S2187 Submucosal Injection Versus Non-Injection Technique in Endoscopic Papillectomy: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes

Introduction: The utility of submucosal injection (SI) in endoscopic papillectomy (EP) remains debated. This meta-analysis compares outcomes between SI and non-injection (NI) techniques. Methods: A systematic search of PubMed, Scopus, and Web of Science (through May 2025) identified studies comparing SI and NI in EP. Primary outcomes included technical success, en bloc resection, and complete (R0) resection. Secondary outcomes were recurrence/residual disease and adverse events (AEs). A random-effects model was used; heterogeneity was assessed via the I² statistic. SI: submucosal injection. NI: non-injection. Results: Forty-six studies (3 RCTs, 5 prospective, 38 retrospective) comprising 461 SI and 1,868 NI patients were included. The mean age was 61.6 years; 48.7% were woman. Lesion size averaged 17.3 mm (SI) vs 18.8 mm (NI), with mean follow-up of 30.2 months. Technical success was 93.5% (95% CI: 87.5–96.7; I² = 58.1) in SI vs 97.4% (95.6–98.5; I² = 63.8) in NI. En bloc resection was 84.7% (72.0–92.3; I² = 83.4) in SI and 88.5% (84.9–91.2; I² = 54.8) in NI; RCTs showed 91.7% (83.0–96.1; I² = 0) for NI. Complete (R0) resection was higher in SI (89.0%; 73.2–96.0; I² = 81.5) vs NI (72.2%; 64.4–79.0; I² = 87.4); in RCTs, NI had 83.0% (72.4–90.1; I² = 0). Recurrence/residual tumor rates were similar: 15.7% (10.8–22.4; I² = 45.5) in SI vs 15.4% (11.9–19.7; I² = 73.2) in NI. Mean time to recurrence was ∼14.2 months. Overall AEs were 32.2% (22.3–43.9; I² = 70.2) in SI vs 29.9% (23.0–37.9; I² = 87.3) in NI. Pancreatitis occurred in 10.5% (5.6–18.7; I² = 71.7) of SI cases, reduced to 7.8% (4.1–14.2; I² = 0) with stenting. In NI, pancreatitis was 12.3% (9.9–15.2; I² = 58.2), reduced to 10.9% (6.2–18.7; I² = 69.5) with stenting. Bleeding was higher in SI (22.7%; 14.5–33.8; I² = 78.1) vs NI (14.2%; 10.4–19.1; I² = 83.6). Perforation was 5.1% (3.3–7.7; I² = 0) in SI and 2.6% (1.9–3.6; I² = 0) in NI. Conclusion: While SI improves R0 resection rates, it does not significantly enhance en bloc resection, technical success, or recurrence rates. Moreover, SI is associated with increased bleeding and perforation risk. Pancreatitis rates are similar and can be reduced with prophylactic stenting. The NI technique offers comparable efficacy with a more favorable safety profile in selected patients. Further high-quality RCTs are warranted to confirm these findings and inform procedural strategy.