Masahiko Kinoshita1, Shoji Kubo1, Yasuni Nakanuma2, Yasunori Sato3, Shigekazu Takemura1, Shogo Tanaka1, Genya Hamano1, Tokuji Ito1, Hiroaki Terajima4, Terumasa Yamada5, Shoji Nakamori6, Akira Arimoto7, Masahiro Fujikawa8, Yasuhiko Sugawara9, Takatsugu Yamamoto10, Makoto Abue11, Kei Nakagawa12, Michiaki Unno12, Toru Mizuguchi13, Kenji Takenaka14, Ken Shirabe15, Toshihiko Shibata1. 1. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 2. Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan. 3. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. 4. Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Tazuke Kofukai Medical Institute, Osaka, Japan. 5. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. 6. Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan. 7. Department of Hepato-Biliary-Pancreatic Surgery, Osaka Red Cross Hospital, Osaka, Japan. 8. Department of Surgery, Nissey Hospital, Osaka, Japan. 9. Artificial Organ & Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan. 10. Department of Surgery, Ishikiriseiki Hospital, Higashi-Osaka, Japan. 11. Department of Gastroenterology, Miyagi Cancer Center, Natori, Miyagi, Japan. 12. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 13. Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 14. Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan. 15. Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND: We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. METHODS: We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. RESULTS: BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. CONCLUSIONS: The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging.
BACKGROUND: We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. METHODS: We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. RESULTS:BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. CONCLUSIONS: The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging.
Keywords:
1,2-dichloropropane; Biliary intraepithelial neoplasia; Intraductal papillary neoplasm of the bile duct; Occupational cholangiocarcinoma; Printing company