Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study

Abstract

ObjectiveRoutine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings.DesignA multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013–2017) applying the same study design.ResultsOverall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17–23) after hospital presentation and at a median of 29 hours (IQR 23–41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92).ConclusionIn patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group.Trial registration numberISRCTN15545919.

Performance of European and American Societies of Gastrointestinal Endoscopy Guidelines for Prediction of Choledocholithiasis in Patients with Acute Biliary Pancreatitis

“…To the contrary, ERCP may be associated with significant procedurerelated complications [42]. Here it should also be acknowledged that our approach with early EUS might not have always been justified since the EUS-guided ERCP approach, even in predicted severe pancreatitis, did not reduce major complications or mortality compared to the conservative strategy in APEC trials [37,38]. This might be even more relevant in predicted mild pancreatitis.…”

“…The APEC trials failed to demonstrate a difference for the primary outcome, which was a composite of mortality or major complication occurring within 6 months of randomization. The only component of the primary outcome with a difference between groups was cholangitis, which was less common in the urgent ERCP group than in the conservative treatment group (2% versus 10%) [37,38]. The findings of the APEC studies, in conjunction with prior work, emphasize that expecting ERCP to stop or reverse the pathophysiological mechanisms resulting in systemic and local complications in acute pancreatitis is overly optimistic.…”

“…However, it should be noted that we did not address the timing of ERCP in our cohort. This is relevant since early ERCP with sphincterotomy did not change the outcome of patients with predicted severe pancreatitis and nor did EUS-guided ERCP [37,38].…”

Recent Treatment Strategies for Acute Pancreatitis

“…In a systemic review of eight RCTs, early ERCP in patients without cholangitis did not reduce the risk of overall pancreatic complications, organ failure or death [59]. Especially among patients with predicted severe acute biliary pancreatitis but without cholangitis, the results of recent APEC and APEC-2 trials showed that urgent ERCP, even when guided by EUS to select patients with biliary stones and sludges in the APEC-2 trial, failed to significantly reduce major complications or mortality compared to conservative treatment [69,70]. As a result, there has been a growing inclination towards a more conservative strategy, reserving ERCP for cases where there is a clear indication, such as the presence of cholangitis or persistent biliary obstruction.…”

Gallstones: Prevention, Diagnosis, and Treatment

“…in a historical control group [67]. If ES has been performed because of biliary pancreatitis, it very likely prevents recurrent biliary pancreatitis or at least significantly reduces the risk of pancreatitis, hence cholecystectomy after ES serves to prevent other complications caused by the gallbladder stones (e.g., acute cholecystitis).…”