Study on the Effect of Pancreaticobiliary Maljunction on the Gallbladder Epithelium

胰胆管畸形是一种胰胆管系统的异常排列，是一种先天性异常，在日本很常见。无胆管扩张的胰胆管畸形是发生胆囊癌的高危因素。我们成功地制作了胰胆管畸形无胆管扩张的实验模型。利用该模型，我们利用增殖细胞核抗原（PCNA）抗体研究了无胆管扩张的胰胆管畸形对胆囊上皮细胞动力学的影响。免疫组织化学显示胆囊上皮内PCNA阳性细胞增多，提示胆管不扩张的胰胆管畸形对胆囊上皮有增殖作用，可能与癌变有关。文献中没有关于调节这种增殖效应的报道。由于转化生长因子- α (TGFalpha)是一种可使胃、结肠和肝脏上皮细胞增殖的生理性细胞因子，我们也通过免疫组织化学方法研究了TGFalpha在胰胆管异常患者胆囊上皮细胞中的表达。结果显示胰胆管异常区表达较高，而对照组表达较弱。该结果提示TGFalpha也是胆囊的一种生理性细胞因子，TGFalpha可能在胰胆管异常的胆囊上皮增生中起重要作用。

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.