Study on the Effect of Pancreaticobiliary Maljunction on the Gallbladder Epithelium

胰胆管合流异常是胰胆管系统的一种异常排列，是日本常见的先天性异常。胰胆管合流异常无胆管扩张是已知的发展为胆囊癌的一个较高的危险因素。我们成功地制作了一种无胆管扩张的胰胆管合流异常的实验模型。使用这个模型，我们研究了胰胆管合流异常的胆囊上皮细胞动力学的增殖细胞核抗原（PCNA）的抗体，没有胆管扩张的影响。免疫组化显示胆囊上皮细胞PCNA阳性细胞增多，提示无胆管扩张的胰胆管合流异常对胆囊上皮细胞有增殖作用，可能与胆囊癌的发生有关。在文献中没有关于调节这种增殖效应的尝试报道。由于转化生长因子-α（TGF α）是一种可使胃、结肠和肝脏的上皮细胞增殖的生理细胞因子，我们还通过化学方法研究了胰胆管连接异常患者胆囊上皮中TGF α的表达。结果显示，在胰胆管合流异常组中表达较高，而在对照组中表达较低。这一结果表明，TGF-α也是一种生理细胞因子在胆囊和TGF-α可能发挥重要作用的增殖胆囊上皮与胰胆管连接异常。

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.