Current ESGE guidelines recommend hot snare polypectomy for Sessile Serrated Lesions with Dysplasia (SSLD) based on theoretical benefits regarding malignant potential and resection depth. However, no randomized trials have specifically compared resection techniques for SSLD >10 mm. While recent meta-analyses demonstrate significant safety advantages of cold Endoscopic Mucosal Resection (EMR) for non-dysplastic serrated lesions, these studies excluded dysplastic lesions, leaving the applicability of cold techniques to SSLD undetermined. This study represents the first comparative analysis evaluating a novel Modified Underwater Submucosal Injection Cold Lesion Excision (MUSCLE) technique versus conventional hot EMR exclusively in patients with SSLD ≥10 mm.

We retrospectively identified consecutive patients with SSLD >10 mm treated at two Italian tertiary centers. Lesions removed by conventional hot EMR or by the MUSCLE technique, which combines underwater cold snare resection with prior submucosal lifting, were propensity score matched 1:1. Matching variables included lesion size (>2 cm vs. ≤2 cm), location (left vs. right colon), anatomical access difficulty, operator expertise (expert vs. non-expert), and Paris morphology (flat vs. sessile). The primary outcome was the recurrence rate at ≥1-year surveillance colonoscopy. Secondary outcomes included technical success and adverse events, specifically immediate/delayed bleeding, perforation, and post-polypectomy electrocoagulation syndrome (PECS).

From 190 pre-propensity lesions with ≥1-year follow-up, 172 eligible lesions remained after excluding 18 ESD cases. Propensity score matching yielded 102 analyzed lesions (51 matched pairs) with balanced characteristics (61% ≤ 2cm, 32% expert operators, 94% flat morphology, 86% right colon, 80% good access). Technical success was 100% in both groups. Recurrence occurred in 1/51 lesions (1.96%) in both groups at ≥1-year follow-up, with no significant difference (p= ns; 95% CI: -5.4% to 5.4%). The composite outcome of any adverse event showed a trend favoring MUSCLE (0% vs 9.80%, p=0.063).

The MUSCLE technique represents a novel hybrid approach integrating the safety advantages of non-thermal cold snare resection with the technical benefits of underwater mucosal buoyancy and enhanced snare capture, while preserving adequate resection depth through submucosal injection. In this first propensity score-matched analysis targeting SSLD >10 mm, MUSCLE achieved equivalent technical success and comparable one-year recurrence rates to conventional hot EMR, with a favorable trend toward improved safety. These findings provide the first specific clinical evidence challenging current ESGE guidelines that mandate thermal resection for this high-risk subtype, suggesting cold resection techniques may be a viable, safer alternative. Larger multicenter prospective trials are warranted to confirm these results.