Biliary carcinogenesis in pancreaticobiliary maljunction

Abstract

The coexistence of bile duct carcinoma in choledochal cysts is well known. With large number of cases of congenital bile duct dilatation and pancreaticobiliary maljunction (PBM), it is now apparent that gallbladder carcinoma is more frequent in PBM without bile duct dilatation. The incidence of Gallbladder cancer in choledochal cyst and bile duct cancer in PBM, regardless of the presence of bile duct dilatation is significantly higher than that in control patients with biliary cancer but without PBM. A recent survey shows that the incidence of bile duct cancer in PBM without dilatation is equivalent to that of gallbladder cancer and bile duct cancer in patients with choledochal dilatation. Pathology in PBM is a result of reflux of pancreatic juice and stasis of the mixture in the biliary system. Carcinogenic factors thus present in the biliary contents induce epithelial changes in the biliary tract. In the biliary contents, activated pancreatic enzymes and secondary or deconjugated bile acids are markedly increased and they irritate the biliary mucosa. Mutagens are proven to form in the bile of PBM. In the epithelia of PBM, hyperplasia, metaplasia, and dysplasia are often found, and proliferative activity is increased; furthermore, K-ras gene mutation and overexpression of p53 protein are demonstrated. As for treatment of PBM, whether it is symptomatic or not, an operative procedure, is necessary, to prevent carcinogenic changes in the gallbladder and bile duct. Regardless of whether dilatation is present or not, total excision of the extrahepatic bile duct, along with gallbladder, is the treatment of choice, followed by hepaticojejunostomy or hepaticoduodenostomy.