Third-space endoscopy is the standard of care for neoplastic and motility disorders; however, it is technically challenging because of the high risk of intraprocedural bleeding. Such a risk may be reduced by prophylactic coagulation of the submucosal vessels, but it requires instrument exchange. A new approach involves pre-sealing the submucosal vessels using standard electrocautery settings under brief saline immersion using the same knife. The aim of this randomized trial was to further assess the efficacy of underwater pre-sealing in the prevention of intraprocedural bleeding and the overall efficiency of third-space endoscopy.

Patients undergoing third space procedures (ESD or POEM) were randomized to receive either targeted saline-immersion pre-sealing (study group) or conventional coagulation (CO₂ insufflation, control group) for prophylactic management of vessels ≥1.2 mm. Dissection settings were identical (HybridKnife, SWIFT COAG mode). Rate of intraprocedural bleeding requiring retreatment for vessels ≥1.2 mm was the main outcome. Both per-patient and per-vessel analyses were also performed. The use of an adjunctive device and coagulation time were also assessed. 

Seventy patients (37 immersion, 33 control) with 864 ≥1.2 mm vessels were included. Saline-immersion pre-sealing significantly reduced bleeding rates both at per patient (32.4% vs 75.8%, RR 0.43, 95% CI 0.26-0.71; NNT 2.3; p=0.01) and at per vessel analysis (6.3% vs 29.9%, RR 0.21; 95% CI 0.14-0.31; NNT 4.2; p<0.01). The use of coagulation forceps for bleeding treatment also decreased (0% vs 24.2% and 0% vs 8.3%; p<0.01). A significant reduction in coagulation time was reported in the saline-immersion group (22.7±26.4 seconds vs 29.6±49.8 seconds; p<0.01). 

A substantial reduction in the risk of intraprocedural bleeding was achieved by saline-immersion pre-sealing in per-patient and per-vessel analyses, prompting its implementation in clinical practice.