Advertisement

Response

      We thank Deng et al
      • Deng K.
      • Jing W.-N.
      • Chen M.
      Caution should be exercised in denying the protective effect of clip closure on post-EMR perforation of a proximal large nonpedunculated colorectal polyp.
      for their interest in our meta-analysis
      • Forbes N.
      • Gupta S.
      • Frehlich L.
      • et al.
      Clip closure to prevent adverse events following endoscopic mucosal resection of proximal large non-pedunculated colorectal polyps: meta-analysis of individual patient data from randomized controlled trials.
      and for their letter to the editor. In their letter, the authors raise concerns regarding our observed result that prophylactic clip closure was not associated with the incidence of delayed perforation after EMR of proximal large nonpedunculated colorectal polyps (LNPCPs). Deng et al correctly point out that a type II error could potentially be responsible for the lack of association between clipping and perforation, given the low event rate of 0.6%. Whereas this is technically true, we would like to point out 2 important points.
      First, we would like to restate that the odds ratio of perforation with clip closure (vs no clip closure) from individual patient data in our study was 0.78 (95% confidence interval, .17-3.54). Although a lack of adequate power could theoretically be blamed for the failure to show a statistically significant association when in fact there is a true association (type II error), the modest odds ratio point estimate we observed would argue against this possibility. To illustrate this, if we were to imagine that the point estimate from our results was statistically significant, we would arrive at a number needed to treat of 631 patients to avoid 1 perforation. Even with a higher theoretical rate of perforation of 1.5%,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      as Deng et al
      • Deng K.
      • Jing W.-N.
      • Chen M.
      Caution should be exercised in denying the protective effect of clip closure on post-EMR perforation of a proximal large nonpedunculated colorectal polyp.
      cite, using our cohort size, which represents all patients from randomized trials to date examining this population, the number needed to treat would still be 232 to prevent perforation, which is of doubtful clinical benefit. Although several meta-analyses have examined both the ideal efficacy and the real-world effectiveness of prophylactic clipping,
      • Forbes N.
      • Frehlich L.
      • James M.
      • et al.
      Routine prophylactic endoscopic clipping is not efficacious in the prevention of delayed post-polypectomy bleeding: a systematic review and meta-analysis of randomized controlled trials.
      • Spadaccini M.
      • Albéniz E.
      • Pohl H.
      • et al.
      Prophylactic clipping after colorectal endoscopic resection prevents bleeding of large, proximal polyps: meta-analysis of randomized trials.
      • Bishay K.
      • Meng Z.W.
      • Frehlich L.
      • et al.
      Prophylactic clipping to prevent delayed colonic post-polypectomy bleeding: meta-analysis of randomized and observational studies.
      ours was the first to report the risk of perforation specifically for proximal LNPCPs, but is still underpowered despite including data on >1200 patients. Given the difficulties with designing adequately powered trials to address this clinical question, future large-scale observational studies are likely required to further elucidate the real-world incidences of non-bleeding adverse events following prophylactic clipping.
      • Forbes N.
      • Hilsden R.J.
      • Lethebe B.C.
      • et al.
      Prophylactic endoscopic clipping does not prevent delayed postpolypectomy bleeding in routine clinical practice: a propensity score-matched cohort study.
      Second, as we noted in our article, our data provide conclusive support for contemporary guidelines recommending that prophylactic clip closure should be the standard of care after EMR of proximal LNPCPs because of the established benefit on the prevention of delayed bleeding.
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions: recommendations by the US multi-society task force on colorectal cancer.
      Thus, given the established benefits of prophylactic clipping in this clinical context, the small theoretical added benefits on mitigating the risk of delayed perforation, while possible, could arguably be considered a moot point, because clip closure of these lesions should be attempted in any event. After EMR of nonproximal LNPCPs or other lesions for which the guidelines do not recommend routine prophylactic clip closure, we maintain that the decision on whether or not to clip to prevent perforation should be based on the extent of deep mural injury observed at the time of resection,
      • Burgess N.G.
      • Bassan M.S.
      • McLeod D.
      • et al.
      Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors.
      rather than performed routinely.

      Disclosure

      Dr Forbes is a consultant for Boston Scientific, Pentax Medical, AstraZeneca, and Pendopharm; is on the speaker’s bureau for Boston Scientific and Pentax Medical; and has received research support from Pentax Medical. Dr Bourke has received research support from Olympus , Cook Medical, and Boston Scientific.

      References

        • Deng K.
        • Jing W.-N.
        • Chen M.
        Caution should be exercised in denying the protective effect of clip closure on post-EMR perforation of a proximal large nonpedunculated colorectal polyp.
        Gastrointest Endosc. 2022; 96: 1094-1095
        • Forbes N.
        • Gupta S.
        • Frehlich L.
        • et al.
        Clip closure to prevent adverse events following endoscopic mucosal resection of proximal large non-pedunculated colorectal polyps: meta-analysis of individual patient data from randomized controlled trials.
        Gastrointest Endosc. 2022; 96: 721-731
        • Ferlitsch M.
        • Moss A.
        • Hassan C.
        • et al.
        Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
        Endoscopy. 2017; 49: 270-297
        • Forbes N.
        • Frehlich L.
        • James M.
        • et al.
        Routine prophylactic endoscopic clipping is not efficacious in the prevention of delayed post-polypectomy bleeding: a systematic review and meta-analysis of randomized controlled trials.
        J Can Assoc Gastroenterol. 2019; 2: 105-117
        • Spadaccini M.
        • Albéniz E.
        • Pohl H.
        • et al.
        Prophylactic clipping after colorectal endoscopic resection prevents bleeding of large, proximal polyps: meta-analysis of randomized trials.
        Gastroenterology. 2020; 159 (e11): 148-158
        • Bishay K.
        • Meng Z.W.
        • Frehlich L.
        • et al.
        Prophylactic clipping to prevent delayed colonic post-polypectomy bleeding: meta-analysis of randomized and observational studies.
        Surg Endosc. 2022; 36: 1251-1262
        • Forbes N.
        • Hilsden R.J.
        • Lethebe B.C.
        • et al.
        Prophylactic endoscopic clipping does not prevent delayed postpolypectomy bleeding in routine clinical practice: a propensity score-matched cohort study.
        Am J Gastroenterol. 2020; 115: 774-782
        • Kaltenbach T.
        • Anderson J.C.
        • Burke C.A.
        • et al.
        Endoscopic removal of colorectal lesions: recommendations by the US multi-society task force on colorectal cancer.
        Gastrointest Endosc. 2020; 91: 486-519
        • Burgess N.G.
        • Bassan M.S.
        • McLeod D.
        • et al.
        Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors.
        Gut. 2017; 66: 1779-1789

      Linked Article