Post ESD bleeding prevention: Are polyglycolic acid sheets here to stay?

Endoscopic submucosal dissection (ESD) has been widely accepted as a minimally invasive treatment of early gastric cancer without risk of lymph node metastasis [1]. ESD is technically demanding even for expert endoscopists, and several techniques and devices have been introduced as a result. A recent large, multicenter, prospective, cohort study from Japan demonstrated rates of 99.2 % for en bloc resection and 91.6 % for R0 resection. Intraoperative perforation was reported to be 2.3 % and was mostly managed by endoscopic clip closure, and emergency surgery was rarely performed [2]. Furthermore, several studies have demonstrated excellent long-term outcomes [1] [3].

“Although this study failed to demonstrate the preventive effect of PGA sheets for post-ESD bleeding, the result revealed how rapidly the ESD technique has evolved.”

Although ESD is accepted as the standard of care according to Japanese guidelines, the current clinical concerns are late adverse events such as post-ESD bleeding and delayed perforation. Among them, delayed bleeding is reported to be 4.4 %, even with proton pump inhibitor use and prophylactic endoscopic coagulation of visible vessels on the mucosal defect. Transfusion, as well as emergency endoscopy and hospitalization may be required to manage the complication [2]. These events represent a serious clinical issue, particularly in high risk patients with risk factors such as sizeable mucosal defects or antithrombotic drug use.

Thus, prevention of post-ESD bleeding is a matter that requires urgent attention. Tissue shielding methods using a polyglycolic acid (PGA) sheet and fibrin glue were initially introduced during surgery. This technique has been adopted to prevent late adverse events after ESD. Although endoscopic delivery of the PGA sheet is technically challenging, there have been no reports of related adverse events.

In this issue of Endoscopy, Kataoka et al. present a randomized controlled trial that was conducted to investigate whether there is additional benefit of the tissue shielding method for preventing post-ESD bleeding compared with standard practice [4]. A total of 140 high risk patients were enrolled and allocated to either the PGA group or the control group. There was no significant difference in the post-ESD bleeding rates between the two groups (4.5 % and 5.7 %).

Although this study failed to demonstrate the preventive effect of PGA sheets for post-ESD bleeding, the result revealed how rapidly the ESD technique has evolved. Based on knowledge gained regarding the complications of ESD, procedural techniques and practices are constantly being updated, even over a period from study design to completion. Progressive advancement of the ESD technique needs to be considered when interpreting the data of clinical studies. For instance, the impact of each antithrombotic drug on post-ESD bleeding would not have been thoroughly analyzed in 2014. This may have contributed to the lower-than-expected post-ESD bleeding rate in the control group. It is difficult to show with certainty, but alteration in ESD practices, such as more extended and careful prophylactic coagulation of visible vessels, over the recent few years may also have influenced the result. It would have been very challenging to design a randomized controlled trial that took into account future developments, as these changes in practice leading to lower complication rates could not have been predicted.

ESD to date has overcome several technical limitations and failures, as the ESD masters were required to solve problems along the way [5]. The PGA application itself, delivering and securing the sheet onto the mucosal defect, was considered technically very challenging and a time-consuming procedure. Nevertheless, the corresponding institution has developed an innovative technique utilizing the clip-and-pull method for optimal fixation of PGA sheets [4]. The journey to overcoming post-ESD bleeding continues. It is not appropriate to regret the development of PGA sheets nor should the result of the study be disregarded. Further well-designed and refined large-scale studies are warranted to provide evidence for PGA application in the prevention of post-ESD bleeding. Moreover, other novel endoscopic approaches to closure or suturing of the mucosal defect, such as the combination of endoloop and endoclips, the endoscopic suturing device, and over-the-scope clips, have clinical potential to reduce the risk of post-ESD bleeding [6] [7] [8]. The combination of PGA sheets with these closure devices is also worth investigating in future studies.

The negative result of the study was helpful in the search for more effective methods to reduce post-ESD bleeding. Ongoing scientific effort brings us closer to the solution and better management of ESD patients.

• References

• 1 Ono H, Yao K, Fujishiro M. et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc 2016; 28: 3-15
• 2 Suzuki H, Takizawa K, Hirasawa T. et al. Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: ‘real-world evidence’ in Japan. Dig Endosc 2019; 31: 30-39
• 3 Hasuike N, Ono H, Boku N. et al. A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study (JCOG0607). Gastric Cancer 2018; 21: 114-123
• 4 Kataoka Y, Tsuji Y, Hirasawa K. et al. Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trial. Endoscopy 2019; 51: 619-627
• 5 Suzuki H, Oda I, Sekiguchi M. et al. Process of technical stabilization of gastric endoscopic submucosal dissection at the National Cancer Center in Japan. Turk J Gastroenterol 2014; 25: 619-623
• 6 Abe S, Oda I, Mori G. et al. Complete endoscopic closure of a large gastric defect with endoloop and endoclips after complex endoscopic submucosal dissection. Endoscopy 2015; 47 (Suppl. 01) E374-375
• 7 Kantsevoy SV, Bitner M, Mitrakov AA. et al. Endoscopic suturing closure of large mucosal defects after endoscopic submucosal dissection is technically feasible, fast, and eliminates the need for hospitalization (with videos). Gastrointest Endosc 2014; 79: 503-507
• 8 Nishiyama N, Mori H, Kobara H. et al. Efficacy and safety of over-the-scope clip: including complications after endoscopic submucosal dissection. World J Gastroenterol 2013; 19: 2752-2760