Clip closure to prevent adverse events after EMR of proximal large nonpedunculated colorectal polyps: meta-analysis of individual patient data from randomized controlled trials

      Background and Aims

      After EMR, prophylactic clipping is often performed to prevent clinically significant post-EMR bleeding (CSPEB) and other adverse events (AEs). Prior evidence syntheses have lacked sufficient power to assess clipping in relevant subgroups or in nonbleeding AEs. We performed a meta-analysis of individual patient data (IPD) from randomized trials assessing the efficacy of clipping to prevent AEs after EMR of proximal large nonpedunculated colorectal polyps (LNPCPs) ≥20 mm.


      We searched EMBASE, MEDLINE, Cochrane Central Registry of Controlled Trials, and PubMed from inception to May 19, 2021. Two reviewers screened citations in duplicate. Corresponding authors of eligible studies were invited to contribute IPD. A random-effects 1-stage model was specified for estimating pooled effects, adjusting for patient sex and age and for lesion location and size, whereas a fixed-effects model was used for traditional meta-analyses.


      From 3145 citations, 4 trials were included, representing 1248 patients with proximal LNPCPs. The overall rate of CSPEB was 3.5% and 9.0% in clipped and unclipped patients, respectively. IPD were available for 1150 patients, in which prophylactic clipping prevented CSPEB with an odds ratio (OR) of .31 (95% confidence interval [CI], .17-.54). Clipping was not associated with perforation or abdominal pain, with ORs of .78 (95% CI, .17-3.54) and .67 (95% CI, .20-2.22), respectively.


      Prophylactic clipping is efficacious in preventing CSPEB after EMR of proximal LNPCPs. Therefore, clip closure should be considered a standard component of EMR of LNPCPs in the proximal colon.

      Graphical abstract


      AE (adverse event), CI (confidence interval), CSPEB (clinically significant post-EMR bleeding), GRADE (Grading of Recommendations Assessment, Development and Evaluation), IPD (individual patient data), LNPCP (large nonpedunculated colorectal polyp), OR (odds ratio), PPS (postpolypectomy syndrome), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses), RCT (randomized controlled trial), RR (relative risk), UHU (unplanned healthcare utilization)
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        • Hassan C.
        • Repici A.
        • Sharma P.
        • et al.
        Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.
        Gut. 2016; 65: 806-820
        • Ma C.
        • Teriaky A.
        • Sheh S.
        • et al.
        Morbidity and mortality after surgery for nonmalignant colorectal polyps: a 10-year nationwide analysis.
        Am J Gastroenterol. 2019; 114: 1802-1810
        • Jayanna M.
        • Burgess N.G.
        • Singh R.
        • et al.
        Cost analysis of endoscopic mucosal resection vs surgery for large laterally spreading colorectal lesions.
        Clin Gastroenterol Hepatol. 2016; 14: 271-278
        • Ahlenstiel G.
        • Hourigan L.F.
        • Brown G.
        • et al.
        Actual endoscopic versus predicted surgical mortality for treatment of advanced mucosal neoplasia of the colon.
        Gastrointest Endosc. 2014; 80: 668-676
        • 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
        • Klein A.
        • Tate D.J.
        • Jayasekeran V.
        • et al.
        Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.
        Gastroenterology. 2019; 156: 604-613
        • Metz A.J.
        • Bourke M.J.
        • Moss A.
        • et al.
        Factors that predict bleeding following endoscopic mucosal resection of large colonic lesions.
        Endoscopy. 2011; 43: 506-511
        • Burgess N.G.
        • Metz A.J.
        • Williams S.J.
        • et al.
        Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.
        Clin Gastroenterol Hepatol. 2014; 12: 651-661
        • Bahin F.F.
        • Rasouli K.N.
        • Byth K.
        • et al.
        Prediction of clinically significant bleeding following wide-field endoscopic resection of large sessile and laterally spreading colorectal lesions: a clinical risk score.
        Am J Gastroenterol. 2016; 111: 1115-1122
        • Burgess N.G.
        • Williams S.J.
        • Hourigan L.F.
        • et al.
        A management algorithm based on delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.
        Clin Gastroenterol Hepatol. 1525; 12: 1525-1533
        • Fujiya M.
        • Tanaka K.
        • Dokoshi T.
        • et al.
        Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection.
        Gastrointest Endosc. 2015; 81: 583-595
        • 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
        • Hirasawa K.
        • Sato C.
        • Makazu M.
        • et al.
        Coagulation syndrome: delayed perforation after colorectal endoscopic treatments.
        World J Gastrointest Endosc. 2015; 7: 1055-1061
        • Kim H.H.
        • Kim J.H.
        • Park S.J.
        • et al.
        Risk factors for incomplete resection and complications in endoscopic mucosal resection for lateral spreading tumors.
        Dig Endosc. 2012; 24: 259-266
        • Sawhney M.S.
        • Salfiti N.
        • Nelson D.B.
        • et al.
        Risk factors for severe delayed postpolypectomy bleeding.
        Endoscopy. 2008; 40: 115-119
        • Rutter M.D.
        • Nickerson C.
        • Rees C.J.
        • et al.
        Risk factors for adverse events related to polypectomy in the English Bowel Cancer Screening Programme.
        Endoscopy. 2014; 46: 90-97
        • Buddingh K.T.
        • Herngreen T.
        • Haringsma J.
        • et al.
        Location in the right hemi-colon is an independent risk factor for delayed post-polypectomy hemorrhage: a multi-center case-control study.
        Am J Gastroenterol. 2011; 106: 1119-1124
        • Pohl H.
        • Grimm I.S.
        • Moyer M.T.
        • et al.
        Clip closure prevents bleeding after endoscopic resection of large colon polyps in a randomized trial.
        Gastroenterology. 2019; 157: 977-984
        • Albéniz E.
        • Gimeno-García A.Z.
        • Fraile M.
        • et al.
        Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.
        Gastrointest Endosc. 2020; 91: 868-878
        • Zhang Q.
        • An S.
        • Chen Z.
        • et al.
        Assessment of risk factors for delayed colonic post-polypectomy hemorrhage: a study of 15553 polypectomies from 2005 to 2013.
        PLoS One. 2014; 9e108290
        • 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
        • Spadaccini M.
        • Albeniz 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: 148-158.e11
        • 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
        • Albéniz E.
        • Alvarez M.A.
        • Espinos J.C.
        • et al.
        Clip closure after resection of large colorectal lesions with substantial risk of bleeding.
        Gastroenterology. 2019; 157: 1213-1221
        • Feagins L.A.
        • Smith A.D.
        • Kim D.
        • et al.
        Efficacy of prophylactic hemoclips in prevention of delayed post-polypectomy bleeding in patients with large colonic polyps.
        Gastroenterology. 2019; 157: 967-976
        • Gupta S.
        • Sidhu M.
        • Shahidi N.
        • et al.
        Impact of prophylactic endoscopic clip placement on clinically significant post endoscopic mucosal resection bleeding in the right colon—a randomized controlled trial.
        Lancet Gastroenterol Hepatol. 2022; 7: 152-160
        • Moher D.
        • Shamseer L.
        • Clarke M.
        • et al.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
        Syst Rev. 2015; 4: 1
        • Riley R.D.
        • Lambert P.C.
        • Abo-Zaid G.
        Meta-analysis of individual participant data: rationale, conduct, and reporting.
        BMJ. 2010; 340: c221
        • Stewart L.A.
        • Clarke M.
        • Rovers M.
        • et al.
        Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD statement.
        JAMA. 2015; 313: 1657-1665
      1. Higgins JPT, Thomas J, Chandler J, et al (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available at: Accessed April 30, 2022.

        • Guyatt G.H.
        • Oxman A.D.
        • Vist G.E.
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
        • Cotton P.B.
        • Eisen G.M.
        • Aabakken L.
        • et al.
        A lexicon for endoscopic adverse events: report of an ASGE workshop.
        Gastrointest Endosc. 2010; 71: 446-454
        • 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
        • Debray T.P.
        • Moons K.G.
        • Abo-Zaid G.M.
        • et al.
        Individual participant data meta-analysis for a binary outcome: one-stage or two-stage?.
        PLoS One. 2013; 8e60650
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • et al.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Begg C.B.
        • Mazumdar M.
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        • Cullen S.
        New classification of physical status.
        Anesthesiology. 1963; 24: 110-111
        • 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.
        Gastroenterology. 2020; 158: 1095-1129
        • van Hattem W.A.
        • Shahidi N.
        • Vosko S.
        • et al.
        Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
        Gut. 2021; 70: 1691-1697
        • Albéniz E.
        • Enguita-Germán M.
        • Gimeno-García A.Z.
        • et al.
        The answer to “when to clip” after colorectal endoscopic mucosal resection based on a cost-effectiveness analysis.
        Am J Gastroenterol. 2021; 116: 311-318
        • Dokoshi T.
        • Fujiya M.
        • Tanaka K.
        • et al.
        A randomized study on the effectiveness of prophylactic clipping during endoscopic resection of colon polyps for the prevention of delayed bleeding.
        Biomed Res Int. 2015; 2015: 490272
        • Zhang Q.S.
        • Han B.
        • Xu J.H.
        • et al.
        Clip closure of defect after endoscopic resection in patients with larger colorectal tumors decreased the adverse events.
        Gastrointest Endosc. 2015; 82: 904-909

      Linked Article

      • Prevention of clinically significant post-EMR bleeding: To clip or not to clip?
        Gastrointestinal EndoscopyVol. 96Issue 5
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          Endoscopic mucosal resection (EMR) is the existing standard of care for the management of large nonpedunculated colon polyps (LNPCPs), having a high safety and cost profile compared with other resection techniques such as endoscopic submucosal dissection and surgery.1 Adverse events (AEs) related to EMR include post-EMR bleeding, perforation, and postpolypectomy syndrome. Clinically significant post-EMR bleeding (CSPEB) occurs in 5% to 7.2% of cases and is more common in the right side of the colon.
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