Study on the Effect of Pancreaticobiliary Maljunction on the Gallbladder Epithelium

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Pancreaticobiliary maljunction, an anomalous arrangement of the pancreaticobiliary ductal system, is a congenital anomaly, common in Japanese. Pancreaticobiliary maljunction without bile duct dilatation is known to be a higher risk factor of developing carcinoma of the gallbladder. We have succeeded in making an experimental model of pancreaticobiliary maljunction without bile duct dilatation. Using this model, we studied the effect of pancreaticobiliary maljunction without bile duct dilatation on cell kinetics of the gallbladder epithelium using an antibody to the proliferating cell nuclear antigen (PCNA). Increased PCNA positive cells were demonstrated in the gallbladder epithelium immunohistochemically, revealing that pancreaticobiliary maljunction without bile duct dilatation has a proliferative effect on the gallbladder epithelium, which may be related to carcinogenesis. No attempt has been reported in literature as to the regulation of this proliferative effect. Since transforming growth factor-alpha (TGFalpha) is a physiological cytokine that may proliferate epithelial cells of stomach, colon, and liver, expression of TGFalpha was also studied in the gallbladder epithelium of patients with pancreaticobiliary maljunction immunohistochemically by us. The result showed higher expression in pancreaticobiliary maljunction as contrasted with weak expression in controls. This result suggests that TGFalpha is also a physiological cytokine in the gallbladder and that TGFalpha may play an important role in proliferation of the gallbladder epithelium with pancreaticobiliary maljunction.