Prophylactic clip closure after colorectal endoscopic submucosal dissection: lessons from a European multicenter analysis and the Japanese experience

In this issue of Endoscopy, De Cristofaro et al. present a secondary analysis of the landmark French randomized controlled trial (RCT) comparing endoscopic submucosal dissection (ESD) with endoscopic mucosal resection (EMR), and specifically address the role of prophylactic clip closure after colorectal ESD. The investigators analyzed post-ESD bleeding outcomes between closure and non-closure groups, using propensity score matching (PSM) to reduce bias.

“…this large, multicenter, European cohort demonstrated that prophylactic clip closure after colorectal ESD did not significantly reduce clinically significant delayed bleeding, even in high-risk or anticoagulated patients.”

In both the full cohort and after PSM, clip closure did not significantly reduce the risk of clinically significant delayed bleeding (CSDB). After PSM, CSDB occurred in 5.7% of patients without closure and 7.7% with closure. In the subgroup of patients on anticoagulants, the CSDB rates were 17.1% vs. 13.4%, while in high-risk patients with a Limoges Bleeding Score (LBS) ≥5, CSDB was 14.1% vs. 15.6%, again with no significant difference [1].

The efficacy of prophylactic closure after colorectal ESD remains controversial. In contrast to EMR, where multiple RCTs have established the protective effect of clip closure [2] [3], the literature for ESD is scarce. Only two RCTs from Japan and Korea are available, neither demonstrating a significant difference, as delayed bleeding was not the primary end point. Nomura et al. reported lower post-ESD bleeding in the closure arm (1.4% vs. 3.6%), but this was a secondary end point and the trial was stopped early [4]. Similarly, Lee et al. reported reduced bleeding (0.9% vs. 1.8%), but again the trial was underpowered and discontinued prematurely [5]. Several retrospective Japanese studies, however, have shown significant reductions in post-ESD bleeding with closure [6].

Recent advances in Japan, particularly for duodenal ESD, include novel closure techniques such as the reopenable clip over-the-line method, origami method, and the Easy & Eco clip-over-the-line method, developed at our institution [7]. These approaches employ numerous inexpensive reloadable clips and nylon threads to achieve dense, durable closure. Such techniques differ from the representative image of complete closure shown in Fig. 1b of the De Cristofaro et al. article, where gaps between clips are visible and may allow bleeding. Indeed, in their single-center analysis of 350 cases, the mean number of clips for a 3-cm lesion was only 4 (range 1–10), suggesting insufficient closure density and potentially explaining the negative results [1].

“It is not realistic to recommend complete closure for all colorectal ESD ulcers, given the cost, time, and technical demands.”

It is not realistic to recommend complete closure for all colorectal ESD ulcers, given the cost, time, and technical demands. However, the present study confirmed that patients with an LBS ≥5 had a CSDB incidence of ~15%. As post-ESD bleeding often requires hospitalization, transfusion, or emergency endoscopy, its socioeconomic burden cannot be ignored. Particularly in Western countries where outpatient or day-surgery ESD is increasing, complete closure should be considered in selected high-risk patients.

The environmental and economic aspects, highlighted in this study, are important. The mean carbon footprint per closure exceeded 2 kg of carbon dioxide equivalents when single-use clips were employed [1]. While these concerns are valid, they must be balanced against the potential consequences of uncontrolled bleeding. Development of reusable and more efficient closure devices may help resolve this dilemma.

In conclusion, this large, multicenter, European cohort demonstrated that prophylactic clip closure after colorectal ESD did not significantly reduce CSDB, even in high-risk or anticoagulated patients. Nevertheless, evidence from Japan suggests that dense and technically complete closure can lower bleeding risk. Future randomized trials, incorporating advanced closure techniques and targeting well-defined high-risk populations, are essential. Until then, individualized decision making, rather than routine closure, seems the most rational strategy.

Publication History

Article published online:
21 January 2026

• References

• 1 De Cristofaro E, Jacques J, Montori S. et al. Impact of prophylactic clipping on delayed bleeding after colorectal endoscopic submucosal dissection: a multicenter propensity score-matched study. Endoscopy 2025;
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