REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY Acute Pancreatitis: Bench to the Bedside

Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems. The severity of the disease varies widely from mild forms only affecting the pancreas to severe disease with multisystemic organ failure and death. In this review, a synopsis of our current understanding of the pathobiologic processes that underlie pancreatitis and its sequelae is provided; and a current approach to the management of patients with this disorder is reviewed. We conclude this review with suggestions for future directions for research to improve outcomes for patients who have acute pancreatitis. The major pathobiologic processes underlying acute pancreatitis are inflammation, edema, and necrosis of pancreatic tissue as well as inflammation and injury of extrapancreatic organs. The overall mortality in patients with acute pancreatitis is approximately 5%. 1 Mortality is higher in patients with necrotizing pancreatitis compared with those with interstitial pancreatitis in which there is little necrosis (approximately 17% vs 3%, respectively). Among patients with necrotizing pancreatitis, mortality is greater in patients with infected necrosis than in those with sterile necrosis (approximately 30% vs 12%, respectively). The prevalence of infected necrosis in patients with necrotizing pancreatitis now appears to be approximately 15%–20% compared with approximately 35% several years ago. Far more patients have interstitial pancreatitis than necrotizing pancreatitis (approximately 85% vs 15%, respectively). Organ failure occurs more commonly in patients with necrotizing pancreatitis compared with those with interstitial pancreatitis (approximately 50% vs 5%– 10%, respectively). In necrotizing pancreatitis, mortality is very low in the absence of organ failure (close to 0%); in the presence of single organ failure, mortality is generally less than 10%; with multisystem organ failure, mortality is in the range of 35%–50%. Approximately half of deaths in acute pancreatitis occur within the first 2 weeks of illness and are generally attributed to organ failure. The remainder of deaths occurs weeks to months after this interval, and death is generally related to organ failure associated with infected necrosis or complications of sterile necrosis. Although alcohol abuse and gallstone disease account for 70%– 80% of the cases of acute pancreatitis, the exact mechanisms by which these factors initiate acute pancreatitis are presently unknown. In addition, because of the rapid course of the disease and the relative inaccessibility of pancreatic tissue for examination during pancreatitis, investigations of the mechanisms underlying these pathobiologic processes have been hampered. Considering these obstacles, investigators have turned to animal models of acute pancreatitis to reveal the molecular steps initiating these pathobiologic responses to identify potential targets for therapeutic intervention. The premise underlying this approach is that, although the exact triggering mechanism(s) for acute pancreatitis caused by alcohol and gallstones in humans is not established, key steps in mediating the pathobiologic processes that define acute pancreatitis can be identified from animal models, and used to develop therapies that can be ultimately tested in human pancreatitis. In this article, we will first describe our current state of knowledge about the mechanisms of pancreatitis, which are largely based on studies in animal models, followed by a discussion of the clinical disorder and its management, especially related to issues that give rise to severe disease. Finally, in the last section, we will provide our perspective about future research directions needed to improve outcome in this group of patients.