To close or not to close after colorectal endoscopic submucosal dissection: that is the question!

En bloc resection by endoscopic submucosal dissection (ESD) is increasingly adopted worldwide as the first-line treatment for large (≥20 mm) superficial colorectal neoplasia. Its advantages include complete pathological analysis, the potential to cure selected T1 colorectal cancers, and single-session R0 resection that can obviate the need for early follow-up colonoscopies.

Adverse events, primarily post-procedural bleeding, occur in 2%–8% of cases according to the literature. In the only randomized controlled trial comparing ESD with piecemeal endoscopic mucosal resection (EMR) in the colon, the clinically significant delayed bleeding rate was similar between the two strategies, at approximately 7.5% [1]. The latest guidelines from the European Society of Gastrointestinal Endoscopy recommend closure of large, right-sided colon lesions resected via piecemeal EMR (≥2 cm) or in patients on anticoagulants [2]. Should the same approach be applied for ESD?

The risk factors for bleeding after colorectal ESD differ from those after EMR. For instance, rectal lesions are the most at-risk location for ESD, whereas right-sided colon lesions carry the highest risk with EMR [3]. This discrepancy complicates extrapolation of results from three large, randomized trials with positive outcomes for EMR [4] [5] [6]. In ESD, two randomized controlled trials from Asia reported negative results regarding closure [6] [7]. These studies included small, low-risk lesions, few patients on anticoagulants, and were not designed primarily to investigate delayed bleeding prevention.

Pull Quote

“Closing all ESD scars does not appear to be effective (or cost effective) at this time, as at least two-thirds of patients have a low bleeding risk (<4%).”

Nevertheless, to avoid complications that are potentially clinically, costly, and legally concerning, many gastroenterologists routinely close all dissection scars, especially in the right colon.

In this issue of Endoscopy, a large, retrospective, multicenter, Japanese study sheds light on this issue [8]. The study focused on high-risk patients (those on anticoagulants) and demonstrated that effective clip closure reduced delayed bleeding rates from 10.8% to 5.2% in patients on direct oral anticoagulants and from 17.1% to 6.1% in patients on warfarin. The effect was more pronounced for right-sided lesions compared with rectal or left-sided lesions.

The strengths of this study lie in its substantial cohort size, spanning 10 years (2012–2021) and encompassing more than 34 000 lesions, including 1478 resections in patients on anticoagulants. Additionally, the use of propensity score matching helped minimize confounding and bias, enabling a more balanced comparison between groups.

Can we consider the question resolved without a well-designed randomized trial? The answer is no. Despite the quality of this work, several limitations persist.

1. Retrospective design: event reporting in retrospective studies is inherently less robust than in prospective trials with rigorous data monitoring.

2. Incomplete closure rates: the proportion of patients in the overall study cohort in whom full clip closure was attempted but only partial closure was achieved is unavailable, limiting the generalizability of the findings.

3. Methodological limitations: while propensity score matching is valuable, it does not equate to randomization. It accounts only for observed variables, leaving room for bias from unmeasured confounders (e.g. American Society of Anesthesiologists [ASA] scores in this study). Furthermore, individuals without suitable matches may be excluded, reducing sample size and introducing potential selection bias in controls.

4. Specific recommendations of periprocedural management of anticoagulants in Japan: Japanese guidelines differ from European or American guidelines (notably regarding vitamin K antagonists, which are not discontinued for ESD), making it challenging to extrapolate all the results.

Closing all ESD scars does not appear to be effective (or cost effective) at this time, as at least two-thirds of patients have a low bleeding risk (<4%) [3]. Moreover, randomized trials have not demonstrated that closure prevents post-procedural perforation or post-polypectomy syndrome – the other major adverse events following colorectal ESD. However, closing high-risk lesions (e.g. large lesions, patients classified as ASA III or IV, elderly patients with comorbidities, and patients on anticoagulants) may be justified based on these recent findings.

Advances in clipping systems and suturing devices enable more effective closure of post-ESD scars. Complete closure, which appears to be a key factor in preventing delayed bleeding, is increasingly achievable. Technically all “closures” are not equivalent and experts emphasize the importance of tight closure that captures deep tissue layers rather than superficial mucosal apposition, which can create dead spaces (resulting in a tent-like appearance without achieving the compression effect required for potential hemostasis).

Well-designed randomized trials are urgently needed to confirm these findings and determine whether closure is essential for high-risk colorectal ESD cases in terms of bleeding prevention, cost-effectiveness, and ecological impact. Similarly, high-quality evidence is needed to justify the growing use of expensive topical agents after complex endoscopic resections, which currently lack proven efficacy in a prophylactic setting.

A robust level of evidence is critical to protect both patients and physicians. It ensures better patient care, greater economic efficiency, and reduced ecological impact within our healthcare systems. This should remain a priority as we continue to refine and optimize colorectal ESD practices.

Publikationsverlauf

Artikel online veröffentlicht:
28. Januar 2025

• References

• 1 Jacques J, Schaefer M, Wallenhorst T. et al. Endoscopic en bloc versus piecemeal resection of large nonpedunculated colonic adenomas: a randomized comparative trial. Ann Intern Med 2024; 177: 29-38
• 2 Ferlitsch M, Hassan C, Bisschops R. et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – update 2024. Endoscopy 2024; 56: 516-545
• 3 Albouys J, Montori Pina S, Boukechiche S. et al. Risk of delayed bleeding after colorectal endoscopic submucosal dissection: the Limoges Bleeding Score. Endoscopy 2024; 56: 110-118
• 4 Albéniz E, Álvarez MA, Espinós JC. et al. Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Gastroenterology 2019; 157: 1213-1221.e4
• 5 Pohl H, Grimm IS, Moyer MT. et al. Clip closure prevents bleeding after endoscopic resection of large colon polyps in a randomized trial. Gastroenterology 2019; 157: 977-984.e3
• 6 Lee SP, Sung I, Kim JH. et al. Effect of prophylactic endoscopic closure for an artificial ulceration after colorectal endoscopic submucosal dissection: a randomized controlled trial. Scand J Gastroenterol 2019; 54: 1291-1299
• 7 Nomura S, Shimura T, Katano T. et al. A multicenter, single-blind randomized controlled trial of endoscopic clipping closure for preventing coagulation syndrome after colorectal endoscopic submucosal dissection. Gastrointest Endosc 2020; 91: 859-867.e1
• 8 Takada K, Yoshida N, Hayashi Y. et al. Prophylactic clip closure in preventing delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulants: a multicenter retrospective cohort study in Japan. Endoscopy 2024;