Reply:

Abstract

In our recent HEPATOLOGY article, we found that patients with biliary pancreatitis exhibit more and smaller gallbladder stones, better postprandial gallbladder emptying, and faster cholesterol crystallization than patients with symptomatic but uncomplicated gallbladder stones.1 These findings may explain in part why some gallstone patients experience pancreatitis, whereas other gallstone patients never suffer from this potentially lethal complication. We hypothesize that small gallbladder stones may migrate into the common bile duct more easily than large stones, especially in cases of preserved gallbladder emptying. Also, excess cholesterol crystals (possibly secondary to increased biliary mucin levels) could be involved: in a rat model for pancreatitis, we found that adding cholesterol crystals to hydrophobic bile salt–containing model biles infused into biliopancreatic duct markedly enhances severity of the induced pancreatitis.2 In contrast to the suggestion in the letter by Costi et al., we do not propose that “patients with asymptomatic gallstones and/or preserved motility of the gallbladder undergo prophylactic cholecystectomy.” Instead, we were careful to state that “potential benefit of prophylactic cholecystectomy in these patients remains to be elucidated.”1 Although ideally this question should be answered in a prospective randomized study, such studies will probably not be performed in the near future. In a yet unpublished study, we therefore developed a Markov model to investigate potential effects of prophylactic cholecystectomy versus “wait and see” strategy. With the aid of Monte Carlo simulations, we calculated mortality as well as number of life-years gained or lost for a 10-year period in characteristic patients with asymptomatic small (diameter < 5 mm) gallbladder stones (5,000 patients, 67% females; age 45 years). We found that prophylactic cholecystectomy may cost more life-years than treatment according to “wait and see” strategy, depending on overall pancreatitis incidence (assumed to be 0.05%, 0.1%, 0.15%, or 0.2%/year)3-5 and pancreatitis mortality (assumed to be 2.5%, 5%, 7.5%, or 10%).6-8 In 6 of 16 possible scenarios, mortality during 10 years' follow-up proved to be reduced, but only in 4 of 16 possible scenarios life-years were gained by prophylactic cholecystectomy, because surgical death occurs early, whereas gained lives occur later. Further data on incidence and subsequent mortality of pancreatitis (as well as other complications) in asymptomatic gallstone carriers are clearly needed, and further cost–benefit analyses with full-scale economic evaluations are required to determine total costs and potential benefits of prophylactic cholecystectomy versus “wait and see” strategy in the different scenarios. Niels G. Venneman*, Karel J. van Erpecum*, * Gastrointestinal Research Unit, Department of Gastroenterology and Surgery, University Medical Center Utrecht, The Netherlands.