Acute pancreatitis is among the most common gastrointestinal diagnoses for acute inpatient hospital admission, and its incidence is increasing worldwide because of increased rates of obesity and gallstones.1, 2 Gallstones are the most common cause of acute pancreatitis.3, 4 The initiating event is impaction of gallstone stones or sludge in the common bile duct and ampulla.5, 6 Patients with gallstone pancreatitis can develop cholangitis, organ failure, and other life-threatening complications.7, 8, 9 During endoscopic retrograde cholangiopancreatography (ERCP), retained gallstones are visualised, biliary sphincterotomy is done, and gallstones are extracted.
Research in context
Evidence before this study
Patients with gallstone pancreatitis frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy to remove obstructing gallstones with the intention to ameliorate the disease course. Before initiation of this trial, we searched PubMed, Embase, the Cochrane Library, and the NHS Economic Evaluation Database for studies published in English up to May 22, 2012, with the terms “ERCP” and “gallstone” and “pancreatitis”. Six trials fulfilled the inclusion criteria. Findings from this systematic review suggested that ERCP did not reduce mortality but did reduce complications in patients with gallstone pancreatitis at high risk for developing complications. However, these trials had substantial shortcomings, such as heterogeneous patient populations, ERCPs performed late after hospital admission, no routine sphincterotomy, no separate assessment of patients with cholestasis, and use of various endpoint definitions. More importantly, the pooled sample size of patients with predicted severe gallstone pancreatitis without cholangitis was too small to detect differences in endpoints such as major complications or mortality between urgent ERCP and conservative treatment. As widely agreed, it therefore remains unclear whether ERCP truly improves outcome in these patients.
Added value of this study
This trial answers the question of whether urgent ERCP with biliary sphincterotomy should be done in patients with predicted severe acute gallstone pancreatitis, with or without cholestasis, but without cholangitis. Our findings suggest that urgent ERCP with biliary sphincterotomy did not reduce the composite endpoint of major complications or mortality compared with conservative treatment. Although cholangitis occurred more often in patients treated conservatively, this had no negative impact on overall outcome.
Implications of all the available evidence
Urgent ERCP with biliary sphincterotomy should not be done routinely in patients with predicted severe acute gallstone pancreatitis and is indicated only in patients with concomitant cholangitis. With this strategy, around two-thirds of patients are spared an invasive procedure from which they gain no benefit but could have procedure-associated complications.
Guidelines recommend urgent ERCP in patients with gallstone pancreatitis with concomitant cholangitis and suggest that ERCP might be beneficial in patients with cholestasis but without cholangitis.8, 10, 11, 12 In patients with gallstone pancreatitis without cholangitis and without significant cholestasis, it is unclear whether urgent ERCP is beneficial. Nevertheless, observational studies have shown that in as much as half of such patients an ERCP is performed.13, 14 Unfortunately, previous randomised trials on this subject have substantial shortcomings. First, patients with concomitant cholangitis, patients with a predicted mild disease course, and even patients with a non-gallstone aetiology were included.15, 16, 17, 18, 19 Second, in most trials ERCP was done up to 3 days after hospital admission. Presumably, for biliary decompression to be effective in preventing complications, ERCP needs to be done as early as possible after onset of the disease—ie, after onset of symptoms.15, 17, 20 Third, in previous trials only a small proportion of patients had a biliary sphincterotomy.16, 17, 19, 21 Because microlithiasis can easily be missed on cholangiogram during ERCP, and as small gallstones in particular are known to cause pancreatitis, this limitation is particularly relevant.22, 23 Performing sphincterotomy routinely during ERCP is also supported by a previous study showing that sphincterotomy reduced complications irrespective of the presence of gallstones on cholangiogram.13 Furthermore, biliary sphincterotomy decompresses the biliary tract, which potentially ameliorates the disease course.5, 24, 25, 26, 27 In return, ERCP with sphincterotomy is an invasive procedure that is associated with complications in up to 10% of patients.28, 29 Finally, the study populations of the individual trials and of subsequent meta-analyses were too small to detect an effect of ERCP in the group of patients with gallstone pancreatitis with a predicted severe disease course. It therefore remains unclear whether urgent ERCP with biliary sphincterotomy is beneficial in patients with predicted severe acute gallstone pancreatitis, with and without cholestasis, but without cholangitis.
We did a multicentre randomised controlled trial to investigate whether urgent ERCP with sphincterotomy is superior to conservative treatment in patients with predicted severe acute gallstone pancreatitis.
