Introduction

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 different endoscopists. The use of epinephrine added solution may facilitate the procedure by inducing vasoconstriction, thus minimizing intra-operative haemorrhage and allowing clearer dissection plane. The efficacy of epinephrine added solution was previously reported in a single center retrospective study, demonstrating reduction in procedure time with the addition of epinephrine¹. 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.

Aims & Methods

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 agent, warfarin and other direct oral anticoagulants would be excluded. They would be randomized to epinephrine group which 0.2ml 1:1000 epinephrine diluted into each 20ml of the original injection solution mixture, and control group which no epinephrine would be added. Randomization was stratified with lesion location (upper/middle vs lower), size () 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 haemorrhage requiring use of hemostatic forceps, peri-procedure blood pressure, pulse and post-procedure adverse events. Patients, endoscopists and assessors were blinded to the treatment allocation.

Results

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 epinephrine and control group respectively. One hundred thirty-three (17.2%), 286 (37.0%), 355 (45.9%) of the lesions were located in the upper, middle and lower part of the stomach respectively, and majority (87.3%) of the lesions were 46.21 vs 68.0645.37min, adjusted mean difference -6.977min, [-12.756, -1.198], p=0.01). The number of intra-operative bleeding episodes requiring 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 event between the two groups.

Conclusion

Conclusion
The use of epinephrine added solution significantly shortens the procedure time and reduces intraoperative bleeding events during gastric ESD.

References

1, Inoue S, Uedo N, Tabuchi T, Nakagawa K, Ohmori M, Iwagami H, Matsuno K, Iwatsubo T, Nakahira H, Matsuura N, Shichijo S, Maekawa A, Kanesaka T, Takeuchi Y, Higashino K, Ishihara R. Usefulness of epinephrine-added injection solution to reduce procedure time for gastric endoscopic submucosal dissection. Endosc Int Open. 2020 Aug;8(8):E1044-E1051. doi: 10.1055/a-1192-4202. Epub 2020 Jul 21. PMID: 32743058; PMCID: PMC7373655.

Disclosure

This study was supported by Asian Endoscopic Research Forum (AERF)