臨床外科78巻1号

2023年01月発行

特集 外科医が知っておくべき！ 免疫チェックポイント阻害薬 症例紹介

職業性胆管癌再発に対しニボルマブで完全寛解後長期間durable responseが認められた1例

著者： 田中肖吾¹ 久保正二¹ 石沢武彰¹

所属機関： ¹大阪公立大学大学院肝胆膵外科学

ページ範囲：P.74 - P.82

【ポイント】
◆職業性胆管癌は，塩素系有機溶剤の高濃度・長期曝露による化学発癌である．
◆広範囲の肝内外胆管に慢性胆管傷害，前癌病変（胆管上皮層内腫瘍および胆管内乳頭状腫瘍）が認められ，同部ではDNA損傷が引き起こされている．
◆通常の胆管癌の約30倍に相当する高い腫瘍遺伝子変異量を有し，胆管癌でPD-L1の発現が確認されている．

参考文献

1）Kumagai S, Kurumatani N, Arimoto A, et al：Cholangiocarcinoma among offset colour proof-printing workers exposed to 1,2-dichloropropane and/or dichloromethane. Occup Environ Med 70：508-510, 2013

2）Kubo S, Nakanuma Y, Takemura S, et al：Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan. J Hepatobiliary Pancreat Sci 21：479-488, 2014

3）厚生労働省：「印刷事業場で発生した胆管がんの業務上外に関する検討会」報告書．化学物質ばく露と胆管がん発症との因果関係について〜大阪の印刷事業場の症例からの検討〜．2013年3月　http://www.mhlw.go.jp/stf/houdou/2r9852000002x6at-att/2r9852000002x6zy.pdf

4）Tanaka S, Kubo S：Programmed death-1 inhibitor for occupational intrahepatic cholangiocarcinoma caused by chlorinated organic solvents. J Hepatobiliary Pancreat Sci 26：242-243, 2019

5）Tanaka S, Umemoto K, Kubo S, et al：Nivolumab for treating patients with occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci, 2022 Jul 6. doi：10.1002/jhbp.1215

6）Benbrahim-Tallaa L, Lauby-Secretan B, Loomis D, et al：Carcinogenicity of perfluorooctanoic acid, tetrafluoroethylene, dichloromethane, 1,2-dichloropropane, and 1,3-propane sultone. Lancet Oncol 15：924-925, 2014

7）Kinoshita M, Sato Y, Nebiki H, et al：Occupational cholangiocarcinoma diagnosed 18 years after the end of exposure to 1,2-dichloropropane and dichloromethane at a printing company：a case report. Surg Case Rep 5：65, 2019

8）Kubo S, Kinoshita M, Takemura S, et al：Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci 21：809-817, 2014

9）Kubo S, Takemura S, Tanaka S, et al：Screening and surveillance for occupational cholangiocarcinoma in workers exposed to organic solvents. Surg Today 46：705-712, 2016

10）Kinoshita M, Kubo S, Nakanuma Y, et al：Pathological spectrum of bile duct lesions from chronic bile duct injury to invasive cholangiocarcinoma corresponding to bile duct imaging findings of occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci 23：92-101, 2016

11）Koyama K, Kubo S, Ueki A, et al：MR imaging and MR cholangiopancreatography of cholangiocarcinoma developing in printing company workers. Jpn J Radiol 35：233-241, 2017

12）Kubo S, Takemura S, Tanaka S, et al：Occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane. Ann Gastroenterol Surg 2：99-105, 2018

13）Sato Y, Kubo S, Takemura S, et al：Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan. Int J Clin Exp Pathol 7：4745-4754, 2014

14）Kubo S, Takemura S, Tanaka S, et al：Outcomes after resection of occupational cholangiocarcinoma. J Hepatobiliary Pancreat Sci 23：556-564, 2016

15）Mimaki S, Totsuka Y, Suzuki Y, et al：Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes. Carcinogenesis 37：817-826, 2016

16）Mimaki S, Watanabe M, Kinoshita M, et al：Multifocal origin of occupational cholangiocarcinoma revealed by comparison of multilesion mutational profiles. Carcinogenesis 41：368-376, 2020

17）Sato Y, Kinoshita M, Takemura S, et al：The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma. Pathol Int 67：163-170, 2017

18）Sato Y, Tanaka S, Kinoshita M, et al：Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma：supportive evidence for the efficacy of immune checkpoint inhibitor therapy. J Hepatobiliary Pancreat Sci 27：860-869, 2020