Details of the Researcher

PHOTO

Daisuke Douchi
Section
Institute for Excellence in Higher Education
Job title
Assistant Professor
Degree

  • 博士（医学）（東北大学）

e-Rad No.
30907704

Research History 11

  • 2022/06 - Present
    東北大学 高度教養教育・学生支援機構 臨床医学開発室　助教

  • 2022/04 - Present
    東北大学病院 総合外科 助教

  • 2021/10 - 2022/03
    五戸総合病院　外科　科長

  • 2021/04 - 2022/03
    Tohoku University

  • 2021/04 - 2021/09
    国立療養所東北新生園　厚生労働技官

  • 2017/09 - 2021/03
    シンガポール国立大学(NUS) がん科学研究所(CSI)　リサーチフェロー

  • 2016/10 - 2017/08
    みやぎ県南中核病院　外科　科長

  • 2014/04 - 2016/09
    帯広第一病院　外科　主任医長

  • 2010/04 - 2014/03
    東北大学大学院医学系研究科　外科病態学講座 消化器外科学分野　大学院生

  • 2008/04 - 2010/03
    仙台オープン病院　外科系後期研修医

  • 2006/04 - 2008/03
    仙台オープン病院　外科系初期研修医

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Education 3

  • 東北大学大学院 医学系研究科 消化器外科学分野

    2010/04 - 2014/03

  • 東北大学 医学部

    2000/04 - 2006/03

  • ラ・サール高等学校

    1997/04 - 2000/03

Professional Memberships 8

  • 日本消化器病学会

  • 日本膵臓学会

  • 日本胆道学会

  • 日本癌学会

  • 日本肝胆膵外科学会

  • 日本内視鏡外科学会

  • 日本消化器外科学会

  • 日本外科学会

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Research Interests 3

  • Hepatobiliary and Pancreas Surgery

  • Carcinogenesis

  • Stem Cell Biology

Research Areas 1

  • Life sciences / Digestive surgery /

Awards 3

  1. 第14回丙辰会金賞

    2021/11

  2. Poster Prizes at Frontiers in Cancer Science 2020

    2020/11

  3. 第7回丙辰会銀賞

    2015/11

Papers 28

  1. 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.

  2. IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth International-journal

    Mitsuhiro Shimura, Junichi Matsuo, ShuChin Pang, Nawaphat Jangphattananont, Aashiq Hussain, Muhammad Bakhait Rahmat, Jung-Won Lee, Daisuke Douchi, Jasmine Jie Lin Tong, Khine Myint, Supriya Srivastava, Ming Teh, Vivien Koh, Wei Peng Yong, Jimmy Bok Yan So, Patrick Tan, Khay-Guan Yeoh, Michiaki Unno, Linda Shyue Huey Chuang, Yoshiaki Ito

    Gut　74　(3)　364-386　2025/03

    DOI： 10.1136/gutjnl-2023-330390 　

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    BACKGROUND: The elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear. OBJECTIVE: We define the function of IQGAP3 in gastric cancer (GC) development and progression. DESIGN: We studied the phenotypic changes caused by IQGAP3 knockdown in three molecularly diverse GC cell lines by RNA-sequencing. In vivo tumorigenesis and lung metastasis assays corroborated IQGAP3 as a mediator of oncogenic signalling. Spatial analysis was performed to evaluate the intratumoral transcriptional and functional differences between control tumours and IQGAP3 knockdown tumours. RESULTS: Transcriptomic profiling showed that IQGAP3 inhibition attenuates signal transduction networks, such as KRAS signalling, via phosphorylation blockade. IQGAP3 knockdown was associated with significant inhibition of MEK/ERK signalling-associated growth factors, including TGFβ1, concomitant with gene signatures predictive of impaired tumour microenvironment formation and reduced metastatic potential. Xenografts involving IQGAP3 knockdown cells showed attenuated tumorigenesis and lung metastasis in immunodeficient mice. Accordingly, immunofluorescence staining revealed significant reductions of TGFβ/SMAD signalling and αSMA-positive stromal cells; digital spatial analysis indicated that IQGAP3 is indispensable for the formation of two phenotypically diverse cell subpopulations, which played crucial but distinct roles in promoting oncogenic functions. CONCLUSION: IQGAP3 knockdown suppressed the RAS-TGFβ signalling crosstalk, leading to a significant reduction of the tumour microenvironment. In particular, IQGAP3 maintains functional heterogeneity of cancer cells to enhance malignant growth. IQGAP3 is thus a highly relevant therapy target in GC.

  3. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. International-journal

    E Rangelova, T F Stoop, T M E van Ramshorst, M Ali, E A van Bodegraven, A A Javed, D Hashimoto, E Steyerberg, A Banerjee, A Jain, A Sauvanet, A Serrablo, A Giani, A Giardino, A Zerbi, A Arshad, A G Wijma, A Coratti, A Zironda, A Socratous, A Rojas, A Halimi, A Ejaz, A Oba, B Y Patel, B Björnsson, B N Reames, B Tingstedt, B K P Goh, C Payá-Llorente, C D Del Pozo, C González-Abós, C Medin, C H J van Eijck, C de Ponthaud, C Takishita, C Schwabl, C Månsson, C Ricci, C A Thiels, D Douchi, D L Hughes, D Kilburn, D Flanking, D Kleive, D S Silva, B H Edil, E Pando, E Moltzer, E F Kauffman, E Warren, E Bozkurt, E Sparrelid, E Thoma, E Verkolf, F Ausania, F Giannone, F J Hüttner, F Burdio, F R Souche, F Berrevoet, F Daams, F Motoi, G Saliba, G Kazemier, G Roeyen, G Nappo, G Butturini, G Ferrari, G Kito Fusai, G Honda, G Sergeant, H Karteszi, H Takami, H Suto, I Matsumoto, I Mora-Oliver, I Frigerio, J M Fabre, J Chen, J G Sham, J Davide, J Urdzik, J de Martino, K Nielsen, K Okano, K Kamei, K Okada, K Tanaka, K J Labori, K E Goodsell, L Alberici, L Webber, L Kirkov, L de Franco, M Miyashita, M Maglione, M Gramellini, M Ramera, M J Amaral, M Ramaekers, M J Truty, M A van Dam, M W J Stommel, M Petrikowski, M Imamura, M Hayashi, M D'Hondt, M Brunner, M E Hogg, C Zhang, M Á Suárez-Muñoz, M D Luyer, M Unno, M Mizuma, M Janot, M A Sahakyan, N B Jamieson, O R Busch, O Bilge, O Belyaev, O Franklin, P Sánchez-Velázquez, P Pessaux, P S Holka, P Ghorbani, R Casadei, R Sartoris, R D Schulick, R Grützmann, R Sutcliffe, R Mata, R B Patel, R Takahashi, S Rodriguez Franco, S S Cabús, S Hirano, S Gaujoux, S Festen, S Kozono, S K Maithel, S M Chai, S Yamaki, S van Laarhoven, J S D Mieog, T Murakami, T Codjia, T Sumiyoshi, T M Karsten, T Nakamura, T Sugawara, U Boggi, V Hartman, V E de Meijer, W Bartholomä, W Kwon, Y X Koh, Y Cho, Y Takeyama, Y Inoue, Y Nagakawa, Y Kawamoto, Y Ome, Z Soonawalla, K Uemura, C L Wolfgang, J Y Jang, R Padbury, S Satoi, W Messersmith, J W Wilmink, M Abu Hilal, M G Besselink, M Del Chiaro

    Annals of oncology : official journal of the European Society for Medical Oncology　2025/01/13

    DOI： 10.1016/j.annonc.2024.12.015 　

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    BACKGROUND: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. PATIENTS AND METHODS: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. RESULTS: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. CONCLUSIONS: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

  4. [Ⅱ. Precision Medicine in Cholangiocarcinoma].

    Kei Nakagawa, Hideaki Sato, Masahiro Iseki, Shuichi Aoki, Akiko Kusaka, Daisuke Douchi, Takayuki Miura, Masaharu Ishida, Masamichi Mizuma, Michiaki Unno

    Gan to kagaku ryoho. Cancer & chemotherapy　51　(10)　989-992　2024/10

    ISSN： 0385-0684

  5. GFPT2 expression is induced by gemcitabine administration and enhances invasion by activating the hexosamine biosynthetic pathway in pancreatic cancer

    Kent Miyazaki, Kyohei Ariake, Satoko Sato, Takayuki Miura, Jingyu Xun, Daisuke Douchi, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Takashi Kamei, Michiaki Unno

    Clinical & Experimental Metastasis　2024/10

    DOI： 10.1007/s10585-024-10298-y 　

  6. 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.

  7. Deep learning predicts the 1-year prognosis of pancreatic cancer patients using positive peritoneal washing cytology

    Aya Noguchi, Yasushi Numata, Takanori Sugawara, Hiroshu Miura, Kaori Konno, Yuzu Adachi, Ruri Yamaguchi, Masaharu Ishida, Takashi Kokumai, Daisuke Douchi, Takayuki Miura, Kyohei Ariake, Shun Nakayama, Shimpei Maeda, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Hiromu Morikawa, Jun Akatsuka, Ichiro Maeda, Michiaki Unno, Yoichiro Yamamoto, Toru Furukawa

    Scientific Reports　14　(1)　2024/08/02

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-024-67757-5 　

    eISSN： 2045-2322

  8. Clonal analysis of metachronous double biliary tract cancers. International-journal

    Yuko Omori, Shuichi Aoki, Yusuke Ono, Takashi Kokumai, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kei Nakagawa, Yusuke Mizukami, Toru Furukawa, Michiaki Unno

    The Journal of pathology　263　(1)　113-127　2024/05

    DOI： 10.1002/path.6265 　

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    The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

  9. 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.

  10. Reduced expression of phosphorylated ataxia-telangiectasia mutated gene is related to poor prognosis and gemcitabine chemoresistance in pancreatic cancer. International-journal Peer-reviewed

    Jingyu Xun, Hideo Ohtsuka, Katsuya Hirose, Daisuke Douchi, Shun Nakayama, Masaharu Ishida, Takayuki Miura, Kyohei Ariake, Masamichi Mizuma, Kei Nakagawa, Takanori Morikawa, Toru Furukawa, Michiaki Unno

    BMC cancer　23　(1)　835-835　2023/09/06

    DOI： 10.1186/s12885-023-11294-3 　

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    BACKGROUND: Loss of expression of the gene ataxia-telangiectasia mutated (ATM), occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. In this study, we investigated the detailed molecular mechanism through which ATM expression affects the prognosis of patients with pancreatic cancer. METHODS: The levels of expression of ATM and phosphorylated ATM in patients with pancreatic cancer who had undergone surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ATM-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the invlovement of ATM in pancreatic cancer. RESULTS: Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ATM and phosphorylated ATM, respectively. Low expression of phosphorylated ATM substantially reduced overall and disease-free survival in patients with pancreatic cancer. In the pancreatic cancer cell lines with ATM low expression, resistance to gemcitabine was demonstrated. The RNA sequence demonstrated that ATM knockdown induced the expression of MET and NTN1. In ATM knockdown cells, it was also revealed that the protein expression levels of HIF-1α and antiapoptotic BCL-2/BAD were upregulated. CONCLUSIONS: These findings demonstrate that loss of ATM expression increases tumor development, suppresses apoptosis, and reduces gemcitabine sensitivity. Additionally, loss of phosphorylated ATM is associated with a poor prognosis in patients with pancreatic cancer. Thus, phosphorylated ATM could be a possible target for pancreatic cancer treatment as well as a molecular marker to track patient prognosis.

  11. 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

  12. RUNX3 in Stem Cell and Cancer Biology Peer-reviewed

    Linda Shyue Huey Chuang, Junichi Matsuo, Daisuke Douchi, Nur Astiana Bte Mawan, Yoshiaki Ito

    Cells　12　(3)　408-408　2023/01/25

    Publisher: MDPI AG

    DOI： 10.3390/cells12030408 　

    eISSN： 2073-4409

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    The runt-related transcription factors (RUNX) play prominent roles in cell cycle progression, differentiation, apoptosis, immunity and epithelial–mesenchymal transition. There are three members in the mammalian RUNX family, each with distinct tissue expression profiles. RUNX genes play unique and redundant roles during development and adult tissue homeostasis. The ability of RUNX proteins to influence signaling pathways, such as Wnt, TGFβ and Hippo-YAP, suggests that they integrate signals from the environment to dictate cell fate decisions. All RUNX genes hold master regulator roles, albeit in different tissues, and all have been implicated in cancer. Paradoxically, RUNX genes exert tumor suppressive and oncogenic functions, depending on tumor type and stage. Unlike RUNX1 and 2, the role of RUNX3 in stem cells is poorly understood. A recent study using cancer-derived RUNX3 mutation R122C revealed a gatekeeper role for RUNX3 in gastric epithelial stem cell homeostasis. The corpora of RUNX3R122C/R122C mice showed a dramatic increase in proliferating stem cells as well as inhibition of differentiation. Tellingly, RUNX3R122C/R122C mice also exhibited a precancerous phenotype. This review focuses on the impact of RUNX3 dysregulation on (1) stem cell fate and (2) the molecular mechanisms underpinning early carcinogenesis.

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

    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

  14. Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse Peer-reviewed

    Junichi Matsuo, Linda Shyue Huey Chuang, Jasmine Jie, Lin Tong, Daisuke Douchi, Yoshiaki Ito

    Methods in Molecular Biology　2691　3-17　2023

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

    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.

  16. A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells International-journal Peer-reviewed

    Junichi Matsuo, Naing Naing Mon, Daisuke Douchi, Akihiro Yamamura, Madhura Kulkarni, Dede Liana Heng, Sabirah Chen, Napat Nuttonmanit, Ying Li, Henry Yang, May Yin Lee, Wai Leong Tam, Motomi Osato, Linda Shyue Huey Chuang, Yoshiaki Ito

    Stem Cells　40　(1)　112-122　2022/03/03

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/stmcls/sxab009 　

    ISSN： 1066-5099

    eISSN： 1549-4918

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    Abstract Mammary gland homeostasis is maintained by adult tissue stem-progenitor cells residing within the luminal and basal epithelia. Dysregulation of mammary stem cells is a key mechanism for cancer development. However, stem cell characterization is challenging because reporter models using cell-specific promoters do not fully recapitulate the mammary stem cell populations. We previously found that a 270-basepair Runx1 enhancer element, named eR1, marked stem cells in the blood and stomach. Here, we identified eR1 activity in a rare subpopulation of the ERα-negative luminal epithelium in mouse mammary glands. Lineage-tracing using an eR1-CreERT2 mouse model revealed that eR1+ luminal cells generated the entire luminal lineage and milk-secreting alveoli—eR1 therefore specifically marks lineage-restricted luminal stem cells. eR1-targeted-conditional knockout of Runx1 led to the expansion of luminal epithelial cells, accompanied by elevated ERα expression. Our findings demonstrate a definitive role for Runx1 in the regulation of the eR1-positive luminal stem cell proliferation during mammary homeostasis. Our findings identify a mechanistic link for Runx1 in stem cell proliferation and its dysregulation in breast cancer. Runx1 inactivation is therefore likely to be an early hit in the cell-of-origin of ERα+ luminal type breast cancer.

  17. A point mutation R122C in RUNX3 promotes the expansion of isthmus stem cells and inhibits their differentiation in the stomach International-journal Peer-reviewed

    Daisuke Douchi, Akihiro Yamamura, Junichi Matsuo, Jung-Won Lee, Napat Nuttonmanit, Yi Hui Melissa Lim, Kazuto Suda, Mitsuhiro Shimura, Sabirah Chen, ShuChin Pang, Kazuyoshi Kohu, Mari Kaneko, Hiroshi Kiyonari, Atsushi Kaneda, Hideyuki Yoshida, Ichiro Taniuchi, Motomi Osato, Henry Yang, Michiaki Unno, Jimmy Bok-Yan So, Khay Guan Yeoh, Linda Shyue Huey Chuang, Suk-Chul Bae, Yoshiaki Ito

    Cellular and Molecular Gastroenterology and Hepatology　13　(5)　1317-1345　2022/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.jcmgh.2022.01.010 　

    ISSN： 2352-345X

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    BACKGROUND & AIMS: RUNX transcription factors play pivotal roles in embryonic development and neoplasia. We previously identified the single missense mutation R122C in RUNX3 from human gastric cancer. However, how RUNX3R122C mutation disrupts stem cell homeostasis and promotes gastric carcinogenesis remained unclear. METHODS: To understand the oncogenic nature of this mutation in vivo, we generated the RUNX3R122C knock-in mice. Stomach tissues were harvested, followed by histologic and immunofluorescence staining, organoid culture, flow cytometry to isolate gastric corpus isthmus and nonisthmus epithelial cells, and RNA extraction for transcriptomic analysis. RESULTS: The corpus tissue of RUNX3R122C/R122C homozygous mice showed a precancerous phenotype such as spasmolytic polypeptide-expressing metaplasia. We observed mucous neck cell hyperplasia; massive reduction of pit, parietal, and chief cell populations; as well as a dramatic increase in the number of rapidly proliferating isthmus stem/progenitor cells in the corpus of RUNX3R122C/R122C mice. Transcriptomic analyses of the isolated epithelial cells showed that the cell-cycle-related MYC target gene signature was enriched in the corpus epithelial cells of RUNX3R122C/R122C mice compared with the wild-type corpus. Mechanistically, RUNX3R122C mutant protein disrupted the regulation of the restriction point where cells decide to enter either a proliferative or quiescent state, thereby driving stem cell expansion and limiting the ability of cells to terminally differentiate. CONCLUSIONS: RUNX3R122C missense mutation is associated with the continuous cycling of isthmus stem/progenitor cells, maturation arrest, and development of a precancerous state. This work highlights the importance of RUNX3 in the prevention of metaplasia and gastric cancer.

  18. Induction of Gastric Cancer by Successive Oncogenic Activation in the Corpus Peer-reviewed

    Douchi, D., Yamamura, A., Matsuo, J., Melissa Lim, Y.H., Nuttonmanit, N., Shimura, M., Suda, K., Chen, S., Pang, S., Kohu, K., Abe, T., Shioi, G., Kim, G., Shabbir, A., Srivastava, S., Unno, M., Bok-Yan So, J., Teh, M., Yeoh, K.G., Huey Chuang, L.S., Ito, Y.

    Gastroenterology　161　(6)　1907-1923.e26　2021/12

    Publisher: Elsevier BV

    DOI： 10.1053/j.gastro.2021.08.013 　

    ISSN： 1528-0012 0016-5085

  19. 【膵と胆道の先天性形成異常〜発生から臨床まで〜】膵動静脈奇形

    堂地 大輔, 水間 正道, 海野 倫明

    胆と膵　42　(10)　947-951　2021/10

    Publisher: 医学図書出版(株)

    ISSN： 0388-9408

  20. Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair International-journal Peer-reviewed

    Junichi Matsuo, Daisuke Douchi, Khine Myint, Naing Naing Mon, Akihiro Yamamura, Kazuyoshi Kohu, Dede Liana Heng, Sabirah Chen, Nur Astiana Mawan, Napat Nuttonmanit, Ying Li, Supriya Srivastava, Shamaine Wei Ting Ho, Nicole Yee Shin Lee, Hong Kai Lee, Makoto Adachi, Atsushi Tamura, Jinmiao Chen, Henry Yang, Ming Teh, Jimmy Bok-Yan So, Wei Peng Yong, Patrick Tan, Khay Guan Yeoh, Linda Shyue Huey Chuang, Sachiko Tsukita, Yoshiaki Ito

    Gut　70　(10)　1833-1846　2021/10

    Publisher: BMJ

    DOI： 10.1136/gutjnl-2020-322779 　

    ISSN： 0017-5749

    eISSN： 1468-3288

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    <sec><title>Objective</title>Tissue stem cells are central regulators of organ homoeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus. </sec><sec><title>Design</title>We uncovered the specific expression of Iqgap3 in proliferating isthmus stem cells through immunofluorescence and in situ hybridisation. We performed lineage tracing and transcriptomic analysis of Iqgap3 +isthmus stem cells with the <italic>Iqgap3-2A-tdTomato</italic> mouse model. Depletion of Iqgap3 revealed its functional importance in maintenance and proliferation of stem cells. We further studied Iqgap3 expression and the associated gene expression changes during tissue repair after tamoxifen-induced damage. Immunohistochemistry revealed elevated expression of Iqgap3 in proliferating regions of gastric tumours from patient samples. </sec><sec><title>Results</title>Iqgap3 is a highly specific marker of proliferating isthmus stem cells during homoeostasis. Iqgap3+isthmus stem cells give rise to major cell types of the corpus unit. Iqgap3 expression is essential for the maintenance of stem potential. The Ras pathway is a critical partner of Iqgap3 in promoting strong proliferation in isthmus stem cells. The robust induction of Iqgap3 expression following tissue damage indicates an active role for Iqgap3 in tissue regeneration. </sec><sec><title>Conclusion</title>IQGAP3 is a major regulator of stomach epithelial tissue homoeostasis and repair. The upregulation of IQGAP3 in gastric cancer suggests that IQGAP3 plays an important role in cancer cell proliferation. </sec>

  21. Silencing of LRRFIP1 enhances the sensitivity of gemcitabine in pancreatic cancer cells by activating JNK/c-Jun signaling. International-journal Peer-reviewed

    Shuhei Kawasaki, Hideo Ohtsuka, Yoshihiro Sato, Daisuke Douchi, Masaki Sato, Kyohei Ariake, Kunihiro Masuda, Koji Fukase, Masamichi Mizuma, Kei Nakagawa, Hiroki Hayashi, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno

    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]　21　(4)　771-778　2021/06

    DOI： 10.1016/j.pan.2021.02.018 　

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    BACKGROUND: The epithelial-mesenchymal transition (EMT) in cancer cells has been shown to closely associate with the survival and drug resistance of cancer cells. We recently provided evidence that Wnt signal activator leucine-rich repeat in flightless-1-interacting protein 1 (LRRFIP1) regulates EMT in pancreatic cancer. LRRFIP1 silencing inhibits the translocation of β-catenin to the nucleus, which led to reverse EMT in cancer cells. It was suggested that LRRFIP1 was implicated in gemcitabine sensitivity by regulating EMT signaling. METHODS: Gemcitabine chemosensitivity was investigated in LRRFIP1-knockdown pancreatic cancer cells (PANC-1 and MIA Paca-2). In addition, the effects of LRRFIP1 knockdown on JNK/SAPK (stress activated-protein kinase) signaling and apoptosis were evaluated. RESULTS: LRRFIP1 silencing accelerates gemcitabine-induced caspase activity and cell death in pancreatic cancer cells. It was also revealed that gemcitabine-induced phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun were increased in LRRFIP1 knockdown cells. The activation of JNK/c-Jun in LRRFIP1-knockdown cells was significantly diminished by the inhibition of Rac activity. It was confirmed that the acquisition of gemcitabine sensitivity by LRRFIP1 silencing largely depends on the stimulation of JNK/SAPK (stress activated-protein kinase) signaling. CONCLUSIONS: Our findings suggest that reversing EMT and transient activation of JNK might be essential for the gemcitabine sensitivity in LRRFIP1 knockdown pancreatic cancer cells. Our discoveries highlight the potential role of LRRFIP1 in the chemosensitivity related to the regulation of EMT signaling.

  22. Stomach corpus stem cells in homeostasis, tissue repair, and cancer

    Junichi Matsuo, Daisuke Douchi, Yoshiaki Ito

    Research and Clinical Applications of Targeting Gastric Neoplasms　1-24　2021/01/01

    DOI： 10.1016/B978-0-323-85563-1.00014-9 　

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

    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.

  24. Optimal timing of cholecystectomy after percutaneous gallbladder drainage for severe cholecystitis. International-journal Peer-reviewed

    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.

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

    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.

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

    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.

  27. Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/β-catenin signaling pathway International-journal Peer-reviewed

    Daisuke Douchi, Hideo Ohtsuka, Kyohei Ariake, Kunihiro Masuda, Shuhei Kawasaki, Kei Kawaguchi, Koji Fukase, Masaya Oikawa, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno

    Cancer letters　365　(1)　132-40　2015/08/28

    DOI： 10.1016/j.canlet.2015.05.023 　

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    The canonical Wnt/β-catenin signaling pathway has been shown to promote the epithelial-mesenchymal transition (EMT), which is a crucial process in multiple embryonic developmental processes and the progression of carcinomas. We recently provided evidence that leucine-rich repeat flightless-1-interacting protein 1 (LRRFIP1) promotes cancer metastasis and invasion. In the present study, we identified the signaling elements targeted by LRRFIP1 for promotion of the EMT in pancreatic and lung cancer. LRRFIP1 silencing reversed the EMT, as shown by increased expression of E-cadherin (an epithelial marker) and decreased expression of vimentin (a mesenchymal marker). Silencing of LRRFIP1 up-regulated phosphorylation of β-catenin and decreased its nuclear localization by targeting the β-catenin destruction complex. The expression of β-catenin and E-cadherin in the plasma membrane fraction was increased in LRRFIP1 silenced cancer cells, and the migration and invasion capabilities were strongly inhibited. In addition, this protein was highly expressed at the invasion front of malignant tissue collected from pancreatic cancer patients. Consequently, our data strongly suggested that LRRFIP1 played an important role in the invasion of carcinoma cells. Our data provide experimental evidence that LRRFIP1 is an attractive candidate for targeted therapy in human cancers.

  28. GCF2/LRRFIP1 promotes colorectal cancer metastasis and liver invasion through integrin-dependent RhoA activation. International-journal Peer-reviewed

    Kyohei Ariake, Hideo Ohtsuka, Fuyuhiko Motoi, Daisuke Douchi, Masaya Oikawa, Toshiki Rikiyama, Koji Fukase, Yu Katayose, Shinichi Egawa, Michiaki Unno

    Cancer letters　325　(1)　99-107　2012/12/01

    DOI： 10.1016/j.canlet.2012.06.012 　

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    The precise relationship between GCF2 expression and carcinogenesis has not yet been established. To clarify the metastatic potential of GCF2 in colorectal cancer, HT-29 cells stably suppressing GCF2 expression were injected into the spleens of severe combined immunodeficient (SCID) mice. GCF2 suppression reduced the number of metastatic foci in the liver and reduced fibronectin-induced cell adhesion, migration, and invasion. Downstream from the integrin signaling pathways, GCF2 regulates RhoA interaction with the RGS domain of Leukemia associated RhoGEF (LARG). Altogether, our results suggest that GCF2 plays an important role in colorectal cancer metastasis by regulating RhoA-induced cell adhesion, migration, and invasion.

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Misc. 77

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. がん遺伝子パネル検査を受けた胆道癌症例に関する前向き観察研究

    堂地 大輔, 大塚 英郎, 廣岡 芳樹, 海野 倫明

    日本外科学会定期学術集会抄録集　123回　SF-1　2023/04

    Publisher: (一社)日本外科学会

  9. 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

  10. 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

  11. 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

  12. GATA6とCK5の発現表現型が術前化学療法後の膵癌の予後を層別化する

    國米 崇, 大森 優子, 石田 晶玄, 伊達 文子, 三浦 晋, 中山 瞬, 堂地 大輔, 三浦 孝之, 粂 潔, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 正宗 淳, 亀井 尚, 海野 倫明, 古川 徹

    日本外科学会定期学術集会抄録集　123回　SF-1[Y]　2023/04

    Publisher: (一社)日本外科学会

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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(Web)　56　(Supplement2)　2023

    ISSN： 1348-9372

  20. 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

  21. 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

  22. 鏡視下胆道再建術-安全な普及を目指した戦略について- 定型化を目指した先天性胆道拡張症成人例に対する腹腔鏡下肝外胆管切除・胆道再建術

    森川 孝則, 石田 晶玄, 三浦 孝之, 千葉 和治, 青木 修一, 堂地 大輔, 伊関 雅裕, 有明 恭平, 川口 桂, 益田 邦洋, 水間 正道, 大塚 英郎, 中川 圭, 亀井 尚, 海野 倫明

    日本内視鏡外科学会雑誌　26　(7)　CSY18-2　2021/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  23. 消化器外科領域における周術期感染対策 術前亜鉛欠乏が膵癌周術期に与える影響の検討

    伊関 雅裕, 水間 正道, 青木 修一, 堂地 大輔, 三浦 孝之, 有明 恭平, 川口 桂, 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, 海野 倫明

    日本外科感染症学会雑誌　18　(1)　141-141　2021/11

    Publisher: (一社)日本外科感染症学会

    ISSN： 1349-5755

    eISSN： 2434-0103

  24. 切除不能消化器癌に対するconversion surgeryの適応とタイミング 術前治療時代における膵癌微小遠隔転移に対するコンバージョン切除を企図した治療戦略

    有明 恭平, 水間 正道, 青木 修一, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 川口 桂, 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, 海野 倫明

    日本癌治療学会学術集会抄録集　59回　WS17-5　2021/10

    Publisher: (一社)日本癌治療学会

  25. 膵癌に対するnal-IRI療法の治療効果および安全性の検討

    森川 孝則, 青木 修一, 伊関 雅裕, 三浦 孝之, 堂地 大輔, 有明 恭平, 川口 桂, 益田 邦洋, 石田 晶玄, 水間 正道, 大塚 英郎, 中川 圭, 大沼 忍, 亀井 尚, 海野 倫明

    日本癌治療学会学術集会抄録集　59回　O43-5　2021/10

    Publisher: (一社)日本癌治療学会

  26. 胃がん多段階発癌モデルの確立

    堂地 大輔, 山村 明寛, 松尾 純一, 志村 充広, 大沼 忍, 亀井 尚, 海野 倫明, 伊藤 嘉明

    日本癌学会総会記事　80回　[E2-2]　2021/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  27. 腹腔鏡下胆道拡張症手術 膵・胆管合流異常成人例に対する腹腔鏡下肝外胆管切除・胆道再建術

    森川 孝則, 石田 晶玄, 三浦 孝之, 千葉 和治, 青木 修一, 堂地 大輔, 伊関 雅裕, 有明 恭平, 川口 桂, 益田 邦洋, 水間 正道, 大塚 英郎, 中川 圭, 亀井 尚, 海野 倫明

    日本膵・胆管合流異常研究会プロシーディングス　44　70-70　2021/08

    Publisher: 日本膵・胆管合流異常研究会

    ISSN： 1883-4116

  28. 術前診断が困難であった、妊娠中に発症した胆道癌合併先天性胆道拡張症の1例

    林 秀一郎, 大塚 英郎, 青木 修一, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 有明 恭平, 川口 桂, 益田 邦洋, 石田 晶玄, 水間 正道, 中川 圭, 森川 孝則, 海野 倫明

    日本膵・胆管合流異常研究会プロシーディングス　44　98-99　2021/08

    Publisher: 日本膵・胆管合流異常研究会

    ISSN： 1883-4116

  29. 当科におけるGroove膵癌の臨床的特徴

    林 秀一郎, 石田 晶玄, 千葉 和治, 青木 修一, 伊関 雅裕, 堂地 大輔, 三浦 孝之, 有明 恭平, 川口 桂, 益田 邦洋, 大塚 英郎, 水間 正道, 中川 圭, 森川 孝則, 粂 潔, 正宗 淳, 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　211回　56-56　2021/07

    Publisher: 日本消化器病学会-東北支部

  30. 胃癌におけるRunx3遺伝子のR122C変異は前癌病変の腸上皮化生を誘導する(Gastric cancer derived RUNX3 mutation, R122C, induces intestinal metaplasia-like lesion in the antrum of knock-in mouse)

    山村 明寛, 堂地 大輔, 松尾 純一, リムイーフイ・メリッサ, 河府 和義, ディディー・リアナヘン, ムハンマドザキール・ホサイン, 内藤 剛, 亀井 尚, 海野 倫明, 伊藤 嘉明

    日本癌学会総会記事　77回　1106-1106　2018/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  31. Runx3変異は腸上皮化生を引き起こし胃癌の起源となる

    山村 明寛, 松尾 純一, 堂地 大輔, Lim Yi Hui Melissa, Dede Liana Heng, Hosain Md Zakir, 亀井 尚, 内藤 剛, 海野 倫明, 伊藤 嘉明

    日本消化器外科学会総会　73回　152-152　2018/07

    Publisher: (一社)日本消化器外科学会

  32. 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

  33. 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

  34. 術前化学放射線療法中に直腸穿孔によるフルニエ症候群を発症した直腸癌の1例

    秋重 尚貴, 堂地 大輔, 嶋 健太郎, 上野 達也, 後藤 慎二, 高橋 道長, 内藤 広郎

    日本臨床外科学会雑誌　78　(増刊)　886-886　2017/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  35. LRRFIP1発現抑制膵癌細胞におけるJNKを介したアポトーシス誘導とゲムシタビン感受性変化の検討

    川崎 修平, 大塚 英郎, 堂地 大輔, 有明 恭平, 益田 邦洋, 深瀬 耕二, 元井 冬彦, 内藤 剛, 海野 倫明

    日本消化器外科学会総会　72回　PK1-5　2017/07

    Publisher: (一社)日本消化器外科学会

  36. 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

  37. 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

  38. 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

  39. 高度便秘が誘因となった閉塞性大腸炎の1例

    井伊 貴幸, 菊地 大介, 堂地 大輔, 松田 泰史, 国米 崇, 福田 啓人, 山並 秀章

    日本臨床外科学会雑誌　77　(増刊)　877-877　2016/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  40. 外科における基礎的研究 セレンディピティーを求めて 膵癌細胞におけるWnt関連蛋白LRRFIP1による上皮間葉転換の制御と、浸潤転移機構の解析

    大塚 英郎, 堂地 大輔, 有明 恭平, 川崎 修平, 深瀬 耕二, 益田 邦洋, 元井 冬彦, 内藤 剛, 海野 倫明

    日本消化器外科学会総会　71回　WS7-8　2016/07

    Publisher: (一社)日本消化器外科学会

  41. 直腸固定術(Ripstein法)後の直腸狭窄、腹腔内膿瘍に対してメッシュ除去が奏功した1例

    井伊 貴幸, 菊地 大介, 堂地 大輔, 吉町 信吾, 国米 崇, 山並 秀章

    日本外科学会定期学術集会抄録集　116回　PS-5　2016/04

    Publisher: (一社)日本外科学会

  42. シートベルト損傷による小腸穿孔に対して腹腔鏡手術が有用であった1例

    国米 崇, 堂地 大輔, 吉町 信吾, 菊地 大介, 井伊 貴幸, 山並 秀章

    日本腹部救急医学会雑誌　36　(2)　373-373　2016/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  43. リンパ節転移、小腸転移を認めた小腸GISTの1例

    井伊 貴幸, 堂地 大輔, 吉町 信吾, 山並 秀章

    日本内視鏡外科学会雑誌　20　(7)　OS146-1　2015/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  44. 当院における腹腔鏡下鼠径ヘルニア根治術(TAPP)の検討

    吉町 信吾, 堂地 大輔, 佐瀬 友彦, 井伊 貴之, 山並 秀章

    日本内視鏡外科学会雑誌　20　(7)　OS273-6　2015/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  45. 魚骨による下行結腸穿通に対して 内視鏡的治療が奏功した一例

    国米 崇, 吉町 信吾, 堂地 大輔, 菊地 大介, 井伊 貴幸, 山並 秀章

    日本臨床外科学会雑誌　76　(増刊)　1132-1132　2015/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  46. 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

  47. イレウスチューブ留置による腸重積の1例

    佐藤 みちる, 堂地 大輔, 吉町 信吾, 佐瀬 友彦, 井伊 貴幸, 山並 秀章

    日本腹部救急医学会雑誌　35　(2)　379-379　2015/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  48. HALS、術中内視鏡が有用であった巨大胃GISTの1例

    井伊 貴幸, 佐瀬 友彦, 堂地 大輔, 吉町 信吾, 佐藤 みちる, 山並 秀章, 富永 剛

    日本内視鏡外科学会雑誌　19　(7)　570-570　2014/10

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  49. 盲腸憩室炎・盲腸周囲膿瘍に対して腹腔鏡下に緊急手術を施行した血液透析患者の1例

    井伊 貴幸, 佐瀬 友彦, 堂地 大輔, 吉町 信吾, 佐藤 みちる, 山並 秀章, 富永 剛

    日本内視鏡外科学会雑誌　19　(7)　579-579　2014/10

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  50. 腹腔鏡下胆嚢摘出術(Lap-C)中Rendezvous TechniqueでERCPを行った傍十二指腸憩室を伴う胆嚢管結石症の1例

    吉町 信吾, 佐瀬 友彦, 佐藤 みちる, 石居 健太郎, 堂地 大輔, 井伊 貴幸, 山並 秀章, 富永 剛

    日本内視鏡外科学会雑誌　19　(7)　605-605　2014/10

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  51. 腹腔鏡補助下高位前方切除術中に発見・治療された潜在性両側閉鎖孔ヘルニアの1例

    佐藤 みちる, 井伊 貴幸, 吉町 信吾, 堂地 大輔, 佐瀬 友彦, 山並 秀章

    日本内視鏡外科学会雑誌　19　(7)　840-840　2014/10

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  52. LRRFIP1の発現抑制はWnt/β-カテニン経路を抑制することによりReversing EMTを起こす(Silencing LRRFIP1 reverses epithelial-mesenchymal transition through inhibition of Wnt/β-catenin signaling pathway)

    堂地 大輔, 大塚 英郎, 有明 恭平, 川崎 修平, 川口 桂, 益田 邦洋, 深瀬 耕二, 元井 冬彦, 内藤 剛, 片寄 友, 江川 新一, 海野 倫明

    日本癌学会総会記事　73回　P-2162　2014/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  53. がん微小環境における新規細胞骨格調節因子GCF2/LRRFIP1の機能解析

    堂地 大輔, 大塚 英郎, 有明 恭平, 深瀬 耕二, 吉田 寛, 元井 冬彦, 内藤 剛, 片寄 友, 江川 新一, 海野 倫明

    日本消化器外科学会総会　68回　P-3　2013/07

    Publisher: (一社)日本消化器外科学会

  54. PS-070-4 新規RhoA調節蛋白GCF2/LRRFIP1による大腸癌浸潤転移制御の可能性(PS ポスターセッション,第113回日本外科学会定期学術集会)

    大塚 英郎, 有明 恭平, 堂地 大輔, 元井 冬彦, 深瀬 耕二, 青木 豪, 乙供 茂, 水間 正道, 坂田 直昭, 中川 圭, 林 洋毅, 森川 孝則, 岡田 恭穂, 吉田 寛, 鹿郷 昌之, 内藤 剛, 三浦 康, 片寄 友, 柴田 近, 海野 倫明

    日本外科学会雑誌　114　(2)　617-617　2013/03/05

    Publisher: 一般社団法人日本外科学会

    ISSN： 1880-1129

  55. 新規RhoA調節蛋白GCF2/LRRFIP1による大腸癌浸潤転移制御の可能性

    大塚 英郎, 有明 恭平, 堂地 大輔, 元井 冬彦, 深瀬 耕二, 青木 豪, 乙供 茂, 水間 正道, 坂田 直昭, 中川 圭, 林 洋毅, 森川 孝則, 岡田 恭穂, 吉田 寛, 鹿郷 昌之, 内藤 剛, 三浦 康, 片寄 友, 柴田 近, 海野 倫明

    日本外科学会雑誌　114　(臨増2)　617-617　2013/03

    Publisher: (一社)日本外科学会

    ISSN： 0301-4894

  56. 残膵全摘10例の検討

    堂地 大輔, 大塚 英郎, 青木 豪, 深瀬 耕二, 水間 正道, 坂田 直昭, 乙供 茂, 岡田 恭穂, 中川 圭, 森川 孝則, 林 洋毅, 吉田 寛, 元井 冬彦, 内藤 剛, 三浦 康, 片寄 友, 柴田 近, 海野 倫明

    日本消化器病学会雑誌　110　(臨増総会)　A244-A244　2013/02

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  57. 膵転移を認めた胸腺神経内分泌腫瘍(NET)の1例

    堂地 大輔, 大塚 英郎, 乙供 茂, 坂田 直昭, 岡田 恭穂, 中川 圭, 林 洋毅, 森川 孝則, 小野川 徹, 吉田 寛, 元井 冬彦, 力山 敏樹, 片寄 友, 江川 新一, 海野 倫明

    日本臨床外科学会雑誌　72　(増刊)　845-845　2011/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  58. 直達手術遠隔期に生じた門脈血栓症に対し上腸間膜静脈-右卵巣静脈短絡術が奏効した特発性門脈圧亢進症・難治性食道静脈瘤の一例

    堂地 大輔, 竹内 丙午, 力山 敏樹, 片寄 友, 海野 倫明, 鈴木 正徳

    日本門脈圧亢進症学会雑誌　17　(3)　107-107　2011/08

    Publisher: (一社)日本門脈圧亢進症学会

    ISSN： 1344-8447

    eISSN： 2186-6376

  59. 十二指腸副乳頭部神経内分泌癌の1切除例

    堂地 大輔, 大塚 英郎, 深瀬 耕二, 水間 正道, 坂田 直昭, 乙供 茂, 中川 圭, 林 洋毅, 岡田 恭穂, 吉田 寛, 小野川 徹, 元井 冬彦, 力山 敏樹, 片寄 友, 江川 新一, 海野 倫明

    日本肝胆膵外科学会・学術集会プログラム・抄録集　23回　439-439　2011/06

    Publisher: (一社)日本肝胆膵外科学会

  60. 浸潤性膵管癌におけるEpidermal growth facter receptor(EGFR)発現と臨床病理学的因子の検討

    三浦 孝之, 元井 冬彦, 石田 和之, 堂地 大輔, 藤川 奈々子, 有明 恭平, 深瀬 耕二, 大塚 英郎, 力山 敏樹, 片寄 友, 江川 新一, 菅野 敦, 佐藤 賢一, 下瀬川 徹, 海野 倫明

    日本外科学会雑誌　112　(臨増1-2)　873-873　2011/05

    Publisher: (一社)日本外科学会

    ISSN： 0301-4894

  61. 膵管融合不全を合併した膵・胆管合流異常症例の検討

    三浦 孝之, 大塚 英郎, 荒木 孝明, 堂地 大輔, 深瀬 耕二, 元井 冬彦, 力山 敏樹, 片寄 友, 江川 新一, 海野 倫明

    日本膵・胆管合流異常研究会プロシーディングス　33　51-51　2010/09

    Publisher: 日本膵・胆管合流異常研究会

    ISSN： 1883-4116

  62. IPNBで胆管切除後に遺残胆管再発を疑われた膵神経内分泌癌の1例

    堂地 大輔, 片寄 友, 力山 敏樹, 元井 冬彦, 小野川 徹, 乙供 茂, 岡田 恭穂, 水間 正道, 船場 泰文, 石田 和之, 江川 新一, 海野 倫明

    胆道　24　(3)　469-469　2010/08

    Publisher: 日本胆道学会

    ISSN： 0914-0077

    eISSN： 1883-6879

  63. 当院における進行胃癌に対する術前化学療法の治療成績

    矢澤 貴, 宮川 菊雄, 土屋 誉, 本多 博, 福山 尚治, 及川 昌也, 柿田 徹也, 小山 淳, 宮地 智洋, 梶原 大輝, 堂地 大輔, 松田 泰史, 土屋 堯裕

    日本胃癌学会総会記事　82回　305-305　2010/03

    Publisher: (一社)日本胃癌学会

  64. 胃癌胃全摘術後の早期経腸栄養についてrapid turnover proteinを中心とした栄養学的指標の検討

    梶原 大輝, 本多 博, 土屋 誉, 福山 尚治, 及川 昌也, 柿田 徹也, 小山 淳, 矢澤 貴, 宮地 智洋, 堂地 大輔, 松田 泰史, 土屋 堯裕

    日本胃癌学会総会記事　82回　340-340　2010/03

    Publisher: (一社)日本胃癌学会

  65. 進行大腸癌に対する腹腔鏡下手術の臨床成績

    内藤 剛, 小山 淳, 土屋 誉, 本多 博, 及川 昌也, 柿田 徹也, 矢沢 貴, 宮地 智洋, 梶原 大輝, 堂地 大輔, 松田 泰史, 土屋 堯裕, 宮川 菊雄

    東北医学雑誌　121　(2)　202-202　2009/12

    Publisher: 東北医学会

    ISSN： 0040-8700

  66. 胆嚢摘出術と虫垂切除術におけるSingle Incision Surgeryの経験

    内藤 剛, 土屋 誉, 本多 博, 及川 昌也, 柿田 徹也, 小山 淳, 矢澤 貴, 宮地 智洋, 梶原 大輝, 堂地 大輔, 松田 泰史, 土屋 堯弘, 宮川 菊雄

    日本内視鏡外科学会雑誌　14　(7)　428-428　2009/12

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  67. 神経性食思不振症患者に発症した非閉塞性腸管虚血症(non-occlusive mesenteric ischemia)の1例

    梶原 大輝, 小山 淳, 土屋 誉, 本多 博, 内藤 剛, 及川 昌也, 柿田 徹也, 矢澤 貴, 宮地 智洋, 堂地 大輔, 松田 泰史, 土屋 堯裕, 宮川 菊雄

    日本臨床外科学会雑誌　70　(増刊)　555-555　2009/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  68. EMR後に外科的追加腸切除を施行し、3年後に肝転移、その1年後に肺転移を来たした大腸sm癌の1例

    堂地 大輔, 土屋 誉, 本多 博, 内藤 剛, 及川 昌也, 柿田 徹也, 小山 淳

    日本臨床外科学会雑誌　70　(増刊)　721-721　2009/10

    Publisher: 日本臨床外科学会

    ISSN： 1345-2843

    eISSN： 1882-5133

  69. 胃切除後の早期経腸栄養は術後のエネルギー消費量の増加を抑制する

    土屋 誉, 宮地 智洋, 小山 淳, 堂地 大輔, 梶原 大輝, 松田 泰史, 土屋 尭裕, 矢澤 貴, 及川 昌也, 柿田 徹也, 内藤 剛, 本多 博, 宮川 菊雄

    外科と代謝・栄養　43　(3)　116-116　2009/06

    Publisher: 日本外科代謝栄養学会

    ISSN： 0389-5564

    eISSN： 2187-5154

  70. メタボリックアナライザーMedGemを用いた大腸癌周術期における安静時代謝量の測定

    小山 淳, 土屋 誉, 堂地 大輔, 阿部 尚美, 佐藤 敦子, 本多 博, 内藤 剛, 及川 昌也, 柿田 徹也, 小松 弘武, 矢澤 貴, 宮地 智洋, 梶原 大輝, 宮川 菊雄

    静脈経腸栄養　24　(2)　664-664　2009/03

    Publisher: (株)ジェフコーポレーション

    ISSN： 1344-4980

    eISSN： 1881-3623

  71. 良好な結果が得られた特発性直腸穿孔の2例

    堂地 大輔, 土屋 誉, 本多 博, 内藤 剛, 及川 昌也, 柿田 徹也, 小山 淳

    日本腹部救急医学会雑誌　29　(2)　353-353　2009/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  72. メタボリックアナライザーMedGemを用いた大腸癌周術期における安静時エネルギー消費量の測定

    小山 淳, 土屋 誉, 阿部 尚美, 佐藤 敦子, 堂地 大輔

    静脈経腸栄養　24　(1)　248-248　2009/01

    Publisher: (株)ジェフコーポレーション

    ISSN： 1344-4980

    eISSN： 1881-3623

  73. メタボリックアナライザーMedGemを用いた胃癌周術期における安静時エネルギー消費量の測定

    堂地 大輔, 土屋 誉, 小山 淳, 佐藤 敦子, 阿部 尚美

    静脈経腸栄養　24　(1)　248-248　2009/01

    Publisher: (株)ジェフコーポレーション

    ISSN： 1344-4980

    eISSN： 1881-3623

  74. pStage II/III大腸癌に対する腹腔鏡下手術の遠隔成績

    内藤 剛, 土屋 誉, 本多 博, 及川 昌也, 柿田 徹也, 大森 洋平, 小松 弘武, 梶原 大輝, 堂地 大輔

    日本内視鏡外科学会雑誌　13　(7)　267-267　2008/09

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  75. OR-1および医療画像統合システムを融合した内視鏡手術専用手術室の構築

    内藤 剛, 土屋 誉, 本多 博, 及川 昌也, 柿田 徹也, 大森 洋平, 小松 弘武, 梶原 大輝, 堂地 大輔

    日本内視鏡外科学会雑誌　13　(7)　397-397　2008/09

    Publisher: (一社)日本内視鏡外科学会

    ISSN： 1344-6703

    eISSN： 2186-6643

  76. 【縫合・吻合手技 安全・確実な技術を習得するために】消化器手術に必要な腹腔鏡下縫合結紮手技

    内藤 剛, 土屋 誉, 本多 博, 及川 昌也, 柿田 徹也, 大森 洋平, 小松 弘武, 梶原 大輝, 堂地 大輔

    消化器外科　31　(8)　1299-1304　2008/07

    Publisher: (株)へるす出版

    ISSN： 0387-2645

  77. 膵石嵌頓により胆管炎を併発した一手術例

    齋藤 雄康, 土屋 誉, 本多 博, 内藤 剛, 及川 昌也, 長谷川 康弘, 小松 弘武, 荒木 孝明, 井本 博文, 片平 晋太郎, 永井 智之, 辻 圭太, 梶原 大輝, 堂地 大輔, 中村 隆司, 目黒 敬義, 山崎 匡

    膵臓　22　(3)　351-351　2007/05

    Publisher: (一社)日本膵臓学会

    ISSN： 0913-0071

    eISSN： 1881-2805

Show all ︎Show first 5

Books and Other Publications 1

  1. Research and Clinical Applications of Targeting Gastric Neoplasms

    Linda Shyue Huey Chuang, Junichi Matsuo, Daisuke Douchi, Yoshiaki Ito

    Elsevier　2021

Presentations 17

  1. Evaluation of Safety and Prognosis of Pancreatic Resection in Patients Aged 85 and Older

    第80回日本消化器外科学会総会　2025/07/16

  2. Safety and Long-Term Outcomes of Pancreatic Resection in Super- Elderly Patients Aged 85 Years and Older

    第37回日本肝胆膵外科学会学術集会　2025/06/14

  3. 85歳以上の浸潤性膵管癌に対する膵切除の安全性と長期成績の検討

    堂地大輔

    第125回日本外科学会定期学術集会　2025/04/12

  4. 術前補助化学療法を施行した膵癌切除症例の長期予後と血液型との関連について

    堂地 大輔

    JDDW2024　2024/11/01

  5. 膵癌に対する術前治療における 画像上の腫瘍縮小率およびCA19-9の変化率と 組織学的効果判定基準との乖離

    堂地 大輔

    第124回日本外科学会定期学術集会　2024/04/20

  6. Our strategy of the conversion surgery for locally advanced unresectable pancreatic cancer

    2023/07/13

  7. Molecular characterization of gallbladder carcinoma with pancreaticobiliary maljunction

    2023/07/01

  8. がん遺伝子パネル検査を受けた胆道癌症例に関する前向き観察研究

    堂地 大輔

    第123回日本外科学会定期学術集会　2023/04/27

  9. A point mutation RUNX3 R122C promotes the expansion of isthmus stem cells and inhibits their differentiation in stomach

    堂地 大輔

    第81回日本癌学会学術総会　2022/09/29

  10. 上皮内癌を認め二期的手術を行った 胆管癌合併先天性胆道拡張症の1例

    堂地大輔

    第45回日本膵・胆管合流異常研究会　2022/09/03

  11. がん抑制遺伝子RUNX3の点変異体RUNX3(R122C) は、胃の上皮幹細胞の増殖を促進し、その分化を阻害する

    堂地 大輔

    第122回日本外科学会定期学術集会　2022/04/16

  12. 胃がんの起源をめぐる日米間の対立

    NEXTSURG Conference 3rd 2021　2021/10/15

  13. Induction of gastric cancer by successive oncogenic activation in the corpus

    Daisuke Douchi, Akihiro Yamamura, Junichi Matsuo, Mitsuhiro Shimura, Shinobu Ohnuma, Takashi Kamei, Michiaki Unno, Yoshiaki Ito

    The 80th Annual Meeting of the Japanese Cancer Association　2021/09/30

  14. RUNX3 restricts the “Point of No Return” in the cell cycle of gastric stem cells

    Daisuke Douchi

    CSI Research meeting　2021/01/08

  15. Induction of invasive and metastatic cancer in the oxyntic stomach through isthmal stem/progenitor cells

    Daisuke Douchi, Akihiro Yamamura, Junichi Matsuo, Yi Hui Melissa Lim, Mitsuhiro Shimura, Kazuto Suda, Sabirah Chen, Napat Nuttonmanit, Pang ShuChin, Linda Shyue Huey Chuang, Yoshiaki Ito

    Frontiers in Cancer Science 2020　2020/11/02

  16. RUNX3 mutation, R122C, induces stem cell expansion probably due to the defective cell cycle checkpoint

    Daisuke Douchi

    RUNX meeting 2019 in Seoul　2019/06/19

  17. RUNX3 mutation, R122C, induces stem cell expansion

    Daisuke Douchi

    Joint SGCC-CSI Gastric Cancer Seminar　2019/01/08

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Research Projects 3

  1. 膵・胆管合流異常を伴う胆嚢癌の分子病理学的発癌メカニズムの解明と治療戦略の開発

    堂地 大輔

    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 - 2028/03

  2. 胃癌の発生メカニズムと幹細胞との関連

    堂地 大輔

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 研究活動スタート支援

    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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    ピロリ菌を使用した実験系に先立ち、正常胃上皮幹細胞を標識できる遺伝子改変マウスであるIqgap3マウスと胃癌の発生に関連するRUNX3のmutationを持つRUNX3(R122C)ノックインマウスを使用して、胃癌発生と幹細胞との関連を探索する実験計画を立てることにした。RUNX3(R122C)マウスから胃組織を採取したあと、組織学的および蛍光免疫染色、オルガノイド培養を実施した。また、Iqgap3マウスとRUNX3(R122C)マウスを掛け合わせて、フローサイトメトリーにより胃の上皮幹細胞と非上皮幹細胞を分離してトランスクリプトーム解析を行った。6か月齢のRUNX3(R122C)ホモマウスの胃体部組織は、組織学的に前癌状態を呈することが判明した。また、急速に増殖する胃上皮幹細胞/前駆細胞の増加と分化停止を認めた。フローサイトメトリーから単離した胃上皮細胞のトランスクリプトーム解析からは、野生型と比較して、RUNX3(R122C)マウスの上皮幹細胞では、細胞周期に関連するMYC遺伝子の関連遺伝子群が上昇していることが判明して。また、in vitroの実験では、RUNX3(R122C)変異は、細胞周期の増殖状態(G1)と静止状態(G0)のどちらに入るかを決定する制限点 (Restriction point) の制御を乱し、幹細胞の増殖 (self-renewal)を促す一方で、その分化(differentiation)を抑制していることがわかった。したがって、胃上皮幹細胞/前駆細胞の細胞周期が崩れることにより、前癌状態が形成されることが示唆された重要な結果が得られた。

  3. Regulation of epithelial-mesenchymal transition and application to new treatment for pancreatic cancer

    Unno Michiaki, OHTSUKA HIDEO, ARIAKE KYOHEI, DOUCHI DAISUKE

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2014/04 - 2016/03

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    Outcome of pancreatic cancer is very miserable due to the recurrence of distant metastasis. The distant metastases were associated with epithelial-mesenchymal transition (EMT) . In this study, we examined the relationship between Wnt signal and EMT, and also relationship if EMT and sensitivity of anti-cancer drug. When Wnt signal was inhibited by introducing SiRNA of LRRFIP1 into pancreatic cancer cell line Panc-1, we showed that reverse EMT was observed. Moreover, we revealed that the sensitivity of anti-cancer drug was increased in this situation. Therefore, we indicated that there was a strong relationship between the EMT and sensitivity for anti-cancer drugs in pancreatic cancer cells.