Carcinogenetic Effect of Bile on the Development of Gallbladder Carcinoma

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BACKGROUND.Changes in bile composition induce the development of gallbladder cancer.METHODS.The aim of this study is to clarify the role of gallbladder bile in the development of gallbladder cancer experimentally and clinically.(1) Experimental sutdy. The effect of lithogenic diet on biliary tract neoplasms induced by oral administration of BOP in female hamsters (n=50) was examined. (2) Clinical Study. Gallbladder bile composition was examined in the cases of gallbladder cancer (n=15), anomalous union of pancreaticobiliary ductal system (n=13), and segmental adenomyomatosis (n=20), and compared with that of control patients (n=13).RESULTS.(1) Experimental study. The incidence of biliary tract neoplasms in the hamsters fed with BOP plus inthogenic diet was similar to that in those fed with BOP plus normal diet. (2) Clinical Study. In gallbladder cancer, the concentrations of total bile acids (29.3(〕SY.+-.〔)21.5mumol/ml) and secondary bile acids (7.7(〕SY.+-.〔)5.4mumol/ml) were significantly lower than those of normal patients (P<0.001). Also in anomalous union of pancreaticobiliary ductal system and segmental adenomyomatosis, the concentrations of total bile acids (56.1(〕SY.+-.〔)64.8 and 74.8(〕SY.+-.〔)19.3, respectively) and secondary bile acids (6.8(〕SY.+-.〔)7.0 and 13.7(〕SY.+-.〔)15.2, respectively) were significantly lower than normal patients (P<0.01).CONCLUSIONS.(1) Experimental study. In hamsters, lithogenic diet does not promote BOP (20ppm)-induced biliary tract neoplasms. (2) Clinical study. Lower concentrations of bile acids are characteristic in the gallbladder bile of gallbladder cancer and precancerous conditions. That is, it is unlikely that bile acids in gallbladder contribute to the development of gallbladder cancer. Further investigations are mandatory to elucidate carcinogenic factors in gallbladder bile.