title: Pathological spectrum of bile duct lesions from chronic bile duct injury to invasive cholangiocarcinoma corresponding to bile duct imaging findings of occupational cholangiocarcinoma.
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.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
authors.affiliation: Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Genya
authors.initials: G
authors.lastname: Hamano
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tokuji
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Tazuke Kofukai Medical Institute, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Terajima
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Arimoto
authors.affiliation: Department of Surgery, Nissey Hospital, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujikawa
authors.affiliation: Artificial Organ & Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.affiliation: Department of Surgery, Ishikiriseiki Hospital, Higashi-Osaka, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Miyagi Cancer Center, Natori, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Abue
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.affiliation: Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takenaka
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000328:Adult; D001650:Bile Duct Neoplasms / Q000473:pathology*; D001652:Bile Ducts / Q000293:injuries* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000032:analysis; D018281:Cholangiocarcinoma / Q000473:pathology*; D003952:Diagnostic Imaging; D004106:Dilatation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009784:Occupational Diseases / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human
keywords: 1,2-dichloropropane; Biliary intraepithelial neoplasia; Intraductal papillary neoplasm of the bile duct; Occupational cholangiocarcinoma; Printing company