|Budget Amount *help
¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1996 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1995 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1994 : ¥2,200,000 (Direct Cost : ¥2,200,000)
We carried out cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CDDB) in hamsters in such a way that the pancreatic juice and duodenal contents would enter the biliary tract. The CDDB group were, 4 weeks later, treated with weekly subcutaneous injection of BOP at a dose of 10mg/kg body weight for 9 weeks. The animals were killed at the 12th, 16th and 20th week after the initiation of BOP treatment. Extrahepatic bile duct carcinoma developed in 16%, 24% and 41%, gallbladder carcinoma in 58%, 81% and 82%, intrahepatic bile duct carcinoma in 37%, 76% and 86% or pancreatic carcinoma in 53%, 81% and 82% of the hamsters, respectively, at the corresponding times of killing. The induced extrahepatic bile duct carcinomas were predominantly of the polypoid type and gallbladder carcinomas were of the papillary type in growth form, being morphologically similar to early stage biliary carcinoma in humans. In the next study, we evaluated the
effects of cholecystokinin (CCK), which has a trophic action on the gastro-intestinal tract and on the pancreaticobiliary system, on biliary and pancreatic carcinogenesis in this hamster model. CCK significantly promoted the carcinogenetic effect of BOP in the intra-and extrahepatic bile ducts but not in the gallbladder and pancreas. CCK receptor antagonist exerted an inhibitory effect on carcinogenesis in the intrahepatic bile duct.
In the third study we examined the effects of duodenal or ileal juice reflux into the biliary tract by cholecystoduodenostomy (CDDP) or cholecystoileostomy (CIDB) respectively, on biliary and pancreatic carcinogenesis in the hamster model. In the CDDB group the extrahepatic bile duct was significantly dilated and carcinogenesis of the gallbladder and extrahepatic bile ducts was enhanced. In the CIDB group the CCK bioactivity was stimulated and intrahepatic biliary duct but not gallbladder, extrahepatic bile duct and pancreas, carcinogenesis was promoted more than that observed in the CDDB group.
Proliferation of the biliary duct epithelium was enhanced in both the CDDB and CIDB groups. Cholecystoduodenostomy enhanced intra-and extrahepatic bile duct carcinoma, whereas cholecystoileostomy promoted only intrahepatic bile duct carcinoma. Some factors in the intestinal juice seen to play a role in the promotion of biliary tract carcinoma. Less