Development of high sensitivity diagnostic system for intrahepatic cholangiocarcinoma using glycoprotein molecular marker

• Project/Area Number: 15K10197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Higuchi Ryota 東京女子医科大学, 医学部, 講師 (20318059)
• Co-Investigator(Kenkyū-buntansha): 有泉 俊一 東京女子医科大学, 医学部, 准教授 (40277158) ; 山本 雅一 東京女子医科大学, 医学部, 教授 (60220498) ; 宇都宮 洋才 和歌山県立医科大学, 共同利用施設, 准教授 (60264876) ; 正田 純一 筑波大学, 医学医療系, 教授 (90241827)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胆道癌 / 胆管癌 / 胆嚢癌 / 診断 / マーカー / WFA / 糖鎖 / 術前 / バイオマーカー / 糖鎖医学 / レクチン / 腫瘍マーカー / 臨床試験

Outline of Final Research Achievements

Diagnosis with a new glycoprotein molecular marker (WFA-sialylated MUC1; WFA) was superior in patients with biliary cancer or intrahepatic cholangiocarcinoma compared to the control subjects and patients with benign biliary tract disease. WFA does not depend on the cancer stage or tissue type in the diagnosis of benign biliary tract disease, biliary cancer, intrahepatic cholangiocarcinoma and stage I / II cancers it also showed more accurate diagnostic ability than conventional tumor markers. WFA in the bile was also significantly higher in patients with biliary cancer and intrahepatic cholangiocarcinoma than in those with benign biliary tract disease. It's diagnostic ability was superior to conventional tumor markers and bile cytology, and the diagnosis was accurate.
WFA is a useful biomarker for the diagnosis of biliary cancer and intrahepatic cholangiocarcinoma and is suggested that it should be used in the clinical setting in the future.

Research Products

• [Journal Article] ENBD is Associated with Decreased Tumor Dissemination Compared to PTBD in Perihilar Cholangiocarcinoma. (2017)
  • Author(s): Higuchi R, Yazawa T, Uemura S, Izumo W, Chaudhary RJ, Furukawa T, Yamamoto M.
  • Journal Title: J Gastrointest Surg Volume: 21 Issue: 9 Pages: 1506-1514
  • DOI: 10.1007/s11605-017-3492-0
  • Peer Reviewed
• [Journal Article] High-grade dysplasia/carcinoma in situ of the bile duct margin in patients with surgically resected node-negative perihilar cholangiocarcinoma is associated with poor survival: a retrospective study. (2017)
  • Author(s): Higuchi R, Yazawa T, Uemura S, Izumo W, Furukawa T, Yamamoto M.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 21 Issue: 8 Pages: 1506-1514
  • DOI: 10.1002/jhbp.481
  • Peer Reviewed / Open Access
• [Journal Article] An opportunity in difficulty: Japan-Korea-Taiwan expert Delphi consensus on surgical difficulty during laparoscopic cholecystectomy. (2017)
  • Author(s): Iwashita Y, Hibi T, Ohyama T, Honda G, Yoshida M, Miura F, Takada T, Han HS, Hwang TL, Shinya S, Suzuki K, Umezawa A, Yoon YS, Choi IS, Huang WS, Chen KH, Watanabe M, Abe Y, Misawa T, Nagakawa Y, Yoon DS, Jang JY, Yu HC, Ahn KS, Kim SC, Song IS, Kim JH, Yun SS, Choi SH, Jan YY, …, Higuchi R, et al
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 24 Issue: 4 Pages: 191-198
  • DOI: 10.1002/jhbp.440
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Delphi consensus on bile duct injuries during laparoscopic cholecystectomy: an evolutionary cul-de-sac or the birth pangs of a new technical framework? (2017)
  • Author(s): Iwashita Y, Hibi T, Ohyama T, Umezawa A, Takada T, Strasberg SM, Asbun HJ, Pitt HA, Han HS, Hwang TL, Suzuki K, Yoon YS, Choi IS, Yoon DS, Huang WS, Yoshida M, Wakabayashi G, Miura F, Okamoto K, Endo I, de Santibanes E, Gimenez ME, Windsor JA, Garden OJ, …, Higuchi R, et al
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 24 Issue: 11 Pages: 591-602
  • DOI: 10.1002/jhbp.503
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wisteria floribunda Agglutinin-Sialylated Mucin Core Polypeptide 1 is a Sensitive Biomarker for Biliary Tract Carcinoma and Intrahepatic Cholangiocarcinoma: A Multicenter Study. (2016)
  • Author(s): Shoda J, Matsuda A, Shida T, Yamamoto M, Nagino M, Tsuyuguchi T, Yasaka T, Tazuma S, Uchiyama K, Unno M, Ohkohchi N, Nakanuma Y, Kuno A, Narimatsu H.
  • Journal Title: J Gastroenterol Volume: 52 Issue: 2 Pages: 218-228
  • DOI: 10.1007/s00535-016-1230-0
  • Peer Reviewed / Open Access
• [Journal Article] Improved surgical outcomes for hilar cholangiocarcinoma: changes in surgical procedures and related outcomes based on 40 years of experience at a single institution. (2016)
  • Author(s): Higuchi R, Ota T, Yazawa T, Kajiyama H, Araida T, Furukawa T, Yoshikawa T, Takasaki K, Yamamoto M.
  • Journal Title: Surg Today Volume: 46 Pages: 74-83
  • Peer Reviewed / Open Access
• [Journal Article] Anterior approach for perihilar cholangiocarcinoma (with video). (2016)
  • Author(s): Higuchi R, Yazawa T, Uemura S, Yamamoto M.
  • Journal Title: J Surg Res Volume: 202 Pages: 71-6
  • Peer Reviewed / Open Access
• [Journal Article] Verification of WFA-Sialylated MUC1 as a Sensitive Biliary Biomarker for Human Biliary Tract Cancer. (2016)
  • Author(s): Yamaguchi T, Yokoyama Y, Ebata T, Matsuda A, Kuno A, Ikehara Y,Shoda J, Narimatsu H, Nagino M.
  • Journal Title: Ann Surg Oncol. Volume: 23(2) Issue: 2 Pages: 671-677
  • DOI: 10.1245/s10434-015-4878-4
  • Peer Reviewed / Open Access
• [Journal Article] Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. (2016)
  • Author(s): Yachida S, Wood LD, Suzuki M, Takai E, Totoki Y, Kato M, Luchini C, Arai Y, Nakamura H, Hama N, Elzawahry A, Hosoda F, Shirota T, Morimoto N, Hori K, Funazaki J, Tanaka H, Morizane C, Okusaka T, Nara S, Shimada K, Hiraoka N, Taniguchi H, Higuchi R, et al.
  • Journal Title: Cancer Cell Volume: 23 Pages: 533-47
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] What are the appropriate indicators of surgical difficulty during laparoscopic cholecystectomy? Results from a Japan-Korea-Taiwan multinational survey. (2016)
  • Author(s): Iwashita Y, Ohyama T, Honda G, Hibi T, Hwang TL, Shinya S, Suzuki K, Umezawa A, Yoon YS, Choi IS, Huang WS, Chen KH, Watanabe M, Abe Y, Misawa T, Nagakawa Y, Yoon DS, Jang JY, Yu HC, Ahn KS, Kim SC, Song IS, Kim JH, Yun SS, Choi SH, Jan YY, Sheen-Chen SM, Shan YS, Ker CG, Chan DC, Lee KT, Toyota N, Higuchi R, et al.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 29 Pages: 229-40
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 肝切除後腹腔内出血による再開腹例の検討 (2016)
  • Author(s): 片桐聡, 有泉俊一, 小寺由人, 高橋豊, 樋口亮太, 江川裕人, 新井田達雄, 山本雅一
  • Journal Title: 日本腹部救急医学会雑誌 Volume: 36 Pages: 843-847
  • Peer Reviewed
• [Journal Article] Highly sensitive measurement of qualitative changes in glycosylation of mucin 1 for serodiagnosis of cholangiocarcinoma. (2015)
  • Author(s): Matsuda A, Kuno A, Nakagawa T, Ikegara Y, Irimura T, Yamamoto M, Nakanuma Y, Miyoshi E, Nakamori S, Nakanishi H, Viwatthanasittiphong C, Strivatanakul P, Miwa M, Shoda J, Narimatsu H.
  • Journal Title: Anal Chem Volume: 87 Pages: 7274-81
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 行胆嚢癌に対する膵頭十二指腸切除の適応と限界 (2015)
  • Author(s): 樋口亮太, 谷澤武久, 植村修一郎, 岡野美々, 矢川陽介, 太田岳洋, 新井田達雄, 古川徹, 山本雅一
  • Journal Title: 胆と膵 Volume: 36 Pages: 67-71
• [Journal Article] 胆管癌切除の肝十二指腸間膜剥離時のnon-touch isolation (2015)
  • Author(s): 樋口亮太†, 谷澤武久, 植村修一郎, 岡野美々, 矢川陽介, 山本雅一
  • Journal Title: 臨床外科 Volume: 70 Pages: 30-34
  • Peer Reviewed
• [Presentation] 局所進行胆嚢癌に対する根治を目指した新たな外科治療戦略 局所進行胆嚢癌に対する外科治療方針とその成績 (2017)
  • Author(s): 樋口 亮太, 谷澤 武久, 植村 修一郎, 出雲 渉, 松永 雄太郎, 椎原 正尋, 柿本 忠俊, 太田 岳洋, 古川 徹, 山本 雅一
  • Organizer: 日本消化器外科学会総会
• [Presentation] HER2陽性胆道がん細胞株に対するtrastuzumab emtansineの抗腫瘍効果の検討 (2017)
  • Author(s): 藤村 多嘉朗, 山下 依子, 周 正, 柳沢 美恵子, 望月 万里江, 河野 美玲, 萬 啓悟, 古垣 耕, 樋口 亮太, 正田 純一, 原田 直樹, 吉村 康史
  • Organizer: 日本癌治療学会
• [Presentation] 早期十二指腸乳頭部癌の診断と治療 早期十二指腸乳頭部癌にPD以外の縮小手術の適応はあるのか? (2017)
  • Author(s): 樋口 亮太, 古川 徹, 山本 雅一
  • Organizer: 日本消化器病学会
• [Presentation] 治療成績の向上に向けた取り組み 肝門部胆管癌に対する治療成績向上にむけた取り組み (2017)
  • Author(s): 樋口 亮太, 谷澤 武久, 山本 雅一
  • Organizer: 日本胆道学会
• [Presentation] リンパ節転移のない肝門部胆管癌切除例における胆管断端の上皮内癌遺残は予後不良因子である (2017)
  • Author(s): 樋口 亮太, 谷澤 武久, 植村 修一郎, 出雲 渉, 松永 雄太郎, 柿本 忠俊, 椎原 正尋, 古川 徹, 山本 雅一
  • Organizer: 日本外科学会
• [Presentation] 新規胆管癌糖蛋白質マーカー，WFA-positive sialyl-MUC1の臨床的意義―多施設臨床試験の結果より (2015)
  • Author(s): 志田隆史，中沼安二，正田純一
  • Organizer: 第57回日本消化器病学会
  • Place of Presentation: グランドプリンスホテル新高輪・高輪（東京都港区）
  • Year and Date: 2015-10-08
• [Presentation] 新規胆管癌糖蛋白質マーカー，WFA-positive sialyl-MUC1の臨床的意義―多施設臨床試験の結果より (2015)
  • Author(s): 志田隆史，樋口亮太，山本雅一，梛野正人，露口利夫，八坂貴宏，田妻 進，内山和久，海野倫明，大河内信弘，松田 厚，久野 敦，成松 久，正田純一
  • Organizer: 第51回日本胆道学会学術集会
  • Place of Presentation: ホテル東日本宇都宮（栃木県宇都宮市）
  • Year and Date: 2015-09-17
• [Presentation] 胆道癌取り扱い規約第6版 遠位胆管癌の評価 (2015)
  • Author(s): 樋口亮太, 谷澤武久, 山本雅一
  • Organizer: 第51回日本胆道学会学術集会
  • Place of Presentation: ホテル東日本宇都宮（栃木県宇都宮市）
  • Year and Date: 2015-09-17
• [Presentation] 進行胆嚢癌に対する外科治療－単施設40年の症例における予後因子と切除適応の検討－ (2015)
  • Author(s): 樋口亮太, 谷澤武久, 植村修一郎, 岡野美々, 矢川陽介, 梶山英樹, 太田岳洋, 新井田達雄, 古川徹, 山本雅一
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2015-07-15
• [Book] 外科 (2016)
  • Author(s): 樋口亮太, 太田岳洋, 山本雅一
  • Publisher: 南江堂
• [Book] 手術 (2016)
  • Author(s): 樋口亮太, 出雲渉, 山本雅一
  • Publisher: 金原出版
• [Book] コンセンサス癌治療 (2016)
  • Author(s): 樋口亮太, 森田賢, 山本雅一
  • Publisher: へるす出版
• [Book] 膵・胆道癌Frontier (2016)
  • Author(s): 樋口亮太, 太田岳洋, 山本雅一
  • Publisher: メディカルビュー社
• [Book] 手術 (2016)
  • Author(s): 片桐聡, 有泉俊一, 樋口亮太, 江川裕人, 新井田達雄, 山本雅一
  • Publisher: 金原出版