Non-invasive modality for diagnosis of pancreatic neoplasm

• Project/Area Number: 25461029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital
• Principal Investigator: Mizukami Yusuke 医療法人徳洲会札幌東徳洲会病院付属臨床研究センター, その他部局等, その他 (30400089)
• Co-Investigator(Kenkyū-buntansha): ASHIDA Toshifumi 医療法人徳洲会 札幌東徳洲会病院, 付属臨床研究センター IBD研究部, 研究員 (50261409) ; MORIICHI Kentaro 旭川医科大学, 医学部 内科学講座, 講師 (70455715) ; 井内 康之 医療法人徳洲会札幌東徳洲会病院付属臨床研究センター, その他部局等, 研究員 (90640615)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵癌 / 低侵襲診断 / がん低侵襲診断 / 液体生検 / 血管新生 / 血漿遊離DNA

Outline of Final Research Achievements

Recent technologies are emerging to allow genotyping of plasma cell-free DNA (cfDNA) shed from tumors into the general circulation. There are two main types of pathologically distinct precursors for PDA, pancreatic intraepithelial neoplasias and intraductal papillary mucinous cystic neoplasias (IPMNs), and the mutations in KRAS and/or GNAS mediate key signaling during early development of the tumors. The clinical viability of cfDNA genotyping using digital PCR targeting mutations in KRAS and GNAS were examined. Ten PDA and 21 IPMN patients were recruited. The primary endpoint of this study was to evaluate whether such an approach can appropriately monitor the risk IPMN progression and detect localized early-stage PDA non-invasively. The major technical challenge of widespread implementation of this clinical test is the coverage for uncommon forms of KRAS mutation, as well as sensitivity for early stages cancer where the amount of cfDNA may be limited.

Research Products

• [Journal Article] Tracking the clonal evolution of adenosquamous carcinoma, a rare variant of intraductal papillary mucinous neoplasm of the pancreas. (2016)
  • Author(s): Matsuzaka S, Karasaki H, Ono Y, Ogata M, Oikawa K, Tamakawa S, Chiba S, Muraki M, Yokochi T, Funakoshi H, Kono T, Nagashima K, Mizukami Y.
  • Journal Title: Pancreas Volume: xx
  • Peer Reviewed
• [Journal Article] The protein expression level of Gli2 is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms. (2016)
  • Author(s): Sugiyama Y, Sasajima J, Mizukami Y, Koizumi K, Kawamoto T, Karasaki H, Yusuke Ono, Tanabe H, Fujiya M, Kohgo Y.
  • Journal Title: Pol J Pathol Volume: xx
  • Peer Reviewed
• [Journal Article] A Rare Case of Epidermoid Cyst in the Pancreatic Tail Invaginated from the Splenic Hilum: Long-term Alteration in Imaging Findings. (2016)
  • Author(s): Sugiyama Y, Kawamoto T, Sasajima J, Koizumi K, Karasaki H, Mizukami Y.
  • Journal Title: Internal Medicine Volume: xx
  • Peer Reviewed
• [Journal Article] Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias (PanINs) (2015)
  • Author(s): Imai K, Karasaki K, Ono Y, Sasajima J, Chiba S, Funakoshi H, Muraki M, Hanaoka H, Furukawa T, Furukawa H, Kono T, Nagashima K, Mizukami Y
  • Journal Title: The Journal of Pathology: Clinical Research Volume: 1 Issue: 2 Pages: 76-82
  • DOI: 10.1002/cjp2.8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas. (2014)
  • Author(s): Gala MK, Mizukami Y, Le LP, Moriichi K, Austin T, Yamamoto M, Lauwers GY, Bardeesy N, Chung DC
  • Journal Title: Gastroenterology Volume: 146 Issue: 2 Pages: 520-9
  • DOI: 10.1053/j.gastro.2013.10.045
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyst infection of intraductal papillary mucinous neoplasms of the pancreas: management of a rare complication: report of 2 cases. (2014)
  • Author(s): Watanabe K, Karasaki H, Mizukami Y, Kawamoto T, Kono T, Imai K, Einama T, Taniguchi M, Kohgo Y, Furukawa H
  • Journal Title: Pancreas Volume: 43 Issue: 3 Pages: 478-81
  • DOI: 10.1097/mpa.0000000000000036
  • Peer Reviewed
• [Journal Article] Macrophages in pancreatic cancer: starting things off on the wrong track. (2013)
  • Author(s): Deschenes-Simard X, Mizukami Y, Bardeesy N
  • Journal Title: J Cell Biol Volume: 202 Issue: 3 Pages: 403-5
  • DOI: 10.1083/jcb.201307066
  • Peer Reviewed
• [Journal Article] Ex vivo activation of angiogenic property in human peripheral blood-derived monocytes by thrombopoietin. (2013)
  • Author(s): Kawamoto T, Sasajima J, Sugiyama Y, Nakamura K, Tanabe H, Fujiya M, Nata T, Iuchi Y, Ashida T, Torimoto Y, Mizukami Y, Kohgo Y.
  • Journal Title: Int J Hematol Volume: 98 Issue: 4 Pages: 417-429
  • DOI: 10.1007/s12185-013-1423-8
  • Peer Reviewed
• [Presentation] Plasma DNA genotyping using digital PCR for early detection of pancreatic neoplasm (2015)
  • Author(s): Mizukami Y, Ono Y, Karasaki H, Ogata M, Koizumi K, Ando K, Yokochi T, Yamada M, Kono T, Nagashima K
  • Organizer: 46th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: San Diego
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Plasma DNA genotyping using digital PCR for early detection of pancreatic cancer (2015)
  • Author(s): Mizukami Y, Ono Y, Karasaki H, Asahara S, Ando K, Shinohara T, Nagashima K
  • Organizer: 第74回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 液体生検による膵癌リスク評価 (2015)
  • Author(s): 水上裕輔、真口宏介、小泉一也
  • Organizer: 第23回日本消化器関連学会週間
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08
• [Presentation] Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias. (2015)
  • Author(s): Ono Y, Karasaki H, Imai K, Sasajima J, Chiba S, Funakoshi H, Muraki M, Hanaoka H, Furukawa T, Furukawa H, Kono T, Nagashima K, Mizukami Y.
  • Organizer: 2015 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] Adenosquamous cell carcinoma derived from intraductal papillary mucinous neoplasm of the pancreas confirmed by genetic analysis. (2015)
  • Author(s): Karasaki H, Kono T, Ono Y, Maejima T, Mizukami Y.
  • Organizer: 2015 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] A case of metachronous ductal adenocarcinomas (PDAs) with unique KRAS mutation. (2014)
  • Author(s): Mizukami Y, Imai K,Chiba S, Ono Y, Sasajima J, Karasaki H, Kono T, Nagashima K.
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-26
• [Remarks] 札幌東徳洲会病院付属臨床研究センター
  • URL: http://www.higashi-tokushukai.or.jp/clinical_study/research/detail.php?pid=434583114140