Endoscopic submucosal dissection (ESD) has become a standard therapy for early gastric cancer. The type of submucosal injection solution used during gastric ESD varies among endoscopists. Using an epinephrine-added solution may facilitate the procedure by inducing vasoconstriction, thus minimizing intra-operative hemorrhage and allowing a clearer dissection plane. The efficacy of epinephrine-added solution was previously reported in a single-center retrospective study, demonstrating a reduction in procedure time with the addition of epinephrine. In this prospective double-blinded international randomized study, we aim to investigate whether using epinephrine-added solution, could significantly reduce procedure time and the number of intra-operative bleeding episodes.
This trial was conducted in 12 institutions across four countries. Adult patients with biopsy-confirmed gastric mucosal neoplasia undergoing ESD would be recruited. Patients with multiple or anastomotic lesions, on dual antiplatelet agents, warfarin, and other direct oral anticoagulants would be excluded. They would be randomized to the epinephrine group which is 0.2 ml 1:1000 epinephrine diluted into each 20 ml of the original injection solution mixture, and the control group which no epinephrine would be added. Randomization was stratified with lesion location (upper/middle vs lower), size (≤ 2cm vs > 2cm), and institution. The primary outcome was procedure time defined from the beginning of mucosal incision to the completion of resection. Secondary outcomes include intra-operative hemorrhage requiring the use of hemostatic forceps, peri-procedure blood pressure, pulse, and post-procedure adverse events. Patients, endoscopists, and assessors were blinded to the treatment allocation.
From March 2020 to January 2023, 800 patients were recruited with 774 included in the final intention-to-treat analysis. Three hundred and eighty-six (49.9%) and 388 (50.1%) patients were randomized to the epinephrine and control groups respectively. One hundred thirty-three (17.2%), 286 (37.0%), and 355 (45.9%) of the lesions were located in the upper, middle, and lower part of the stomach respectively, and the majority (87.3%) of the lesions were ≤ 2cm. The procedure time was significantly shorter with the use of epinephrine-added solution during gastric ESD (Mean duration 59.96 ±46.21 vs 68.06 ±45.37 min, adjusted mean difference -6.977 min, [-12.756, -1.198], p=0.018). The number of intra-operative bleeding episodes requiring the use of hemostatic forceps was also significantly lower in the epinephrine group (Mean count 1.76 vs 3.02, adjusted OR 0.59 [0.54-0.65], p<0.001). No significant difference was identified in post-procedural adverse events between the two groups.
The epinephrine-added solution significantly shortens the procedure time and reduces intraoperative bleeding events during gastric ESD.

Table. Endoscopic lesion characteristics and procedural main results

James Weiquan Li

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