Dye-free versus dye-containing submucosal injection solutions in ESD for colorectal LST: a multi-center retrospective...

Although various submucosal injection solutions are used in endoscopic submucosal dissection (ESD), whether they should routinely contain a staining agent remains debated. This study aimed to compare the efficacy and safety of dye-free submucosal injection solutions (DFSIs) versus dye-containing submucosal injection solution (DCSIs) for colorectal laterally spreading tumors (LSTs).

This retrospective study included 526 patients with colorectal LSTs who underwent ESD between January 2021 and December 2025. Patients were divided into two groups based on the injection solution used: DFSIs (n = 138) and DCSIs (n = 388). The primary safety endpoint was severe intraoperative bleeding. Primary efficacy endpoints included total procedure time, mucosal dissection time, and submucosal dissection speed. Subgroup analyses were performed according to tumor characteristics and technical factors.

Baseline characteristics were comparable between groups. While R0 resection, perforation, and postoperative complication rates were similar (all P > 0.05), the DFSIs group was associated with a significantly lower rate of severe intraoperative bleeding (0.0 vs. 3.9%, P = 0.015). Sensitivity analysis using Firth's penalized logistic regression confirmed a reduced odds of severe bleeding associated with DFSIs (odds ratio 0.096, 95% CI 0.002-0.960, P = 0.026). Subgroup analyses revealed that DFSIs were associated with a statistically significant reduction in total procedure time for lesions ≥ 3.5 cm (P = 0.005), left colon lesions (P = 0.007), fibrotic lesions (P = 0.040), and when traction (P = 0.009) or pocket-creation methods (P = 0.024) were used. Mucosal dissection time was also shorter for lesions ≥ 3.5 cm (P = 0.001), left colon lesions (P = 0.008), fibrotic lesions (P = 0.027), and with traction method (P = 0.036).

DFSIs are safe and effective for colorectal LST ESD. Despite comparable overall outcomes, exploratory subgroup analyses suggested potential advantages of DFSIs in complex cases, including shorter procedure times for larger or fibrotic lesions.