title: A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.
abstract: BACKGROUND
  Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction.
  
  
  METHODS
  Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated.
  
  
  RESULTS
  The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis.
  
  
  CONCLUSIONS
  Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy.
authors.affiliation: Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Kitasato
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kuroki
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Adachi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ono
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Tsuneoka
authors.forename: Masataka
authors.initials: M
authors.lastname: Hirabaru
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Takatsuki
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000517:prevention & control*; D001662:Biliary Tract Surgical Procedures / Q000009:adverse effects*; D002761:Cholangitis / Q000150:complications / Q000188:drug therapy / Q000209:etiology; D002768:Choledochostomy / Q000009:adverse effects; D006224:Cricetinae; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004766:Enterostomy / Q000009:adverse effects*; D017308:Etodolac / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000378:metabolism; D008647:Mesocricetus; D008953:Models, Anatomic; D023421:Models, Animal
chemical_list: D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D017308:Etodolac; D015232:Dinoprostone