Matsumoto Yoshiro, Fujii Hideki, Itakura Jun, Matsuda Masanori, Nobukawa Bunsei, Suda Kohichi
First Department of Surgery, Faculty of Medicine, Yamanashi Medical University, Tamaho, Yamanashi 409-3898, Japan.
J Hepatobiliary Pancreat Surg. 2002;9(1):45-54. doi: 10.1007/s005340200004.
The purpose of this review is to evaluate our current knowledge of the embryologic etiology of pancreaticobiliary maljunction (PBM), its diagnosis, clinical aspects, and treatment, and to clarify the mechanisms of PBM involvement in carcinogenesis. Although the embryologic etiology of PBM still awaits clarification, an arrest of the migration of the common duct of the biliary and pancreatic ducts inwards in the duodenal wall has hitherto been speculated to result in a long common channel in PBM. However, we propose the hypothesis that the etiology of PBM is caused by a disturbance in the embryonic connections (misarrangement) of the choledochopancreatic duct system in the extremely early embryo. That is, PBM is an anomaly caused by a misarrangement whereby the terminal bile duct joins with a branch of the ventral pancreatic duct system, including the main pancreatic duct. PBM is frequently associated with congenital bile duct cyst (CCBD). However, these two anomalies are thought to have different embryonic etiologies. The diagnostic criteria for PBM are the radiological and anatomical detection of the extramural location of the junction of the pancreatic and biliary ducts in the duodenal wall. However, in PBM patients with a short common duct (less than 1 cm in length), detection of the extramural location is difficult. The clinical features of PBM are intermittent abdominal pain, with or without elevation of pancreatic enzyme levels; and obstructive jaundice, with or without acute pancreatitis, while the clinical features of PBM patients with CCBD are primary bile duct stone and acute cholangitis. The optimum approach for the treatment of PBM is the prevention of the reciprocal reflux of bile and pancreatic juice in the pancreas and the bile duct system. To achieve these aims, the surgical approach is most effective, and complete biliary diversion procedures with bile duct resection (for example, choledochoduodenostomy or choledochojejunostomy of the Roux-en-Y type) are most useful. Recently, it has been recognized that the development of biliary ductal carcinoma is associated with PBM. That is, the development of gallbladder cancer occurs frequently in PBM patients without CCBD, and bile duct cancer originating from the cyst wall also occurs in PBM patients with CCBD. It is speculated that the pathogenesis of the bile duct or gallbladder cancer in PBM patients involves the reciprocal reflux of bile and pancreatic juice. Investigations of epithelial cell proliferation in the gallbladder of PBM patients, and of K- ras mutations and p53 suppressor gene mutations, loss of heterozygosity of p53, and overexpression of the p53 gene product in gallbladder cancer and noncancerous lesions in PBM patients have been carried out in various laboratories around the world. The results support the conclusion that PBM is a high risk factor for the development of bile duct carcinoma.
本综述的目的是评估我们目前对胰胆管合流异常（PBM）的胚胎学病因、诊断、临床特征及治疗的认识，并阐明PBM参与致癌作用的机制。尽管PBM的胚胎学病因仍有待阐明，但迄今推测胆管和胰管的共同管道向十二指肠壁内迁移受阻会导致PBM出现长共同通道。然而，我们提出一个假说，即PBM的病因是极早期胚胎中胆总管胰腺管系统的胚胎连接紊乱（排列错误）。也就是说，PBM是一种由排列错误导致的异常，即终末胆管与包括主胰管在内的腹侧胰管系统的一个分支相连。PBM常与先天性胆管囊肿（CCBD）相关。然而，这两种异常被认为具有不同的胚胎学病因。PBM的诊断标准是通过影像学和解剖学检测十二指肠壁内胰胆管交界处的壁外位置。然而，对于共同管道较短（长度小于1厘米）的PBM患者，检测壁外位置较为困难。PBM的临床特征为间歇性腹痛，伴或不伴胰酶水平升高；以及梗阻性黄疸，伴或不伴急性胰腺炎，而合并CCBD的PBM患者的临床特征为原发性胆管结石和急性胆管炎。治疗PBM的最佳方法是防止胆汁和胰液在胰腺和胆管系统中相互反流。为实现这些目标，手术方法最为有效，而胆管切除的完全胆管转流手术（例如，Roux-en-Y型胆总管十二指肠吻合术或胆总管空肠吻合术）最为有用。最近，人们认识到胆管癌的发生与PBM有关。也就是说，胆囊癌在无CCBD的PBM患者中频繁发生，起源于囊肿壁的胆管癌也在合并CCBD的PBM患者中出现。据推测，PBM患者胆管或胆囊癌的发病机制涉及胆汁和胰液的相互反流。世界各地的多个实验室对PBM患者胆囊中的上皮细胞增殖、K-ras突变和p53抑癌基因突变、p53杂合性缺失以及胆囊癌和PBM患者非癌性病变中p53基因产物的过表达进行了研究。结果支持PBM是胆管癌发生的高危因素这一结论。
