka Hatanaka, Yoshihiko Hirohshi, Toshihiko Torigoe, Satoshi Hirano
  Neuroendocrinology, 115, 3-4, 295, 307, 2025, [International Magazine]
  English, Scientific journal, INTRODUCTION: Although neuroendocrine neoplasms (NENs) have a good prognosis, distant metastasis remains a crucial prognostic factor. Survivin, a tumor-associated antigen, is overexpressed in several solid tumors, indicating poor prognosis. We aimed to evaluate the clinical significance and role of survivin as a therapeutic target for NEN. METHODS: We assessed the cytotoxicity of Survivin-2B (a splicing variant of survivin) 80-88 specific CTL clone with HLA-A24 restriction against NEN cell lines using intracellular staining for interferon-γ and assessed the frequency of Survivin-2B 80-88 CTL precursors in nine HLA-A24-positive patients with NEN using tetramer staining and compared it before and after resection. Finally, we evaluated the association between survivin expression and prognosis in 74 patients with pancreatic NEN using immunohistochemistry. RESULTS: Survivin-2B 80-88 CTL clone showed high cytotoxicity against QGP-1 (HLA-A24 positive) cocultured with the Survivin-2B 80-88 peptide. Only three patients were positive for tetramer staining; two showed decreased Survivin-2B 80-88 CTL precursor following resection. The nuclear survivin-low group had a significantly better prognosis than the nuclear survivin-high group. CONCLUSION: Survivin in NEN is antigenic and may induce cellular immunity via the Survivin-2B CTL precursor. Survivin-targeting immunotherapy can be used to treat NEN with highly expressed Survivin-2B.
• Short- and Long-term Surgical Results of Extended Surgery for Widespread Gallbladder Carcinoma.
  Takehiro Noji, Shintaro Takeuchi, Masataka Wada, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Toru Nakamura, Yasuyuki Kawamoto, Satoshi Hirano
  In vivo (Athens, Greece), 39, 2, 1022, 1032, 2025, [International Magazine]
  English, Scientific journal, BACKGROUND/AIM: Hepatectomy with extrahepatic bile duct resection (Hx+EBDR), pancreaticoduodenectomy (PD), and occasionally hepatopancreaticoduodenectomy (HPD) are required for the treatment of advanced gallbladder cancer (GBC). This study aimed to clarify the clinical value of these extended surgeries for GBC. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients who underwent curative resection (Surg-G, n=59), and their survival rates were compared with those of patients with unresectable GBC who underwent chemotherapy (CTx-G, n=63). RESULTS: We performed PD (n=15), Hx+EBDR (n=37), and HPD (n=7). The postoperative complication and death rates were as follows: PD, 40% and 7%, respectively; Hx+EBDR, 89% and 14%, respectively; and HPD, 57% and 0%, respectively. Concomitant vascular resection (VR) was required in 61% of the patients. The 5-year overall survival rate and median survival time (MST) for Surg-G were 25.1% and 26 months, respectively, whereas those for CTx-G were 4.6% and 14.4 months, respectively. There were no significant differences between the surgical procedures. Patients who underwent VR had similar prognoses (5-year overall survival rate and MST: 14.5% and 22.3 months, respectively) as the patients in CTx-G. CONCLUSION: Although extended surgery may be considered for patients with GBC, careful patient selection and new therapeutic strategies are required, especially for those requiring VR.
• Middle Pancreatectomy for Traumatic Main Pancreatic Duct Injury with Delayed Presentation: Two Case Series.
  Yuki Itagaki, Shintaro Takeuchi, Takehiro Noji, Yuma Ebihara, Masataka Wada, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Toru Nakamura, Satoshi Hirano
  Surgical case reports, 11, 1, 2025, [Domestic magazines]
  English, Scientific journal, INTRODUCTION: Pancreatic trauma is an uncommon, yet potentially lethal condition, with main pancreatic duct (MPD) disruption guiding surgical management. Middle pancreatectomy (MP) with Roux-en-Y pancreatojejunostomy (PJ) offers an organ-preserving alternative to distal pancreatectomy, particularly for young patients. However, the extent of its applicability and the specific surgical techniques-including key technical tips-remain unclear in the context of traumatic pancreatic injury. This is especially true in cases of delayed presentation, where severe intra-abdominal inflammation further complicates surgical intervention. CASE PRESENTATION: We report 2 cases of young patients with MPD injuries from blunt trauma, both presenting late with significant peripancreatic contamination. Case 1 included a 22-year-old male who sustained pancreatic and liver injuries while skiing. He was transferred 30 hours post-injury with stable hemodynamics. Endoscopic retrograde pancreatography (ERP) confirmed MPD disruption. Intraoperatively, saponification obscured the anatomical structures, but MP with PJ was successfully performed. The patient recovered without major complications. Case 2 involved a 17-year-old female who was initially observed at another hospital after a traffic accident. Three days later, she developed peritonitis, and a retrospective computed tomography review revealed a pancreatic body rupture. An ERP confirmed MPD disruption. During surgery, extensive inflammation and adhesions were noted, and the MPD was extremely small. Despite technical complexities, an MP with PJ was successfully completed. The pancreatic fistula from the pancreatic head stump required drainage treatment following spinal surgery for vertebral fractures, and the patient recovered without sequelae. CONCLUSIONS: MP with Roux-en-Y PJ is a technically challenging but viable approach for MPD injuries in young patients, even with delayed presentation. It preserves the pancreatic and splenic functions, making it a valuable approach for young patients when performed by experienced surgeons. These cases demonstrate the clinical impact and potential implications of MP as a viable treatment approach for pancreatic trauma.
• The efficacy of wrapping with polyglycolic acid mesh and fibrin glue in preventing clinically relevant pancreatic fistula after minimally invasive distal pancreatectomy (WRAP Study): study protocol for a multicenter randomized controlled trial in Japan.
  Hayato Baba, Atsushi Oba, Kimitaka Tanaka, Takayuki Miura, Daisuke Ban, Motonori Edanami, Yoshiya Ishikawa, Katsuhisa Ohgi, Haruyoshi Tanaka, Ryuta Shintakuya, Naoki Ikenaga, Tetsuya Ijichi, Yoshitaka Kiya, Ryo Muranushi, So Yamaki, Naoki Miyazaki, Shintaro Takeuchi, Shuichi Aoki, Takahiro Mizui, Masayuki Tanaka, Hiroki Ueda, Hideyuki Dei, Hideki Takami, Kenjiro Okada, Kohei Nakata, Yuko Mataki, Hiroaki Osakabe, Kazuto Shibuya, Daisuke Hashimoto, Yosuke Inoue, Satoshi Hirano, Michiaki Unno, Minoru Esaki, Minoru Kitago, Keiichi Akahoshi, Teiichi Sugiura, Tomoki Ebata, Kenichiro Uemura, Masafumi Nakamura, Takao Otsuka, Yuichi Nagakawa, Tsutomu Fujii, Sohei Satoi, Yu Takahashi
  BMC surgery, 24, 1, 314, 314, 16 Oct. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. METHODS: This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). DISCUSSION: The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).
• Initial validation of the clinical significance of the NETest in Japanese gastroenteropancreatic neuroendocrine tumor patients.
  Hao Zhang, Takahiro Tsuchikawa, Satoshi Takeuchi, Kenji Hirata, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toru Nakamura, Shintaro Takeuchi, Masataka Wada, Satoshi Hirano
  Endocrine journal, 71, 9, 873, 880, 02 Sep. 2024, [Domestic magazines]
  English, Scientific journal, As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49-66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.
• Perioperative chemotherapy with nivolumab for HER2-negative locally advanced gastric cancer: a case series.
  Yuta Toji, Shintaro Takeuchi, Yuma Ebihara, Yo Kurashima, Kazuaki Harada, Mariko Hayashi, Hirotake Abe, Hideyuki Wada, Satoko Yorinaga, Toshiaki Shichinohe, Utano Tomaru, Yoshito Komatsu, Satoshi Hirano
  Surgical case reports, 10, 1, 200, 200, 28 Aug. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: Nivolumab with chemotherapy has been transformative for metastatic gastric cancer (GC). The potential of this regimen for local tumor control could be utilized for perioperative chemotherapy in locally advanced GC with bulky tumors or lymph node metastasis involving other organs. CASE PRESENTATION: Five patients with HER2-negative advanced GC were treated with nivolumab and oxaliplatin-based chemotherapy. All patients presented with clinical stage III or IVA GC with tumors in contact with either the pancreas or liver. Following chemotherapy, all tumors demonstrated shrinkage, allowing successful radical gastrectomies including four minimally invasive approach without postoperative complications. Four patients avoided combined resection of other organs. CONCLUSIONS: Perioperative chemotherapy with nivolumab was effective for local disease control in this case series. This regimen could be a promising treatment approach for locally advanced GC; however, its survival benefits should be evaluated in clinical trials.
• Distinct clinicopathological features of neuroendocrine liver metastases originating from the pancreas and rectum.
  Hao Zhang, Takahiro Tsuchikawa, Satoshi Takeuchi, Hang Deng, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toru Nakamura, Shintaro Takeuchi, Masataka Wada, Jian Xu, Yu Zhang, Satoshi Hirano
  World journal of surgical oncology, 22, 1, 209, 209, 03 Aug. 2024, [International Magazine]
  English, Scientific journal, INTRODUCTION: Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs. METHODS: Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I). RESULTS: Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts. CONCLUSION: Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size.
• 肝胆膵 局所進行胆道癌・膵癌手術における門脈・動脈再建の工夫 当科における肝門部領域胆管癌に対する肝動脈・門脈同時切除再建症例の手技と周術期成績　　　　　　　　　　　　　　　
  田中 公貴, 武内 慎太郎, 和田 雅孝, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 中村 透, 土川 貴裕, 平野 聡
  日本消化器外科学会総会, 79回, 452, 453, (一社)日本消化器外科学会, Jul. 2024
  Japanese
• 切除不能膵癌に対するconversion surgeryにおける術後再発の検討　　　　　　　　　　　　　　　
  浅野 賢道, 平野 聡, 中村 透, 土川 貴裕, 野路 武寛, 中西 喜嗣, 松井 あや, 田中 公貴, 和田 雅孝, 武内 慎太郎
  日本消化器外科学会総会, 79回, 725, 725, (一社)日本消化器外科学会, Jul. 2024
  Japanese
• 折り鶴トレーニングの臨床効果と普及への課題　　　　　　　　　　　　　　　
  松井 あや, 武内 慎太郎, 和田 雅孝, 田中 公貴, 中西 喜嗣, 浅野 賢道, 野路 武寛, 中村 透, 土川 貴裕, 平野 聡
  日本消化器外科学会総会, 79回, 752, 752, (一社)日本消化器外科学会, Jul. 2024
  Japanese
• 外科医が基礎研究を行う意義-PhysiologyとOncologyの観点から- 膵癌immunochemotherapy実現への道筋 術前治療による微小環境修飾の臨床的不均一性と組織学的不均一性の解明　　　　　　　　　　　　　　　
  武内 慎太郎, 中村 透, 土川 貴裕, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 平野 聡
  日本外科学会定期学術集会抄録集, 124回, SY, 8, (一社)日本外科学会, Apr. 2024
  Japanese
• 切除不能膵癌における集学的治療の現状と課題 切除不能膵癌に対するconversion surgeryの長期成績および主要動脈温存手術の妥当性の検討　　　　　　　　　　　　　　　
  浅野 賢道, 平野 聡, 中村 透, 土川 貴裕, 野路 武寛, 中西 喜嗣, 松井 あや, 田中 公貴, 和田 雅孝, 武内 慎太郎
  日本外科学会定期学術集会抄録集, 124回, WS, 5, (一社)日本外科学会, Apr. 2024
  Japanese
• 肝胆膵癌手術中のトラブルシューティング 高難易度肝胆膵手術での予期せぬ術中大量出血により2期的手術の周術期管理　　　　　　　　　　　　　　　
  田中 公貴, 武内 慎太郎, 和田 雅孝, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 中村 透, 海老原 裕磨, 倉島 庸, 村上 壮一, 土川 貴裕, 七戸 俊明, 平野 聡
  日本外科学会定期学術集会抄録集, 124回, WS, 4, (一社)日本外科学会, Apr. 2024
  Japanese
• 門脈塞栓術施行症例の術後肝不全発生症例解析結果による肝門部胆管癌診療の今後の方向性　　　　　　　　　　　　　　　
  野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  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, Apr. 2024
  Japanese
• 術前化学療法後の膵癌手術症例における術前ヘモグロビン値の術後アウトカムに与える影響　　　　　　　　　　　　　　　
  和田 雅孝, 中村 透, 武内 慎太郎, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 土川 貴裕, 七戸 俊明, 平野 聡
  日本外科学会定期学術集会抄録集, 124回, SF, 6, (一社)日本外科学会, Apr. 2024
  Japanese
• 肝外胆管癌のリンパ節転移過程におけるEMT関連タンパク発現に関する検討　　　　　　　　　　　　　　　
  林 真理子, 中西 喜嗣, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 中村 透, 土川 貴裕, 七戸 俊明, 平野 聡
  日本外科学会定期学術集会抄録集, 124回, PS, 2, (一社)日本外科学会, Apr. 2024
  Japanese
• 80歳以上のResectable膵癌症例に対する治療成績　　　　　　　　　　　　　　　
  藤井 正和, 中村 透, 浅野 賢道, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 土川 貴裕, 七戸 俊明, 平野 聡
  日本臨床外科学会雑誌, 85, 3, 432, 432, 日本臨床外科学会, Mar. 2024
  Japanese
• 同時性多発肝転移を伴う膵神経内分泌腫瘍に対する原発巣切除後に薬物治療を行い長期生存中の1例　　　　　　　　　　　　　　　
  室井 論大, 土川 貴裕, 林 真理子, 武内 慎太郎, 和田 雅孝, 三浦 巧, 岡村 国茂, 田中 公貴, 松井 あや, 中西 義嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 中村 透, 七戸 俊明, 平野 聡
  日本臨床外科学会雑誌, 85, 3, 432, 432, 日本臨床外科学会, Mar. 2024
  Japanese
• 最新技術を用いた消化器診療 ロボット支援下膵切除手術における新規導入後の手術成績と脾温存手術の比較検討　　　　　　　　　　　　　　　
  田中 公貴, 武内 慎太郎, 和田 雅孝, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 海老原 裕磨, 中村 透, 土川 貴裕, 平野 聡
  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, 134回・128回, 36, 36, 日本消化器病学会-北海道支部, Mar. 2024
  Japanese
• 【胆膵疾患診療～病理医との対話～】胆道疾患 肝側胆管断端術の術中迅速診断を行わない肝門部領域胆管癌手術の成績
  野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 善嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  胆と膵, 44, 8, 713, 717, 医学図書出版(株), Aug. 2023
  Japanese
• 胆嚢癌同時性肝転移に対しconversion surgeryを施行した1例
  武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 善嗣, 浅野 賢道, 野路 武寛, 中村 透, 土川 貴裕, 平野 聡, 桑谷 将成, 郷 雅, 三橋 智子
  胆道, 37, 3, 653, 653, (一社)日本胆道学会, Aug. 2023
  Japanese
• 重複胆管に発生した肝門部領域胆管癌の1例
  内藤 善, 野路 武寛, 吉見 泰典, 武内 慎太郎, 岡村 国茂, 和田 雅孝, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  胆道, 37, 3, 732, 732, (一社)日本胆道学会, Aug. 2023
  Japanese
• 肝門部領域胆管癌術後の遺残膵内胆管拡張を契機に発見された十二指腸乳頭部癌の1例
  熊谷 健太郎, 野路 武寛, 吉見 泰典, 武内 慎太郎, 岡村 国茂, 和田 雅孝, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  胆道, 37, 3, 738, 738, (一社)日本胆道学会, Aug. 2023
  Japanese
• A Case of Loss of Consciousness Due to Thrombosis of the Inferior Vena Cava and Portal Vein.
  Shintaro Takeuchi, Tatsuya Hayakawa
  Cureus, 15, 7, e41306, Jul. 2023, [International Magazine]
  English, Scientific journal, We present a case where intraperitoneal venous thrombosis was difficult to treat. It is difficult to suspect intraperitoneal venous thrombosis in patients who have visited the hospital due to loss of consciousness, and it is necessary to administer anticoagulants early for treatment and to determine the appropriate timing for surgical intervention. The patient was a 78-year-old male who independently performed his daily activities. On the day of admission, he lost consciousness and was brought to our hospital. Computed tomography (CT) angiography revealed thrombi from the inferior vena cava and portal vein to the superior mesenteric vein, and the patient was started on anticoagulant therapy. The CT angiography images on day 7 of the illness revealed that the thrombus in the superior mesenteric vein expanded to the caudal side. Intestinal necrosis occurred on day 22 of the illness, and emergency laparotomy was performed. The chosen course of treatment was successful, and the patient was discharged on the 48th day.
• 膵神経内分泌腫瘍のバイオマーカーの展望 Multigene liquid biopsy NETestの有用性の検証
  武内 慎太郎, 土川 貴裕, 藤井 正和, 和田 雅孝, 田中 公貴, 松井 あや, 中西 善嗣, 浅野 賢道, 野路 武寛, 中村 透, 平野 聡
  膵臓, 38, 3, A195, A195, (一社)日本膵臓学会, Jul. 2023
  Japanese
• Borderline resectable膵癌術前治療施行症例における予後予測因子の検討
  浅野 賢道, 中村 透, 土川 貴裕, 野路 武寛, 中西 喜嗣, 松井 あや, 田中 公貴, 和田 雅孝, 武内 慎太郎, 平野 聡
  膵臓, 38, 3, A312, A312, (一社)日本膵臓学会, Jul. 2023
  Japanese
• 【肝胆膵】胆道癌取扱い規約第7版に基づいた遠位胆管癌の治療成績の再評価 遠位胆管癌におけるInvasive tumor thickness測定値の予後予測因子としての有用性　　　　　　　　　　　　　　　
  中西 喜嗣, 土川 貴裕, 中村 透, 野路 武寛, 浅野 賢道, 松井 あや, 田中 公貴, 和田 雅孝, 武内 慎太郎, 平野 聡
  日本消化器外科学会総会, 78回, WS27, 10, (一社)日本消化器外科学会, Jul. 2023
  Japanese
• 【肝胆膵】肝膵同時切除術の安全性と長期予後向上を目指した取り組み 肝膵同時切除における膵消化管再建法の選択およびリンパ節転移状態による手術適応決定　　　　　　　　　　　　　　　
  野路 武寛, 武内 慎太郎, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  日本消化器外科学会総会, 78回, WS28, 2, (一社)日本消化器外科学会, Jul. 2023
  Japanese
• 【肝胆膵】切除可能膵癌に対する術前化学療法の至適戦略 術前治療症例の予後因子から考察する切除可能膵癌に対する周術期治療のネクストステージ　　　　　　　　　　　　　　　
  武内 慎太郎, 中村 透, 浅野 賢道, 和田 雅孝, 田中 公貴, 松井 あや, 中西 善嗣, 野路 武寛, 土川 貴裕, 平野 聡
  日本消化器外科学会総会, 78回, WS30, 5, (一社)日本消化器外科学会, Jul. 2023
  Japanese
• 【切除不能胆道癌:定義・診断・治療】局所(解剖学的)因子からみた切除不能の定義 肝門部領域胆管癌
  和田 雅孝, 中西 喜嗣, 野路 武寛, 松井 あや, 田中 公貴, 武内 慎太郎, 浅野 賢道, 中村 透, 平野 聡
  胆と膵, 44, 6, 495, 499, 医学図書出版(株), Jun. 2023
  Japanese
• 【切除不能胆道癌:定義・診断・治療】局所(解剖学的)因子からみた切除不能の定義 肝門部領域胆管癌　　　　　　　　　　　　　　　
  和田 雅孝, 中西 喜嗣, 野路 武寛, 松井 あや, 田中 公貴, 武内 慎太郎, 浅野 賢道, 中村 透, 平野 聡
  胆と膵, 44, 6, 495, 499, 医学図書出版(株), Jun. 2023
  Japanese
• 肝門部胆管癌に対する拡大手術の定義と手技 肝門部胆管癌に対する三区域切除・動脈合併切除・肝膵同時切除術施行の妥当性の検討　　　　　　　　　　　　　　　
  野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 平野 聡
  日本外科学会定期学術集会抄録集, 123回, SY, 6, (一社)日本外科学会, Apr. 2023
  Japanese
• 膵頭十二指腸領域の内視鏡合併症に対するSurgical Rescueの取り組み　　　　　　　　　　　　　　　
  村上 壮一, 東嶋 宏泰, 岡村 国茂, 和田 雅孝, 武内 慎太郎, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 中村 透, 土川 貴裕, 七戸 俊明, 平野 聡
  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, Apr. 2023
  Japanese
• 膵癌治療中に経験した症候性椎体圧迫骨折の6例　　　　　　　　　　　　　　　
  藤井 正和, 中村 透, 浅野 賢道, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 野路 武寛, 倉島 庸, 海老原 祐磨, 村上 壮一, 土川 貴裕, 七戸 俊明, 平野 聡
  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, Apr. 2023
  Japanese
• 遠位肝外胆管癌のCT所見による術式選択の可能性　　　　　　　　　　　　　　　
  中西 喜嗣, 野路 武寛, 土川 貴裕, 中村 透, 浅野 賢道, 松井 あや, 田中 公貴, 和田 雅孝, 寺村 紘一, 岡村 国茂, 武内 慎太郎, 村上 壮一, 海老原 裕磨, 倉島 庸, 七戸 俊明, 平野 聡
  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, Apr. 2023
  Japanese
• 膵頭十二指腸切除術後膵空腸吻合部結石の臨床的意義　　　　　　　　　　　　　　　
  松井 あや, 武内 慎太郎, 和田 雅孝, 岡村 国茂, 寺村 紘一, 田中 公貴, 中西 喜嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 中村 透, 土川 貴裕, 七戸 俊明, 平野 聡
  日本外科学会定期学術集会抄録集, 123回, DP, 8, (一社)日本外科学会, Apr. 2023
  Japanese
• 肝内胆管癌と胆嚢癌肉腫の衝突癌の1例　　　　　　　　　　　　　　　
  内藤 善, 野路 武寛, 伊野 永隼, 郷 雅, 吉見 泰典, 武内 慎太郎, 岡村 国茂, 和田 雅孝, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 中島 正人, 三橋 智子, 平野 聡
  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, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• 進行胆嚢癌に対する肝・膵切除術の妥当性　　　　　　　　　　　　　　　
  野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 原田 一顕, 川本 泰之, 平野 聡
  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, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• 肝内胆管癌と胆嚢癌肉腫の衝突癌の1例　　　　　　　　　　　　　　　
  内藤 善, 野路 武寛, 伊野 永隼, 郷 雅, 吉見 泰典, 武内 慎太郎, 岡村 国茂, 和田 雅孝, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 中島 正人, 三橋 智子, 平野 聡
  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, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• 進行胆嚢癌に対する肝・膵切除術の妥当性　　　　　　　　　　　　　　　
  野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 原田 一顕, 川本 泰之, 平野 聡
  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, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• 膵癌外科治療における術前治療と術後補助化学療法中の血液毒性発現の関連
  武内 慎太郎, 中村 透, 田中 公貴, 松井 あや, 中西 善嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 裕磨, 村上 壮一, 土川 貴裕, 七戸 俊明, 平野 聡, 桑原 健, 田中 伸哉
  北海道外科雑誌, 67, 2, 190, 191, 北海道外科学会, Dec. 2022
  Japanese
• 膵癌治療中に経験した症候性椎体圧迫骨折の5例
  藤井 正和, 中村 透, 浅野 賢道, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 善嗣, 野路 武寛, 倉島 庸, 海老原 祐磨, 村上 壮一, 土川 貴裕, 七戸 俊明, 平野 聡
  北海道外科雑誌, 67, 2, 194, 194, 北海道外科学会, Dec. 2022
  Japanese
• 高Na血症による意識障害を併発した膿瘍形成性虫垂炎の1例　　　　　　　　　　　　　　　
  内藤 善, 村上 壮一, 和田 雅孝, 吉見 泰典, 武内 慎太郎, 岡村 国茂, 寺村 紘一, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 野路 武寛, 倉島 庸, 海老原 祐磨, 中村 透, 七戸 俊明, 平野 聡
  Japanese Journal of Acute Care Surgery, 12, Suppl., 144, 144, 日本Acute Care Surgery学会, Sep. 2022
  Japanese
• Preoperative embolization strategy for the combined resection of replaced right hepatic artery in pancreaticoduodenectomy: a small case series.
  Shintaro Takeuchi, Yoshiyasu Ambo, Yoshihisa Kodama, Minoru Takada, Kentaro Kato, Fumitaka Nakamura, Satoshi Hirano
  Surgical case reports, 8, 1, 49, 49, 22 Mar. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: Replaced right hepatic artery (rRHA) is a common vascular variation, and combined resection of this vessel is sometimes needed for the curative resection of pancreatic head malignancy. Safe surgical management has not been established, and there is a small number of reported cases. Here, we reported five cases, wherein preoperative embolization of rRHA was performed for combined resection. CASE PRESENTATION: All patients had pancreatic head malignancies that were in contact with rRHA. We performed a preoperative embolization of the rRHA before the scheduled pancreaticoduodenectomy for the combined resection. Arterial embolization was safely accomplished, and the communicating arcade from the left hepatic artery via the hilar plate was clearly revealed in all cases. Four patients underwent the operative procedure, except for one patient who had liver metastasis at laparotomy. No patient suffered from a severe abnormal liver function during the management; however, one patient had multiple liver infarctions during the postoperative course. CONCLUSIONS: Preoperative embolization for the combined resection of rRHA in pancreaticoduodenectomy can be a management option for the precise evaluation of hemodynamics after sacrificing rRHA. In our cases, arterial flow to the right liver lobe was supplied by the left hepatic artery via the bypass route, including the communicating arcade of the hilar plate.
• Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial.
  Takayuki Yoshino, Takeharu Yamanaka, Eiji Oki, Masahito Kotaka, Dai Manaka, Tetsuya Eto, Junichi Hasegawa, Akinori Takagane, Masato Nakamura, Takeshi Kato, Yoshinori Munemoto, Shintaro Takeuchi, Hiroyuki Bando, Hiroki Taniguchi, Makio Gamoh, Manabu Shiozawa, Tsunekazu Mizushima, Shigetoyo Saji, Yoshihiko Maehara, Atsushi Ohtsu, Masaki Mori
  JAMA oncology, 5, 11, 1574, 1581, 01 Nov. 2019, [International Magazine]
  English, Scientific journal, Importance: Oxaliplatin-based chemotherapy is associated with debilitating peripheral sensory neuropathy (PSN) for patients with stage III colon cancer. Objective: To assess disease-free survival (DFS) and long-lasting PSN in patients treated with 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. Design, Setting, and Participants: An open-label, multicenter, phase 3 randomized clinical trial of 1313 Asian patients with stage III colon cancer was conducted investigating the noninferiority of 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. From August 1, 2012, to June 30, 2014, participants were randomized to the 2 treatment groups. Data were analyzed from July 2017 to June 2018. Interventions: Patients were randomized to receive 3 or 6 months of adjuvant chemotherapy. The choice of chemotherapy regimen, with the drugs modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine plus oxaliplatin (CAPOX), was at the discretion of the treating physician. Main Outcomes and Measures: The primary outcome was DFS. Secondary end points included the evaluation of PSN for up to 3 years and overall survival. Results: Of the 1313 patients (651 were women and mean age was 66 [range, 28-85] years) enrolled and randomized, 22 were not treated because 10 were unable to begin treatment within 2 weeks of enrollment, 7 withdrew their consent, and 5 were not treated for various other reasons. Of 1291 patients treated (650 in the 3-month arm and 641 in the 6-month arm), 969 (75%) received the chemotherapy drug CAPOX. The hazard ratio (HR) for DFS of the 3-month arm compared with the 6-month arm was 0.95 (95% CI, 0.76-1.20). Hazard ratios were 1.07 (95% CI, 0.71-1.60) and 0.90 (95% CI, 0.68-1.20) for the drugs mFOLFOX6 and CAPOX, and 0.81 (95% CI, 0.53-1.24) and 1.07 (95% CI, 0.81-1.40) for patients with low-risk disease (TNM classification stages T1-3 and N1) and high-risk disease (stages T4 or N2), respectively. The rates of any grade of PSN lasting for 3 years in the 3-month vs 6-month treatment arms were 9.7% vs 24.3% (P < .001). Incidence of PSN lasting for 3 years was significantly lower for patients treated with CAPOX than for patients treated with mFOLFOX6 in both the 3-month (7.9% vs 15.7%; P = .04) and 6-month arms (21.0% vs 34.1%; P = .02). Conclusions and Relevance: The incidence of long-lasting PSN was significantly lower for 3 months than for 6 months of therapy, and significantly lower for treatment with the drug CAPOX than with mFOLFOX6. Since the shortened therapy duration did not compromise outcomes, a 3-month course of CAPOX may be the most appropriate treatment option, particularly for patients with low-risk disease. Trial Registration: UMIN Clinical Trials Registry: UMIN000008543.
• Therapeutic activity of retroviral replicating vector-mediated prodrug activator gene therapy for pancreatic cancer.
  Kazuho Inoko, Kei Hiraoka, Akihito Inagaki, Mizuna Takahashi, Toshihiro Kushibiki, Koji Hontani, Hironobu Takano, Shoki Sato, Shintaro Takeuchi, Toru Nakamura, Takahiro Tsuchikawa, Toshiaki Shichinohe, Harry E Gruber, Douglas J Jolly, Noriyuki Kasahara, Satoshi Hirano
  Cancer gene therapy, 25, 7-8, 184, 195, Aug. 2018, [International Magazine]
  English, Scientific journal, Toca 511, a retroviral replicating vector (RRV) encoding the yeast cytosine deaminase (yCD) prodrug activator gene, which mediates conversion of the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), is currently being evaluated in Phase II/III clinical trials for glioma, and showing highly promising evidence of therapeutic activity. Here we evaluated RRV-mediated prodrug activator gene therapy as a new therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). RRV spread rapidly and conferred significant cytotoxicity with prodrug in a panel of PDAC cells. Efficient intratumoral replication and complete inhibition of tumor growth upon 5-FC administration were observed in both immunodeficient and immunocompetent subcutaneous PDAC models. Biodistribution of RRV was highly restricted in normal tissues, especially in immunocompetent hosts. Tumor growth inhibition by Toca 511 followed by 5-FC was also confirmed in the orthotopic PDAC model. This study provides the first proof-of-concept for application of Toca 511 and Toca FC (extended release 5-FC) to the treatment of human PDAC, and provided support for inclusion of PDAC in a Phase I study evaluating Toca 511 in various systemic malignancies, (NCT02576665), which has recently been initiated.
• Pathological complete response of locally advanced colon cancer after preoperative radiotherapy: a case report and narrative review of the literature.
  Sho Sekiya, Kiyotaka Imamura, Shintaro Takeuchi, Koichi Teramura, Yusuke Watanabe, Eiji Tamoto, Minoru Takada, Yoshihiro Kinoshita, Yoshiyasu Anbo, Fumitaka Nakamura, Nobuichi Kashimura, Hiroko Noguchi, Katsutoshi Miura, Satoshi Hirano
  Surgical case reports, 4, 1, 58, 58, 15 Jun. 2018, [International Magazine]
  English, Scientific journal, BACKGROUND: The oncological effectiveness of preoperative radiotherapy for locally advanced colon cancer is unclear. We report a case of pathological complete response in a patient with locally advanced ascending colon cancer after preoperative radiotherapy following failure of chemotherapy. CASE PRESENTATION: A 65-year-old Japanese woman presented with malaise and hematochezia. A computed tomography (CT) revealed a tumor in the ascending colon which seemed to infiltrate the adjacent structures. She was diagnosed with locally advanced ascending colon cancer stages T4b, N2a, M0, and IIIC. We selected modified FOLFOX6 with panitumumab as neoadjuvant chemotherapy. However, we discontinued the chemotherapy after the 8th cycle because of disease progression and severe adverse effects. The patient then underwent radiotherapy of 60 Gy in 30 fractions, resulting in significant tumor size reduction. One month after the radiotherapy, we performed a right hemicolectomy with multivisceral resection without complications. Histopathologically, we found no residual cancer cells in the resected specimen. The patient remains alive and has not required additional therapies for 24 months, as there are no signs of recurrence. CONCLUSIONS: The present case suggests that preoperative radiotherapy might be an effective treatment options for locally advanced colon cancer.
• 【チーム医療による手術侵襲軽減策とアウトカム】消化器外科におけるチーム医療による実践的手術侵襲軽減策とアウトカム
  中村 文隆, 藤井 正和, 七里 圭子, 西 智史, 篠原 良仁, 伊橋 卓文, 横山 新一郎, 武内 慎太郎, 今村 清隆, 渡邊 祐介, 田本 英司, 高田 実, 加藤 健太郎, 木ノ下 義宏, 安保 義恭, 成田 吉明, 樫村 暢一
  外科と代謝・栄養, 52, 2, 71, 77, 日本外科代謝栄養学会, Apr. 2018
  Japanese
• Clinical Implications of CD4+CD25+Foxp3+Regulatory T Cell Frequencies After CHP-MAGE-A4 Cancer Vaccination.
  Masataka Wada, Takahiro Tsuchikawa, Noriaki Kyogoku, Takehiro Abiko, Kengo Miyauchi, Shintaro Takeuchi, Toshihiko Kuwatani, Toshiaki Shichinohe, Yoshihiro Miyahara, Shinichi Kageyama, Hiroaki Ikeda, Hiroshi Shiku, Satoshi Hirano
  Anticancer research, 38, 3, 1435, 1444, Mar. 2018, [International Magazine]
  English, Scientific journal, BACKGROUND/AIM: The aim of this study was to explore whether the treatment effect or immune response to a cancer vaccine can be predicted by the percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) after vaccination. PATIENTS AND METHODS: Sixteen patients (9 men, 7 women; median age 61.5 years) enrolled in the CHP-MAGE-A4 cancer vaccine clinical trial who had a fixed dose (300 μg of CHP-MAGE-A4 cancer vaccine and 0.5 Klinische Einheit (KE) of OK432 and received at least four vaccinations were investigated. Safety, immune response, and clinical effects were assessed before and after the cancer vaccination. RESULTS: Treg ratios that remained low both before and after vaccination were associated with a good prognosis, and a low Treg/CD4 lymphocyte ratio 7-weeks after the initial vaccination was correlated with a better prognosis. CONCLUSION: The Treg ratio following vaccination appears to have some utility for predicting patient prognosis.
• 膵頭十二指腸切除におけるERASの有用性
  寺村 紘一, 中村 文隆, 武内 慎太郎, 今村 清隆, 渡邊 祐介, 田本 英司, 高田 実, 安保 義恭, 樫村 暢一, 石原 聡, 平野 聡
  日本臨床外科学会雑誌, 79, 3, 467, 475, 日本臨床外科学会, Mar. 2018
  Japanese
• Laparoscopic repair with cone-shaped mesh implantation for perineal hernia occurred after laparoscopic abdominoperineal resection.
  Koichi Teramura, Yusuke Watanabe, Shintaro Takeuchi, Fumitaka Nakamura, Satoshi Hirano
  International journal of surgery case reports, 49, 115, 117, 2018, [International Magazine]
  English, Scientific journal, INTRODUCTION: Perineal hernia after abdominoperineal resection (APR) is a rare complication, and no standard surgical procedures are established. We describe a simple laparoscopic mesh implantation technique utilizing a large synthetic flat mesh. PRESENTATION OF CASE: We report a case of perineal hernia after APR. We performed laparoscopic repair using a soft and large synthetic mesh with simple technique. The essence of this technique is that mesh is inserted into the abdominal cavity without trimming and it forms in a conical shape to better adjust to the pelvic cavity. DISCUSSION: The perineal and laparoscopic approaches for perineal hernia repair have been performed most commonly in recent years, but the recurrence rate after repair remains high (24.1%). Using a large mesh could cover the hernial orifice with a sufficient margin, reducing a risk of recurrence caused by shrinkage and slippage of the mesh. CONCLUSION: Our technique utilizing a large, lightweight, synthetic mesh can be practical and useful for perineal hernia repair after laparoscopic APR.
• Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation.
  Shoki Sato, Toru Nakamura, Toyomasa Katagiri, Takahiro Tsuchikawa, Toshihiro Kushibiki, Kouji Hontani, Mizuna Takahashi, Kazuho Inoko, Hironobu Takano, Hirotake Abe, Shintaro Takeuchi, Masato Ono, Shota Kuwabara, Kazufumi Umemoto, Tomohiro Suzuki, Osamu Sato, Yusuke Nakamura, Satoshi Hirano
  Oncotarget, 8, 69, 113662, 113672, 26 Dec. 2017, [International Magazine]
  English, Scientific journal, BACKGROUND: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo. METHOD: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. RESULT: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. CONCLUSION: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.
• 腹壁浸潤が疑われる上行結腸癌に対して、術前化学放射線療法で病理的寛解が得られた1例　　　　　　　　　　　　　　　
  関谷 翔, 今村 清隆, 西 智史, 篠原 良仁, 伊橋 卓文, 横山 新一郎, 水沼 謙一, 武内 慎太郎, 寺村 紘一, 渡邊 祐介, 田本 英司, 高田 実, 木ノ下 義宏, 安保 義恭, 中村 文隆, 樫村 暢一, 野口 寛子, 三浦 勝利
  日本消化器外科学会雑誌, 50, Suppl.2, 377, 377, (一社)日本消化器外科学会, Oct. 2017
  Japanese
• 【大腸癌治療におけるERAS導入とその実践】大腸癌に対するERAS導入の効果
  中村 文隆, 篠原 良仁, 伊橋 卓文, 横山 新一郎, 水沼 謙一, 武内 慎太郎, 今村 清隆, 寺村 紘一, 渡邊 祐介, 田本 英司, 高田 実, 木ノ下 義宏, 安保 義恭, 樫村 暢一, 山下 翠, 田中 智美, 鐵野 麻美, 田牧 直也, 島田 文, 湯田 華奈美
  癌の臨床, 63, 1, 27, 34, (株)篠原出版新社, Feb. 2017
  Japanese, 2011年より、結腸癌における待機的結腸切除の周術期管理にERASプロトコルを導入した。結腸癌(結腸および直腸S状部)の待機手術患者を対象とし、ERAS群(E群)372例(男性203名、女性169名、26〜96歳)とERAS導入以前の従来群(C群)178例(男性100名、女性78名、24〜96歳)の2群に分けた。腹腔鏡手術率はE群で有意に高率であった。E群では手術時間が有意に長く、出血量は有意に減少した。E群ではC群に比べ、術中総輸液量、術中輸液バランスとも有意に減少した。麻酔方法では、E群で有意に全静脈麻酔Total Intravenous Anesthesiaの割合が増加した。術後合併症は、E群4.3%(16例)、C群7.8%(14例)であった。術後の在院期間は、E群で有意に短縮した。術後30日以内の化学療法目的での再入院を除いた手術関連の再入院は2群間に差を認めなかった。DPC算定総医療費は、E群1364731円、C群1531413円で、有意にE群で医療費は減少した。E群のERASプロトコル達成率(食事遅延なし)は91.9%であった。
• Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer.
  Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Toshiaki Shichinohe, Satoshi Hirano
  World journal of gastrointestinal oncology, 8, 11, 786, 792, 15 Nov. 2016, [International Magazine]
  English, Scientific journal, A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.
• Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice.
  Hironobu Takano, Toru Nakamura, Takahiro Tsuchikawa, Toshihiro Kushibiki, Kouji Hontani, Kazuho Inoko, Mizuna Takahashi, Shoki Sato, Hirotake Abe, Shintaro Takeuchi, Nagato Sato, Kei Hiraoka, Hiroshi Nishihara, Toshiaki Shichinohe, Satoshi Hirano
  Oncotarget, 6, 38, 41063, 76, 01 Dec. 2015, [International Magazine]
  English, Scientific journal, Ephrin receptor A4 (EphA4) is overexpressed in human pancreatic adenocarcinoma (PDAC) and activate cell growth. Recent studies have identified small molecules that block EphA4. In this study, we investigated the correlation between EphA4 expression and the prognosis of patients with PDAC. We also examined the cytostatic efficacy of 2,5-dimethylpyrrolyl benzoic acid (compound 1), a small molecule that blocks EphA4, in PDAC cells. Overall survival of patients with EphA4 positivity was significantly shorter than that of patients with EphA4 negativity (P = 0.029). In addition, multivariate analysis revealed that EphA4 expression was an independent prognostic factor in PDAC patients (P = 0.039). Compound 1 showed a cytostatic efficacy in PDAC cells expressing EphA4 in vitro and in vivo. Our study indicated that compound 1 suppressed both EphA4 and Akt phosphorylations, and induced apoptosis in PDAC cells expressing EphA4. In conclusion, compound 1 has a high potential as a therapeutic agent for patients with PDAC.
• Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer.
  Shintaro Takeuchi, Muhammad Baghdadi, Takahiro Tsuchikawa, Haruka Wada, Toru Nakamura, Hirotake Abe, Sayaka Nakanishi, Yuu Usui, Kohtaro Higuchi, Mizuna Takahashi, Kazuho Inoko, Syoki Sato, Hironobu Takano, Toshiaki Shichinohe, Ken-ichiro Seino, Satoshi Hirano
  Cancer research, 75, 13, 2629, 40, 01 Jul. 2015, [International Magazine]
  English, Scientific journal, Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. PDAC builds a tumor microenvironment that plays critical roles in tumor progression and metastasis. However, the relationship between chemotherapy and modulation of PDAC-induced tumor microenvironment remains poorly understood. In this study, we report a role of chemotherapy-derived inflammatory response in the enrichment of PDAC microenvironment with immunosuppressive myeloid cells. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a major cytokine associated with oncogenic KRAS in PDAC cells. GM-CSF production was significantly enhanced in various PDAC cell lines or PDAC tumor tissues from patients after treatment with chemotherapy, which induced the differentiation of monocytes into myeloid-derived suppressor cells (MDSC). Furthermore, blockade of GM-CSF with monoclonal antibodies helped to restore T-cell proliferation when cocultured with monocytes stimulated with tumor supernatants. GM-CSF expression was also observed in primary tumors and correlated with poor prognosis in PDAC patients. Together, these results describe a role of GM-CSF in the modification of chemotherapy-treated PDAC microenvironment and suggest that the targeting of GM-CSF may benefit PDAC patients' refractory to current anticancer regimens by defeating MDSC-mediated immune escape.
• The key role of calreticulin in immunomodulation induced by chemotherapeutic agents.
  Yoshiyuki Yamamura, Takahiro Tsuchikawa, Kengo Miyauchi, Shintaro Takeuchi, Masataka Wada, Toshihiko Kuwatani, Noriaki Kyogoku, Aki Kuroda, Takehiro Maki, Toshiaki Shichinohe, Satoshi Hirano
  International journal of clinical oncology, 20, 2, 386, 94, Apr. 2015, [Domestic magazines]
  English, Scientific journal, BACKGROUND: It has recently been shown that certain chemotherapeutic agents can improve host immune responses. The present study aimed to demonstrate the mechanism by which chemotherapeutic agents modify the tumor microenvironment and induce tumor-specific immune responses. METHODS: Three mouse cancer cell lines [CT26 mouse colon cancer cells, B16 melanoma cells and Lewis lung carcinoma (LLC)], 5 human carcinoma cell lines (human esophageal squamous cell carcinoma cell lines TE8 and HEC46 and the human pancreatic carcinoma cell lines PK-9, AsPC-1 and SUIT-2) and 5 chemotherapeutic agents [mitoxantrone (MIT), mitomycin C(MMC), 5-fluorouracil (5FU), camptothecin (CPT-11) and cisplatin (CDDP)] that are frequently used in a clinical setting for cancer treatment were utilized to investigate the surface expression level of calreticulin and HLA class I after exposure to chemotherapeutic agents. RESULTS: Increased calreticulin (CRT) expression on the surface of mouse cell lines and, moreover, increased surface expression levels of both CRT and HLA class I in all human cell lines were observed in cells treated by the chemotherapeutic agents as compared with non-treated cells. The surface expression level of CRT was significantly correlated with the HLA class I expression level in all human cell lines. CONCLUSIONS: In conclusion, chemotherapeutic drugs can improve the immunogenicity of cancer cells in a cell-specific manner through the mechanism of translocation of CRT.
• α-MSH stimulation contributes to TGF-β1 production via MC1R-MITF signaling pathway in melanoma cell
  Hayashi Erika, Hachiya Kaori, Kojo Satoshi, Baghdadi Muhammad, Takeuchi Shintaro, Yamanaka Hiroyuki, Abe Hirotak, Wada Haruka, Seino Ken-ichiro
  Inflammation and Regeneration, 35, 5, 244, 254, 日本炎症・再生医学会, 2015
  Japanese, Transforming growth factor-β (TGF-β) is a multifunctional cytokine that play critical roles in melanoma progression. Although the impact of TGF-β signaling on melanoma progression has been well characterized, little is known about the molecular mechanisms that control TGF-β production in melanoma cells. In this study, we describe a novel role for Melanocortin Receptor 1 (MC1R) in the regulation of TGF-β production. MC1R is a cell surface endocytic receptor expressed in melanoma cells and serves as a receptor for α-Melanocyte Stimulating Hormone (α-MSH). The activation of MC1R with α-MSH resulted in increased levels of TGF-β, which was mediated by ERK1/2 and p38 signaling pathways. Furthermore, Microphthalmia Transcription Factor (MITF), the master regulator of melanocytes, was found to act downstream of MC1R to regulate TGF-β production. Targeting of MC1R-MITF axis was effective to decrease TGF-β production, and resulted in delayed tumor growth of B16 melanoma in vivo. Collectively, these results give new insight into the molecular mechanisms that control TGF-β production in melanoma cells.
• 膵癌は化学療法投与環境下でMyeloid derived suppressor cellの形成を促進する(Pancreatic cancer facilitates myeloid derived suppressor cell formation under chemotherapy treated conditions)　　　　　　　　　　　　　　　
  武内 慎太郎, 土川 貴裕, 和田 はるか, 中村 透, 七戸 俊明, 清野 研一郎, 平野 聡
  日本癌学会総会記事, 73回, E, 2042, (一社)日本癌学会, Sep. 2014
  English
• Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response.
  Muhammad Baghdadi, Shintaro Takeuchi, Haruka Wada, Ken-Ichiro Seino
  mAbs, 6, 5, 1124, 32, 2014, [International Magazine]
  English, Scientific journal, Monoclonal antibody (mAb)-based treatment of cancer has a significant effect on current practice in medical oncology, and is considered now as one of the most successful therapeutic strategies for cancer treatment. MAbs are designed to initiate or enhance anti-tumor immune responses, which can be achieved by either blocking inhibitory immune checkpoint molecules or triggering activating receptors. TIM gene family members are type-I surface molecules expressed in immune cells, and play important roles in the regulation of both innate and adaptive arms of the immune system. Therapeutic strategies based on anti-TIMs mAbs have shown promising results in experimental tumor models, and synergistic combinations of anti-TIMs mAbs with cancer vaccines, adoptive T-cell therapy, radiotherapy and chemotherapy will have great impact on cancer treatment in future clinical development.
• 原発性肺腺癌における術前血清CYFRA値と予後との関連に関する検討　　　　　　　　　　　　　　　
  武内 慎太郎, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 中田 玲子, 大高 和人, 武藤 潤, 井上 玲, 平野 聡, 松居 喜郎
  日本呼吸器外科学会雑誌, 26, 3, O02, 02, (NPO)日本呼吸器外科学会, Apr. 2012, [Peer-reviewed]
  Japanese
• 術後早期血管造影による評価が有用であった上腸間膜動脈塞栓症の3例
  武内 慎太郎, 真名瀬 博人, 平 康二, 小山 基弘, 上山 圭史, 大滝 憲二
  日本臨床外科学会雑誌, 72, 12, 3154, 3159, 日本臨床外科学会, Dec. 2011
  Japanese
• 消化管Behcet病手術症例の検討
  武内 慎太郎, 大野 耕一, 長谷 龍之介, 鈴木 善法, 高田 実, 関下 芳明
  日本臨床外科学会雑誌, 72, 7, 1685, 1689, 日本臨床外科学会, Jul. 2011
  Japanese
• 爪楊枝を誤飲し小腸穿通を起こした1例　　　　　　　　　　　　　　　
  玉手 雅人, 大野 耕一, 和田 秀之, 武内 慎太郎, 長谷 龍之介, 鈴木 善法, 高田 実, 大竹 節之, 竹内 幹也, 藤森 勝, 関下 芳明
  北海道外科雑誌, 55, 1, 60, 60, 北海道外科学会, Jun. 2010
  Japanese
• 12. 巨大メッケル憩室の腸重積による小腸壊死の1例(一般演題,第81回日本小児外科学会北海道地方会)
  関下 芳明, 武内 慎太郎, 和田 秀之, 長谷 龍之介, 鈴木 善法, 高田 実, 竹内 幹也, 大竹 節之, 大野 耕一
  日本小児外科学会雑誌, 46, 1, 121, 122, 特定非営利活動法人 日本小児外科学会, 2010
  Japanese