Prevention and Intervention Strategies in Acute Pancreatitis

Acute pancreatitis is a common, costly, potentially lethal, and poorly understood disease, mostly caused by gallstones. In the past decade the incidence of acute pancreatitis in the Netherlands increased by 50% to over 3400 admissions in 2006, most likely due to an increase of gallstone disease. About 20% of patients will develop severe acute pancreatitis, a disease characterized by organ failure and/or pancreatic necrosis, resulting in a high mortality rate. Because the incidence of acute pancreatitis is increasing rapidly and it is estimated that about 80% of deaths are associated with infections, especially infected pancreatic necrosis, the main aim of this thesis was to develop and test (A) Prevention strategies; aimed at preventing acute pancreatitis and associated infections, and (B) Intervention strategies; aimed at improving outcome of intervention in patients with infected pancreatic necrosis. Most studies described in this thesis are performed by the centres participating in the Dutch Acute Pancreatitis Study Group (2002), including all Dutch university medical centres. Prevention Strategies Previous, small, retrospective studies had suggested that ursodeoxocholic acid was capable of preventing biliary pancreatitis in patients with symptomatic gallstone disease. We disproved this suggestion in a randomised, double-blind, placebo-controlled multicenter trial. Previous, small, placebo-controlled randomised trials had suggested a beneficial effect of probiotic prophylaxis in acute pancreatitis. We performed a randomised double-blind placebo-controlled trial on probiotic prophylaxis in 296 patients and found that in fact mortality doubled due to the use of probiotic prophylaxis. In a follow-up study we found that the negative effect of probiotics was related to intestinal small bowel mucosal damage but solely in patients with organ failure receiving probiotics. In a second follow-up study we found that infections complications occurred much earlier in the course of acute pancreatitis, already in the first days, than previously expected. New studies should therefore start prophylactic therapy earlier than is currently practiced. Intervention Strategies The overall mortality rate for infected pancreatic necrosis in 11 large hospitals in the Netherlands was found to be as high as 34%. The results of minimally invasive approaches seemed promising but their general applicability in patients with infected necrotizing pancreatitis was unknown. In a follow-up study we found that 84% of patients could have been treated via a minimally invasive approach. It had furthermore been suggested that delaying surgical intervention in infected pancreatic necrosis facilitates safer intervention. We confirmed this hypothesis in a systematic review and concluded that, whenever possible, necrosectomy should be postponed until 30 days after initial hospital admission so that the collection becomes encapsulated. The type of intervention in patients with infected peripancreatic collections containing depends on their content (fluid and/or necrosis) as depicted by CT scan. We performed the first interobserver study on the international Atlanta classification (1992) and found that five experienced radiologists agreed in only 4% of cases on the definition of the collection. It was concluded that the Atlanta classification should be revised, a process that is currently indeed underway.