Early detection of pancreatic ductal adenocarcinoma based on the molecular assessment of pancreatic ductal adenocarcinoma concomitant with IPMN of the pancreas.

• Project/Area Number: 25293285
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: OHTSUKA Takao 九州大学, 大学病院, 講師 (20372766)
• Co-Investigator(Kenkyū-buntansha): TANAKA Masao 九州大学, 医学研究院, 教授 (30163570) ; MIZUMOTO Kazuhiro 九州大学, 大学病院, 准教授 (90253418) ; TAKAHATA Shunichi 九州大学, 医学研究院, 共同研究員 (50437779) ; OHUCHIDA Kenoki 九州大学, 大学病院, 助教 (20452708) ; SAKAI Hiroshi 九州大学, 医学研究院, 共同研究員 (80611665)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: IPMN / 膵癌 / 併存膵癌 / GNAS / 早期診断

Outline of Final Research Achievements

The clinicopathologic features of the patients with IPMN with distinct pancreatic ductal adenocarcinoma (PDAC) were reviewed. The GNAS status in the IPMN tissue and DF specimens was assessed by sensitive mutation scanning methods. The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC. By multivariate analysis, GNAS wild-type and gastric type IPMN were significantly associated with distinct PDAC. The GNAS status in DF was consistent with that in tissue in over 90% of the patients. Taken together, distinct PDACs frequently develops in the pancreas with gastric type IPMN without GNAS mutations. DF DNA test would predict the GNAS status of IPMN, while the detection of the gastric subtype using noninvasive test remains to be determined. Another insight in this study is that it may be possible to distinguish invasive IPMM from concomitant PDAC by assessing molecular biomarkers, especially by KRAS/GNAS mutation status.

Research Products

• [Journal Article] Predictive factors for the metachronous development of malignant lesions in the remnant pancreas after partial pancreatectomy for IPMN. (2016)
  • Author(s): Miyasaka Y, Ohtsuka T, Tamura K, Mori Y, Shindo K, Yamada D, Takahata S, Ishigami K, Ito T, Tokunaga S, Oda Y, Mizumoto K, Nakamura M, Tanaka M.
  • Journal Title: Ann Surg Volume: 印刷中 Issue: 6 Pages: 1180-1187
  • DOI: 10.1097/sla.0000000000001368
  • Peer Reviewed
• [Journal Article] Distinction of invasive carcinoma derived from IPMNs from concomitant ductal adenocarcinoma of the pancreas using molecular biomarkers. (2016)
  • Author(s): Tamura K, Ohtsuka T, Date K, Fujimoto T, Matsunaga T, Kimura H, Watanabe Y, Miyazaki T, Ohuchida K, Takahata S, Ishigami K, Oda Y, Mizumoto K, Nakamura M, Tanaka M.
  • Journal Title: Pancreas Volume: 印刷中 Issue: 6 Pages: 826-835
  • DOI: 10.1097/mpa.0000000000000563
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Assessment of Clonality of Multisegmental Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas Based on GNAS Mutation Analysis (2015)
  • Author(s): Tamura K, Ohtsuka T, Matsunaga T, Kimura H, Watanabe Y, Ideno N, Aso T, Miyazaki T, Ohuchida K, Takahata S, Ito T, Ushijima Y, Oda Y, Mizumoto K, Tanaka M
  • Journal Title: Surgery Volume: 157 Issue: 2 Pages: 277-284
  • DOI: 10.1016/j.surg.2014.09.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical Significance of GNAS Mutation in Intraductal Papillary Mucinous Neoplasm of the Pancreas With Concomitant Pancreatic Ductal Adenocarcinoma (2015)
  • Author(s): Ideno N, Ohtsuka T, Matsunaga T, Kimura H, Watanabe Y, Tamura K, Aso T, Aishima S, Miyasaka Y, Ohuchida K, Ueda J, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • Journal Title: Pancreas Volume: 44 Issue: 2 Pages: 311-320
  • DOI: 10.1097/mpa.0000000000000258
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Predictors and diagnostic strategies for early-stage pancreatic ductal adenocarcinoma. A retrospective review (2015)
  • Author(s): Kimura H, Ohtsuka T, Matsunaga T, Watanabe Y, Tamura K, Ideno N, Aso T, Miyazaki T, Osoegawa T, Aishima S, Miyasaka Y, Ueda J, Ushijima Y, Igarashi H, Ito T, Takahata S, Oda Y, Mizumoto K, Tanaka M.
  • Journal Title: Pancreas Volume: 44 Issue: 7 Pages: 1148-1154
  • DOI: 10.1097/mpa.0000000000000393
  • Peer Reviewed
• [Journal Article] GNAS and KRAS mutational analyses of intraductal papillary neoplasms of the pancreas and bile duct developing in the same individual: A case report. (2015)
  • Author(s): Date K, Ohtsuka T, Fujimoto T, Gotoh Y, Nakashima Y, Kimura H, Matsunaga T, Mori Y, Mochidome N, Miyazaki T, Oda Y, Tanaka M, Nakamura M
  • Journal Title: Pancreatology Volume: 15 Issue: 6 Pages: 713-716
  • DOI: 10.1016/j.pan.2015.09.013
  • Peer Reviewed
• [Journal Article] 膵管内乳頭粘液性腫瘍；危険因子. (2015)
  • Author(s): 伊達健治朗、大塚隆生、渡邉雄介、高畑俊一、田中雅夫
  • Journal Title: 日本臨床 Volume: 73 Pages: 206-209
• [Journal Article] 膵管内乳頭粘液性腫瘍；術後経過観察法. (2015)
  • Author(s): 大塚隆生、宮坂義浩、田村公二、高畑俊一、田中雅夫
  • Journal Title: 日本臨床 Volume: 73 Pages: 256-259
• [Journal Article] 膵管内乳頭粘液性腫瘍；予後. (2015)
  • Author(s): 宮坂義浩、大塚隆生、山田大輔、高畑俊一、田中雅夫
  • Journal Title: 日本臨床 Volume: 73 Pages: 260-263
• [Journal Article] IPMN/MCN国際診療ガイドライン2012年の概要. (2015)
  • Author(s): 田村公二、大塚隆生、田中雅夫
  • Journal Title: 日本臨床 Volume: 73 Pages: 400-404
• [Journal Article] Role of pancreatic juice cytology in the preoperative management of intraductal papillary mucinous neoplasm of the pancreas in the era of international consensus guidelines 2012 (2014)
  • Author(s): Ohtsuka T, Matsunaga T, KImura H, Watanabe Y, Tamura K, ideno N, Aso T, Miyasaka Y, Ueda J, Takahata S, Osoegawa T, Igarashi H, Ito T, Ushijima Y, Ookubo F, Oda Y, Mizumoto K, Tanaka M
  • Journal Title: World J Surg Volume: 38 Issue: 5 Pages: 2994-3001
  • DOI: 10.1007/s00268-015-2948-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. (2014)
  • Author(s): Akagawa S, Ohuchida K, Torata N, Hattori M, Eguchi D, Fujiwara K, Kozono S, Cui L, Ikenaga N, Ohtsuka T, Oishima S, Mizumoto K, Oda Y, Tanaka M
  • Journal Title: Int J Oncol Volume: 45 Issue: 1 Pages: 113-120
  • DOI: 10.3892/ijo.2014.2391
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion (2014)
  • Author(s): Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, Tanaka M
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: S4 Pages: 564-574
  • DOI: 10.1245/s10434-014-3676-8
  • Peer Reviewed
• [Journal Article] CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells. (2014)
  • Author(s): Fujiwara K, Ohuchida K, Sada M, Horioka K, Ulrich CD 3rd, Shindo K, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M.
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: 1-11
  • DOI: 10.1371/journal.pone.0107247
  • Peer Reviewed / Open Access
• [Journal Article] Treatment strategy for main duct intraductal papillary mucinous neoplasms of the pancreas based on the assessment of the recurrences in the remnant pancreas after resection: a retrospective review. (2014)
  • Author(s): Tamura K, Ohtsuka T, et al.
  • Journal Title: Annals of Surgery Volume: 259 Issue: 2 Pages: 360-368
  • DOI: 10.1097/sla.0b013e3182a690ff
  • Peer Reviewed
• [Journal Article] Intraoperative irrigation cytology of the remnant pancreas to detect remnant distinct pancreatic ductal adenocarcinoma in patients with IPMN undergoing partial pancreatectomy. (2014)
  • Author(s): Mori Y, Ohtsuka T, et al.
  • Journal Title: Surgery Volume: 155 Issue: 1 Pages: 67-73
  • DOI: 10.1016/j.surg.2013.06.059
  • Peer Reviewed
• [Journal Article] Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. (2013)
  • Author(s): Ideno N, Ohtsuka T, et al.
  • Journal Title: Annals of Surgery Volume: 258 Issue: 1 Pages: 141-151
  • DOI: 10.1097/sla.0b013e31828cd008
  • Peer Reviewed
• [Journal Article] Unresectable pancreatic ductal adenocarcinoma in the remnant pancreas diagnosed during every-6-month surveillance after resection of branch duct IPMN: A case report. (2013)
  • Author(s): Tamura K, Ohtsuka T, et al.
  • Journal Title: Journal of the Pancreas Volume: 14 Pages: 450-453
  • DOI: 10.6092/1590-8577/1494
  • Peer Reviewed
• [Presentation] 膵IPMNにおけるGNAS変異の臨床的意義 (2015)
  • Author(s): 大塚隆生
  • Organizer: 第20回日本外科病理学会学術集会
  • Place of Presentation: 和歌山市
  • Year and Date: 2015-11-07
• [Presentation] 九州大学での膵管内乳頭粘液性腫瘍(IPMN)の切除方針 (2015)
  • Author(s): 大塚隆生, 高畑俊一, 宮坂義浩, 山田大輔, 田中雅夫
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2015-06-12
• [Presentation] Surgical treatment strategy for IPMN of the pancreas based on Fukuoka consensus guidelines 2012. (2015)
  • Author(s): 大塚隆生, 田村公二, 宮坂義浩, 高畑俊一, 田中雅夫
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-17
• [Presentation] 集学的アプローチに基づいた主膵管型膵管内乳頭粘液性腫瘍の至適治療方針(統合プログラム) (2014)
  • Author(s): 大塚隆生、田村公二、田中雅夫
  • Organizer: 第21回日本消化器関連学会週間(JDDW)
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-25
• [Presentation] Clinical experiences in Japan: Surgical treatment of IPMN (International session) (2014)
  • Author(s): 大塚隆生
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 北九州
  • Year and Date: 2014-07-11
• [Presentation] 内視鏡によるIPMN併存膵癌高危険群の同定（シンポジウム） (2014)
  • Author(s): 大塚隆生, 井手野昇, 田中雅夫
  • Organizer: 第87回日本消化器内視鏡学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-16
• [Presentation] Intraoperative irrigation cytology to detect unexpected significant lesion of the remnant pancreas in patients with IPMN undergoing partial pancreatectomy.
  • Author(s): Ohtsuka T, Mori Y, et al.
  • Organizer: 44th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Miami, FL, USA
• [Presentation] Clinical significance of GNAS mutation for invasive pancreatic carcinoma from/derived from IPMN of the pancreas.
  • Author(s): Ideno N, Ohtsuka T, et al.
  • Organizer: 44th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Miami, FL, USA
• [Presentation] 分子生物学的解析によるIPMN併存膵癌ハイリスク群の同定
  • Author(s): 大塚隆生、井手野昇、田中雅夫
  • Organizer: 第21回日本消化器関連学会週間 (JDDW 2013)
  • Place of Presentation: 東京
• [Presentation] 膵液細胞診を用いたIPMN併存膵癌の早期診断の試み
  • Author(s): 大塚隆生、井手野昇、他
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台
• [Book] The Pancreapedia (2014)
  • Author(s): Ohtsuka T, Tanaka M
  • Total Pages: 19
  • Publisher: Michigan Publishing
• [Book] Intraductal Papillary Mucinous Neoplasm of the Pancreas. (2014)
  • Author(s): Ohtsuka T, et al.
  • Total Pages: 204
  • Publisher: Springer