Analysis based on the progression of pancreatic cancer and validation by prospective clinical trial

• Project/Area Number: 17K10689
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ban Daisuke 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40376736)
• Co-Investigator(Kenkyū-buntansha): 渡邊 秀一 東京医科歯科大学, 医学部附属病院, 助教 (20771827) ; 田中 真二 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30253420) ; 田邉 稔 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50197513)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膵癌 / 局所進行膵癌 / オリゴ転移 / 局所進行切除不能膵癌 / 薬剤感受性 / 術前化学療法 / Conversion Surgery

Outline of Final Research Achievements

It has been suggested that there may be cases in which surgical treatment is successful even in advanced pancreatic cancer. In general, cases that would benefit from resection are considered to be tumors of a localized nature with no distant metastases. It was examined in oligo metastases cases, and in clinical trial to introduce surgical treatment for advanced pancreatic cancer.
Although we intended to include patients with no distant metastases in the clinical trial, some patients developed distant metastases as a result of the study were found to be unsuitable for this study. A longitudinal analysis of the gene mutation profile was performed by reviewing previous cases of oligo metastasis. Phylogenetic analysis of the profile revealed that the next metastasis arose from a metastasis and that a new subclone was formed at the metastasis.

Academic Significance and Societal Importance of the Research Achievements

現在、遠隔転移を伴う膵癌や局所進行膵癌に対する標準治療は化学療法であるが、根治性が得られる治療選択はなく、予後も不良である。本研究の目的はそのような進行膵癌であっても根治性が期待できるような、あるいは予後に有効な外科的治療介入の可能性を探索することであった。切除後に再発を来した膵癌であってもオリゴ転移と考えて良い過去の再発巣切除例の遺伝子プロファイルを検討することによって、その機序と遺伝子プロファイルの一端を明らかにできたことは今後の患者選択を検討する上での基盤を提供することできたと考える。さらにこれらの研究を進めていくことによって臨床に実装されることを期待したい。

Research Products

• [Journal Article] Combination of weekly streptozocin and oral S-1 treatment for patients of unresectable or metastatic pancreatic neuroendocrine neoplasms. (2020)
  • Author(s): Ono H, Kudo A, Akahoshi K, Ogura T, Ogawa K, Ban D, Tanaka S, Tanabe M.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 146 Issue: 3 Pages: 793-799
  • DOI: 10.1007/s00432-019-03109-5
  • Peer Reviewed
• [Journal Article] Position of the pancreas division line and postoperative outcomes after distal pancreatectomy. (2020)
  • Author(s): Matsui S, Ogura T, Ban D, Ogawa K, Ono H, Mitsunori Y, Kudo A, Tanaka S, Tanabe M.
  • Journal Title: World Journal of Surgery Volume: 44 Issue: 4 Pages: 1244-1251
  • DOI: 10.1007/s00268-019-05305-3
  • Peer Reviewed
• [Journal Article] Reticular pattern around SMA in CT imaging predicting poor prognosis of pancreatic head cancer. (2020)
  • Author(s): Kato T, Ban D, Tateishi U, Ogura T, Ogawa K, Ono H, Mitsunori Y, Kudo A, Tanaka S, Tanabe M.
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 27 Issue: 3 Pages: 114-123
  • DOI: 10.1002/jhbp.700
  • Peer Reviewed
• [Journal Article] The clinical implications of peripancreatic fluid collection after distal pancreatectomy. (2019)
  • Author(s): Yoshino J, Ban D, Ogura T, Ogawa K, Ono H, Mitsunori Y, Kudo A, Tanaka S, Tanabe M.
  • Journal Title: World Journal of Surgery Volume: 43 Issue: 8 Pages: 2069-2076
  • DOI: 10.1007/s00268-019-05009-8
  • Peer Reviewed / Open Access
• [Journal Article] Loss of KDM6A characterizes a poor prognostic subtype of human pancreatic cancer and potentiates HDAC inhibitor lethality (2019)
  • Author(s): Watanabe S, Shimada S, Akiyama Y, Ishikawa Y, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Yamaoka S, Tanabe M, Tanaka S.
  • Journal Title: International Journal of Cancer Volume: - Issue: 1 Pages: 192-205
  • DOI: 10.1002/ijc.32072
  • Peer Reviewed
• [Journal Article] A simple and practical index predicting the prognoses of the patients with well-differentiated pancreatic neuroendocrine neoplasms. (2019)
  • Author(s): Liu B, Kudo A, Kinowaki Y, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Tanaka S, Akashi T, Tanabe M.
  • Journal Title: J Gastroenterol. Volume: - Issue: 9 Pages: 819-828
  • DOI: 10.1007/s00535-019-01570-0
  • Peer Reviewed
• [Journal Article] Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence. (2019)
  • Author(s): Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Tanabe M, Wands JR, Tanaka S.
  • Journal Title: EBioMedicine Volume: 40 Pages: 457-470
  • DOI: 10.1016/j.ebiom.2018.12.058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rapid growth speed of cysts can predict malignant intraductal mucinous papillary neoplasms. (2018)
  • Author(s): Akahoshi K, Ono H, Akasu M, Ban D, Kudo A, Konta A, Tanaka S, Tanabe M.
  • Journal Title: J Surg Res Volume: 231 Pages: 195-200
  • DOI: 10.1016/j.jss.2018.05.056
  • Peer Reviewed
• [Journal Article] Difficulty scoring system in laparoscopic distal pancreatectomy. (2018)
  • Author(s): Ohtsuka T, Ban D, Nakamura Y, Nagakawa Y, Tanabe M, Gotoh Y, Velasquez VVDM, Nakata K, Sahara Y, Takaori K, Honda G, Misawa T, Kawai M, Yamaue H, Morikawa T, Kuroki T, Mou Y, Lee WJ, Shrikhande SV, Tang CN, Conrad C, Han HS, Palanivelu C, Asbun HJ, Kooby DA, Wakabayashi G, Takada T, Yamamoto M, Nakamura M.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 25 Issue: 11 Pages: 489-497
  • DOI: 10.1002/jhbp.578
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Downregulated Pancreatic Beta Cell Genes Indicate Poor Prognosis in Patients With Pancreatic Neuroendocrine Neoplasms. (2018)
  • Author(s): Kudo A, Akahoshi K, Ito S, Akashi T, Shimada S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Tateishi U, Tanaka S, Tanabe M.
  • Journal Title: Ann Surg. Volume: - Issue: 4 Pages: 732-739
  • DOI: 10.1097/sla.0000000000002911
  • Peer Reviewed
• [Journal Article] Minimally invasive preservation versus splenectomy during distal pancreatectomy: a systematic review and meta-analysis. (2018)
  • Author(s): Nakata K, Shikata S, Ohtsuka T, Ukai T, Miyasaka Y, Mori Y, Velasquez VVDM, Gotoh Y, Ban D, et al.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 25 Issue: 11 Pages: 476-488
  • DOI: 10.1002/jhbp.569
  • Peer Reviewed
• [Journal Article] Current topics in the surgical treatments for hepatocellular carcinoma (2018)
  • Author(s): Ban Daisuke、Ogura Toshiro、Akahoshi Keiichi、Tanabe Minoru
  • Journal Title: Annals of Gastroenterological Surgery Volume: 2 Issue: 2 Pages: 137-146
  • DOI: 10.1002/ags3.12065
  • Peer Reviewed / Open Access
• [Journal Article] Three-dimensional computed tomography analysis of the vascular anatomy of the splenic hilum for gastric cancer surgery. (2018)
  • Author(s): Ishikawa Y, Ehara K, Yamada T, Matsuzawa N, Arai S, Ban D, Kudo A, Tanabe M, Kawashima Y, Sakamoto H.
  • Journal Title: Surg Today. Volume: 48 Issue: 9 Pages: 841-847
  • DOI: 10.1007/s00595-018-1679-y
  • Peer Reviewed
• [Journal Article] Splenic artery as a simple landmark indicating difficulty during laparoscopic distal pancreatectomy (2018)
  • Author(s): Ishikawa Yoshiya、Ban Daisuke、Watanabe Shuichi、Akahoshi Keiichi、Ono Hiroaki、Mitsunori Yusuke、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Asian Journal of Endoscopic Surgery Volume: - Issue: 1 Pages: 81-87
  • DOI: 10.1111/ases.12485
  • Peer Reviewed
• [Journal Article] Sunitinib shrinks NET-G3 pancreatic neuroendocrine neoplasms (2018)
  • Author(s): Mizuno Yuki、Kudo Atsushi、Akashi Takumi、Akahoshi Keiichi、Ogura Toshiro、Ogawa Kosuke、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Tanaka Shinji、Tateishi Ukihide、Tanabe Minoru
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: - Issue: 6 Pages: 1155-1163
  • DOI: 10.1007/s00432-018-2636-2
  • Peer Reviewed
• [Journal Article] Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors. (2018)
  • Author(s): Chiyonobu N, Shimada S, Akiyama Y, Mogushi K, Itoh M, Akahoshi K, Matsumura S, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Suganami T, Yamaoka S, Ogawa Y, Tanabe M, Tanaka S.
  • Journal Title: Am J Pathol. Volume: 188 Pages: 1213-1224
  • Peer Reviewed
• [Journal Article] DEPDC5 deficiency contributes to resistance to leucine starvation via p62 accumulation in hepatocellular carcinoma (2018)
  • Author(s): Mizuno Y, Shimada S, Akiyama Y, Watanabe S, Aida T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Yamaoka S, Tanabe M, Tanaka S
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 106-106
  • DOI: 10.1038/s41598-017-18323-9
  • Peer Reviewed / Open Access
• [Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs. (2018)
  • Author(s): Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Endocr Relat Cancer Volume: 25(6) Issue: 6 Pages: 619-631
  • DOI: 10.1530/erc-17-0328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors (2018)
  • Author(s): Chiyonobu Norimichi、Shimada Shu、Akiyama Yoshimitsu、Mogushi Kaoru、Itoh Michiko、Akahoshi Keiichi、Matsumura Satoshi、Ogawa Kosuke、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Kudo Atsushi、Arii Shigeki、Suganami Takayoshi、Yamaoka Shoji、Ogawa Yoshihiro、Tanabe Minoru、Tanaka Shinji
  • Journal Title: Am. J. Pathol. Volume: 188 Issue: 5 Pages: 1213-1224
  • DOI: 10.1016/j.ajpath.2018.01.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A simple morphological classification to estimate the malignant potential of pancreatic neuroendocrine tumors (2017)
  • Author(s): Oba Atsushi、Kudo Atsushi、Akahoshi Keiichi、Kishino Mitsuhiro、Akashi Takumi、Katsuta Eriko、Iwao Yasuhito、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Tanaka Shinji、Eishi Yoshinobu、Tateishi Ukihide、Tanabe Minoru
  • Journal Title: Journal of Gastroenterology Volume: 52 Issue: 10 Pages: 1140-1146
  • DOI: 10.1007/s00535-017-1349-7
  • Peer Reviewed
• [Journal Article] Surgical pitfalls of jejunal vein anatomy in pancreaticoduodenectomy (2017)
  • Author(s): Ishikawa Yoshiya、Ban Daisuke、Matsumura Satoshi、Mitsunori Yusuke、Ochiai Takanori、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 24 Issue: 7 Pages: 394-400
  • DOI: 10.1002/jhbp.451
  • Peer Reviewed
• [Journal Article] Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma. (2017)
  • Author(s): Ohata Y, Akiyama Y, Shimada S, Mogushi K, Nakao K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Molecular Cancer Therapeutics Volume: in press Issue: 6 Pages: 1155-1165
  • DOI: 10.1158/1535-7163.mct-16-0728
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ARID2 modulates DNA damage response in human hepatocellular carcinoma cells. (2017)
  • Author(s): Oba A, Shimada S, Akiyama Y, Nishikawaji T, Mogushi K, Ito H, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Asahara H, Kaida A, Miura M, Tanabe M, Tanaka S.
  • Journal Title: Journal of Hepatology Volume: in press Issue: 5 Pages: 942-951
  • DOI: 10.1016/j.jhep.2016.12.026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Refractory Long-Term Cholangitis After Pancreaticoduodenectomy: A Retrospective Study (2017)
  • Author(s): Ueda Hiroki、Ban Daisuke、Kudo Atsushi、Ochiai Takanori、Tanaka Shinji、Tanabe Minoru
  • Journal Title: World Journal of Surgery Volume: 41 Issue: 7 Pages: 1882-1889
  • DOI: 10.1007/s00268-017-3912-z
  • Peer Reviewed
• [Presentation] THE IMPLICATION OF INDUCTION CHEMOTHERAPY FOLLOWED BY CHEMORADIOTHERAPY FOR LOCALLY ADVANCED PANCREATIC CANCER, INTENDED CONVERSION SURGERY (2019)
  • Author(s): Daisuke Ban, Toshitaka Sugawara, Tomotaka Kato, Atsushi Kudo, Minoru Tanabe
  • Organizer: 53rd annual meeting of Pancreas club
  • Int'l Joint Research
• [Presentation] PREOPERATIVE FACTORS FOR EARLY RECURRENCE OF RESECTED PANCREATIC DUCTAL ADENOCARCINOMA (2019)
  • Author(s): Toshitaka Sugawara, Daisuke Ban, Shuichi Watanabe, Toshiro Ogura, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Atsushi Kudo, Minoru Tanabe
  • Organizer: 53rd annual meeting of Pancreas club
  • Int'l Joint Research
• [Presentation] 膵 癌の縦断的whole exome sequence 解析によるfounder mutation 推定の試み. (2019)
  • Author(s): 渡辺秀一、伴 大輔、西野 穣、石井 武、松井 聡、菅原俊喬、赤須雅文、加藤智敬、浅野大輔、吉野 潤、小倉俊郎、小川康介、小野宏晃、光法雄介、工藤 篤、田中真二、鎌谷高志、宮 冬樹、田邉 稔.
  • Organizer: 第119 回日本外科学会定期学 術集会
• [Presentation] The efficacy of induction chemotherapy for locally advanced pancreatic cancer, intended conversion surgery. (2019)
  • Author(s): Daisuke Ban.
  • Organizer: The 65th annual congress of international college of surgeons Japan section
• [Presentation] 局所進行切除不能膵癌に対する導 入化学療法と化学放射線療法によるConvwrsion surgery の意義. (2019)
  • Author(s): 伴 大輔、加藤智敬、小倉俊郎、小川康介、小野宏晃、工藤 篤、田邉 稔.
  • Organizer: 第28 回日本癌病態治療研究会
• [Presentation] 下大静脈高度腫瘍浸潤・腫瘍栓症例に対する多領域外科の協力による総合戦略 (2017)
  • Author(s): 伴大輔、大井啓司、工藤敏文、齋藤一隆、巌康仁、松村聡、光法雄介、小野宏晃、落合高徳、工藤篤、水野友裕、田中真二、藤井靖久、井上芳徳、荒井裕国、田邉稔
  • Organizer: 第117回 日本外科学会定期学術集会
• [Presentation] How to set up difficulty scoring system in laparoscopic liver resection (2017)
  • Author(s): Daisuke Ban、Minoru Tanabe
  • Organizer: 6th A-PHPBA 29th JSHBPS
  • Int'l Joint Research
• [Presentation] Safely expanding of the laparoscopic liver resection according to difficulty scoring system (2017)
  • Author(s): Daisuke Ban, Jun Yoshino, Toshiro Ogura, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Atsushi Kudo, Minoru Tanabe
  • Organizer: The 63rd Annual Congress of International College of Surgeons Japan Section
  • Int'l Joint Research
• [Presentation] Safely expanding of the laparoscopic liver resection according to difficulty scoring system (2017)
  • Author(s): Ban Daisuke, Ogura Toshiro, Yoshino Jun, Akahoshi Keiichi, Mitsunori Yusuke, Ono Hiroaki, Kudo Atsushi, Tanabe Minoru
  • Organizer: International Laparoscopic Liver Society 2017
  • Int'l Joint Research
• [Presentation] BR膵癌のCT画像膵外進展評価における淡い網目状高吸収所見の意義 (2017)
  • Author(s): 伴 大輔、浅野 大輔、吉野 潤、渡辺 秀一、水野 裕貴、千代延 記道、赤星 径一、小倉 俊郎、小川 康介、小野 宏晃、光法 雄介、工藤 篤、田中 真二、田邉 稔
  • Organizer: 第48回 日本膵臓学会大会
• [Presentation] 膵体尾部切除における膵液瘻予防のためのBest Practice～断端被覆と管理の変遷 (2017)
  • Author(s): 伴大輔、吉野潤、加藤智敬、赤須雅文、赤星径一、小川康介、小野宏晃、光法雄介、工藤篤、田中真二、田邉稔
  • Organizer: 第44回 日本膵切研究会
• [Presentation] 腹腔鏡下肝切除におけるDifficulty Scoring Systemの課題と今後の展望 (2017)
  • Author(s): 伴大輔、加藤智敬、赤須雅文、吉野潤、渡辺秀一、千代延記道、水野裕貴、赤星径一、小倉俊郎、小川康介、小野宏晃、光法雄介、工藤篤、田中真二、田邉稔
  • Organizer: 第30回日本内視鏡外科学会総会