The key event of acute pancreatitis: Pancreatic duct obstruction and bile reflux, not a single one can be omitted

Summary

Acute pancreatitis (AP) is an acute inflammatory disease of the pancreas. Severe acute pancreatitis (SAP) is the serious forms of AP with high mortality rate. However, the frequency of SAP remains stable over time. Biliary calculi and alcohol abuse are the most common causes of AP. Other causes such as iatrogenic factors, sphincter of Oddi dysfunction (SOD) and eating disorders also cannot be omitted. Blockage of duodenal papilla or ampulla of Vater is common characteristics of AP. Once the blockage appears, the occurrence of pancreatic duct obstruction and bile reflux is inevitable. Obstruction of the pancreatic duct leads to increased intraductal pressure, which results in damage to the integrity of the duct system to a certain extent. Bile reflux can activate trypsin and once trypsin is activated, it activates a variety of injurious pancreatic digestive enzymes with subsequent release of a series of inflammatory mediators. We hypothesized that pancreatic duct obstruction and bile reflux are the key event of AP induced by a variety of other upstream causes. Pancreatic duct obstruction and bile reflux, not a single one can be omitted. Whenever pancreatic duct obstruction and bile reflux are triggered simultaneously, activated digestive enzymes and inflammatory mediators can infiltrate into the parenchyma of the pancreas through impaired pancreatic barrier and induce AP. Blocking the key event of AP is of a great interest with potential therapeutic implications. Endoscopic sphincterotomy (EST) and nasobiliary drainage, which target the cause of AP, may prevent the transformation from AP to SAP and this may be adopted as an essential treatment strategy.

Introduction

AP is an acute inflammatory process of the pancreas, which frequently involves peripancreatic tissues and at times other systemic organs [1], [2]. In 80% of AP patients, the condition is relatively mild, only affects the pancreas and could recover without causing serious morbidity, but in up to 20%, AP is a severe disease with multisystemic organ failure and death [3], [4]. Although the upstream causes of AP are known, the incidence of AP increased in the past two decades [5] and the proportion of SAP remained stable over time in many countries [6], [7], [8]. In spite of controversy, most investigators believe that AP is caused by the unregulated activation of trypsin within pancreatic acinar cells [5], therefore, circumstances that related to the activation are suggested as key events which leads to AP.

To treat AP effectively and to prevent the transformation from AP to SAP, it is necessary to clarify the key event of AP. Directly aiming at the key event may bring about a therapeutic revolution.