Primary Needle-Knife Fistulotomy Reduces Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

BACKGROUND AND AIMS

Selective biliary cannulation is one of the most crucial steps in endoscopic retrograde cholangiopancreatography (ERCP), and the standard transpapillary cannulation (STC) technique carries a risk of post-ERCP pancreatitis (PEP). Primary needle-knife fistulotomy (PNF) has been recently shown as a safer alternative technique to reduce PEP by avoiding papillary trauma to the pancreatic orifice. A prior meta-analysis suggested a trend toward lower PEP incidence with PNF without a significant difference in overall cannulation success. This systematic review and meta-analysis, including only randomized controlled trials, incorporates recent data to show the efficacy and safety of PNF compared with STC.

METHODS

A systematic search of PubMed, Embase, Scopus, and the Cochrane Library identified randomized controlled trials comparing PNF with STC for ERCP through March 2025. Data were analyzed using Review Manager 5.4. Pooled risk ratios (RRs) with 95% CIs were calculated using the Mantel-Haenszel test. Fixed- or random-effects models were used based on heterogeneity (I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using the Cochrane risk of bias tool 2.0. This review is registered with the International Prospective Register of Systematic Reviews (CRD420251051410).

RESULTS

PNF was associated with a significantly lower risk of PEP compared with standard cannulation (RR, 0.30; 95% CI, 0.14-0.63; absolute risk difference, 4.5%; 95% CI, 2.0%-7.0%; number needed to treat = 23). This corresponded to a 70% relative risk reduction in pancreatitis with PNF as the initial technique and minimal I² (I² = 10%). Biliary cannulation success rates were comparable (risk difference, 0.07; 95% CI, −0.01 to 0.15; P = 0.09) with substantial I² (I² = 77%). Rates of procedure-related complications, such as cholangitis, bleeding, and perforation, were not significantly different (RR, 1.01; 95% CI, 0.41-2.51; P = 0.98).

CONCLUSION

This meta-analysis provides robust evidence that PNF significantly reduces the risk of PEP compared with standard cannulation without increasing the risk of other adverse events.