Pancreaticobiliary Maljunction‐Associated Pancreatitis: An Experimental Study on the Activation of Pancreatic Phospholipase A₂

Abstract

Congenital dilatation of the bile duct (CDBD), or choledochalcyst, is often complicated by recurrent pancreatitis. Reflux of pancreatic juice into the bile duct through pancreaticobiliary maljunction (PBM), an anomaly commonly associated with CDBD, and ensuing activation of pancreatic enzymes could be involved in the pathophysiologic mechanism of recurrent pancreatitis. A study was undertaken to follow the time course of the activity of phospholipase A2 (PLA2) in animal models of PBM. The assay procedures for PLA2 were evaluated, as were the conditions for separating the active enzyme from its inactive proenzyme (pro-PLA2) by immunoblotting. A rat model was designed according to Block's method with some modifications. The kinetics of prophospholipase A2 (proPLA2) activation in bile was examined by measuring PLA2 activity and by immunoblotting using anti-rat pancreatic enzyme antibody after separating PLA2 from its zymogen under nonreducing conditions. Experimental animals were divided into three groups: group 1 (PBM group) in which bile and pancreatic juice were mixed with occlusion of the papilla; group 2, in which the papilla and hepatic hillus were occluded without mixing the two juices; and group 3, in which simple laparotomy was done. In group 1 animals, pro-PLA2 in bile was activated to its active form. In group 2 animals, where proPLA2 was predominant, there was only slight elevation of PLA2 activity in bile. In group 1 an immunohistologic study demonstrated localization of PLA2 around necrotic foci in the pancreatic parenchyma. These results suggest the involvement of activated PLA2 in the pathogenesis of choledochal cystassociated pancreatitis.

Recurrent acute pancreatitis caused by malrotation of the intestine and effective treatment with laparoscopic Ladd’s procedure

“…The etiology of pancreatitis in children is varied, and the recurrent form is mostly associated with congenital etiology, such as dilatation of the bile duct combined with pancreaticobiliary maljunction, pancreas divisum, intrapancreatic duplication of the intestine, and so on [1][2][3][4][5]. However, malrotation of the intestine has been reported as a very rare cause of recurrent pancreatitis [6].…”

Bile from a patient with anomalous pancreaticobiliary ductal union promotes the proliferation of human cholangiocarcinoma cellsviaCOX-2 pathway

“…A frequent association of biliary tract carcinoma and APBDU is well recognized [12][13][14][15][16][17][18][19] , especially in the undilated type APBDU [20,21] . Mori [7] had reported that among 698 patients subjected to endoscopic retrograde cholangiopancreatography, APBDU was found in 6 patients (0.9 %).…”

Management Dilemmas With Choledochal Cysts

“…This may be due to the activation of pancreatic enzymes by bile reflux, 31 in association with an anomalous pancreaticobiliary union. Certainly, the anomalous ductal union seems to predispose to pancreatitis, as in one study, 57% of patients with choledochal cysts had anomalous ductal union demonstrated by ERCP.…”

“…The high incidence of anomalous pancreaticobiliary union cannot be ignored, but may just reflect an association with distal obstruction. Alternatively, pancreatic juice reflux into the common bile duct may be activated by bile, 31 and activated enzymes subsequently weaken the common bile duct wall, exacerbating the dilatation.…”