In patients with unexplained acute recurrent pancreatitis who have pancreas divisum, the widely used procedure endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy does not reduce the risk for more episodes of acute pancreatitis or protect against longer-term consequences, a new randomized, sham-controlled study concludes. The findings run contrary to long-held beliefs that have been based mostly on observational data.

The double-blind randomized clinical Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) trial, conducted in 21 centers in the US and Canada, included 148 adults who had the congenital variant pancreas divisum and had experienced two or more episodes of acute pancreatitis. Participants were randomly assigned in a 1:1 ratio either to ERCP with minor papillotomy or to sham ERCP and were followed for 34 months. Findings of the trial, led by Gregory A. Coté, MD, MS, Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, were published in JAMA.

Lack of Benefit for ERCP With Minor Papillotomy

The primary outcome was development of acute pancreatitis more than 30 days after randomization. Of the 75 participants in the ERCP with minor papillotomy group, 26 (34.7%) developed acute pancreatitis compared with 32 of 73 participants (43.8%) in the sham ERCP group (adjusted hazard ratio, 0.83; 95% CI, 0.49-1.41). The incidence rate for acute recurrent pancreatitis frequency was 0.25 (95% CI, 0.18-0.34) in the ERCP group vs 0.30 (95% CI, 0.23-0.41) in the sham ERCP group.

There were no between-group differences in frequency and incidence of chronic calcific pancreatitis (4.0% in the ERCP group vs 2.7% in the sham ERCP group; risk difference [RD], 0.01; 95% CI, -0.05 to 0.07). Additionally, there was no difference in the groups regarding diabetes incidence (15.8% vs 12.8%; RD, 0.03; 95% CI, -0.13 to 0.19) and exocrine pancreatic dysfunction (7.7% vs 17.2%; RD, -0.10; 95% CI, -0.27 to 0.08).

Randomized, Sham-Controlled Study a First

Whether pancreas divisum is connected to recurrent acute pancreatitis has long been debated, Vivek Kaul, MD, professor of medicine, Division of Gastroenterology & Hepatology, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News.

“The vast majority of patients with pancreas divisum have no issues,” he said. Additionally, he said, results have been very mixed in clinical practice and in previously described experiences when ERCP has been performed in patients with both pancreas divisum and recurrent pancreatitis.

“With the SHARP trial, it was the first time that we were able to study the role of ERCP prospectively in a randomized, sham-controlled format study in this disease state and in this patient population,” Kaul said.

‘No Longer Can it Be an Automatic Response’

These data confirm a concern that ERCP may not have been that helpful for routine practice in this patient population, Kaul said. “It should give all our colleagues some pause with the routine application of ERCP with pancreas divisum. No longer can it be an automatic response.” He noted that ERCP “can actually do more harm than good when not indicated.”

It’s too early to know what practice-changing impact the study has or will have, he said. Limitations included the relatively small number of patients that resulted when the study closed early with lack of funding. He pointed out that the study also focuses on a relatively well-selected narrow subset of patients, and “there may be other populations with pancreas divisum that may still benefit from ERCP,” he said, adding, “Whether some patients may still potentially benefit from this procedure, that assessment should be done at expert centers by people who are experienced in ERCP and pancreatitis care and for very focused indications.”

The findings of this study should also encourage exploration into what else is causing the recurrent episodes of pancreatitis in this population, Kaul said, “whether they are genetic reasons, metabolic reasons, environmental reasons, or other reasons we have not found yet.”

Results May Help Avoid Costly and Invasive Interventions

“This analysis leads the field toward more evidence-based endoscopic care,” editorialists Daryl Ramai, MD, MPH, with the Division of Gastroenterology, Hepatology and Nutrition at the University of Utah School of Medicine in Salt Lake City, and V. Raman Muthusamy, MD, MAS, with the Division of Digestive Diseases at the University of California, Los Angeles, wrote in an accompanying editorial. “For patients with acute recurrent pancreatitis and pancreas divisum, the absence of benefit from minor papillotomy allows them to avoid costly and invasive interventions.”

The SHARP trial shows the danger in assuming anatomical variants cause a condition when some people with the variant have no symptoms. Gallbladder surgery is not recommended universally for people with incidental gallstones, they noted as an example.

For practicing endoscopists, Ramai and Muthusamy wrote, “the message is clear: The finding of pancreas divisum in patients with unexplained recurrent pancreatitis should not, by itself, justify ERCP with minor papillotomy. Instead, conservative management and investigation for alternative causes is likely a safer and more cost-effective approach.”

Coté declared having no relevant financial relationships. Several co-authors reported receiving support from multiple pharmaceutical companies. Muthusamy reported receiving personal fees from Boston Scientific, Medtronic, Castle Biosciences, and PENTAX Medical; serving on an advisory board for Merit Medical; and being a shareholder in CapsoVision. Ramai reported having no financial disclosures. Kaul reported being a consultant for Cook Medical. 

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape.