Details of the Researcher

PHOTO

Koetsu Inoue
Section
Tohoku University Hospital
Job title
Assistant Professor
e-Rad No.
30912711

Papers 56

  1. A case of perihilar cholangiocarcinoma with peritoneal dissemination that achieved a pathological complete response using immune checkpoint inhibitors: A case report

    Takehiko Saijo, Hideaki Sato, Shuichi Aoki, Masahiro Iseki, Mika Ando, Yuichiro Umino, Mitsuhiro Shimura, Koetsu Inoue, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kazuhiro Kikuta, Atsushi Masamune, Keigo Murakami, Toru Furukawa, Michiaki Unno

    INTERNATIONAL CANCER CONFERENCE JOURNAL　15　(2)　203-209　2026/04

    DOI： 10.1007/s13691-025-00842-2 　

    ISSN： 2192-3183

  2. A case of perihilar cholangiocarcinoma with peritoneal dissemination that achieved a pathological complete response using immune checkpoint inhibitors: A case report. International-journal

    Takehiko Saijo, Hideaki Sato, Shuichi Aoki, Masahiro Iseki, Mika Ando, Yuichiro Umino, Mitsuhiro Shimura, Koetsu Inoue, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kazuhiro Kikuta, Atsushi Masamune, Keigo Murakami, Toru Furukawa, Michiaki Unno

    International cancer conference journal　15　(2)　203-209　2026/04

    DOI： 10.1007/s13691-025-00842-2 　

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    Surgical resection is considered the only potentially curative treatment for biliary tract cancer (BTC). However, for patients with locally advanced or metastatic BTC, systemic chemotherapy remains the primary therapeutic option. Historically, chemotherapies such as gemcitabine plus cisplatin (GC), gemcitabine plus S-1, and GC plus S-1 have been employed; however, the prognosis remains poor. Recently, combined therapy with immune checkpoint inhibitors (ICIs) has emerged as a promising therapeutic approach for unresectable BTC. In cases with long-term efficacy to systemic chemotherapy, sequential surgical resection, known as conversion surgery, has also shown potential to improve overall outcomes in unresectable BTC. This case report presents a case of advanced perihilar cholangiocarcinoma with histologically confirmed peritoneal dissemination that achieved a pathological complete response after combination therapy with GC and durvalumab, followed by conversion surgery. Achieving a pathological complete response in the presence of peritoneal dissemination is rare. This case provides valuable insights into treatment strategies for this aggressive malignancy, demonstrating that a pathological complete response is possible even in the presence of peritoneal dissemination.

  3. SMAD3 activation in pancreatic stellate cells correlates with PTGDR2 expression and favorable stromal features in pancreatic cancer. International-journal

    Naohiro Hirano, Koetsu Inoue, Shuichi Aoki, Shingo Yoshimachi, Hideaki Sato, Mitsuhiro Shimura, Hajime Taniguchi, Masahiro Iseki, Daisuke Douchi, Keigo Murakami, Shimpei Maeda, Takayuki Miura, Masaharu Ishida, Masamichi Mizuma, Atsushi Masamune, Michiaki Unno

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]　2026/03/12

    DOI： 10.1016/j.pan.2026.03.007 　

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    BACKGROUND: Pancreatic cancer is characterized by a dense tumor microenvironment enriched with cancer-associated fibroblasts (CAFs), which display context-dependent tumor-promoting and tumor-restraining properties. However, the molecular basis of stromal heterogeneity remains incompletely understood. METHODS: We examined stromal responses of pancreatic stellate cells (PSCs), a major source of CAFs, using an orthotopic mouse co-implantation model, RNA sequencing, conditioned medium-based functional assays, and immunohistochemical analysis of resected pancreatic cancer specimens. RESULTS: Co-implantation of PSCs with pancreatic cancer cells was associated with smaller primary tumor volumes and selective activation of SMAD3 in PSCs. Cancer cell-derived conditioned medium activated SMAD3 signaling in PSCs but not in cancer cells, suggesting cell type-specific pathway activation. Transcriptomic analysis identified prostaglandin D2 receptor 2 (PTGDR2) as a gene upregulated in association with SMAD3 activation, and its expression decreased following SMAD3 inhibition. Functional assays showed that SMAD3 activation was associated with modulation of PTGDR2 and inflammatory gene expression in PSCs. In clinical samples, higher p-SMAD3 expression in CAFs correlated with favorable overall survival. CONCLUSIONS: SMAD3 activation in PSCs was observed in association with PTGDR2 expression, altered inflammatory profiles, and reduced tumor growth in vivo. These findings support the presence of distinct stromal phenotypes in pancreatic cancer and warrant further investigation into CAF modulation strategies.

  4. Survival Impact After Resection for Postoperative Recurrence or Metastasis of Pancreatic Ductal Adenocarcinoma Analyzed Using a Time-Dependent Cox Regression Model.

    Denys Tsybulskyi, Daisuke Hashimoto, Kimitaka Tanaka, Kenta Murotani, Masataka Taguri, So Yamaki, Shoki Sato, Atsushi Oba, Yosuke Inoue, Shimpei Otsuka, Katsuhisa Ohgi, Teiichi Sugiura, Ryuta Shintakuya, Kenjiro Okada, Kenichiro Uemura, Koetsu Inoue, Masamichi Mizuma, Michiaki Unno, Toshimichi Asano, Nobuhiko Nakagawa, Hideki Takami, Ryosuke Takahashi, Fuyuhiko Motoi, Keiichi Akahoshi, Daisuke Ban, Aiste Gulla, Hideki Ishikawa, Satoshi Hirano, Sohei Satoi

    Journal of hepato-biliary-pancreatic sciences　2026/01/07

    DOI： 10.1002/jhbp.70054 　

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    BACKGROUND: Recently, surgical resection has been attempted for postoperative recurrence of pancreatic ductal adenocarcinoma (PDAC). This multicenter study aimed to investigate whether resection of any recurrent lesion contributes to the survival of patients with PDAC. METHODS: This retrospective study of the Hepato-Pancreato-Biliary Scientific Network for Clinical Oncology Research Working Cohort involved patients with resectable/borderline resectable PDAC who underwent surgery between 2013 and 2019 and who subsequently developed recurrence after resection of the primary PDAC. A time-dependent Cox regression model adjusted for various patient background and clinicopathological factors was used. RESULTS: The study cohort comprised 1527 patients; 96 underwent resection for recurrence, including hepatectomy in 12 patients, pneumonectomy in 40, and pancreatectomy in 42. Overall survival after the initial treatment of primary PDAC was significantly better in patients who underwent resection compared with those who did not (75.0 vs. 25.8 months). The time-dependent Cox regression model indicated that pneumonectomy for lung metastasis (HR = 0.12) and pancreatectomy for recurrence in the pancreatic remnant (HR = 0.20) significantly affected overall survival, whereas hepatectomy for liver metastasis was not (HR = 0.46). CONCLUSION: Resection for postoperative recurrence of PDAC may offer survival benefits for selected patients, especially for lung metastasis and residual pancreatic recurrence. TRIAL REGISTRATION: https://ClinicalTrials.gov identifier: UMIN000049664.

  5. Local Recurrence and Survival Outcomes after Portal Vein/Superior Mesenteric Vein Separation without Resection Preceding Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma. International-journal

    Koetsu Inoue, Masamichi Mizuma, Fuyuhiko Motoi, Keigo Murakami, Shuichiro Hayashi, Aya Noguchi, Shingo Yoshimachi, Hideaki Sato, Mitsuhiro Shimura, Akiko Kusaka, Shuichi Aoki, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Kei Nakagawa, Takashi Kamei, Michiaki Unno

    Pancreas　2025/05/07

    DOI： 10.1097/MPA.0000000000002503 　

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    In patients with pancreatic ductal adenocarcinoma (PDAC) and portal vein/superior mesenteric vein (PV/SMV) contact, we can often separate the tumor from the PV/SMV and avoid PV/SMV resection (VR) owing to the favorable efficacy of neoadjuvant therapy (NAT). However, there is a risk that tumor cells may remain around the PV/SMV. This study aimed to elucidate whether separating a tumor from a PV/SMV is justified in the NAT setting. Methods: We reviewed patients with PDAC who underwent pancreaticoduodenectomies or total pancreatectomies between 2005 and 2019. We usually attempt the skeletonization of PV/SMV as long as possible. We explored recurrence patterns and overall survival (OS). Results: In total, 248 patients were enrolled and divided based on PV/SMV contact (PVC), NAT, and VR. In the NAT setting, local recurrence around PV the SMV occurred at almost the same rate among the three groups (8.1%, NAT+/PVC-; 11.8%, NAT+/PVC+/VR-; 13.6%, NAT+/PVC+/VR+), while the NAT-/PVC+/VR- had a higher local recurrence rate in upfront surgery (10.0%, NAT-/PVC-; 33.3%, NAT-/PVC+/VR-; 12.2%, NAT-/PVC+/VR+, P=0.021). In addition, the OS in the NAT+/PVC+/VR- was not inferior to that in the NAT+/PVC- (Median survival time: 46.6 months, NAT+/PVC-; 61.1, NAT+/PVC+/VR-; 33.0, NAT+/PVC+/VR+). Conclusions: Separation of the PV/SMV in NAT+/PVC+ patients did not enhance local recurrence or aggravate OS if PV/SMV invasion was not suspected intraoperatively. Therefore, an attempt to separate the PV/SMV is acceptable.

  6. Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers. International-journal

    Shin Ito, Mika Ando, Shuichi Aoki, Satoshi Soma, Jie Zhang, Naohiro Hirano, Ryosuke Kashiwagi, Keigo Murakami, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Koetsu Inoue, Masamichi Mizuma, Kiyoshi Kume, Kei Nakagawa, Atsushi Masamune, Naoki Asano, Jun Yasuda, Michiaki Unno

    Cancer science　115　(12)　4054-4063　2024/12

    DOI： 10.1111/cas.16365 　

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    Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

  7. 胆道癌ドライバー遺伝子探索における胆汁リキッドバイオプシー遺伝子パネル検査の有用性(Multi-gene Liquid Biopsy for bile juice may be useful to search driver genes of biliary duct cancers)

    伊藤 信, 安藤 未佳, 青木 修一, Zhang Jie, 平野 直大, 柏木 良介, 村上 圭吾, 吉町 信吾, 佐藤 英昭, 日下 彬子, 伊関 雅裕, 井上 亨悦, 水間 正道, 中川 圭, 安田 純, 海野 倫明, 安田 純

    日本癌学会総会記事　83回　P-3275　2024/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  8. Preoperative chemotherapy with Gemcitabine for pancreatic cancer causes zinc deficiency. International-journal

    Masahiro Iseki, Masamichi Mizuma, Mitsuhiro Shimura, Takashi Kokumai, Hideaki Sato, Akiko Kusaka, Shuichi Aoki, Koetsu Inoue, Shun Nakayama, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Kei Nakagawa, Takashi Kamei, Michiaki Unno

    Pancreas　2024/08/06

    DOI： 10.1097/MPA.0000000000002396 　

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    OBJECTIVES: The aim of this study was to investigate how preoperative chemotherapy affected the serum zinc concentrations in patients with pancreatic cancer (PC). METHODS: Two hundreds and thirty-one patients with PC who underwent pancreatectomy at our department from 2013 to 2019 were enrolled in this study and measured for the serum zinc concentrations before pancreatectomy. Patient characteristics, course of treatment, and laboratory data were analyzed. RESULTS: One hundred thirty-five patients underwent upfront pancreatectomy and 58 received preoperative Gemcitabine + S1 (GEM + S1) and 29 received Gemcitabine + nab-Paclitaxel (GEM + nab-PTX). Comparing the serum zinc concentrations before and after preoperative treatment, it was found to decrease after treatment with statistical difference (79.3 μg/dl vs. 68.7 μg/dl, p < 0.001). The result was consistent with the investigation for both the patients who received GEM + S1 and those who received GEM + nab-PTX (p = 0.019, p < 0.001, respectively). CONCLUSIONS: The preoperative chemotherapy consistently reduced the serum zinc concentrations in the PC patients, regardless of their regimen such as GEM + S1 and GEM + nab-PTX. Monitoring the serum zinc concentration and appropriate zinc supplementation may be essential for PC patients undergoing preoperative chemotherapy and pancreatectomy.

  9. Thick mesopancreas is a novel predictor of surgical outcomes of patients who undergo pancreaticoduodenectomy. International-journal

    Yuhei Endo, Hiroshi Noda, Masahiro Iseki, Hidetoshi Aizawa, Koetsu Inoue, Shimpei Maeda, Takaharu Kato, Fumiaki Watanabe, Toshiki Rikiyama

    Langenbeck's archives of surgery　409　(1)　181-181　2024/06/10

    DOI： 10.1007/s00423-024-03357-1 　

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    PURPOSE: Mesopancreas resection is a crucial but difficult procedure when performing pancreaticoduodenectomy. This study evaluated the influence of mesopancreas thickness on surgical outcomes in patients undergoing pancreaticoduodenectomy. METHODS: We measured the thickness of the fat tissue on the right side of the superior mesenteric artery from the dorsal margin of the confluence of the superior mesenteric vein and portal vein to the ventral margin of the left renal vein on preoperative contrast-enhanced computed tomography and defined it as the mesopancreas thickness. We evaluated the correlation between mesopancreas thickness and intraoperative and postoperative variables in 357 patients who underwent pancreaticoduodenectomy. RESULTS: Multivariate analysis revealed that a thick mesopancreas was significantly associated with a long operative time (β = 10.361; 95% confidence interval, 0.370-20.353, p = 0.042), high estimated blood loss (β = 36.038; 95% confidence interval, -27.192-99.268, p = 0.013), and a low number of resected lymph nodes (β = -1.551; 95% confidence interval, -2.662--0.439, p = 0.006). This analysis further revealed that thick mesopancreas was a significant risk factor for overall morbidity (odds ratio 2.170; 95% confidence interval 1.340-3.520, p = 0.002), major morbidity (odds ratio 2.430; 95% confidence interval 1.360-4.340, p = 0.003), and a longer hospital stay (β = 2.386; 95% confidence interval 0.299-4.474, p = 0.025). CONCLUSION: A thick mesopancreas could predict a longer operation time, higher estimated blood loss, fewer resected lymph nodes, more frequent overall and major morbidities, and a longer hospital stay in patients who underwent pancreaticoduodenectomy more precisely than the body mass index.

  10. Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial. International-journal

    Shota Fukai, Yuki Mizusawa, Hiroshi Noda, Shingo Tsujinaka, Yukihisa Maeda, Ryuji Hasebe, Yusuke Eguchi, Rina Kanemitsu, Natsumi Matsuzawa, Iku Abe, Yuhei Endo, Taro Fukui, Yuji Takayama, Kosuke Ichida, Koetsu Inoue, Yuta Muto, Fumiaki Watanabe, Kazushige Futsuhara, Yasuyuki Miyakura, Toshiki Rikiyama

    Trials　25　(1)　327-327　2024/05/17

    DOI： 10.1186/s13063-024-08167-w 　

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    BACKGROUND: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed. METHODS: We propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery. DISCUSSION: This trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates. TRIAL REGISTRATION: UMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205.

  11. Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD-1 Therapy. International-journal

    Jiang Chen, Zohreh Amoozgar, Xin Liu, Shuichi Aoki, Zelong Liu, Sarah M Shin, Aya Matsui, Alexei Hernandez, Zhangya Pu, Stefan Halvorsen, Pin-Ji Lei, Meenal Datta, Lingling Zhu, Zhiping Ruan, Lei Shi, Daniel Staiculescu, Koetsu Inoue, Lance L Munn, Dai Fukumura, Peigen Huang, Slim Sassi, Nabeel Bardeesy, Won Jin Ho, Rakesh K Jain, Dan G Duda

    Cancer immunology research　12　(4)　400-412　2024/04/02

    DOI： 10.1158/2326-6066.CIR-23-0486 　

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    Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti-programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti-PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels and, when combined with dual CTLA-4/PD-1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+ T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient because CD8+ T cells from Cxcr3+/+ but not Cxcr3-/- mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti-CTLA-4 "priming" with chemotherapy followed by anti-PD-1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.

  12. A postoperative body weight increase is a novel risk factor for incisional hernia of midline abdominal incision after elective gastroenterological surgery. International-journal

    Yuki Mizusawa, Hiroshi Noda, Kosuke Ichida, Shota Fukai, Natsumi Matsuzawa, Sawako Tamaki, Iku Abe, Yuhei Endo, Taro Fukui, Yuji Takayama, Koetsu Inoue, Yuta Muto, Fumiaki Watanabe, Yasuyuki Miyakura, Toshiki Rikiyama

    Langenbeck's archives of surgery　408　(1)　452-452　2023/11/30

    DOI： 10.1007/s00423-023-03193-9 　

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    PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

  13. CA19-9 With Two-stage Resection Is Useful for Conversion Surgery in PDAC With Synchronous Oligometastases. International-journal

    Koetsu Inoue, Masamichi Mizuma, Fuyuhiko Motoi, Takashi Kokumai, Hideaki Sato, Akiko Kusaka, Shuichi Aoki, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Hideo Ohtsuka, Kei Nakagawa, Takashi Kamei, Michiaki Unno

    Anticancer research　43　(11)　5223-5234　2023/11

    DOI： 10.21873/anticanres.16724 　

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    BACKGROUND/AIM: Pancreatic adenocarcinoma (PDAC) with synchronous oligometastases may indicate a surgical benefit after chemotherapy. We investigated whether primary and metastatic resection of PDAC with oligometastases can improve the survival and then explored prognostic factors to identify indications for conversion surgery. PATIENTS AND METHODS: We reviewed 425 patients with PDAC who underwent pancreatic resection from 2005 to 2019. Clinical characteristics and outcomes were analyzed. Two-stage resection was defined as preceding metastasectomy and subsequent primary resection after chemotherapy. RESULTS: Fifteen patients (3.5%) had synchronous oligometastases. We evaluated the overall survival of the patients with oligometastases and those without metastases. The survival curves almost completely overlapped (median survival time: 35.9 vs. 32.1 months). The univariate Cox regression analysis revealed a normal level of preoperative CA19-9 (p=0.075), two-stage resection (p=0.072), and R0 resection (p=0.064) were likely promising prognostic factors. The combination of a normal level of preoperative CA19-9 with two-stage resection was a significant prognostic factor (p=0.038). In addition, patients with a normal preoperative CA19-9 level and two-stage resection had better survival (46.1 vs. 28.1 months, p=0.026). CONCLUSION: The combination of normal preoperative CA19-9 with two-stage resection can be a useful way to identify patients with PDAC and oligometastases for surgical indication.

  14. Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment. International-journal

    Ryosuke Kashiwagi, Ryo Funayama, Shuichi Aoki, Aya Matsui, Sebastian Klein, Yukihiro Sato, Tsubasa Suzuki, Keigo Murakami, Koetsu Inoue, Masahiro Iseki, Kunihiro Masuda, Masamichi Mizuma, Hisamichi Naito, Dan G Duda, Michiaki Unno, Keiko Nakayama

    Cancer science　2023/09/08

    DOI： 10.1111/cas.15952 　

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    Expression of the gene for collagen XVII (COL17A1) in tumor tissue is positively or negatively associated with patient survival depending on cancer type. High COL17A1 expression is thus a favorable prognostic marker for breast cancer but unfavorable for pancreatic cancer. This study explored the effects of COL17A1 expression on pancreatic tumor growth and their underlying mechanisms. Analysis of published single-cell RNA-sequencing data for human pancreatic cancer tissue revealed that COL17A1 was expressed predominantly in cancer cells rather than surrounding stromal cells. Forced expression of COL17A1 did not substantially affect the proliferation rate of the mouse pancreatic cancer cell lines KPC and AK4.4 in vitro. However, in mouse homograft tumor models in which KPC or AK4.4 cells were injected into syngeneic C57BL/6 or FVB mice, respectively, COL17A1 expression promoted or suppressed tumor growth, respectively, suggesting that the effect of COL17A1 on tumor growth was influenced by the tumor microenvironment. RNA-sequencing analysis of tumor tissue revealed effects of COL17A1 on gene expression profiles (including the expression of genes related to cell proliferation, the immune response, Wnt signaling, and Hippo signaling) that differed between C57BL/6-KPC and FVB-AK4.4 tumors. Our data thus suggest that COL17A1 promotes or suppresses cancer progression in a manner dependent on the interaction of tumor cells with the tumor microenvironment.

  15. 膵臓疾患に対する周術期における栄養管理 膵癌術前化学療法が血清亜鉛値に与える影響

    伊関 雅裕, 水間 正道, 國米 崇, 柏木 良介, 日下 彬子, 青木 修一, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 海野 倫明

    膵臓　38　(3)　A278-A278　2023/07

    Publisher: (一社)日本膵臓学会

    ISSN： 0913-0071

    eISSN： 1881-2805

  16. 膵癌におけるEUS-FNAと腹腔洗浄細胞診および予後との関連

    中山 瞬, 水間 正道, 國米 崇, 柏木 良介, 日下 彬子, 青木 修一, 井上 亨悦, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 粂 潔, 正宗 淳, 古川 徹, 海野 倫明

    膵臓　38　(3)　A411-A411　2023/07

    Publisher: (一社)日本膵臓学会

    ISSN： 0913-0071

    eISSN： 1881-2805

  17. 癌治療における術前術後集学的治療の現状と成績 腹腔洗浄細胞診陽性膵癌に対する集学的治療 Conversion Surgeryの適応と治療成績

    平野 直大, 中山 瞬, 水間 正道, 青木 修一, 井上 亨悦, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本外科系連合学会誌　48　(3)　274-274　2023/05

    Publisher: 日本外科系連合学会

    ISSN： 0385-7883

    eISSN： 1882-9112

  18. 膵切除後膵液瘻予防のコツ 腹腔鏡下膵尾側切除における術後膵瘻予防の工夫

    林 秀一郎, 石田 晶玄, 青木 修一, 井上 亨悦, 伊関 雅裕, 中山 瞬, 堂地 大輔, 三浦 孝之, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本外科系連合学会誌　48　(3)　289-289　2023/05

    Publisher: 日本外科系連合学会

    ISSN： 0385-7883

    eISSN： 1882-9112

  19. 肝胆膵良性疾患における標準的術式とその理論的背景 先天性胆道拡張症成人例に対する至適アプローチ法の検討

    森川 孝則, 大塚 英郎, 宮崎 健人, 日下 彬子, 井上 亨悦, 青木 修一, 伊関 雅裕, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 田中 直樹, 西條 文人, 水間 正道, 中川 圭, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SY-4　2023/04

    Publisher: (一社)日本外科学会

  20. 癌免疫療法時代における外科医の役割 Interferon alpha-STAT3 axis制御による新規膵癌免疫治療 KRAS mutation subtype機能解析から得られた知見

    井上 亨悦, 宮崎 健人, 日下 彬子, 青木 修一, 伊関 雅裕, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 亀井 尚, Duda Dan, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SY-5　2023/04

    Publisher: (一社)日本外科学会

  21. 膵癌に対する低侵襲治療の適応とベストプラクティス 当施設での膵癌に対する腹腔鏡下膵尾側切除術の適応と工夫

    石田 晶玄, 森川 孝則, 青木 修一, 井上 亨悦, 伊関 雅裕, 中山 瞬, 堂地 大輔, 三浦 孝之, 水間 正道, 大塚 英郎, 中川 圭, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　PD-3　2023/04

    Publisher: (一社)日本外科学会

  22. 膵管内乳頭粘液性腫瘍における新たな知見と外科治療指針 Intraductal oncocytic papillary neoplasm(IOPN)に対する外科治療成績

    三浦 孝之, 宮崎 健人, 日下 彬子, 井上 亨悦, 青木 修一, 伊関 雅裕, 中山 瞬, 堂地 大輔, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 古川 徹, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　WS-7　2023/04

    Publisher: (一社)日本外科学会

  23. 腹腔洗浄細胞診陽性膵癌に対する化学療法後の腹腔ポート細胞診陰転化の意義

    中山 瞬, 水間 正道, 有明 恭平, 日下 彬, 青木 修一, 井上 亨悦, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SF-7　2023/04

    Publisher: (一社)日本外科学会

  24. 胆道癌に対する審査腹腔鏡・門脈塞栓術併施の取り組み

    伊関 雅裕, 中川 圭, 青木 修一, 宮崎 健人, 日下 彬子, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SF-8　2023/04

    Publisher: (一社)日本外科学会

  25. GFPT2はGemcitabine刺激によって発現が誘導されヘキソサミン経路を介した癌細胞の移動・浸潤能を亢進する

    宮崎 健人, 有明 恭平, 石田 晶玄, 中山 舜, 井上 亨悦, 堂地 大輔, 青木 修一, 伊関 雅裕, 三浦 孝之, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SF-5　2023/04

    Publisher: (一社)日本外科学会

  26. 膵癌細胞におけるAtaxia-telangiectasia Mutated(ATM)の発現とその機能解析

    大塚 英郎, 荀 静宇, 宮崎 健人, 日下 彬子, 井上 亨悦, 青木 修一, 伊関 雅裕, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SF-6　2023/04

    Publisher: (一社)日本外科学会

  27. 肝門部胆管癌の切除適応と治療戦略

    中川 圭, 伊関 雅裕, 青木 修一, 日下 彬子, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　DP-7　2023/04

    Publisher: (一社)日本外科学会

  28. 肝門部領域胆管癌における高齢者フレイルの評価と周術期管理の検討

    青木 修一, 中川 圭, 伊関 雅裕, 宮崎 健人, 日下 彬子, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　DP-1　2023/04

    Publisher: (一社)日本外科学会

  29. 膵切除後残膵病変の発生パターンの検討

    伊関 雅裕, 水間 正道, 國米 崇, 柏木 良介, 日下 彬子, 青木 修一, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本消化器病学会東北支部例会プログラム・抄録集　214回　105-105　2023/02

    Publisher: 日本消化器病学会-東北支部

  30. 術後合併症に対するIVR・内視鏡的ドレナージ治療 消化器外科術後合併症に対するVIABAHNステントグラフトの治療成績

    三浦 孝之, 日下 彬子, 井上 亨悦, 青木 修一, 伊関 雅裕, 堂地 大輔, 中山 瞬, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 高瀬 圭, 亀井 尚, 海野 倫明

    日本腹部救急医学会雑誌　43　(2)　357-357　2023/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  31. 血液透析患者に対する亜全胃温存膵頭十二指腸切除術4例の検討

    平野 直大, 伊関 雅裕, 日下 彬子, 青木 修一, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本腹部救急医学会雑誌　43　(2)　441-441　2023/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  32. 胆管炎を来した胆嚢出血に対する胆嚢摘出術の1例

    秋重 尚貴, 堂地 大輔, 日下 彬子, 青木 修一, 井上 亨悦, 伊関 雅裕, 中山 瞬, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 海野 倫明

    日本腹部救急医学会雑誌　43　(2)　539-539　2023/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  33. A Case of an Elderly Patient Who Underwent Conversion Resection for Pancreatic Cancer with Positive Peritoneal Cytology

    Naohiro Hirano, Shuichi Aoki, Masamichi Mizuma, Kei Nakagawa, Koetsu Inoue, Masahiro Iseki, Shun Nakayama, Daisuke Douchi, Takayuki Miura, Masaharu Ishida, Hideo Ohtsuka, Takanori Morikawa, Shinobu Ohnuma, Takashi Kamei, Michiaki Unno

    Gan to kagaku ryoho. Cancer &amp; chemotherapy　50　(2)　224-226　2023/02/01

    ISSN： 0385-0684

  34. Reprogramming Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD1 Therapy. International-journal

    Jiang Chen, Zohreh Amoozgar, Xin Liu, Shuichi Aoki, Zelong Liu, Sarah Shin, Aya Matsui, Zhangya Pu, Pin-Ji Lei, Meenal Datta, Lingling Zhu, Zhiping Ruan, Lei Shi, Daniel Staiculescu, Koetsu Inoue, Lance L Munn, Dai Fukumura, Peigen Huang, Nabeel Bardeesy, Won Jin Ho, Rakesh K Jain, Dan G Duda

    bioRxiv : the preprint server for biology　2023/01/27

    DOI： 10.1101/2023.01.26.525680 　

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    Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Anti-PD-L1 immunotherapy combined with gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers, but responses are seen only in a minority of patients. Here, we studied the roles of anti-PD1 and anti-CTLA-4 immune checkpoint blockade (ICB) therapies when combined with gemcitabine/cisplatin and the mechanisms of treatment benefit in orthotopic murine ICC models. We evaluated the effects of the combined treatments on ICC vasculature and immune microenvironment using flow cytometry analysis, immunofluorescence, imaging mass cytometry, RNA-sequencing, qPCR, and in vivo T-cell depletion and CD8+ T-cell transfer using orthotopic ICC models and transgenic mice. Combining gemcitabine/cisplatin with anti-PD1 and anti-CTLA-4 antibodies led to substantial survival benefits and reduction of morbidity in two aggressive ICC models, which were ICB-resistant. Gemcitabine/cisplatin treatment increased the frequency of tumor-infiltrating lymphocytes and normalized the ICC vessels, and when combined with dual CTLA-4/PD1 blockade, increased the number of activated CD8+Cxcr3+IFN-γ+ T-cells. Depletion of CD8+ but not CD4+ T-cells compromised efficacy. Conversely, CD8+ T-cell transfer from Cxcr3-/- versus Cxcr3+/+ mice into Rag1-/- immunodeficient mice restored the anti-tumor effect of gemcitabine/cisplatin/ICB combination therapy. Finally, rational scheduling of the ICBs (anti-CTLA-4 "priming") with chemotherapy and anti-PD1 therapy achieved equivalent efficacy with continuous dosing while reducing overall drug exposure. In summary, gemcitabine/cisplatin chemotherapy normalizes vessel structure, increases activated T-cell infiltration, and enhances anti-PD1/CTLA-4 immunotherapy efficacy in aggressive murine ICC. This combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.

  35. Chronic Glucocorticoid Use is a Potential Risk Factor for Delayed Pancreatic Fistula after Laparoscopic Distal Pancreatectomy: A Retrospective Analysis

    Koetsu Inoue, Takanori Morikawa, Masaharu Ishida, Takayuki Miura, Ryosuke Kashiwagi, Takashi Kokumai, Shuichi Aoki, Masahiro Iseki, Shun Nakayama, Daisuke Douchi, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Takashi Kamei, Michiaki Unno

    The Tohoku Journal of Experimental Medicine　2023

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.2023.j072 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  36. 膵頭十二指腸切除術における膵外分泌機能検査(PFD試験)の意義

    石田 晶玄, 森川 孝則, 宮崎 健人, 日下 彬子, 青木 修一, 伊関 雅裕, 井上 亨悦, 堂地 大輔, 中山 瞬, 三浦 孝之, 大塚 英郎, 水間 正道, 中川 圭, 亀井 尚, 海野 倫明

    学会誌JSPEN　4　(Suppl.2)　26-26　2022/12

    Publisher: (一社)日本臨床栄養代謝学会

    eISSN： 2434-4966

  37. Negative prognostic impact of sarcopenia before and after neoadjuvant chemotherapy for pancreatic cancer. International-journal

    Mitsuhiro Shimura, Masamichi Mizuma, Fuyuhiko Motoi, Akiko Kusaka, Shuichi Aoki, Masahiro Iseki, Koetsu Inoue, Daisuke Douchi, Shun Nakayama, Takayuki Miura, Masaharu Ishida, Hideo Ohtsuka, Kei Nakagawa, Takanori Morikawa, Takashi Kamei, Michiaki Unno

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]　2022/11/28

    DOI： 10.1016/j.pan.2022.11.010 　

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    OBJECTIVES: To elucidate the prognostic impact of sarcopenia before and after neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). METHODS: We retrospectively studied 75 consecutive PC patients who underwent neoadjuvant gemcitabine plus S-1 combination therapy followed by pancreatectomy between 2008 and 2016. According to the skeletal muscle volume index (SMI), the patients were divided into the muscle attenuation group (MAG) and normal group (NG) before or after NAC. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards models. RESULTS: The MAG showed significantly poorer OS than the NG before and after NAC. Pre-NAC, median OS was 20.0 months in the MAG versus 49.0 months in the NG (p = 0.006). Post-NAC, median OS was 21.3 months in the MAG versus 48.8 months in the NG (p = 0.014). Multivariate analysis, excluding muscle attenuation after NAC because of confounding factors and lower hazard ratio (2.08, 95% confidence interval: 1.14-3.78, p = 0.016) than that before NAC (2.14, 1.23-3.70, p = 0.007) by univariate analysis, revealed the following independent prognostic factors: muscle attenuation pre-NAC (2.25, 1.26-4.05, p = 0.007); borderline resectability (1.96, 1.04-3.69, p = 0.038); operative blood loss (2.60, 1.38-4.88, p = 0.003); and distant metastasis (3.31, 1.40-7.82, p = 0.006). CONCLUSIONS: Sarcopenia before and after NAC for PC is suggested to be a poor prognostic factor, with a stronger impact before than after NAC.

  38. 十二指腸乳頭部癌術後10年以上経過後に発症した膵管内転移の1例

    赤森 洋太, 伊関 雅裕, 國米 崇, 井上 亨悦, 中山 瞬, 堂地 大輔, 三浦 孝之, 石田 晶玄, 水間 正道, 大塚 英郎, 中川 圭, 森川 孝則, 亀井 尚, 古川 徹, 海野 倫明

    日本臨床外科学会雑誌　83　(増刊)　S314-S314　2022/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  39. 【術前画像の読み解きガイド—的確な術式選択と解剖把握のために】 Frey手術

    堂地 大輔, 水間 正道, 石田 晶玄, 日下 彬子, 青木 修一, 井上 亨悦, 伊関 雅裕, 中山 瞬, 三浦 孝之, 有明 恭平, 高舘 達之, 大塚 英郎, 中川 圭, 森川 孝則, 海野 倫明

    臨床外科　77　(11)　163-167　2022/10

    Publisher: 株式会社医学書院

    DOI： 10.11477/mf.1407213903 　

    ISSN： 0386-9857

    eISSN： 1882-1278

  40. Increased CD8+ T-cell Infiltration and Efficacy for Multikinase Inhibitors After PD-1 Blockade in Hepatocellular Carcinoma. International-journal

    Hiroto Kikuchi, Aya Matsui, Satoru Morita, Zohreh Amoozgar, Koetsu Inoue, Zhiping Ruan, Daniel Staiculescu, Jeffrey Sum-Lung Wong, Peigen Huang, Thomas Yau, Rakesh K Jain, Dan G Duda

    Journal of the National Cancer Institute　114　(9)　1301-1305　2022/09/09

    DOI： 10.1093/jnci/djac051 　

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    Immune checkpoint blockade combined with antiangiogenic therapy induces vascular normalization and antitumor immunity and is efficacious in hepatocellular carcinoma (HCC); but whether and how initial immunotherapy affects the efficacy of subsequent antiangiogenic therapy are unknown. We evaluated a cohort of HCC patients (n = 25) who received the pan-vascular endothelial growth factor receptor multikinase inhibitor sorafenib after initial therapy with an antiprogrammed cell death protein (PD)-1 antibody and found superior outcomes in these patients (12% overall response rate to sorafenib and a median overall survival of 12.1 months). To prove this potential benefit, we examined the impact of an anti-PD-1 antibody on response to subsequent sorafenib treatment in orthotopic models of murine HCC. Prior anti-PD-1 antibody treatment amplified HCC response to sorafenib therapy and increased survival (n = 8-9 mice per group, hazard ratio = 0.28, 95% confidence interval = 0.09 to 0.91; 2-sided P = .04). Anti-PD-1 therapy showed angioprotective effects on HCC vessels to subsequent sorafenib treatment, which enhanced the benefit of this therapy sequence in a CD8+ T-cell-dependent manner. This priming approach using immunotherapy provides an immediately translatable strategy for effective HCC treatment while reducing drug exposure.

  41. Pancreaticoduodenectomy for pancreatic head cancer with cavernous transformation of the portal vein: a case report. International-journal

    Naohiro Hirano, Masahiro Iseki, Takanori Morikawa, Yuuichiro Umino, Shuichi Aoki, Koetsu Inoue, Shun Nakayama, Takayuki Miura, Kunihiro Masuda, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Kiyoshi Kume, Atsushi Masamune, Takashi Kamei, Michiaki Unno

    Surgical case reports　8　(1)　127-127　2022/06/30

    DOI： 10.1186/s40792-022-01463-0 　

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    BACKGROUND: Cavernous transformation of the portal vein (CTPV) due to extrahepatic portal vein obstruction is a rare vascular anomaly. Since its symptoms usually appear in childhood, most of the adult cases are detected unexpectedly with other diseases. Only a few reports have described surgical difficulties in patients with CTPV. We report a case of pancreatic head cancer with CTPV in a patient who underwent pancreaticoduodenectomy. CASE PRESENTATION: A 77-year-old man with epigastric and back pain was referred to our hospital. Computed tomography revealed a tumor in the pancreatic head and a CTPV near the hepatic hilum. CTPV consisted of two main collateral vessels connected by multiple surrounding small vessels. Also, portal vein obstruction was observed near the hepatic hilum, which was far from the pancreatic head tumor. After confirming that there was no distant metastasis by a thorough whole-body search, we performed a pancreaticoduodenectomy following neoadjuvant chemotherapy. During the operation, we carefully manipulated the area of the CTPV and omitted lymph node dissection in the hepatoduodenal ligament to prevent massive venous bleeding and intestinal congestion. Pancreaticoduodenectomy was performed without any intraoperative complications and the postoperative course was uneventful. Complete tumor resection was histologically confirmed. CONCLUSION: Although pancreaticoduodenectomy for patients with CTPV involves many surgical difficulties, we successfully performed it by determining specific treatment strategies tailored to the patient and following careful and delicate surgical procedures.

  42. Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma. International-journal

    Shuichi Aoki, Koetsu Inoue, Sebastian Klein, Stefan Halvorsen, Jiang Chen, Aya Matsui, Mohammad R Nikmaneshi, Shuji Kitahara, Tai Hato, Xianfeng Chen, Kazumichi Kawakubo, Hadi T Nia, Ivy Chen, Daniel H Schanne, Emilie Mamessier, Kohei Shigeta, Hiroto Kikuchi, Rakesh R Ramjiawan, Tyge Ce Schmidt, Masaaki Iwasaki, Thomas Yau, Theodore S Hong, Alexander Quaas, Patrick S Plum, Simona Dima, Irinel Popescu, Nabeel Bardeesy, Lance L Munn, Mitesh J Borad, Slim Sassi, Rakesh K Jain, Andrew X Zhu, Dan G Duda

    Gut　71　(1)　185-193　2021/01/11

    DOI： 10.1136/gutjnl-2020-322493 　

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    OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC)-a rare liver malignancy with limited therapeutic options-is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression. DESIGN: We evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic effect of genetic or pharmacologic inhibition of PlGF in orthotopically grafted ICC mouse models. We evaluated the impact of PlGF stimulation or blockade in ICC cells and cancer-associated fibroblasts (CAFs) using in vitro 3-D coculture systems. RESULTS: PlGF levels were elevated in human ICC stromal cells and circulating blood plasma and were associated with disease progression. Single-cell RNA sequencing showed that the major impact of PlGF blockade in mice was enrichment of quiescent CAFs, characterised by high gene transcription levels related to the Akt pathway, glycolysis and hypoxia signalling. PlGF blockade suppressed Akt phosphorylation and myofibroblast activation in ICC-derived CAFs. PlGF blockade also reduced desmoplasia and tissue stiffness, which resulted in reopening of collapsed tumour vessels and improved blood perfusion, while reducing ICC cell invasion. Moreover, PlGF blockade enhanced the efficacy of standard chemotherapy in mice-bearing ICC.ConclusionPlGF blockade leads to a reduction in intratumorous hypoxia and metastatic dissemination, enhanced chemotherapy sensitivity and increased survival in mice-bearing aggressive ICC.

  43. Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma. International-journal

    Kohei Shigeta, Aya Matsui, Hiroto Kikuchi, Sebastian Klein, Emilie Mamessier, Ivy X Chen, Shuichi Aoki, Shuji Kitahara, Koetsu Inoue, Ayako Shigeta, Tai Hato, Rakesh R Ramjiawan, Daniel Staiculescu, Dieter Zopf, Lukas Fiebig, Gabriela S Hobbs, Alexander Quaas, Simona Dima, Irinel Popescu, Peigen Huang, Lance L Munn, Mark Cobbold, Lipika Goyal, Andrew X Zhu, Rakesh K Jain, Dan G Duda

    Journal for immunotherapy of cancer　8　(2)　2020/11

    DOI： 10.1136/jitc-2020-001435 　

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    BACKGROUND AND PURPOSE: Combining inhibitors of vascular endothelial growth factor and the programmed cell death protein 1 (PD1) pathway has shown efficacy in multiple cancers, but the disease-specific and agent-specific mechanisms of benefit remain unclear. We examined the efficacy and defined the mechanisms of benefit when combining regorafenib (a multikinase antivascular endothelial growth factor receptor inhibitor) with PD1 blockade in murine hepatocellular carcinoma (HCC) models. BASIC PROCEDURES: We used orthotopic models of HCC in mice with liver damage to test the effects of regorafenib-dosed orally at 5, 10 or 20 mg/kg daily-combined with anti-PD1 antibodies (10 mg/kg intraperitoneally thrice weekly). We evaluated the effects of therapy on tumor vasculature and immune microenvironment using immunofluorescence, flow cytometry, RNA-sequencing, ELISA and pharmacokinetic/pharmacodynamic studies in mice and in tissue and blood samples from patients with cancer. MAIN FINDINGS: Regorafenib/anti-PD1 combination therapy increased survival compared with regofarenib or anti-PD1 alone in a regorafenib dose-dependent manner. Combination therapy increased regorafenib uptake into the tumor tissues by normalizing the HCC vasculature and increasing CD8 T-cell infiltration and activation at an intermediate regorafenib dose. The efficacy of regorafenib/anti-PD1 therapy was compromised in mice lacking functional T cells (Rag1-deficient mice). Regorafenib treatment increased the transcription and protein expression of CXCL10-a ligand for CXCR3 expressed on tumor-infiltrating lymphocytes-in murine HCC and in blood of patients with HCC. Using Cxcr3-deficient mice, we demonstrate that CXCR3 mediated the increased intratumoral CD8 T-cell infiltration and the added survival benefit when regorafenib was combined with anti-PD1 therapy. PRINCIPAL CONCLUSIONS: Judicious regorafenib/anti-PD1 combination therapy can inhibit tumor growth and increase survival by normalizing tumor vasculature and increasing intratumoral CXCR3+CD8 T-cell infiltration through elevated CXCL10 expression in HCC cells.

  44. 肝細胞癌における腫瘍微小環境と腫瘍免疫 免疫治療のメカニズムと治療戦略

    茂田 浩平, 松居 彩, Mamessier Emilie, Chen Ivy, 青木 修一, 北原 秀治, 菊池 弘人, 井上 亨悦, 羽藤 泰, Zhu Andrew, Cobbold Mark, Jain Rakesh, Duda Dan, 北川 雄光

    日本外科学会定期学術集会抄録集　119回　SF-2　2019/04

    Publisher: (一社)日本外科学会

  45. What is the optimal risk scoring for predicting complications after colorectal surgery in elderly patients?

    Koetsu Inoue, Tatsuya Ueno, Naoki Akishige, Toshihiro Soeta, Takahiro Tsuchiya, Shun Nakayama, Kentaro Shima, Shinji Goto, Michinaga Takahashi, Takeshi Naitoh, Hiroo Naito

    International Journal of Surgery Open　21　52-57　2019

    Publisher: Elsevier BV

    DOI： 10.1016/j.ijso.2019.11.007 　

    ISSN： 2405-8572

  46. Short–term outcomes of laparoscopic colorectal cancer surgery in elderly patients. -Is it really safe in elderly patients with severe comorbidities?-

    Koetsu Inoue, Tatsuya Ueno, Naoki Akishige, Toshihiro Soeta, Takahiro Tsuchiya, Shun Nakayama, Kentaro Shima, Shinji Goto, Michinaga Takahashi, Hiroo Naito

    International Journal of Surgery Open　17　27-32　2019

    Publisher: Elsevier BV

    DOI： 10.1016/j.ijso.2019.02.001 　

    ISSN： 2405-8572

  47. 腹腔鏡下脾臓摘出術を行ったsclerosing angiomatoid nodular transformation(SANT)の1例

    佐々木 純一, 嶋 健太郎, 堂地 大輔, 井上 亨悦, 上野 達也, 高橋 道長

    日本内視鏡外科学会雑誌　22　(7)　EP185-03　2017/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  48. Risk factors for difficulty of laparoscopic cholecystectomy in grade II acute cholecystitis according to the Tokyo guidelines 2013. International-journal

    Koetsu Inoue, Tatsuya Ueno, Daisuke Douchi, Kentaro Shima, Shinji Goto, Michinaga Takahashi, Takanori Morikawa, Takeshi Naitoh, Chikashi Shibata, Hiroo Naito

    BMC surgery　17　(1)　114-114　2017/11/28

    DOI： 10.1186/s12893-017-0319-6 　

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    BACKGROUND: The Tokyo Guidelines 2013 classifies acute cholecystitis (AC) into three grades and recommends appropriate therapy for each grade. For grade II AC, either early laparoscopic cholecystectomy (LC) or percutaneous transhepatic gallbladder drainage (PTGBD) should be performed. This study aimed to identify the risk factors for difficulty of LC for treating grade II AC. METHODS: Totally, 122 patients who underwent LC for grade II AC were enrolled and divided into difficult LC (DLC) and nondifficult LC (NDLC) groups. The DLC group included patients who experienced one of the following conditions: conversion from LC to open cholecystectomy, operating time ≥ 180 min, or blood loss ≥300 ml. Preoperative characteristics and postoperative outcomes were analyzed. RESULTS: In univariate analysis, risk factors included male sex, interval between symptom onset and admission, interval between symptom onset and LC, and anticoagulant therapy. The incidence of postoperative complications was higher in the DLC group than in the NDLC group (23.5% vs. 4.6%, p = 0.0016). According to receiver operating characteristic curves, the optimal cutoff value was calculated, and multivariate analysis showed that male sex [odds ratio (OR), 5.76; 95% confidence interval (CI), 1.979-19.51; p = 0.0009) and interval between symptom onset and LC of over 96 h (OR, 6.32; 95% CI, 2.126-20.15; p = 0.0009) were independent risk factors for difficulty of LC. CONCLUSIONS: In patients with grade II AC, LC was technically difficult when performed over 96 h after symptom onset. Moreover, male sex was a risk factor. Therefore, PTGBD should be considered in these patients.

  49. Optimal timing of cholecystectomy after percutaneous gallbladder drainage for severe cholecystitis. International-journal

    Koetsu Inoue, Tatsuya Ueno, Orie Nishina, Daisuke Douchi, Kentaro Shima, Shinji Goto, Michinaga Takahashi, Chikashi Shibata, Hiroo Naito

    BMC gastroenterology　17　(1)　71-71　2017/05/31

    DOI： 10.1186/s12876-017-0631-8 　

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    BACKGROUND: The Tokyo guideline for acute cholecystitis recommended percutaneous transhepatic gallbladder drainage followed by cholecystectomy for severe acute cholecystitis, but the optimal timing for the subsequent cholecystectomy remains controversial. METHODS: Sixty-seven patients who underwent either laparoscopic or open cholecystectomy after percutaneous transhepatic gallbladder drainage for severe acute cholecystitis were enrolled and divided into difficult cholecystectomy (group A) and non-difficult cholecystectomy (group B). Patients who had one of these conditions were placed in group A: 1) conversion from laparoscopic to open cholecystectomy; 2) subtotal cholecystectomy and/or mucoclasis; 3) necrotizing cholecystitis or pericholecystic abscess formation; 4) tight adhesions around the gallbladder neck; and 5) unsuccessfully treated using PTGBD. Preoperative characteristics and postoperative outcomes were analyzed. RESULTS: The interval between percutaneous transhepatic gallbladder drainage and cholecystectomy in Group B was longer than that in Group A (631 h vs. 325 h; p = 0.031). Postoperative complications occurred more frequently when the interval was less than 216 h compared to when it was more than 216 h (35.7 vs. 7.6%; p = 0.006). CONCLUSIONS: Cholecystectomy for severe acute cholecystitis was technically difficult when performed within 216 h after percutaneous transhepatic gallbladder drainage.

  50. All-trans retinoic acid enhances gemcitabine cytotoxicity in human pancreatic cancer cell line AsPC-1 by up-regulating protein expression of deoxycytidine kinase. International-journal

    Hiroki Kuroda, Masanori Tachikawa, Yasuo Uchida, Koetsu Inoue, Hideo Ohtsuka, Sumio Ohtsuki, Michiaki Unno, Tetsuya Terasaki

    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences　103　116-121　2017/05/30

    DOI： 10.1016/j.ejps.2017.02.021 　

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    We previously showed that gemcitabine resistance in pancreatic cancer chemotherapy correlates with suppressed expression of deoxycytidine kinase (dCK), which catalyzes the rate-limiting step of gemcitabine activation. The purpose of the present study was to find a drug that might be useful to enhance the cytotoxicity of gemcitabine by increasing dCK expression in gemcitabine-resistant human pancreatic cancer cell line AsPC-1. Screening of 40 prescription drugs identified 35 with no intrinsic cytotoxicity towards AsPC-1 cells. When AsPC-1 cells were pre-incubated with these drugs and then incubated with gemcitabine, we found that all-trans retinoic acid (ATRA) significantly decreased the viability by 28% compared with that of non-treated cells. Luciferase assay showed that ATRA transactivated the DCK promoter in AsPC-1 cells by about 2-fold compared with the untreated control, and an increase of dCK protein expression was confirmed by immunoblotting. ATRA decreased the half-maximal inhibitory concentration (IC50) of gemcitabine by 2.8-fold (ATRA-non-treated cells, 28.8nM; ATRA-treated cells, 10.0nM). The ATRA concentration of 0.03μM was sufficient to enhance gemcitabine cytotoxicity, and the effect was well maintained in the concentration range from 0.03 to 50μM. These results indicate that ATRA enhances gemcitabine cytotoxicity by increasing dCK expression in gemcitabine-resistant human pancreatic cancer cells.

  51. MK2461, a Multitargeted Kinase Inhibitor, Suppresses the Progression of Pancreatic Cancer by Disrupting the Interaction Between Pancreatic Cancer Cells and Stellate Cells. International-journal

    Koetsu Inoue, Hideo Ohtsuka, Masanori Tachikawa, Fuyuhiko Motoi, Masahiro Shijo, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Tetsuya Terasaki

    Pancreas　46　(4)　557-566　2017/04

    DOI： 10.1097/MPA.0000000000000778 　

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    OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRβ and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry. In addition, the effect of MK2461 on PCC-PSC interaction was investigated using PSCs prepared from pancreatic cancer tissues. RESULTS: In PSCs, PDGFRβ and MET were upregulated compared with other receptor tyrosine kinases. Conditioned medium from PSCs promoted the proliferation of PCCs, and vice versa. Moreover, MK2461 suppressed the effects of conditioned medium on PCCs and PSCs. Finally, MK2461 significantly inhibited tumor growth in mice coinjected with PCCs and PSCs. CONCLUSIONS: The PDGFRβ and MET may play a critical role in the interaction between PCCs and PSCs, which was modulated by MK2461. Therefore, MK2461 may have therapeutic potential in the treatment of pancreatic cancer.

  52. Extreme dilatation of the interposed jejunal pouch after proximal gastrectomy associated with portal venous gas: A case report. International-journal

    Michinaga Takahashi, Shinji Goto, Tatsuya Ueno, Kentaro Shima, Koetsu Inoue, Daisuke Douchi, Orie Nishina, Hiroo Naito

    International journal of surgery case reports　37　244-247　2017

    DOI： 10.1016/j.ijscr.2017.06.060 　

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    INTRODUCTION: The jejunal pouch interposition (JPI) after proximal gastrectomy (PG) was proposed as a reconstructive procedure to provide a gastric reservoir substitute and prevent postgastrectomy syndrome. However, food residue remaining in some of the pouches resulted in the adverse effect of abdominal bloating, thereby body weight loss. Here, we report a rare case with an extreme dilation of the interposed jejunal pouch (JP) 8 years after PG, requiring pouch resection. PRESENTATION OF CASE: A 65-year-old-man who had undergone PG with an inverted U-shaped JPI for early gastric cancer 8 years previously, suffered from shock after right hip joint implantation. Abdominal enhanced CT scan revealed an extremely dilated JP accompanied by portal venous gas. After 5 months of conservative therapy, he underwent resection of the JP and gastric remnant with Roux-en-Y esophagojejunostomy reconstruction. After the operation, the patient has remained in good health for over 3 years. DISCUSSION AND CONCLUSION: Long-term operative outcome following pouch operation for gastric cancer still remains controversial. Surgical intervention should be considered when we encounter patients who have refractory pouch dilatation after surgery for gastric cancer.

  53. Indocyanine green蛍光法が胆管損傷の予防に有用であった肝嚢胞の1例

    井上 亨悦, 森川 孝則, 赤田 昌紀, 上野 達也, 海野 倫明, 内藤 広郎

    日本臨床外科学会雑誌　77　(5)　1202-1206　2016/05

    Publisher: 日本臨床外科学会

    DOI： 10.3919/jjsa.77.1202 　

    ISSN： 1345-2843

  54. 続発性ヘモクロマトーシスを背景とした肝細胞癌門脈腫瘍栓再発に対し放射線治療が著効した1例(続報) Peer-reviewed

    井上 亨悦, 水間 正道, 大塚 英郎, 中川 圭, 林 洋毅, 岡田 恭穂, 吉田 寛, 元井 冬彦, 内藤 剛, 片寄 友, 神宮 啓一, 海野 倫明

    肝臓　56　(4)　150-156　2015/04

    DOI： 10.2957/kanzo.41.823 　

  55. [A case of colorectal neuroendocrine carcinoma effectively treated with bevacizumab+levofolinate+5-FU chemotherapy].

    Hiroshi Yabuki, Takeshi Suto, Koetsu Inoue, Hiroto Fujimoto, Toshihiko Sato, Eiichi Ikeda, Hajime Iizawa

    Gan to kagaku ryoho. Cancer & chemotherapy　39　(7)　1139-42　2012/07

    ISSN： 0385-0684

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    A 76-year-old woman was admitted to our hospital with diarrhea and weight loss in February 2007. A CT scan revealed a tumor in the abdominal cavity, and although a thorough investigation was conducted, no diagnosis was made. Therefore, she underwent diagnostic surgery in April 2007. Intraoperatively, the tumor was determined to have originated in the transverse colon, with invasion to other organs. The patient underwent a transverse colectomy, partial ileal resection, and partial resection of the bladder and peritoneum were performed. The pathological diagnosis was colorectal neuroendocrine carcinoma. FOLFOX4 chemotherapy was initiated in May 2007. However, a CT scan in June 2007 revealed a recurrent tumor in the right pelvis. Although right hemicolectomy and right oophorectomy were performed in August, a CT scan in September 2007 revealed a recurrent tumor in the right pelvis. Following treatment with bevacizumab+levofolinate+5-FU, the tumor disappeared. The patient continued to receive this chemotherapy regimen until August 2010, and CT scans showed a complete response. Even though colorectal neuroendocrine carcinoma is known to have a poor prognosis, the present case was effectively treated with bevacizumab+levofolinate+5-FU chemotherapy. Herein we provide discussion and suggestions about treatment for colorectal neuroendocrine carcinoma.

  56. [Adverse events in patients treated with capecitabine as adjuvant chemotherapy after surgery for colorectal cancer--countermeasures against hand-foot syndrome].

    Takeshi Suto, Koushiro Ishiyama, Hiroshi Yabuki, Naoki Mori, Koetsu Inoue, Masato Chiba, Akiko Igawa, Toshihiro Watanabe, Hiroto Fujimoto, Yumi Suzuki, Makoto Sugawara, Tomomi Saito, Yuka Kobayashi, Mikiko Matsuda, Eiichi Ikeda, Toshihiko Sato, Hajime Iizawa

    Gan to kagaku ryoho. Cancer & chemotherapy　37　(9)　1729-33　2010/09

    ISSN： 0385-0684

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    Although the 2009 edition of the Guidelines for Colorectal Cancer Therapy recommend capecitabine as a standard postoperative adjuvant chemotherapy for colorectal cancer therapy, a characteristic adverse event, hand-foot syndrome, develops at a high incidence, and appropriate management is necessary to continue therapy. We investigated countermeasures against adverse events, particularly hand-foot syndrome, in patients treated with capecitabine. The subjects were 47 patients aged 64 years (27-84 years) who underwent surgery for colorectal cancer. They received 8 (2-16) courses of drug administration. No grade 3 blood or non-blood toxicity was noted, and the therapy was relatively safe excluding an enhanced anticoagulant effect. Grade-3 hand-foot syndrome developed in 3 patients, but there were only 10 grade-2/3 cases (21.7%) because humectants and oral vitamin B6 preparation (supportive therapy) were administered from therapy initiation. The incidence increased to 32.6% (15 patients) after June. Symptoms aggravated due to mechanical stimulation of the hands and legs in 5 patients because they were farmers growing cherries, suggesting that investigation of patient living background is also important. The incidence of grade-2/3 hand-foot syndrome was 21.1 and 75% in 39 and 8 patients, respectively, who were treated with supportive therapy from the initiation of drug administration and after several courses of drug administration or development of symptoms. This suggested the usefulness of early supportive therapy. The importance of preventive measures against hand-foot syndrome will increase as capecitabine is increasingly administered. Information exchange between medical staffs and providing patients with appropriate information may lead to management of adverse events and subsequently to continuation and obtaining effects of therapy.

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Misc. 25

  1. IQGAP3 as a gatekeeper of epithelial integrity and prognostic biomarker in extrahepatic cholangiocarcinoma.

    Naoki Rikiyama, Daisuke Douchi, Ming Zhu, Keigo Murakami, Mitsuhiro Shimura, Takehiko Saijo, Shusuke Migita, Shuichiro Hayashi, Hideaki Sato, Koetsu Inoue, Shuichi Aoki, Masahiro Iseki, Takayuki Miura, Shimpei Maeda, Hideaki Karasawa, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Shinobu Ohnuma, Atsushi Masamune, Toru Furukawa, Michiaki Unno

    CANCER RESEARCH　86　(7)　2026/04/03

    DOI： 10.1158/1538-7445.AM2026-3936 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  2. 膵退形成癌に対する術前治療

    水間 正道, 國米 崇, 柏木 良介, 日下 彬子, 青木 修一, 伊関 雅裕, 井上 亨悦, 堂地 大輔, 中山 瞬, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 粂 潔, 正宗 淳, 亀井 尚, 海野 倫明

    日本消化器外科学会雑誌　56　(Suppl.2)　379-379　2023/11

    Publisher: (一社)日本消化器外科学会

    ISSN： 0386-9768

    eISSN： 1348-9372

  3. 膵癌におけるEUS-FNAと腹腔洗浄細胞診および予後との関連

    中山 瞬, 水間 正道, 國米 崇, 柏木 良介, 日下 彬子, 青木 修一, 井上 亨悦, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 粂 潔, 正宗 淳, 古川 徹, 海野 倫明

    膵臓　38　(3)　A411-A411　2023/07

    Publisher: (一社)日本膵臓学会

    ISSN： 0913-0071

    eISSN： 1881-2805

  4. 肝内胆管癌におけるHGF/METシグナルの亢進は免疫抑制的な微小環境を創出する

    海野 裕一郎, 青木 修一, 村上 圭吾, 安藤 未佳, 柏木 良介, 井上 亨悦, 伊関 雅裕, 三浦 孝之, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 石田 孝宣, 亀井 尚, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　DP-7　2023/04

    Publisher: (一社)日本外科学会

  5. 膵癌術前GS療法施行症例におけるABO血液型と予後との関係

    水間 正道, 青木 修一, 伊関 雅裕, 井上 亨悦, 中山 瞬, 三浦 孝之, 益田 邦洋, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 粂 潔, 正宗 淳, 海野 倫明

    日本消化器外科学会雑誌　55　(Suppl.2)　265-265　2022/10

    Publisher: (一社)日本消化器外科学会

    ISSN： 0386-9768

    eISSN： 1348-9372

  6. 膵癌術前GS療法施行症例におけるABO血液型と予後との関係

    水間 正道, 青木 修一, 伊関 雅裕, 井上 亨悦, 中山 瞬, 三浦 孝之, 益田 邦洋, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 粂 潔, 正宗 淳, 海野 倫明

    日本消化器外科学会雑誌　55　(Suppl.2)　265-265　2022/10

    Publisher: (一社)日本消化器外科学会

    ISSN： 0386-9768

    eISSN： 1348-9372

  7. 当科における肝門部胆管癌に対するConversion surgeryの現状と課題

    青木 修一, 中川 圭, 海野 倫明, 伊関 雅裕, 井上 亨悦, 大塚 英郎, 水間 正道, 森川 孝則, 粂 潔, 正宗 淳

    胆道　36　(3)　366-366　2022/09

    Publisher: (一社)日本胆道学会

    ISSN： 0914-0077

    eISSN： 1883-6879

  8. 外科系周術期栄養のアップデート 膵臓外科における周術期栄養評価の重要性

    森川 孝則, 石田 晶玄, 伊関 雅裕, 宮崎 健人, 日下 彬子, 井上 亨悦, 青木 修一, 中山 瞬, 堂地 大輔, 三浦 孝之, 大塚 英郎, 水間 正道, 中川 圭, 大沼 忍, 亀井 尚, 海野 倫明

    New Diet Therapy　38　(2)　100-100　2022/09

    Publisher: (一社)日本臨床栄養協会

    ISSN： 0910-7258

    eISSN： 2434-7159

  9. 当院における亜全胃温存膵頭十二指腸切除術後腹腔内出血の治療成績

    井上 亨悦, 石田 晶玄, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 大沼 忍, 亀井 尚, 高瀬 圭, 海野 倫明

    日本消化器外科学会総会　77回　RS19-3　2022/07

    Publisher: (一社)日本消化器外科学会

  10. 切除可能境界膵体部癌に対して術前治療により病理学的完全奏効が得られた1例

    平野 直大, 伊関 雅裕, 水間 正道, 野口 彩, 青木 修一, 井上 亨悦, 中山 瞬, 三浦 孝之, 石田 晶玄, 大塚 英郎, 中川 圭, 森川 孝則, 佐藤 真広, 粂 潔, 正宗 淳, 廣瀬 勝也, 古川 徹, 大沼 忍, 亀井 尚, 海野 倫明

    日本消化器病学会東北支部例会プログラム・抄録集　213回　71-71　2022/07

    Publisher: 日本消化器病学会-東北支部

  11. 男性膵solid-pseudopapillary neoplasm,pleomorphic variantの1例

    丸山大貴, 三浦孝之, 井上亨悦, 青木修一, 伊関雅裕, 中山瞬, 益田邦洋, 石田晶玄, 大塚英郎, 水間正道, 中川圭, 森川孝則, 大森優子, 古川徹, 亀井尚, 海野倫明

    日本外科系連合学会誌　47　(3)　2022

    ISSN： 0385-7883

  12. 術前に重複胆嚢が疑われた膿瘍形成性慢性胆嚢炎に対し腹腔鏡下胆嚢亜全摘術を施行した1例

    丸山大貴, 三浦孝之, 日下彬子, 井上亨悦, 青木修一, 伊関雅裕, 堂地大輔, 中山瞬, 石田晶玄, 大塚英郎, 水間正道, 中川圭, 森川孝則, 亀井尚, 海野倫明

    日本内視鏡外科学会総会(Web)　35th　2022

  13. 肝細胞癌に対する新規治療の開発 腫瘍微小環境と腫瘍免疫の関連性の検討

    茂田 浩平, 菊池 弘人, 松居 彩, Mamessier Emilie, Chen Ivy, 青木 修一, 井上 亨悦, Jain Rakesh, 北川 雄光, Duda Dan

    日本消化器外科学会総会　74回　P182-6　2019/07

    Publisher: (一社)日本消化器外科学会

  14. 肝細胞癌における腫瘍微小環境と腫瘍免疫 免疫治療のメカニズムと治療戦略

    茂田 浩平, 松居 彩, Mamessier Emilie, Chen Ivy, 青木 修一, 北原 秀治, 菊池 弘人, 井上 亨悦, 羽藤 泰, Zhu Andrew, Cobbold Mark, Jain Rakesh, Duda Dan, 北川 雄光

    日本外科学会定期学術集会抄録集　119回　SF-015　2019/04

    Publisher: (一社)日本外科学会

  15. 当院における高齢者胃癌に対する腹腔鏡手術の短期手術成績

    井上 亨悦, 上野 達也, 堂地 大輔, 嶋 健太郎, 高橋 道長

    日本内視鏡外科学会雑誌　22　(7)　EP213-01　2017/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  16. 腹腔鏡下大腸切除術は高齢者でも安全か? 短期手術成績の検討

    井上 亨悦, 高橋 道長, 仁科 オリエ, 堂地 大輔, 嶋 健太郎, 上野 達也, 後藤 慎二, 内藤 広郎

    日本消化器外科学会総会　72回　PB13-1　2017/07

    Publisher: (一社)日本消化器外科学会

  17. 当院における絞扼性腸閉塞の検討

    嶋 健太郎, 上野 達也, 二科 オリエ, 井上 亨悦, 堂地 大輔, 後藤 慎二, 高橋 道長, 内藤 広郎

    日本消化器外科学会総会　72回　PC16-5　2017/07

    Publisher: (一社)日本消化器外科学会

  18. Precision medicine bench to bedside LC-MS/MS蛋白質絶対定量法をもちいた腫瘍組織中薬物代謝関連蛋白質発現量測定の、周術期ゲムシタビン療法効果予測への応用 前向き臨床試験

    大塚 英郎, 川口 桂, 井上 亨悦, 四條 正浩, 有明 恭平, 高舘 達之, 前田 晋平, 益田 邦洋, 青木 豪, 石田 晶玄, 深瀬 耕二, 水間 正道, 坂田 直昭, 森川 孝則, 林 洋毅, 中川 圭, 内藤 剛, 立川 正憲, 寺崎 哲也, 海野 倫明

    日本外科学会定期学術集会抄録集　117回　SY-7　2017/04

    Publisher: (一社)日本外科学会

  19. 十二指腸潰瘍穿孔を合併した甲状腺クリーゼの一例

    嶋 健太郎, 上野 達也, 二科 オリエ, 井上 亨悦, 堂地 大輔, 後藤 慎二, 高橋 道長, 内藤 広郎

    日本腹部救急医学会雑誌　37　(2)　263-263　2017/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  20. MK2461 suppress progression of pancreatic cancer disrupting interaction between pancreatic cancer cells and stellate cells

    Koetsu Inoue, Hideo Ohtsuka, Fuyuhiko Motoi, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Shinobu Ohnuma, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno

    CANCER RESEARCH　75　2015/08

    DOI： 10.1158/1538-7445.AM2015-404 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  21. 保存的治療が奏効したプロテインC欠損症に伴う上腸間膜静脈血栓症の1例

    前田 晋平, 高橋 道長, 佐藤 俊, 赤田 昌紀, 井上 亨悦, 内藤 広郎

    日本臨床外科学会雑誌　76　(7)　1609-1615　2015/07

    Publisher: 日本臨床外科学会

    DOI： 10.3919/jjsa.76.1609 　

    ISSN： 1345-2843

  22. A case of successful treatment with radiotherapy of hepatocellular carcinoma with portal vein tumor thrombus in secondary hemochromatosis due to myelodysplastic syndrome (2nd report)

    Koetsu Inoue, Masamichi Mizuma, Hideo Ohtsuka, Kei Nakagawa, Hiroki Hayashi, Takaho Okada, Hiroshi Yoshida, Fuyuhiko Motoi, Takeshi Naito, Yu Katayose, Keiichi Jingu, Michiaki Unno

    Acta Hepatologica Japonica　56　(4)　150-156　2015/01/01

    Publisher: 一般社団法人 日本肝臓学会

    DOI： 10.2957/kanzo.56.150 　

    ISSN： 0451-4203

  23. MK2461は膵癌細胞と癌関連線維芽細胞の相互作用を制御し膵癌増殖を抑制する(MK2461 regulated proliferation of pancreatic cancer disrupting interaction between pancreatic cancer cell and CAF)

    井上 亨悦, 大塚 英郎, 深瀬 耕二, 益田 邦洋, 川口 桂, 吉田 寛, 元井 冬彦, 内藤 剛, 片寄 友, 江川 新一, 立川 正憲, 寺崎 哲也, 海野 倫明

    日本癌学会総会記事　73回　P-2268　2014/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  24. LC-MS/MS蛋白質絶対定量法による膵癌薬物代謝酵素群発現量測定とゲムシタビンの効果予測への応用

    大塚 英郎, 川口 桂, 井上 亨悦, 深瀬 耕二, 元井 冬彦, 内藤 剛, 片寄 友, 江川 新一, 寺崎 哲也, 海野 倫明

    日本消化器外科学会総会　68回　O-67　2013/07

    Publisher: (一社)日本消化器外科学会

  25. 外傷性肝損傷に対する治療方針の検討

    長谷川 和住, 石井 範洋, 千葉 眞人, 井上 亨悦, 渡邊 利広, 石田 晶玄, 岡田 恭穂, 櫻井 直樹, 飯澤 肇

    日本肝胆膵外科学会・学術集会プログラム・抄録集　22回　385-385　2010/05

    Publisher: (一社)日本肝胆膵外科学会

Show all ︎Show first 5

Research Projects 5

  1. 癌関連線維芽細胞のSMAD3-PTGDR2 axis活性化による膵癌新規治療の開発

    水間 正道, 青木 修一, 井上 亨悦, 伊関 雅裕

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2025/04/01 - 2028/03/31

  2. A novel pancreatic cancer treatment combined with KRAS inhibitor

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2025/04/01 - 2028/03/31

  3. 膵癌肺転移及び腹膜播種の免疫微小環境をターゲットとした新規治療開発

    青木 修一, 熊田 和貴, 井上 亨悦, 松居 彩, 村上 圭吾

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

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    切除可能膵癌に対する術前化学療法（neoadjuvant therapy:NAT）の有用性が多施設共同前向き試験（PREP02/JSAP05試験）で証明され、NAT後の外科的切除が標準治療となった。しかし、NAT後の手術を行なっても約60%の症例で術後再発を認め、予後不良の原因となる。膵癌術後の再発部位として、肝臓、リンパ節、肺が主であり、転移部位によって治療反応の違いが報告されている。 大腸癌細胞株を用いたマウスモデルによる最近の報告では、大腸癌肝転移に対する免疫チェックポイント阻害薬（ICB）の有用性は示されなかったが、大腸癌皮下腫瘍ではICBが腫瘍増殖を有意に抑制することが報告された。2つの腫瘍では、腫瘍内免疫細胞の構成が全く異なり、ICBの効果の違いに起因している。ヒト膵癌切除サンプルにおいて、肺、腹膜および肝転移の免疫染色解析を行った他の報告では、腹膜や肝転移に比べ、肺転移ではCD8-infilitrated T細胞が増加し、PD-L1の発現が亢進している。さらに、術後肺転移の患者は、腹膜転移や肝転移の患者よりも予後が良好である。 一般に、膵癌腫瘍内は不均一な細胞成分の集合体であり、多クローン性を有する。その中で、転移部位の微小環境に適応した特異的なクローンだけが、遠隔臓器の転移巣を形成することができる。つまり、臓器特異的な微小環境が転移クローンの増殖に重要な役割を果たしており、それら再発部位の微小環境の違いを明らかにすることで、再発部位に即した治療戦略開発が行える。本研究の目的は、膵癌肺転移と肝転移、腹膜播種における腫瘍微小環境の違いを明らかにし、それぞれの転移増殖の分子メカニズムを探り、最終的に膵癌術後再発に対する分子標的治療やICBとの併用療法などの新しい治療戦略を開発することである。

  4. 膵癌間質の再構築による腫瘍免疫賦活化を標的とした革新的膵癌免疫治療の開発

    井上 亨悦

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  5. IFNA-STAT3 axisの制御と免疫治療の併用による革新的膵癌治療の開発

    井上 亨悦

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 研究活動スタート支援

    Institution: 東北大学

    2021/08/30 - 2023/03/31

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    膵癌の腫瘍免疫を評価するために、マウス由来の膵癌細胞株を用いて、IFNAR1 knock down cellを作成し、FVB/NJclマウスの膵尾部に同種移植する(sh-controlおよびsh-IFNAR1)。マウスを2群に分けて治療し、マウスの生存期間を評価する。本実験では、Anti-PD-1 (Programmed cell death 1) antibodyとAnti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibodyの二種類のICBを用いる予定である(2021年度の研究)。 <BR> 二種類のマウス由来の膵癌細胞株を用いて、IFNAR1ノックダウンを樹立し、マウスに樹立した細胞を移植して、腫瘍の増殖を評価した。IFNAR1の高発現しているAK4.4では、IFNAR1ノックダウンは腫瘍の増殖を抑制し、pilot studyと同様の結果を得ることができた。しかし、surivivalでは、IFNAR1ノックダウンの効果は認められなかった。このモデルでは、ほとんどのマウスが、血性胸水で死亡しており、IFNAR1ノックダウンは、腫瘍の増殖は抑制するものの、遠隔転移を制御できない可能性が示唆された。 IFNAR1が低発現のKPCでは、IFNAR1ノックダウンは、腫瘍の増殖及びsurvivalに関与することはなかった。この結果は、予想された結果であった。