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Efficacy and safety of cold snare polypectomy for sessile serrated polyps ≥ 10 mm: A systematic review and meta-analysis

  • De-feng Li
    Affiliations
    Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, Guangdong 518020, China
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  • Lode Van Overbeke
    Affiliations
    AZ St-Maarten, Gastroenterology, Mechelen 2800, Belgium
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  • Ken Ohata
    Affiliations
    Department of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Shinagawa-ku, Tokyo 141-8625, Japan
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Li-sheng Wang
    Correspondence
    Corresponding authors.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, Guangdong 518020, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Jun Yao
    Correspondence
    Corresponding authors.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No.1017, Dongmen North Road, Luohu District, Shenzhen, Guangdong 518020, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:February 12, 2022DOI:https://doi.org/10.1016/j.dld.2022.01.132

      Abstract

      Background

      Cold snare polypectomy (CSP) is a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. However, the efficacy and safety of this technique remain undetermined.

      Aims

      We aimed to comprehensively evaluate the efficacy and safety of CSP for SSPs ≥ 10 mm.

      Methods

      PubMed, EMBASE, Web of Science and Cochrane Library were searched up to January 2021.

      Results

      A total of 10 studies consisting of 1727 SSPs (range, 10–40 mm) from 1021 patients were included. The overall rates of technical success, adverse events (AEs) and residual SSPs were 100%, 0.7% and 2.9%, respectively. Subgroup analysis showed that the rates of technical success and AEs were comparable between CSP and cold endoscopic mucosal resection (EMR) (99.9% vs. 100% and 1.3% vs. 0.5%, respectively), between the proximal and distal colon (100% vs. 99.9% and 0.3% vs. 0, respectively), and between polyps of 10–19 mm and ≥20 mm (99.8% vs. 100% and 0.9% vs. 0, respectively). However, subgroup analysis showed that the rate of residual SSPs was slightly lower in CSP compared with cold EMR (1.3% vs. 3.9%), as well as in polyps of 10–19 mm compared with those ≥20 mm (3.1% vs. 4.7%).

      Conclusion

      CSP was an effective and safe technique for removing SSPs ≥ 10 mm.

      Keywords

      Abbreviations:

      CSP (cold snare polypectomy), SSPs (sessile serrated polyps), AEs (adverse events), EMR (endoscopic mucosal resection), ESD (endoscopic submucosal dissection), PEB (post-EMR bleeding), DMI (deep mural injury), PPB (post-procedure bleeding), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), NOS (Newcastle-Ottawa Scale)

      1. Introduction

      Colorectal cancer (CRC) ranks the fourth most frequently diagnosed cancer and the second leading cause of cancer-related mortality worldwide [
      • Bray F.
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      Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
      ]. Sessile serrated polyps (SSPs) are considered CRC precursors, accounting for up to 30% of all CRC [
      • Rex D.K.
      • Ahnen D.J.
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      • Young J.
      • Church J.
      Serrated lesions of the colorectum: review and recommendations from an expert panel.
      ]. In addition, several studies have demonstrated that SSPs possess the rapid progression potential to invasive carcinomas with lymphatic invasion and metastasis [
      • Goldstein N.S.
      Small colonic microsatellite unstable adenocarcinomas and high-grade epithelial dysplasias in sessile serrated adenoma polypectomy specimens: a study of eight cases.
      ,
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      Update on the serrated pathway to colorectal carcinoma.
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      The serrated pathway to colorectal carcinoma: current concepts and challenges.
      ]. Therefore, the removal of SSPs is critical to CRC prevention (Table 1).
      Table 1Meta-regression analysis.
      Univariate meta-regressionp-valueMultivariate meta-regressionp-value
      studyORa95% CIbOR95% CI
      Technical success rate
       Size (mm)80.0001-0.0007 to 0.00090.7358-0.0001-0.0011 to 0.00100.9258
       Methods
       Cold snare3ReferenceReference
       Cold EMR50.0015-0.0034 to 0.00650.54140.0018-0.0049 to 0.00840.6049
      Adverse event rate
       Size8-0.0012-0.0265 to -0.00010.027*-0.0011-0.0025 to 0.00030.1223
       Methods
       Cold snare3ReferenceReference
       Cold EMR5-0.0092-0.0204 to 0.00200.1070-0.0019-0.0164 to 0.01270.8002
      Residual rate
       Size80.0014-0.0028 to 0.00550.5159-0.0007-0.0074 to 0.00600.8396
       Methods
       Cold snare3ReferenceReference
       Cold EMR50.0215-0.0159 to 0.05890.25980.0254-0.0287 to 0.07940.3576
      Note: OR, Odds ratio; CI, confidence interval; * Statistical significance.
      Cold snare polypectomy (CSP) is effective and safe modality to remove diminutive and small SSPs (< 10 mm) without dysplasia [
      • Lee C.K.
      • Shim J.J.
      • Jang J.Y.
      Cold snare polypectomy vs. cold forceps polypectomy using double-biopsy technique for removal of diminutive colorectal polyps: a prospective randomized study.
      ,
      • Kim J.S.
      • Lee B.I.
      • Choi H.
      • Jun S.Y.
      • Park E.S.
      • Park J.M.
      • Lee I.S.
      • Kim B.W.
      • Kim S.W.
      • Choi M.G.
      Cold snare polypectomy versus cold forceps polypectomy for diminutive and small colorectal polyps: a randomized controlled trial.
      ]. Traditional endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are suggested for lesions larger than 20 mm according to international guidelines, while hot polypectomy is recommended for lesions of 10–20 mm [
      • Ferlitsch M.
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      • Jover R.
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      • Nalankilli K.
      • Fockens P.
      • Hazzan R.
      • Gralnek I.M.
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      • Ponchon T.
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      • Repici A.
      • Rutter M.D.
      • Burgess N.G.
      • Bourke M.J.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European society of gastrointestinal endoscopy (ESGE) clinical guideline.
      ]. Although traditional EMR is an effective therapeutic technique for the treatment of large SSPs using submucosal injection and electrocautery, it is associated with a risk of serious adverse events (AEs) such as post-EMR bleeding (PEB) and deep mural injury (DMI) [
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • Bhandari P.
      • Dumonceau J.M.
      • Paspatis G.
      • Jover R.
      • Langner C.
      • Bronzwaer M.
      • Nalankilli K.
      • Fockens P.
      • Hazzan R.
      • Gralnek I.M.
      • Gschwantler M.
      • Waldmann E.
      • Jeschek P.
      • Penz D.
      • Heresbach D.
      • Moons L.
      • Lemmers A.
      • Paraskeva K.
      • Pohl J.
      • Ponchon T.
      • Regula J.
      • Repici A.
      • Rutter M.D.
      • Burgess N.G.
      • Bourke M.J.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European society of gastrointestinal endoscopy (ESGE) clinical guideline.
      ,
      • Pellise M.
      • Burgess N.G.
      • Tutticci N.
      • Hourigan L.F.
      • Zanati S.A.
      • Brown G.J.
      • Singh R.
      • Williams S.J.
      • Raftopoulos S.C.
      • Ormonde D.
      • Moss A.
      • Byth K.
      • P'Ng H.
      • Mahajan H.
      • McLeod D.
      • Bourke M.J.
      Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions.
      ,
      • Burgess N.G.
      • Bassan M.S.
      • McLeod D.
      • Williams S.J.
      • Byth K.
      • Bourke M.J.
      Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors.
      ]. However, two studies have recently shown that routine use of prophylactic clipping can reduce PEBs after removal of large SSPs (more than 20 mm) and may be cost-effective in patients with a high risk of bleeding [
      • Spadaccini M.
      • Albeniz E.
      • Pohl H.
      • Maselli R.
      • Thoguluva Chandrasekar V.
      • Correale L.
      • Anderloni A.
      • Carrara S.
      • Fugazza A.
      • Badalamenti M.
      • Iwatate M.
      • Antonelli G.
      • Enguita-German M.
      • Alvarez M.A.
      • Sharma P.
      • Rex D.K.
      • Hassan C.
      • Repici A.
      Prophylactic clipping after colorectal endoscopic resection prevents bleeding of large, proximal polyps: meta-analysis of randomized trials.
      ,
      • Albeniz E.
      • Enguita-German M.
      • Gimeno-Garcia A.Z.
      • Herreros de Tejada A.
      • Nogales O.
      • Espinos J.C.
      • Sanchez J.Rodriguez
      • Roson P.
      • Guarner C.
      • Marin J.C.
      • Bhandari P.
      • Spadaccini M.
      • Repici A.
      • Hassan C.
      • Alvarez-Gonzalez M.A.
      • Beroiz B.Ibanez
      The answer to "when to clip" after colorectal endoscopic mucosal resection based on a cost-effectiveness analysis.
      ].
      Currently, CSP, including cold snare and cold EMR, is used to treat large SSPs. van Hattem et al. in their prospective study, have demonstrated that piecemeal-CSP (p-CSP) is comparable to EMR for the removal of SSPs ≥20 mm in terms of technical success rate and recurrence rate (100% vs. 99.6%, P = 1 and 4.3% vs. 4.6%, P = 0.9, respectively). However, p-CSP is associated with lower post-procedure bleeding (PPB) (0 vs.5.1%, P = 0.01) [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ]. Thoguluva Chandrasekar et al. have also reported that for the treatment of SSPs ≥10 mm, CSP has significantly lower rates of PPB and residual rate compared with traditional EMR (0 vs. 2.3%, P-0.03 and 0.9% vs. 5%, P = 0.01, respectively) [
      • Thoguluva Chandrasekar V.
      • Aziz M.
      • Patel H.K.
      • Sidhu N.
      • Duvvuri A.
      • Dasari C.
      • Kennedy K.F.
      • Ashwath A.
      • Spadaccini M.
      • Desai M.
      • Jegadeesan R.
      • Sathyamurthy A.
      • Vennalaganti P.
      • Kohli D.
      • Hassan C.
      • Pellise M.
      • Repici A.
      • Sharma P.
      • Bourke M.J.
      Efficacy and safety of endoscopic resection of sessile serrated polyps 10 mm or larger: a systematic review and meta-analysis.
      ]. Therefore, CSP is considered an alternative technique for treating large SSPs since it can avoid electrocautery and potentially omit PPB and DMI [
      • Piraka C.
      • Saeed A.
      • Waljee A.K.
      • Pillai A.
      • Stidham R.
      • Elmunzer B.J.
      Cold snare polypectomy for non-pedunculated colon polyps greater than 1 cm.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Repici A.
      • Hassan C.
      • Vitetta E.
      • Ferrara E.
      • Manes G.
      • Gullotti G.
      • Princiotta A.
      • Dulbecco P.
      • Gaffuri N.
      • Bettoni E.
      • Pagano N.
      • Rando G.
      • Strangio G.
      • Carlino A.
      • Romeo F.
      • de Paula Pessoa Ferreira D.
      • Zullo A.
      • Ridola L.
      • Malesci A.
      Safety of cold polypectomy for <10 mm polyps at colonoscopy: a prospective multicenter study.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ]. However, the current data are limited by relatively smaller sample size and reported mostly from single-center experiences. Therefore, we comprehensively performed a meta-analysis and assessed the efficacy and safety of CSP for the treatment of SSPs ≥10 mm in size.

      2. Methods

      This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations [
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gotzsche P.C.
      • Ioannidis J.P.
      • Clarke M.
      • Devereaux P.J.
      • Kleijnen J.
      • Moher D.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
      ].

      2.1 Search strategy

      Four independent investigators (D-F L, M-F Y, Y Z, and Y-L B) performed a systematic electronic literature search in PubMed, Embase, Web of Science, and Cochrane library for eligible studies from the beginning of indexing for each database to January 31, 2021. The detailed search strategy is available in supplemental materials (Supplement 1). Moreover, additional studies were included by manual searching. Finally, the study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (No. CRD42021238037).

      2.2 Inclusion and exclusion criteria

      Inclusion criteria were set as follows: 1. studies involving either cold snare or cold EMR for the treatment of SSPs ≥ 10 mm in size; 2. studies including efficacy or safety data on the removal of SSPs; and 3. full-length articles in English.
      Exclusion criteria were set as follows: 1. studies reporting outcomes on SSPs< 10 mm; 2. non-human studies; 3. abstract and case reports; and 4. case series with< 10 patients.

      2.3 Data extraction

      All included studies were independently reviewed by three reviewers (F X, CW, and B-H W). The following details were extracted from each study: first author, the year of publication, study region, age, gender, number of patients, the number of SSPs, the size of SSPs, the location of SSPs, the method of SSPs resection, follow-up duration, complete resection rate, AE rate, and residual rate. Any conflict or disagreement was resolved by discussion and consensus with a third author (J Y).

      2.4 Quality assessment

      Two reviewers (Z-L X and D-G Z) independently assessed the methodologic quality using the Newcastle-Ottawa Scale (NOS) for non-randomized studies, and scores of 0–3, 4–6, and 7–9 corresponded to low, medium, and high quality, respectively [
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • Olkin I.
      • Williamson G.D.
      • Rennie D.
      • Moher D.
      • Becker B.J.
      • Sipe T.A.
      • Thacker S.B.
      Meta-Analysis of Observational Studies in Epidemiology (MOOSE) Group
      Meta-analysis of observational studies in epidemiology: a proposal for reporting.
      ].

      2.5 Definitions

      The technical success rate was defined as the rate of complete macroscopic resection. AEs included immediate bleeding, delayed bleeding, and perforation. The immediate bleeding rate was defined as the rate of clinically significant bleeding requiring endoscopic intervention during SSP resection. In contrast, the delayed bleeding rate was defined as the rate of clinically significant bleeding requiring hospitalization, blood transfusion, endoscopy, surgical intervention, or angiography within 14 days of polypectomy. Perforation was evidenced by diffuse gas or intestinal fluid localized in the peritoneum. The residual rate was the proportion of residual SSPs collected at the resection site during follow-up colonoscopy.

      2.6 Outcomes

      The primary outcome was the technical success rate. The secondary outcomes were rates of AEs and residual SSPs. Beside, subgroup analyses were also performed: 1. outcomes based on techniques for the treatment of SSPs (cold snare vs. cold EMR). 2. outcomes based on the location of SSPs (proximal colon vs. distal colon), and 3. outcomes based on the size of SSPs (10–19 mm vs. ≥ 20 mm).

      2.7 Statistical analysis

      The effect of interest was pooled rates in the form of proportions of overall included patients (%) with 95% confidence limits. A random-effects model was applied to analyze significant heterogeneity (I2 > 50% and P < 0.05); otherwise, a fixed-effects model was adopted. The corresponding forest plots were constructed to express pooled estimates of the outcomes with the weights of individual studies. A funnel plot and Egger test were used to assess publication bias. Sensitivity analysis was performed by systematically removing individual studies in turn to explore its effect on the rates of technical success, AEs, and residual SSPs. Univariate and multivariate meta-regression was performed to investigate the predictive factors of technical success, AEs, and residual SSPs. All statistical analyses were performed using the meta-package in R Statistics 3.6.1 (Lanzhou, China) by two authors (D-F L and L-S W). All tests were two-sided, and P < 0.05 was considered statistically significant.

      3. Results

      3.1 Study characteristics

      A total of 144 studies were retrieved using the search strategy and manual search. Of these 144 studies, 87 potential studies were retained after 57 duplications were removed. After reviewing the titles, abstracts and full texts, 10 studies matched the selection criteria in the final analysis [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
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      • Schoeman S.
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      • Pellise M.
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      • Moss A.
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      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
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      • Hirata T.
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      • Ishii R.
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      • Muramoto T.
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      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
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      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
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      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Mangira D.
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      • Raftopoulos S.
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      Cold snare piecemeal EMR of large sessile colonic polyps >/=20 mm (with video).
      ,
      • Muniraj T.
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      • Deng Y.
      • Aslanian H.R.
      Cold snare polypectomy for large sessile colonic polyps: a single-center experience.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ] (Fig. 1). Origins of these 10 studies were as follows: four were from Australia [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Mangira D.
      • Cameron K.
      • Simons K.
      • Zanati S.
      • LaNauze R.
      • Raftopoulos S.
      • Brown G.
      • Moss A.
      Cold snare piecemeal EMR of large sessile colonic polyps >/=20 mm (with video).
      ], two were from the USA [
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ], two were from Japan [
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ], one was from the UK [
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ] and one was from Belgium [
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ]. These studies were published between 2015 and 2020, four were prospective studies [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ] and the others were retrospective studies [
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Mangira D.
      • Cameron K.
      • Simons K.
      • Zanati S.
      • LaNauze R.
      • Raftopoulos S.
      • Brown G.
      • Moss A.
      Cold snare piecemeal EMR of large sessile colonic polyps >/=20 mm (with video).
      ,
      • Muniraj T.
      • Sahakian A.
      • Ciarleglio M.M.
      • Deng Y.
      • Aslanian H.R.
      Cold snare polypectomy for large sessile colonic polyps: a single-center experience.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ]. In addition, two studies were multi-centers experiences [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Mangira D.
      • Cameron K.
      • Simons K.
      • Zanati S.
      • LaNauze R.
      • Raftopoulos S.
      • Brown G.
      • Moss A.
      Cold snare piecemeal EMR of large sessile colonic polyps >/=20 mm (with video).
      ] and the others were single-center experiences [
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Muniraj T.
      • Sahakian A.
      • Ciarleglio M.M.
      • Deng Y.
      • Aslanian H.R.
      Cold snare polypectomy for large sessile colonic polyps: a single-center experience.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ]. Only SSPs removed by cold snare or cold EMR were included in the final analysis. A total of 1021 patients were included, with 59.5% of patients being females and a median age of the population of 62 years (Table S1).
      A total of 1727 SSPs were included with a mean size of 11.8 mm (range, 10–40 mm). Of these 1727 SSPs, 713 SSPs were resected using cold snare [
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ], and 1014 SSPs were resected using cold EMR [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Mangira D.
      • Cameron K.
      • Simons K.
      • Zanati S.
      • LaNauze R.
      • Raftopoulos S.
      • Brown G.
      • Moss A.
      Cold snare piecemeal EMR of large sessile colonic polyps >/=20 mm (with video).
      ,
      • Muniraj T.
      • Sahakian A.
      • Ciarleglio M.M.
      • Deng Y.
      • Aslanian H.R.
      Cold snare polypectomy for large sessile colonic polyps: a single-center experience.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ]. Seven studies [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ] reported the location of SSPs: 547 SSPs in the proximal colon and 514 SSPs in the distal colon. Six studies [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ] reported data on the size stratification of SSPs, 664 SSPs were 10–19 mm in size, and 356 SSPs were ≥ 20 mm in size (Table S2).

      3.2 Quality of included studies

      Newcastle-Ottawa scores were used to evaluate the methodological quality of non-randomized studies. The results showed that seven studies were moderate-quality studies, and three were low-quality studies (Table S3).

      3.3 Technical success rate

      The technical success rate was reported in all studies (Table S4). Of these 1727 SSPs, 1726 SSPs were successfully removed using CSP and the overall technical success rate was 100% (95% CI, 99.8–100%) with a low level of heterogeneity (I2 = 0%, P = 1) (Fig. 2A).
      Fig. 2
      Fig. 2Technical success rate. A, Overall technical success rate; B, Technical success rate of the cold snare; C, Technical success rate of cold EMR; D, Technical success rate of the proximal colon; E, Technical success rate of the distal colon; F, Technical success rate of 10–19 mm in size; G, Technical success rate of ≥ 20 mm in size.
      Subgroup analysis was performed based on techniques showing that 712 of 713 SSPs were successfully removed using cold snare, and 1014 SSPs were successfully removed using the cold EMR (Table S4). The technical success rate of cold snare and cold EMR was 99.8% (95% CI, 99.0–100%) and 100% (95% CI, 99.8–100%) respectively, with a low level of heterogeneity (Table S4, Fig. 2B, and C).
      Subgroup analysis was performed based on the location of SSPs and showed that the technical success rate was 100% (95% CI, 99.6–100%) and 99.9% (95% CI, 99.3–100%) with a low level of heterogeneity (I2 = 0%, P = 1) when SSPs were located in the proximal and distal colon, respectively (Table S4, Fig. 2D, and E).
      Subgroup analysis was carried out based on the size of SSPs, showing that the technical success rate was 99.8% (95% CI, 98.9–100%) and 100% (95% CI, 99.3–100%) when the size of SSPs was 10–19 mm and ≥ 20 mm, respectively, with a low level of heterogeneity (I2 = 0%, P = 1) (Table S4, Fig. 2F, and G).

      3.4 AEs

      AEs were reported by nine studies for 1593 SSPs [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ,
      • Tate D.J.
      • Awadie H.
      • Bahin F.F.
      • Desomer L.
      • Lee R.
      • Heitman S.J.
      • Goodrick K.
      • Bourke M.J.
      Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.
      ,
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ,
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ,
      • Van Overbeke L.
      • Ilegems S.
      • Mertens G.
      • Mortier L.
      • van Dongen J.
      • Verbeke L.
      • Van Dijck H.
      • Jacomen G.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.
      ,
      • Muniraj T.
      • Sahakian A.
      • Ciarleglio M.M.
      • Deng Y.
      • Aslanian H.R.
      Cold snare polypectomy for large sessile colonic polyps: a single-center experience.
      ,
      • Yoshida N.
      • Inoue K.
      • Tomita Y.
      • Hashimoto H.
      • Sugino S.
      • Hirose R.
      • Dohi O.
      • Naito Y.
      • Morinaga Y.
      • Kishimoto M.
      • Inada Y.
      • Murakami T.
      • Itoh Y.
      Cold snare polypectomy for large sessile serrated lesions is safe but follow-up is needed: a single-centre retrospective study.
      ,
      • McWhinney C.D.
      • Vemulapalli K.C.
      • El Rahyel A.
      • Abdullah N.
      • Rex D.K.
      Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions >/=10 mm.
      ,
      • Rameshshanker R.
      • Tsiamoulos Z.
      • Latchford A.
      • Moorghen M.
      • Saunders B.P.
      Resection of large sessile serrated polyps by cold piecemeal endoscopic mucosal resection: serrated cold piecemeal endoscopic mucosal resection (SCOPE).
      ]. A total of 17 AEs occurred during CSP including 15 cases of immediate bleeding and two cases of delayed bleeding. However, there were no perforations. Therefore, the overall AEs rate was 0.7% (95% CI, 0.2–1.2%) with a low level of heterogeneity (I2 = 0%, P = 0.55) (Table S5 and Fig. 3A).
      Fig. 3
      Fig. 3Adverse events rate. A, Overall AE rate; B, Adverse events rate of the cold snare; C, AE rate of cold EMR; D, AE rate of the proximal colon; E, AE rate of the distal colon; F, AE rate of 10–19 mm in size; G, AE rate of ≥ 20 mm in size.
      Subgroup analysis was conducted based on techniques, and showing that the AE rate was 1.3% (95% CI, 0.4–2.3%) and 0.5% (95% CI, 0–1.1%) when using cold snare and cold EMR, respectively, with a low level of heterogeneity (Table S6, Fig. 3B, and C).
      Subgroup analysis was carried out based on the location of SSPs, showing that the AE rate was 0.3% (95% CI, 0–1.0%) and 0% (95% CI, 0–0.9%) when SSPs were located in the proximal and distal colon, respectively, with a low level of heterogeneity (Table S6, Fig. 3D, and E).
      Subgroup analysis was carried out based on the size of SSPs, showing that the AE rate was 0.9% (95% CI, 0–3.2%) and 0% (95% CI, 0–0.9%) when the size of SSPs was 10–19 mm and ≥ 20 mm, respectively, with a low level of heterogeneity (Table S6, Fig. 3F, and G).

      3.5 Residual SSPs

      All studies reported the rate of residual SSPs, and there were 34 residual SSPs for 1129 SSPs with a median follow-up duration of 6 months (range, 3–24 months). The overall rate of residual SSPs was 2.9% (95% CI, 0.8–5.0%) with a high level of heterogeneity (I2 = 72%, P < 0.01) (Table S7 and Fig. 4A).
      Fig. 4
      Fig. 4Residual SSPs rate. A, Overall residual rate; B, Residual rate of the cold snare; C, Residual rate of cold EMR; D, Residual rate of 10–19 mm in size; E, Residual rate of ≥ 20 mm in size.
      Subgroup analysis was carried out based on techniques used, revealing that the residual rate was 1.3% (95% CI, 0–3.6%) and 3.9% (95% CI, 0.8–6.9%) when using cold snare and cold EMR, respectively, with a high level of heterogeneity (Table S8, Fig. 4B, and C).
      Subgroup analysis was conducted based on the size of SSPs, and indicating that the residual rate was 3.1% (95% CI, 0–6.6%) and 4.7% (95% CI, 0.9–8.5%) when the size of SSPs was 10–19 mm and ≥ 20 mm, respectively, with a low level of heterogeneity (Table S7, Fig. 4D, and E).

      3.6 Meta-regression analysis

      Univariate meta-regression analysis revealed that the mean size of SSPs was an independent factor for the AE rate [odds ratio (OR), -0.0012; 95% CI, -0.0265 to -0.0001; P = 0.027], whereas the mean size of SSPs was not associated with the rate of technical success and residual SSPs (P = 0.7358 and P = 0.5159, respectively). Univariate meta-regression analysis revealed that the techniques (cold snare or cold EMR) were not associated with the rates of technical success, AEs, and residual SSPs (P = 0.5414, P = 0.1070, and P = 0.2598, respectively). Moreover, multivariate meta-regression analysis revealed that the mean size of SSPs and techniques were not associated with the rates of technical success, AE and residual SSPs (P = 0.9258, P = 0.1223, P = 0.8396, P = 0.6049, P = 0.8002, and P = 0.3576, respectively).

      3.7 Publication bias and sensitivity analysis

      The funnel plot and Egger test showed no publication bias for the rates of technical success (P = 0.93) and AEs (P = 0.62) (Fig. S1A and B). However, Egger's test indicated a significant difference of publication bias in the rate of residual SSPs (P = 0.014) (Fig. S1C). Beside, the forest plot showed little sensitivity change by systematically removing each study for technical success rate, AE rate and residual rate (Fig. S2A–C).

      4. Discussion

      To the best of our knowledge, this study was the first systematic analysis of the available studies on the efficacy and safety of CSP (with or without submucosal injection) for the removal of SSPs ≥ 10 mm. The currently available data are limited by smaller sample sizes and reported mainly from single-center studies. Therefore, this systematic review was performed to provide comprehensive outcomes of SSPs removal using CSP and offered comparisons of procedures (cold snare vs. cold EMR), SSPs size (10–19 mm vs. ≥20 mm), and SSPs location (proximal vs. distal colon). In the present study, we found that CSP was an encouraging modality for removing SSPs ≥ 10 mm with a technical success of 100%. At the same time, subgroup analysis showed that the technical success rate was comparable between the cold snare and cold EMR subgroups, between the 10–19 mm and ≥20 mm groups, and between proximal and distal colon subgroups (99.9% vs.100%, 99.8% vs.100% and 100% vs. 99.9%, respectively). Moreover, the AE rate was extremely low at 0.7%. However, subgroup analysis revealed that the AE rate was slightly higher in the cold snare as well as 10–19 mm and proximal colon subgroups (1.3% vs. 0.5%, 0.9% vs. 0 and 0.3% vs. 0, respectively). Furthermore, the residual rate was very low at 2.9%. The subgroup analysis showed the residual rate was slightly lower in the cold snare subgroup compared with the cold EMR subgroup (1.3% vs. 3.9%), as well as in the 10–19 mm subgroup compared with the ≥20 mm subgroup (3.1% vs. 4.7%).
      Thoguluva Chandrasekar et al. have performed a meta-analysis to evaluate the efficacy and safety of removal of SSPs ≥10 mm, which includes 1137 SSPs (901 cases of hot EMR and 236 cases of cold snare) and the pooled technical success rate is 99.5%, which is similar to our results (99.5% vs. 100%) [
      • Thoguluva Chandrasekar V.
      • Aziz M.
      • Patel H.K.
      • Sidhu N.
      • Duvvuri A.
      • Dasari C.
      • Kennedy K.F.
      • Ashwath A.
      • Spadaccini M.
      • Desai M.
      • Jegadeesan R.
      • Sathyamurthy A.
      • Vennalaganti P.
      • Kohli D.
      • Hassan C.
      • Pellise M.
      • Repici A.
      • Sharma P.
      • Bourke M.J.
      Efficacy and safety of endoscopic resection of sessile serrated polyps 10 mm or larger: a systematic review and meta-analysis.
      ]. However, hot EMR has significantly higher rates of immediate bleeding, delayed bleeding, and residual SSPs than CSP (2% vs. 0.7%, 2.3% vs. 0 and 5% vs. 0.9%, respectively) [
      • Thoguluva Chandrasekar V.
      • Aziz M.
      • Patel H.K.
      • Sidhu N.
      • Duvvuri A.
      • Dasari C.
      • Kennedy K.F.
      • Ashwath A.
      • Spadaccini M.
      • Desai M.
      • Jegadeesan R.
      • Sathyamurthy A.
      • Vennalaganti P.
      • Kohli D.
      • Hassan C.
      • Pellise M.
      • Repici A.
      • Sharma P.
      • Bourke M.J.
      Efficacy and safety of endoscopic resection of sessile serrated polyps 10 mm or larger: a systematic review and meta-analysis.
      ]. Our pooled cohort had a lower overall AE rate (0.7%) and residual rate (2.9%) in the follow-up of 1593 CSP and 1129 SSPs. These results implied that CSP was superior to hot EMR for the removal of SSPs.
      Thoguluva Chandrasekar et al. have performed a systematic review and pooled-analysis to explore the efficacy and safety of cold snare endoscopic resection for removing nonpedunculated colorectal polyps ≥10 mm, which contains 552 polyps (304 adenomas and 248 SSPs), and the pooled technical success rate is 99.3%, with a low AE rate of 1.1% as well as a low residual rate of 4.1% [
      • Thoguluva Chandrasekar V.
      • Spadaccini M.
      • Aziz M.
      • Maselli R.
      • Hassan S.
      • Fuccio L.
      • Duvvuri A.
      • Frazzoni L.
      • Desai M.
      • Fugazza A.
      • Jegadeesan R.
      • Colombo M.
      • Dasari C.S.
      • Hassan C.
      • Sharma P.
      • Repici A.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis.
      ]. However, the residual rate was dramatically higher in adenomas than SSPs (11.1% vs. 1%) [
      • Thoguluva Chandrasekar V.
      • Spadaccini M.
      • Aziz M.
      • Maselli R.
      • Hassan S.
      • Fuccio L.
      • Duvvuri A.
      • Frazzoni L.
      • Desai M.
      • Fugazza A.
      • Jegadeesan R.
      • Colombo M.
      • Dasari C.S.
      • Hassan C.
      • Sharma P.
      • Repici A.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis.
      ]. In our analysis, the rates of technical success and AEs were similar to the above-mentioned study, whereas the rate of residual SSPs was 2.9%, which was slightly higher since we focused only on SSPs (2.9% vs. 1%). This might be attributed to the smaller sample size in the above-mentioned study compared with our study (248 SSPs vs. 1129 SSPs). Nevertheless, the rate of residual SSPs in our study was markedly lower compared with adenomas (2.9% vs. 11.1%), especially for all polyps ≥20 mm (4.7% vs. 22.5%) [
      • Thoguluva Chandrasekar V.
      • Spadaccini M.
      • Aziz M.
      • Maselli R.
      • Hassan S.
      • Fuccio L.
      • Duvvuri A.
      • Frazzoni L.
      • Desai M.
      • Fugazza A.
      • Jegadeesan R.
      • Colombo M.
      • Dasari C.S.
      • Hassan C.
      • Sharma P.
      • Repici A.
      Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis.
      ]. Contrary to most adenomas, SSPs tend to be less bulky and protruding beyond the normal surrounding mucosa and are also generally loose with little or no submucosal fibrosis [
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ]. These results indicated that CSP might be significantly feasible and safe for removing SSPs than adenomas. van Hattem et al. have found that cold EMR is similar to hot EMR when removing SSPs ≥20 mm in terms of technical success rate and recurrence rate (100% vs. 99.6% and 4.3% vs. 4.6%, respectively), which is comparable to our results (100% vs. 99.6% vs. 100% and 4.3% vs. 4.6% vs. 2.9%, respectively) [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ]. Meanwhile, the cold EMR-related AEs were similar between the study by van Hattem et al. and our study (0 vs. 0.5%), which was significantly lower compared with hot EMR (5%) [
      • van Hattem W.A.
      • Shahidi N.
      • Vosko S.
      • Hartley I.
      • Britto K.
      • Sidhu M.
      • Bar-Yishay I.
      • Schoeman S.
      • Tate D.J.
      • Byth K.
      • Hewett D.G.
      • Pellise M.
      • Hourigan L.F.
      • Moss A.
      • Tutticci N.
      • Bourke M.J.
      Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: a retrospective comparison across two successive periods.
      ]. This could be attributed to the use of electrocautery in hot EMR, which generated a deeper resection plane, leading to an increased risk of encountering and transecting thinker blood vessels in submucosal layers and unintended transmural capture [
      • Suzuki S.
      • Gotoda T.
      • Kusano C.
      • Ikehara H.
      • Sugita A.
      • Yamauchi M.
      • Moriyama M.
      Width and depth of resection for small colorectal polyps: hot versus cold snare polypectomy.
      ]. Kimoto et al. in their prospective study, have reported that cold snare is a feasible and safe modality to remove SSPs ≥10 mm with a satisfactory technical success rate (99.8%) and extremely low rates of AEs and residual SSPs (3% and 0.2%, respectively), which is comparable to our results (99.8% vs 99.9%, 3% vs. 1.3% and 0.2% vs. 1.3%, respectively) [
      • Kimoto Y.
      • Sakai E.
      • Inamoto R.
      • Kurebayashi M.
      • Takayanagi S.
      • Hirata T.
      • Suzuki Y.
      • Ishii R.
      • Konishi T.
      • Kanda K.
      • Negishi R.
      • Takita M.
      • Ono K.
      • Minato Y.
      • Muramoto T.
      • Ohata K.
      Safety and efficacy of cold snare polypectomy without submucosal injection for large sessile serrated lesions: a prospective study.
      ].
      Tuttici et al. have reported that cold EMR has several advantages: (1) delineating the margins of lesions, (2) expending the submucosal layer, and making tissue transection easier, and (3) preventing the intra-procedure bleeding through a direct tamponade effect [
      • Tutticci N.J.
      • Hewett D.G.
      Cold EMR of large sessile serrated polyps at colonoscopy (with video).
      ]. In our sub-group analysis, the rates of technical success and AEs were comparable between the cold snare and cold EMR (99.9% vs. 100% and 1.3% vs. 0.5%, respectively), whereas cold snare had a slightly lower residual rate than cold EMR (1.3% vs. 3.9). However, univariate and multivariate meta-regression analysis showed that procedure methods (cold snare vs. cold EMR) were not associated with technical success, AEs, and residual SSPs. Of note, cold snare without submucosal injection, might be less costly and more efficient than cold EMR.
      Previous studies have demonstrated that the immediate bleeding rate is 4.6%, and the delayed bleeding rate is between 2.2% and 6.7% for hot EMR for all polyps. In contrast, the rates of immediate bleeding and delayed bleeding are 11.3% and 6.2% for polyps > 20 mm, respectively [
      • Bronsgeest K.
      • Huisman J.F.
      • Langers A.
      • Boonstra J.J.
      • Schenk B.E.
      • de Vos Tot Nederveen Cappel W.H.
      • Vasen H.F.A.
      • Hardwick J.C.H.
      Safety of endoscopic mucosal resection (EMR) of large non-pedunculated colorectal adenomas in the elderly.
      ,
      • Burgess N.G.
      • Metz A.J.
      • Williams S.J.
      • Singh R.
      • Tam W.
      • Hourigan L.F.
      • Zanati S.A.
      • Brown G.J.
      • Sonson R.
      • Bourke M.J.
      Risk factors for intraprocedural and clinically significant delayed bleeding after wide-field endoscopic mucosal resection of large colonic lesions.
      ]. In our pooled analysis, the overall AEs rate was 0.7% for all SSPs when using CSP and 0 for SSPs ≥ 20 mm. Moreover, the overall AE rate was comparable when CSP was used to remove SSPs of 10–19 mm and ≥ 20 mm (0.9% vs. 0). Univariate meta-regression analysis showed that the size of SSPs was an independent factor associated with AEs. However, multivariate meta-regression analysis demonstrated that AEs were not related to the size of SSPs and procedures (cold snare vs. cold EMR). Therefore, CSP was feasible and safe for all SSPs.
      Bronsgeest et al. have reported that the residual rate is 18.8% for traditional (hot) EMR when removing all colorectal polyps ≥ 20 mm in size [
      • Bronsgeest K.
      • Huisman J.F.
      • Langers A.
      • Boonstra J.J.
      • Schenk B.E.
      • de Vos Tot Nederveen Cappel W.H.
      • Vasen H.F.A.
      • Hardwick J.C.H.
      Safety of endoscopic mucosal resection (EMR) of large non-pedunculated colorectal adenomas in the elderly.
      ]. A pooled analysis shows that the residual rate is 12.7% for traditional EMR when resecting colorectal polyps [
      • Fujiya M.
      • Tanaka K.
      • Dokoshi T.
      • Tominaga M.
      • Ueno N.
      • Inaba Y.
      • Ito T.
      • Moriichi K.
      • Kohgo Y.
      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.
      ]. However, our pooled cohort demonstrated that the residual rate was 2.9% for SSPs ≥ 10 mm in size when using CSP, while the rate for residual SSPs of 10–19 mm and ≥ 20 mm was 2.1% and 4.7%, respectively. Pellise et al. have found that several factors are associated with residual SSPs, such as the size of SSPs (P < 0.001), adjunct modality (P = 0.03), and dysplasia (P = 0.031) [
      • Pellise M.
      • Burgess N.G.
      • Tutticci N.
      • Hourigan L.F.
      • Zanati S.A.
      • Brown G.J.
      • Singh R.
      • Williams S.J.
      • Raftopoulos S.C.
      • Ormonde D.
      • Moss A.
      • Byth K.
      • P'Ng H.
      • Mahajan H.
      • McLeod D.
      • Bourke M.J.
      Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions.
      ]. Nevertheless, in our study, univariate and multivariate meta-regression analysis showed that the residual rate was not associated with the size of SSPs and techniques. Therefore, we hypothesized that a meticulous CSP was performed with a wide rim of normal mucosa resection at the peripheral margin. After resection, the margins were carefully checked through narrow-band imaging (NBI). Therefore, CSP appeared to be an efficacious technique for removing SSPs ≥ 10 mm in size.
      The strength of our meta-analysis was the sample size since 1727 SSPs were removed by CSP, which was significantly more compared with the individual studies, thus providing a more reliable and clinically relevant inference. In addition, we performed multiple sub-group analyses to assess the outcomes in terms of procedure methods (cold snare vs. cold EMR), location (proximal colon vs. distal colon), and SSPs size (10–19 mm vs. ≥ 20 mm). Most of our outcomes had only none-to-mild heterogeneity, indicating that our results were reliable.
      Our study has several limitations. First, most of the studies were retrospective and conducted at a single center. Second, the follow-up duration differed from center to center, leading to inaccuracies in the residual SSP rate. Third, studies from different regions might contribute to selection bias, which was an unmanageable issue. Fourth, the data were unavailable to assess the residual rate based on the location of SSPs (proximal colon vs. distal colon). Fifth, we did not calculate the rates of immediate bleeding, delayed bleeding and perforation because of substantially low overall AEs. Sixth, no single standardized technique was used in the studies to remove the rim of normal mucosa and identify the residual SSPs at the polypectomy site. Seventh, only six studies reported data on the size stratification, which may decrease the relevance of the results reported, especially as the quality of included studies is relatively low. Eighth, the SSPs were removed using piecemeal cold snare resection or cold EMR in included studies. Moreover, these studies mainly focused on the AEs and residual lesions and did not report the rate of en-bloc resection and piecemeal resection. Therefore, the data were limited in comparing the en-bloc resection rate and piecemeal resection rate. Ninth, there was a significant difference of publication bias in the rate of residual SSPs. The main reasons may be as follows. 1. The characteristics of the included studies were different as some were prospective studies and others were retrospective studies. 2. The follow-up duration was different between centers, leading to the inconsistent residual SSPs rate.
      Collectively, our meta-analysis demonstrated a high technical success rate of 100% with a low AEs rate of 0.7% as well as a low residual rate of 2.9% when using CSP for the removal of SSPs ≥ 10 mm in size. Therefore, CSP was an efficacious and safe technique for removing SSPs ≥ 10 mm in size.

      Conflict of interest

      None declared.

      Acknowledgments

      Thanks very much to Prof. Lode Van Overbeke and Prof. Ken Ohata for providing raw data.

      Funding

      This work was supported by the Natural Science Foundation of Guangdong Province (No. 2018A0303100024 ), Three Engineering Training Funds in Shenzhen (No. SYLY201718 , SYJY201714 and SYLY201801 ), Technical Research and Development Project of Shenzhen (No. JCYJ20150403101028164 , No. JCYC20170307100911479 and No. JCYJ20190807145617113 ), National Natural Science Foundation of China (No. 81502040 ) and Shenzhen Health Planning Commission (No. SZXJ2017030 ).

      Appendix. Supplementary materials

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