Idiopathic acute pancreatitis accounts for approximately 18% of global acute pancreatitis cases, and expert consensus suggests that genetic testing and selective surgical intervention can meaningfully reduce recurrence risk in carefully evaluated patients, according to a Beyond the Guidelines Grand Rounds discussion published in Annals of Internal Medicine.
The article, by Zahir Kanjee, MD, MPH, and colleagues from Beth Israel Deaconess Medical Center, Boston, and Mayo Clinic, centers on a 29-year-old woman hospitalized with a first episode of acute pancreatitis after a comprehensive negative evaluation, including laboratory testing, transabdominal ultrasound, MRCP, and endoscopic ultrasound (EUS). Her case framed a broader evidence-based debate on three management questions: the role of genetic testing, empiric cholecystectomy, and endoscopic retrograde cholangiopancreatography (ERCP) with or without sphincterotomy
Genetic Testing
Multiple pancreatitis-associated genes—including PRSS1, CFTR, SPINK1, and CTRC—have been implicated in idiopathic acute pancreatitis (IAP) and idiopathic recurrent acute pancreatitis (IRAP). A cited systematic review and meta-analysis found at least one pathogenic CFTR variant in 16% of patients with IRAP. Observational data suggest that among younger patients (those under age 35 years) with IAP or IRAP, more than 50% may harbor pathogenic variants in one of the four major genes when multigene panels are used. The panelists emphasized that mutation prevalence varies widely by population and testing methodology.
Current guidelines diverge. The 2024 American College of Gastroenterology guidelines recommend genetic testing primarily for patients with IAP and a family history of pancreatic disease, whereas the 2025 International Association of Pancreatology guidelines support referral for genetic counseling and testing in younger patients with IRAP after negative EUS and MRCP. Potential benefits include etiologic clarification, prognostic stratification, and avoidance of unnecessary invasive procedures; limitations include incomplete gene coverage, cost, insurance barriers, and psychosocial implications.
Cholecystectomy
Evidence for empiric cholecystectomy in IAP is mixed. A randomized multicenter trial reported fewer recurrences after laparoscopic cholecystectomy, with a number needed to treat of five to prevent one recurrence. A meta-analysis found numerically lower recurrence after cholecystectomy compared with conservative management even after negative EUS and MRCP (11% vs 39%), though this difference did not reach statistical significance because of small sample sizes.
According to the article, subgroup analyses suggest benefit is greatest when occult biliary disease is identified. In a systematic review of patients with biliary pathology detected by EUS, recurrence after cholecystectomy was 2% over approximately 20 months. By contrast, recurrence rates of 15% to 23% have been reported when cholecystectomy is performed empirically after a negative advanced work-up. Major complications of laparoscopic cholecystectomy occur in fewer than 2% of cases.
ERCP and Sphincterotomy
Both article discussants agreed that routine ERCP is not indicated for IAP. A recent systematic review reported post-ERCP pancreatitis in 6.5% of first-time procedures and an ERCP-attributable mortality rate of 0.2%. In IRAP cohorts, recurrence rates after ERCP with sphincterotomy have approached 30%, with serious adverse events reported in nearly one-third of patients in some studies. Potential benefit may be limited to highly selected subgroups, such as patients with specific genetic mutations or pancreas divisum plus objective ductal obstruction.
The authors reported having no relevant disclosures.
Source: Annals of Internal Medicine
