Common Procedure Does Not Prevent Recurrent Pancreatitis, Trial Finds 

A multicenter clinical trial published in JAMA has found that a long-used endoscopic procedure does not prevent recurrent pancreatitis in adults with an anatomic anomaly, challenging decades of conventional wisdom. 

The study, conducted across 21 medical centers in the U.S. and Canada, tested whether endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy could reduce future episodes of acute pancreatitis among adults with recurrent attacks and a congenital duct defect known as pancreas divisum. 

The research was driven by a long-standing gap in evidence, said Rajesh Keswani, MD, associate professor of Medicine in the Division of Gastroenterology and Hepatology and a co-author of the study. 

“Pancreas divisum is a causative factor in a subset of patients with recurrent acute pancreatitis, a painful inflammatory condition of the pancreas,” Keswani said. “Essentially, in pancreas divisum, the pancreas juice drains predominantly through a small opening in the intestine called the minor papilla. While pancreas divisum occurs in 5-10 percent of people, only a small proportion of people develop pancreatic issues.” 

Although many clinicians have long believed that cutting the minor papilla could improve drainage and reduce inflammation, Keswani noted that the practice had never been tested in a rigorous randomized trial.  

“For patients with pancreas divisum and recurrent pancreatitis, an endoscopy procedure called an ERCP has been utilized to perform an internal incision of the minor papilla to ‘improve’ the drainage of the pancreas and presumably reduce pancreatitis episodes,” he said. “However, despite decades of performing this therapy, its efficacy had never been definitively studied.” 

In the clinical trial, investigators studied 148 adults with unexplained recurrent acute pancreatitis and pancreas divisum. Some received a real ERCP with minor papillotomy, while others underwent what’s called a sham procedure — a kind of medical placebo. In this case, study participants underwent an endoscopy, so the experience resembled the real treatment. 

After nearly three years of follow-up, 35 percent of patients who underwent ERCP developed another episode of acute pancreatitis, compared with 44 percent of those who received a sham procedure, a difference that was not statistically significant. 

 “In other words, the ERCP procedure to incise the minor papilla did not reduce pancreatitis episodes. There was also no specific subgroup that demonstrated a benefit of ERCP,” Keswani said. 

The procedure also carried risks: within 30 days, 15 percent of the ERCP group developed pancreatitis, compared with 8 percent in the placebo group. 

The findings challenge long-held assumptions within the field of gastroenterology and are expected to influence how specialists counsel and treat patients with pancreas divisum. 

“These results are surprising and challenge a lot of what has been traditionally taught and performed,” Keswani said. “First, it is important to understand what therapeutic options are available for these patients, who often suffer through repeated pancreatitis episodes. If endoscopy is not the answer, we have to pin our hopes on a pharmacologic option.” 

With no evidence of benefit — and some evidence of harm — the study suggests that clinicians should reconsider recommending ERCP with minor papillotomy solely to prevent recurrent pancreatitis in patients with pancreas divisum. The results highlight the need for safer, more effective alternatives, Keswani said. 

The study was supported by grants U34DK112673 and U01DK116743 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).