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High-definition colonoscopy for improving adenoma detection: a systematic review and meta-analysis of randomized controlled studies

  • Author Footnotes
    ∗ Drs Tziatzios and Gkolfakis contributed equally to this article.
    Georgios Tziatzios
    Footnotes
    ∗ Drs Tziatzios and Gkolfakis contributed equally to this article.
    Affiliations
    Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece
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  • Author Footnotes
    ∗ Drs Tziatzios and Gkolfakis contributed equally to this article.
    Paraskevas Gkolfakis
    Footnotes
    ∗ Drs Tziatzios and Gkolfakis contributed equally to this article.
    Affiliations
    Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece
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  • Lazaros Dimitrios Lazaridis
    Affiliations
    Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece
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  • Antonio Facciorusso
    Affiliations
    Gastroenterology Unit, Department of Medical Sciences, University of Foggia AOU, Ospedali Riunity Viale Pinto, Foggia, Italy
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  • Giulio Antonelli
    Affiliations
    Endoscopy Unit, Sant'Andrea University Hospital, "Sapienza" University of Rome, Rome, Italy
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  • Cesare Hassan
    Affiliations
    Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy
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  • Alessandro Repici
    Affiliations
    Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center and Humanitas University, Rozzano, Italy
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  • Prateek Sharma
    Affiliations
    Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas, Missouri

    Department of Gastroenterology, Veteran Affairs Medical Center, Kansas, Missouri
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  • Douglas K. Rex
    Affiliations
    Division of Gastroenterology/Hepatology, Indiana University Hospital, Indianapolis, Indiana, USA
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  • Konstantinos Triantafyllou
    Correspondence
    Reprint requests: Konstantinos Triantafyllou, Associate Professor of Gastroenterology, Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, 1, Rimini Street, 124 62 Athens, Greece.
    Affiliations
    Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece
    Search for articles by this author
  • Author Footnotes
    ∗ Drs Tziatzios and Gkolfakis contributed equally to this article.
Published:January 15, 2020DOI:https://doi.org/10.1016/j.gie.2019.12.052

      Background and Aims

      Previous meta-analysis showed marginal benefit of high-definition white-light endoscopy (HD-WLE) over standard-definition colonoscopy (SDC) for adenoma detection, but with residual uncertainty due to inclusion of nonrandomized studies. We aimed to further assess the effect of HD-WLE on adenoma detection by including only randomized controlled trials (RCTs).

      Methods

      A literature search was performed for RCTs evaluating HD-WLE versus SDC in terms of adenoma, advanced adenoma, and serrated sessile adenoma detection rates as well as the mean number of adenomas per colonoscopy (MAC), the mean number of advanced adenomas per colonoscopy (MAAC), and the mean number of sessile serrated adenomas per colonoscopy (MSSAC). The effect size on study outcomes is presented as the risk ratio (RR; 95% confidence interval [CI]) or mean difference (MD; 95% CI). We assessed the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

      Results

      Six RCTs involving 4594 individuals (HD-WLE, 2323; SDC, 2271) were included. Clinical indications were screening (1 study), positive result for fecal occult blood test, personal/family history of colorectal cancer (1 study), and mixed indications (4 studies). Withdrawal time was similar between the 2 arms (MD, −0.06; 95% CI, −0.25 to 0.12; P = .50). The adenoma detection rate was significantly higher in the HD-WLE arm compared with the SDC arm (40% vs 35%; RR, 1.13; 95% CI, 1.05-1.22; P = .001; I2 = 0%; GRADE, low). This effect was consistent for advanced and sessile serrated adenoma detection rates (RR, 1.33; 95% CI, 1.03-1.72; P = .03; I2 = 0%; GRADE, low; and RR, 1.55; 95% CI, 1.05-2.28; P = .03; I2 = 0%; GRADE, low, respectively). In contrast, the difference was not significant for MAC, MAAC, and MSSAC.

      Conclusions

      Meta-analyses of RCT data support the use of HD-WLE in clinical practice, although the additional benefit is limited.

      Abbreviations:

      ADR (adenoma detection rate), CI (confidence interval), CRC (colorectal cancer), GRADE (Grading of Recommendations Assessment, Development and Evaluation), HD-WLE (high-definition white-light endoscopy), MAAC (mean number of advanced adenomas per colonoscopy), MAC (mean number of adenomas per colonoscopy), MD (mean difference), MSSAC (mean number of sessile serrated adenomas per colonoscopy), NNT (number needed to treat), RCT (randomized controlled trial), RR (risk ratio), SDC (standard-definition colonoscopy), SSA/P (sessile serrated adenoma/polyp)

      Introduction

      Adenoma detection rate (ADR) is the main colonoscopy quality indicator. It is inversely associated with the risk of interval colorectal cancer (CRC) and the risk of death from this neoplasia.
      • Kaminski M.F.
      • Thomas-Gibson S.
      • Bugajski M.
      • et al.
      Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative.
      ,
      • Kaminski M.F.
      • Wieszczy P.
      • Rupinski M.
      • et al.
      Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death.
      Despite its advent nearly 15 years ago, the incremental efficacy of high-definition white-light endoscopy (HD-WLE) compared with standard-definition colonoscopy (SDC) in detecting adenomas remains elusive.
      • Kaminski M.F.
      • Hassan C.
      • Bisschops R.
      • et al.
      Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      Although early studies showed promising results,
      • Buchner A.M.
      • Shahid M.W.
      • Heckman M.G.
      • et al.
      High-definition colonoscopy detects colorectal polyps at a higher rate than standard white-light colonoscopy.
      ,
      • Longcroft-Wheaton G.
      • Brown J.
      • Cowlishaw D.
      • et al.
      High-definition vs standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.
      the available meta-analyses showed only a marginal increase in adenoma detection when comparing HD-WLE with SDC.
      • Subramanian V.
      • Mannath J.
      • Hawkey C.J.
      • et al.
      High definition colonoscopy vs standard video endoscopy for the detection of colonic polyps: a meta-analysis.
      In addition, the marked heterogeneity attributed to the inclusion of various study designs generated further uncertainty when interpreting these results. Moreover, because SDC replacement with HD-WLE is associated with substantial costs, especially for those health systems with limited financial resources, the incremental efficacy of HD-WLE should be assessed not only from the clinical perspective but also using cost-effectiveness data, which are currently missing. We aimed to further evaluate the effect of HD-WLE on adenoma detection through a systematic review with meta-analysis incorporating data exclusively from randomized controlled trials (RCTs).

      Methods

      Protocol registration

      We conducted this study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations (Appendix 1, available online at www.giejournal.org).
      • Moher D.
      • Shamseer L.
      • Clarke M.
      • et al.
      Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
      The review protocol is available at the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42018110105.

      Eligibility criteria

      We defined eligibility criteria for our study according to the PICO statement (P, patients undergoing colonoscopy for CRC screening, surveillance or symptom evaluation; I, patients undergoing colonoscopy using high-definition white-light endoscopes [HD-WLE]; C, patients undergoing colonoscopy using standard-definition endoscopes [SDC]; O, ADR and mean number of adenomas per colonoscopy [MAC]). Only prospective RCTs, published as full text in the English language, were eligible for inclusion.

      Identification and selection of studies

      Our search strategy included the free-text terms “colonoscopy*,” “adenoma*,” “random*” as medical subject headings (MeSH) and as free-text terms combined with the Boolean set operator “AND” with the term “endoscop*” as a medical subject heading and as a free-text term. We searched PubMed and the Cochrane Central Register of Controlled Trials electronic databases starting from January 1, 2005, the year that high-definition colonoscopies were introduced. The search was performed on January 19, 2019. Two investigators (G.T. and L.D.D.) performed the search independently (Appendix 2, available online at www.giejournal.org). After removal of duplicates, 2 reviewers (G.T. and L.D.D.) first assessed the titles and abstracts of all results for inclusion; then, they judged the eligibility of the selected articles independently, using predesigned eligibility forms. Any disagreement was resolved by discussion. The references of all eligible studies were searched manually to identify potentially studies missed during the first search. In the case of missing or incomplete data, the corresponding author was contacted to provide further information.

      Data extraction and quality assessment

      Two of the authors (G.T. and L.D.D.) independently extracted data from eligible studies onto a Microsoft Excel spreadsheet (Microsoft, Redmond, Wash, USA) using a data extraction form. Data extraction included the name of the first author, publication year, country of origin, number of centers, number of participating endoscopists, indication for colonoscopy, type of endoscope used, total number of participants, definition of adenoma (ie, conventional or sessile serrated adenoma/polyp [SSA/P]), quality of bowel preparation, and withdrawal time. We also extracted data on the number of lesions (adenomas, advanced adenomas
      • Kaminski M.F.
      • Thomas-Gibson S.
      • Bugajski M.
      • et al.
      Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative.
      [≥10 mm, with a villous component and/or with high-grade dysplasia], SSAs), and the mean number of these lesions were calculated per patient. For the purposes of our study, lesion detection rate was defined as the percentage of colonoscopies with at least one histologically proven lesion.

      Assessment of risk of bias

      Risk of bias of individual studies was assessed using the Cochrane Collaboration’s assessment tool.

      Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available at: https://handbook-5-1.cochrane.org/. Accessed December 9, 2019.

      Two independent researchers (G.T. and P.G.) assessed the risk of bias attributed to the methods used to generate the randomization schedule and conceal treatment allocation (selection bias), implementation of blinding for participants or personnel (performance bias), outcomes assessment (detection bias), proportion of participants who completed follow-up (attrition bias), and evidence of selective reporting of outcomes (reporting bias). Each study included in the meta-analysis was classified as having high, low, or unclear risk of bias, with reference to each of the above-mentioned domains.

      Outcomes assessment

      The primary outcomes of the meta-analysis were the measurement of ADR and MAC in the HD-WLE arm compared with the SDC arm. The secondary outcomes comprised the effect of HD-WLE on advanced ADR, the mean number of advanced adenomas per colonoscopy (MAAC), the SSA detection rate, and the mean number of sessile serrated adenomas per colonoscopy (MSSAC).

      Data synthesis and statistical analysis

      For dichotomous outcomes, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. For continuous outcomes, we calculated the mean difference (MD) with 95% CIs using inverse variance. Pooled ADR and MAC per group were calculated using generic inverse variance analysis, and they are presented with their respective 95% CIs. Data were meta-analyzed using the random-effects model (DerSimonian and Laird method) to allow a more conservative estimate of the effect of HD-WLE. The number of patients needed to treat (NNT) for one additional patient with an adenomatous polyp to be detected was calculated as the inverse of the difference in the ADR between the 2 arms. We assessed publication bias visually by checking the funnel plot for asymmetry or by application of Egger’s test.
      • Egger M.
      • Davey Smith G.
      • Schneider M.
      • et al.
      Bias in meta-analysis detected by a simple, graphical test.
      All analyses were performed at the 0.05 significance level. Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and StatsDirect 3 (StatsDirect Ltd, Sale, Cheshire, UK) software packages were used to meta-analyze all data and to construct the forest and funnel plots.

      Heterogeneity assessment and sensitivity analyses

      We assessed the presence of heterogeneity using the I2 statistic. Thresholds for the values of I2 were interpreted as follows: 0% to 40%, heterogeneity might not be important; 30% to 60%, may represent moderate heterogeneity; 50% to 90%, may represent substantial heterogeneity; 75% to 100%, considerable heterogeneity. For I2 > 50%, we undertook sensitivity analysis to identify the source of heterogeneity by excluding 1 study at a time, as proposed by the Cochrane Collaboration. We further aimed to detect those groups of patients or endoscopists who might benefit more from HD-WLE. In this respect, we undertook 2 sensitivity analyses for our primary endpoints: (1) per indication of colonoscopies (studies including ≤50% vs >50% individuals undergoing screening examinations) and (2) per endoscopists ADR level (≤35% vs >35%) in the SDC arm.

      Assessment of quality of body of evidence

      The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence. Two independent researchers (G.T. and P.G.) graded inconsistency, risk of bias, indirectness, imprecision, and publication bias. Overall quality was deemed very low, low, moderate, or high using GRADEpro (GRADE Working Group).

      Schünemann H, Brożek J, Guyatt G, et al, editors. GRADE handbook for grading quality of evidence and strength of recommendations (Updated October 2013). The GRADE Working Group; 2013. Available at: https://gdt.gradepro.org/app/handbook/handbook.html. Accessed January 28, 2019.

      Results

      Study selection

      The initial search yielded 374 citations. Of these, 363 were excluded after title and abstract review as being irrelevant to the study aim or duplicates. Thus, 11 articles were considered eligible for full-text assessment. Among these, a further 5 were excluded for various reasons, leaving 6 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      to be included in the systematic review and meta-analysis. A flowchart of the selection process is shown in Figure 1.
      Figure thumbnail gr1
      Figure 1Flow diagram for assessment of studies. RCT, Randomized controlled trial.

      Characteristics of the studies

      Overall, 6 studies enrolling 4594 individuals were included in the analysis; 2323 and 2271 patients underwent HD-WLE and SDC, respectively. One study was conducted in the United States
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      and the rest in Europe.
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      In terms of design, all studies but one
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      were of parallel groups design; only data from the index colonoscopies of the tandem design study
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      were taken into account. Half of the studies
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      were multicenter; the rest
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      were conducted in a single center. In all 6 studies,
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      Olympus (Olympus, Tokyo, Japan; Olympus Europe, Hamburg, Germany, Olympus, America Inc, Center Valley, Pa, USA) endoscopes were used (first-generation [180 series] and second-generation [190 series] HD-WLE scopes vs the 160, 160/5, and 165 series of SDC scopes), whereas in 1 study,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      Fujfilm (Fujifilm Corp, Saitama, Japan) and Pentax (Pentax Medical, Tokyo, Japan) colonoscopes (590 series vs 250 series and 3890 series vs 3870 and 3710 series, respectively for the HD-WLE and SDC arms) were also used. Different populations were represented in the studies. Four studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      enrolled a mixed population undergoing screening, surveillance, and diagnostic examinations, 1 study enrolled exclusively individuals undergoing screening,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      and in the study by Pioche et al,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      only individuals at higher-than-average risk for CRC were considered eligible for participation. Participants’ gender (male, 45.7% vs 68%) and mean age (58.2 vs 62.5 years) were similar, and there were no significant differences in the bowel preparation quality between the 2 arms among the studies that reported on this outcome.
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      No difference in withdrawal times—assessed in 4 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      with 2517 participants—was noted between the HD-WLE and SDC groups (MD, −0.06; 95% CI, −0.25 to 0.12; P = .50; I2 = 0%; P = .44). Histopathologic samples were analyzed according to the Vienna classification
      • Schlemper R.J.
      • Riddell R.H.
      • Kato Y.
      • et al.
      The Vienna classification of gastrointestinal epithelial neoplasia.
      ,
      • Dixon M.F.
      Gastrointestinal epithelial neoplasia: Vienna revisited.
      in 2 studies,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      World Health Organization classification
      • Nagtegaal I.D.
      • Odze R.D.
      • Klimstra D.
      • et al.
      The 2019 WHO classification of tumours of the digestive system.
      in one study
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      ; the other 3 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      did not provide relevant details. Two studies
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      stated that the definition of ADR included conventional, traditional serrated adenomas. and SSA/P; 1 study
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      defined ADR as the percentage of colonoscopies with at least 1 adenoma; 3 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      provided no details. Table 1 shows the basic characteristics of the 6 studies.
      Table 1Characteristics of the studies
      Author (year)CountryStudy periodNo. of centersNo. of endoscopistsEndoscope typeNo. of patientsAdenoma definitionADR definitionSDC/HD-WLE, n/nIndicationMale SDC/HD-WLE n (%)Withdrawal time SDC/HD-WLE (minutes), mean ± SEAge SD/HD (years), mean ± SDPreparation quality SDC/HD-WLE, n (%)Screening SDC/HD-WLE, n (%)
      Pellise et al, 2008
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      SpainSeptember 2006 to July 200717Olympus Q160 vs Olympus H180620NANA310/310Mixed147 (47)/151 (49)6.3 ± 0.114/6.2 ± 0.10858.6±16/58.5±17.1Excellent
      The quality of preparation was graded by the endoscopist as follows: (1) excellent, no solid or liquid residue; (2) good, complete mucosal examination after aspiration; (3) fair, persistence of residue despite aspiration, thus preventing correct examination of 5% to 20% of the mucosa; and (4) poor, persistence of residue despite aspiration, thus preventing correct examination of >20% of the mucosa. Patients with poor preparation were excluded from the study.
      GoodFair82 (26)/70 (23)
      247 (80)/248 (80)53 (17)/56 (18)10 (3)/6 (2)
      Tribonias et al, 2009
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      GreeceMay to October 200811Olympus CF -Q165 vs Olympus CFH180390NANA197/193Mixed101 (51)/108 (56)8.85 ± 0.096/8.94 ± 0.11660.6± 11/62.4± 9.9NA
      Only adequately prepared patients were included in the analysis.
      38 (19)/35 (18)
      Rastogi et al, 2011
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      USAAugust 2008 to November 200926Olympus PCF 160 vs Olympus PCF H180 AL420Polyps were removed and sent in separate jars for histopathological examinationNA210/210Mixed143 (68) /133 (63)6.9 ± 0.124 /6.6 ± 0.15259.7± 8.4/62±9.3Excellent
      Bowel preparation was evaluated as proposed by Rex et al.30 This bowel preparation classification was discussed and agreed on by all the endoscopists before the start of enrollment. Patients with inadequate bowel preparation (<90% mucosa seen, mixture of semisolid and solid colonic contents that could not be suctioned or washed) were excluded.
      GoodFair143 (68) /132 (63)
      22 (10)/21 (10)141 (67)/142 (68)47 (22)/47 (22)
      Pioche et al, 2018 (tandem design)
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      France, Italy, Germany, NetherlandsJuly 2012 to April 20146NAOlympus 160 –16 5C vs Olympus190-C856According to Vienna classification
      Vienna classification.17,18
      Tubular, villous, tubulovillous, traditional serrated adenomas, and SSA/P were included427/429Increased risk for colorectal neoplasia418 (48.8)NA58.3±12.7/58.2 ± 13.3Adequate
      Bowel cleansing quality was assessed using the Boston Bowel Preparation Scale (BBPS)31. Adequate quality was defined as BBPS ≥ 6.
      InadequateNA
      315 (73.8)/112 (26.2)341 (79.5)/88 (20.5)
      Zimmermann-Fraedrich et al, 2018
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      GermanyNovember 2013 to September 2016714Olympus 160/5 vs Olympus 1901221According to Vienna classification
      Vienna classification.17,18
      Tubular, villous, tubulovillous, and SSA/Ps were included, but not invasive carcinomas622/599Screening289 (46.5)/274 (45,7)7.0 (6.0-8.0)/6.8 (6.0-8.3)
      Study not reporting on this outcome. Median (interquartile range) examination time (minutes).
      61.9± 6.3/62.5 ± 7Excellent
      Bowel cleansing quality was assessed using a modified combined BBPS.32 Colon was assessed and scored (instead of segmental scoring) as follows: 0, largely unprepared colon, large areas not visible due to residual stool and/or dark fluid; 1, only parts of the colonic mucosa visible because of stool and dark fluid; 2, small amounts of residual stool, small stool fragments and/or dark fluid, but colonic mucosa adequately visible in most of the colon; 3, entire colonic mucosa clearly visible, no residual stool (fragments) or dark fluid.
      At least fair100%
      594 (95.5)/579 (96.7)290 (46.6)/314 (52.4)
      Roelandt et al, 2018
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      BelgiumDecember 2010 to June 2014124Fujinon (EC-250WM5, EC-590WI, EC-590WM, and EC- 590ZW/M); Olympus (CF-Q160AI, CF-Q180AI, and CF-H180AI); and Pentax (EC-3870FK2, EC-3870LK, EC- 3810F, EC-3890F12, and EC-3890Fi) colonoscopes1087According to World Health Organization classification
      World Health Organization classification.19
      Percentage of colonoscopies with at least 1 adenoma identified505/582Mixed253 (50)/280 (48.1)10.1 ± 0.3/10.2 ± 0.31NA
      Bowel cleansing quality was assessed using the Boston Bowel Preparation Scale (BBPS)31. Adequate quality was defined as BBPS ≥ 6.
      ,
      Only adequately prepared patients were included in the analysis.
      191 (37.8)/239 (41)
      ADR, Adenoma detection rate; SDC, standard-definition colonoscopy; HD-WLE, high-definition white-light endoscopy; SE, standard error; SD, standard deviation; NA, not available; SSA/P, sessile serrated adenoma/polyp.
      The quality of preparation was graded by the endoscopist as follows: (1) excellent, no solid or liquid residue; (2) good, complete mucosal examination after aspiration; (3) fair, persistence of residue despite aspiration, thus preventing correct examination of 5% to 20% of the mucosa; and (4) poor, persistence of residue despite aspiration, thus preventing correct examination of >20% of the mucosa. Patients with poor preparation were excluded from the study.
      Only adequately prepared patients were included in the analysis.
      Bowel preparation was evaluated as proposed by Rex et al.
      • Rex D.K.
      • Schwartz H.
      • Goldstein M.
      • et al.
      Safety and colon-cleansing efficacy of a new residue-free formulation of sodium phosphate tablets.
      This bowel preparation classification was discussed and agreed on by all the endoscopists before the start of enrollment. Patients with inadequate bowel preparation (<90% mucosa seen, mixture of semisolid and solid colonic contents that could not be suctioned or washed) were excluded.
      § Vienna classification.
      • Schlemper R.J.
      • Riddell R.H.
      • Kato Y.
      • et al.
      The Vienna classification of gastrointestinal epithelial neoplasia.
      ,
      • Dixon M.F.
      Gastrointestinal epithelial neoplasia: Vienna revisited.
      Bowel cleansing quality was assessed using the Boston Bowel Preparation Scale (BBPS)
      • Lai E.J.
      • Calderwood A.H.
      • Doros G.
      • et al.
      The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research.
      . Adequate quality was defined as BBPS ≥ 6.
      Study not reporting on this outcome. Median (interquartile range) examination time (minutes).
      ∗∗ Bowel cleansing quality was assessed using a modified combined BBPS.
      • Aminalai A.
      • Rosch T.
      • Aschenbeck J.
      • et al.
      Live image processing does not increase adenoma detection rate during colonoscopy: a randomized comparison between FICE and conventional imaging (Berlin Colonoscopy Project 5, BECOP-5).
      Colon was assessed and scored (instead of segmental scoring) as follows: 0, largely unprepared colon, large areas not visible due to residual stool and/or dark fluid; 1, only parts of the colonic mucosa visible because of stool and dark fluid; 2, small amounts of residual stool, small stool fragments and/or dark fluid, but colonic mucosa adequately visible in most of the colon; 3, entire colonic mucosa clearly visible, no residual stool (fragments) or dark fluid.
      †† World Health Organization classification.
      • Nagtegaal I.D.
      • Odze R.D.
      • Klimstra D.
      • et al.
      The 2019 WHO classification of tumours of the digestive system.

      Methodological quality and risk of bias

      A summarized assessment of the risk of bias per study using the Cochrane Collaboration’s risk of bias assessment tool is illustrated in Figure 2. Two studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      did not clarify the method used to generate the randomization sequence, and in 1 study,
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      details about allocation concealment were not provided. Participating physicians were not blinded to the equipment used or the outcomes measured in any of the studies. Finally, 1 study
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      presented data on measurements not included in the initial protocol.

      Primary endpoints

      Adenoma detection rate

      All 6 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      (n = 4594) provided data regarding ADR. Overall, at least 1 adenoma was detected in 897 of 2323 individuals and 776 of 2271 individuals in the HD-WLE and SDC arms, respectively. ADR was higher (40; 95% CI, 33%-48% vs 35 95% CI, 30%-41%) (Supplementary Fig. 1A, available online at www.giejournal.org) in the HD-WLE group compared with the SDC group (RR, 1.13; 95% CI, 1.05-1.22; P = .001) (Fig. 3). The NNT to find 1 additional patient with an adenomatous polyp with the high-definition technology was 23. We did not detect heterogeneity (I2 = 0%; P = .91) or evidence of publication bias (Egger test: bias, −0.72; 95% CI, −4.64 to 3.18; P = .63) (Supplementary Fig. 2A, available online at www.giejournal.org). GRADE analysis indicated that the quality of the evidence supporting higher ADR with HD-WLE was low (Appendix 3, GRADE Summary Table, available online at www.giejournal.org).
      Figure thumbnail gr3
      Figure 3Forest plot for studies assessing the effect of high-definition colonoscopy on the adenoma detection rate. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; M-H, Mantel-Haenszel; SDC, standard-definition colonoscopy.

      Mean number of adenomas per colonoscopy

      The MAC was provided or calculated from raw data in 5 studies
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      (n = 4174). MAC did not differ between the HD-WLE and SDC arms (0.77; 95% CI, 0.55-0.99 vs 0.68; 95% CI, 0.49-0.87, respectively) (Supplementary Fig. 1B, available online at www.giejournal.org) (MD, 0.06; 95% CI, −0.02 to −0.14; P = .13; I2 = 0%; P = .41) (Fig. 4). There was no evidence of publication bias (Egger test: bias, 0.000283; 95% CI, −0.66 to 0.66; P = .99) (Supplementary Fig. 2B, available online at www.giejournal.org). Quality of evidence regarding MAC was low (Appendix 3).
      Figure thumbnail gr4
      Figure 4Forest plot for studies assessing the effect of high-definition colonoscopy on the mean number of adenomas per colonoscopy. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; IV, instrumental variable; SDC, standard-definition colonoscopy; SE, standard error.

      Secondary endpoints

      Advanced adenoma detection rate

      Three studies
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      provided data allowing the advanced ADR to be calculated. At least 1 advanced adenoma was detected in 113 of 1206 and 81 of 1210 individuals in in the HD-WLE and SDC arms, respectively (RR, 1.33; 95% CI, 1.03-1.72; P = .03) (Fig. 5). Neither heterogeneity (I2 = 0%; P = .71) nor evidence of publication bias (Egger test: bias, −0.90; 95% CI, −4.34 to 2.54; P = .27) was found. The quality of the evidence supporting higher advanced ADR with HD-WLE was low (Appendix 3).
      Figure thumbnail gr5
      Figure 5Forest plot for studies assessing the effect of high-definition colonoscopy on the advanced adenoma detection rate. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; M-H, Mantel-Haenszel; SDC, standard-definition colonoscopy.

      Mean number of advanced adenomas per colonoscopy

      The MAAC was provided in 2 studies.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      MAAC was not different between the HD-WLE and SDC arms (MD, 0.05; 95% CI, −0.89 to −0.99; P = .91; I2 = 0%; P = .98) (Supplementary Fig. 3, available online at www.giejournal.org). There was no visual evidence of publication bias by checking the funnel plot for asymmetry (Egger test: bias, not applicable). The quality of evidence regarding MAAC was also low (Appendix 3).

      Sessile serrated adenoma detection rate

      The SSA detection rate was calculated from data provided in 3 studies.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      At least 1 lesion was detected in 61 of 1206 and 41 of 1210 examinations in the HD-WLE and SDC arms, respectively (RR, 1.55; 95% CI, 1.05-2.28; P = .03) (Fig. 6). Heterogeneity (I2 = 0%; P = .43) and evidence of publication bias (Egger test: bias, −1.26; 95% CI, −26.8 to 24.4; P = .74) were not found. GRADE analysis indicated that the quality of the evidence supporting higher SSA/P detection rate with HD-WLE was low (Appendix 3).
      Figure thumbnail gr6
      Figure 6Forest plot for studies assessing the effect of high-definition colonoscopy on the sessile serrated adenoma detection rate. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; M-H, Mantel-Haenszel; SDC, standard-definition colonoscopy.

      Mean number of sessile adenomas per colonoscopy

      The MSSAC was derived from 2 studies.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      MSSAC did not differ between the HD-WLE and SDC arms (MD, 0.04; 95% CI, −0.62 to 0.70; P = .9; I2 = 0%; P = .98) (Supplementary Fig. 4, available online at www.giejournal.org). There was no visual evidence of publication bias by checking the funnel plot for asymmetry (Egger test: bias, not applicable). The quality of evidence regarding MSSAC was once again low (Appendix 3).

      Sensitivity analysis

      Our analysis showed that the beneficial effect of HD-WLE for ADR was evident only in studies with >50% of the participants undergoing screening colonoscopy and in studies with endoscopists with an ADR >35% in the SDC arm (RR, 1.16; 95% CI, 1.01-1.32 and RR, 1.18; 95% CI, 1.06-1.32, respectively). In contrast, we did not detect any significant effect of HD-WLE on MAC in these analyses (Table 2).
      Table 2Sensitivity analysis
      ADR I2% (P value)/RR (95%CI)MAC I2% (P value)/MD (95% CI)
      By indication of examinations
      Screening ≤50%
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      0 (.80)/1.08 (0.97-1.21)53 (.12)/0.00 (−0.21 to 0.22)
      Screening >50%
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      0 (.79)/1.16 (1.01-1.32)NA/0.10 (−0.04 to 0.24)
      By ADR in the SDC arm
      ≤35%
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      ,
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      0 (.78)/1.09 (0.99-1.22)43 (.17)/0.00 (−0.14 to 0.14)
      >35%
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      0 (.93)/1.18 (1.06-1.32)0 (.46)/0.17 (−0.01 to 0.35)
      ADR, Adenoma detection rate; RR, risk ratio; CI, confidence interval; MAC, mean number of adenomas per colonoscopy; MD, mean difference; NA, not applicable; SDC, standard-definition colonoscopy.

      GRADE evidence estimate

      Overall, our confidence in the effect estimates for efficacy was deemed low. In detail, we downgraded the quality of the body of evidence by 2 levels; 1 due to concerns of risk of bias because in every study neither operators nor participants were blinded to the technology used and 1 due to the presence of indirectness in the evidence because the studies included were conducted in different settings (different populations, varying indications, different endoscopes per arm; Appendix 3).

      Discussion

      In the present meta-analysis, based only on high-quality trials (6 RCTs with more than 4500 patients), we showed a statistically significant increase in ADR when passing from standard endoscopy to HD-WLE. However, its clinical relevance is somewhat downgraded by the small difference in ADR between the 2 groups, resulting in an NNT of 23, as well as by the lack of a significant difference in MAC, which is also regarded as an important quality indicator for detection studies, similar to the ADR. Interestingly, a similar discordance between lesion detection rate and the mean number of lesions per colonoscopy was also detected regarding advanced and sessile serrated adenomas.
      The methodological strengths of this study must be acknowledged. We undertook a comprehensive search of multiple electronic databases, based on a predefined protocol. Only RCTs were included, and we did not detect differences in withdrawal times between the 2 arms, and we did not detect any heterogeneity for both of our outcomes. An additional strength of our analysis compared with the previous one by Subramanian et al
      • Subramanian V.
      • Mannath J.
      • Hawkey C.J.
      • et al.
      High definition colonoscopy vs standard video endoscopy for the detection of colonic polyps: a meta-analysis.
      is in the level of supporting evidence and the main outcome. In detail, Subramanian et al
      • Subramanian V.
      • Mannath J.
      • Hawkey C.J.
      • et al.
      High definition colonoscopy vs standard video endoscopy for the detection of colonic polyps: a meta-analysis.
      calculated the incremental diagnostic yield for polyps and adenomas for HD-WLE over the standard definition by meta-analyzing data from 2 RCTs, 1 prospective nonrandomized study, and 2 retrospective studies. Although the incremental diagnostic yield increased significantly for polyp detection rate with HD-WLE, this effect was not evident for ADR (incremental diagnostic yield, 3.5%; 95% CI, 0.9–6.1; NNT, 28). In terms of MAC, HD-WLE was related to higher MAC than SDC (MD, 0.098; 95% CI, 0.039-0.157).
      • Subramanian V.
      • Mannath J.
      • Hawkey C.J.
      • et al.
      High definition colonoscopy vs standard video endoscopy for the detection of colonic polyps: a meta-analysis.
      Four more RCTs
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      • Roelandt P.
      • Demedts I.
      • Willekens H.
      • et al.
      Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.
      as well as various observational and retrospective studies
      • Longcroft-Wheaton G.
      • Brown J.
      • Cowlishaw D.
      • et al.
      High-definition vs standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.
      ,
      • Bond A.
      • O'Toole P.
      • Fisher G.
      • et al.
      New-generation high-definition colonoscopes increase adenoma detection when screening a moderate-risk population for colorectal cancer.
      • Jrebi N.Y.
      • Hefty M.
      • Jalouta T.
      • et al.
      High-definition colonoscopy increases adenoma detection rate.
      • Waldmann E.
      • Britto-Arias M.
      • Gessl I.
      • et al.
      Endoscopists with low adenoma detection rates benefit from high-definition endoscopy.
      have since been published. Thus, we analyzed only RCTs to provide robust data in the field of evidence-based decision making.
      Acknowledging the fact that the current and previous meta-analyses
      • Subramanian V.
      • Mannath J.
      • Hawkey C.J.
      • et al.
      High definition colonoscopy vs standard video endoscopy for the detection of colonic polyps: a meta-analysis.
      are not directly comparable, we assume that any discrepancy in the results could be largely attributed to the inclusion of studies of different design (RCTs, retrospective and prospective cohort vs exclusively RCTs). We also showed that the beneficial effect of HD-WLE on ADR was maintained only for studies where >50% of the examinations were performed for CRC screening, in accordance with 2 retrospectives studies that also showed a higher ADR when HD-WLE was used in a screening population compared with SDC.
      • Bond A.
      • O'Toole P.
      • Fisher G.
      • et al.
      New-generation high-definition colonoscopes increase adenoma detection when screening a moderate-risk population for colorectal cancer.
      ,
      • Jrebi N.Y.
      • Hefty M.
      • Jalouta T.
      • et al.
      High-definition colonoscopy increases adenoma detection rate.
      In addition, we showed that endoscopists with an ADR >35% in the SDC arm may benefit more from HD-WLE. One may speculate that the detection of smaller lesions
      • Hassan C.
      • Repici A.
      Intensive post-polypectomy surveillance: too much for too little?.
      contributes to an increased ADR. Among the studies we analyzed, only one provided relevant data
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      showing that significantly more adenomas <1 cm were detected during HD-WLE compared with SDC (120 of 427 [28.1%] vs 67 of 429 [15.6%]). As far as the favorable impact of HD-WLE on high-level detectors is concerned, the finding is consistent with the rationale that HD-WLE is a highlighting technique, allowing detection of small flat lesions rather than larger polypoid ones, making optimal use of the technology. On the other hand, this benefit may not be uniform for low-level detectors, because detection of flat lesions remains beyond their scope. Improved image resolution is likely to be meaningless when endoscopists fail to recognize flat lesions.
      Despite its association with long-term prevention of CRC, ADR remains an imperfect colonoscopy quality indicator.
      • Kaminski M.F.
      • Wieszczy P.
      • Rupinski M.
      • et al.
      Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death.
      ,
      • Rex D.K.
      • Ponugoti P.L.
      Calculating the adenoma detection rate in screening colonoscopies only: Is it necessary? Can it be gamed?.
      In this regard, the adenoma miss rate, measured in crossover design studies, has been introduced as a surrogate quality indicator.
      • Gkolfakis P.
      • Tziatzios G.
      • Facciorusso A.
      • et al.
      Meta-analysis indicates that add-on devices and new endoscopes reduce colonoscopy adenoma miss rate.
      It has recently been proposed that a clinically relevant correlation between adenoma miss and detection rates might provide further insights on how technology improves colonoscopy outcomes.
      • Hassan C.
      • Senore C.
      • Manes G.
      • et al.
      Diagnostic yield and miss rate of EndoRings in an organized colorectal cancer screening program: the SMART (Study Methodology for ADR-Related Technology) trial.
      Unfortunately, lack of relevant studies reporting on adenoma miss rates precluded its inclusion among the endpoints in this meta-analysis. Our analysis showed that ADR was significantly higher with HD-WLE, and no improvement in MAC was evident. Moreover, this result was evident also for advanced and sessile serrated adenomas. An interpretation of this result is challenging and rather speculative; a possible explanation could be that a small number of patients with many polyps were unevenly distributed across both arms. Moreover, it could also be possible that HD-WLE more often leads to first adenoma detection, therefore increasing the ADR. However, it does not reveal additional lesions in those patients with 1 adenoma already detected; thus, its impact on the mean number of lesions per colonoscopy remains minimal.
      Currently, HD-WLE is considered the standard of care for endoscopy, and it is used together with numerous other techniques, new scopes, and various novel devices to optimize performance during colonoscopy and its outcomes.
      • Kaminski M.F.
      • Hassan C.
      • Bisschops R.
      • et al.
      Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Gkolfakis P.
      • Tziatzios G.
      • Spartalis E.
      • et al.
      Colonoscopy attachments for the detection of precancerous lesions during colonoscopy: a review of the literature.
      In this regard, one might refute the principal research question of the current study, because it may refer to an outdated practice. Although the contribution of HD-WLE in meticulous mucosal visualization and endoscopic diagnosis, characterization, and treatment decision making of lesions in the GI tract is of paramount importance by enhancing fine structural and microvascular details,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.
      ,
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
      its exact impact on adenoma detection is still debatable.
      Recently, 2 studies
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      tested the hypothesis that 2 consecutive generational improvements in colonoscopes may be needed to gain significant benefits in colonoscopy outcomes with controversial results. Thus, we undertook a post hoc subgroup analysis of enrolled studies to evaluate whether our results could be influenced by the number (1
      • Pellise M.
      • Fernandez-Esparrach G.
      • Cardenas A.
      • et al.
      Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
      • Tribonias G.
      • Theodoropoulou A.
      • Konstantinidis K.
      • et al.
      Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial.
      • Rastogi A.
      • Early D.S.
      • Gupta N.
      • et al.
      Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.
      vs 2
      • Pioche M.
      • Denis A.
      • Allescher H.D.
      • et al.
      Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.
      ,
      • Zimmermann-Fraedrich K.
      • Groth S.
      • Sehner S.
      • et al.
      Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.
      ) of intervening generational improvements in HD-WLE. Although the positive impact of the second- over the first-generation HD-WLE on ADR was evident in this subgroup analysis (ADR, 1.17; 95% CI, 1.04-1.31 vs ADR, 1.13; 95% CI, 1.00-1.28), the intergroup difference failed to reach statistical significance (test for subgroup differences: χ2 = 0.14; P = .70). Regarding MAC, no difference between the 2 groups (MD, 0.09; 95% CI, −0.19 to 0.37 and MD, 0.11; 95% CI, −0.01 to 0.22; test for subgroup differences: χ2 = 0.02; P = .90) for first- and second-generational improvements was detected.
      Our study is not without limitations. First, lack of available data did not allow analysis of morphology (flat adenomas), which could better show the benefit offered by HD-WLE. Second, the studies in the meta-analysis included different populations and endoscopy settings. Third, effect sizes for the secondary outcomes were calculated using data from a few studies.
      In conclusion, our meta-analysis of RCTs indicates that high-definition colonoscopy is superior to SDC, regarding adenoma (even advanced and sessile serrated) detection. However, the quality of evidence is low.

      Acknowledgments

      We thank Dr R. Bisschops and Dr G.A. Paspatis who kindly provided further information on the data of their studies. Part of this study was presented as an e-poster during ESGE Days 2019.

      Appendix 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist

      Tabled 1
      Section/topicNo.Checklist itemReported on page no.
      TITLE
      Title1Identify the report as a systematic review, meta-analysis, or both1
      ABSTRACT
      Structured summary2Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number3
      INTRODUCTION
      Rationale3Describe the rationale for the review in the context of what is already known5
      Objectives4Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS)5
      METHODS
      Protocol and registration5Indicate if a review protocol exists, if and where it can be accessed (eg, Web address), and, if available, provide registration information including registration number6, PROSPERO database CRD42018110105
      Eligibility criteria6Specify study characteristics (eg, PICOS, length of follow-up) and report characteristics (eg, years considered, language, publication status) used as criteria for eligibility, giving rationale6
      Information sources7Describe all information sources (eg, databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched6
      Search8Present full electronic search strategy for at least 1 database, including any limits used, such that it could be repeated6-7, Appendix 2
      Study selection9State the process for selecting studies (ie, screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis)7
      Data collection process10Describe method of data extraction from reports (eg, piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators7
      Data items11List and define all variables for which data were sought (eg, PICOS, funding sources) and any assumptions and simplifications made7
      Risk of bias in individual studies12Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis7-8
      Summary measures13State the principal summary measures (eg, risk ratio, difference in means)8
      Synthesis of results14Describe the methods of handling data and combining results of studies, if done, including measures of consistency (eg, I2) for each meta-analysis8-9
      Risk of bias across studies15Specify any assessment of risk of bias that may affect the cumulative evidence (eg, publication bias, selective reporting within studies)9
      Additional analyses16Describe methods of additional analyses (eg, sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified9
      RESULTS
      Study selection17Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram10
      Study characteristics18For each study, present characteristics for which data were extracted (eg, study size, PICOS, follow-up period) and provide the citations10, Table 1
      Risk of bias within studies19Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12)11 Figure 2
      Results of individual studies20For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot10-13
      Synthesis of results21Present results of each meta-analysis done, including confidence intervals and measures of consistency10 - 13
      Risk of bias across studies22Present results of any assessment of risk of bias across studies (see item 15)11 Fig 2
      Additional analysis23Give results of additional analyses, if done (eg, sensitivity or subgroup analyses, meta-regression; see item 16)12-13
      DISCUSSION
      Summary of evidence24Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (eg, health care providers, users, and policy makers)14 - 17
      Limitations25Discuss limitations at study and outcome level (eg, risk of bias), and at review level (eg, incomplete retrieval of identified research, reporting bias)17
      Conclusions26Provide a general interpretation of the results in the context of other evidence, and implications for future research17
      FUNDING
      Funding27Describe sources of funding for the systematic review and other support (eg, supply of data); role of funders for the systematic review18

      Appendix 2. Search strategy

      Tabled 1
      IDSearch strategyFound
      Cochrane Central Register of Clinical Trials (Date Run: January 19, 2019)
      #1MeSH descriptor: [Colonoscopy] Explode all trees1837
      #2MeSH descriptor: [adenoma] Explode all trees1227
      #3MeSH descriptor: [Endoscopy] Explode all trees15916
      #4MeSH descriptor: [Randomized Controlled Trial] Explode all trees138
      #5#1 AND #2 AND #3 OR #45
      PubMed Search (Date Run: January 19, 2019)
      colonoscop* AND adenoma* AND endoscop* AND random* AND ( ("2005/01/01"[PDat] : "3000/12/31"[PDat] ) AND English[lang])
      Results: 369

      Appendix 3. Quality of body of evidence: summary of findings table (GRADE): high-definition white-light endoscopy (HD-WLE) compared with standard-definition colonoscopy (SDC) for outcomes

      Tabled 1
      Certainty assessmentSummary of findings
      No. of participants (studies) follow-upRisk of biasInconsistencyIndirectnessImprecisionPublication biasOverall certainty of evidenceStudy event rates, n/N (%)Relative effect, RR (95% CI)Anticipated absolute effects
      With SDCWith HD-WLERisk with SDCRisk difference with HD-WLE
      ADR
      4594 (6 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low776/2271 (34.2)897/2323 (38.6)1.13 (1.05-1.22)342 per 100044 more per 1000 (from 17 more to 75 more)
      MAC
      4174 (5 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low20632111The mean MAC was 0MD 0.06 higher (0.02 lower to 0.14 higher)
      Advanced ADR
      2416 (3 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low81/1210 (6.7)113/1206 (9.4)1.33 (1.03-1.72)67 per 100022 more per 1000 (from 2 more to 48 more)
      MAAC
      1477 (2 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low702775The mean MAAC was 0MD 0.05 higher (0.89 lower to 0.99 higher)
      Sessile serrated ADR
      2416 (3 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low41/1210 (3.4)61/1206 (5.1)1.55 (1.05-2.28)34 per 100019 more per 1000 (from 2 more to 43 more)
      MSSAC
      1477 (2 RCTs)Serious
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      Not seriousSerious
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Not seriousNone⊕⊕◯◯ low702775The mean MSSAC was 0MD 0.04 higher (0.62 lower to 0.7 higher)
      RR, Risk ratio; CI, confidence interval; ADR, adenoma detection rate; RCT, randomized controlled trial; MAC, mean number of adenomas per colonoscopy; MAAC, mean number of advanced adenomas per colonoscopy; MD, mean difference; MSSAC, mean number of sessile serrated adenomas per colonoscopy.
      This domain was downgraded by 1 point, because there was evidence of performance and detection bias in all studies included in this review.
      This domain was downgraded by 1 point, because of differences in population (applicability), interventions, and outcomes measures (surrogate outcomes) among the studies.
      Figure thumbnail fx1a
      Supplementary Figure 1A, Pooled adenoma detection rate. B, Mean number of adenomas per colonoscopy. ADR, Adenoma detection rate; CI, confidence interval; HD-WLE, high-definition white-light endoscopy; IV, instrumental variable; MAC, mean number of adenomas per colonoscopy; SDC, standard-definition colonoscopy; SE, standard error.
      Figure thumbnail fx1b
      Supplementary Figure 1A, Pooled adenoma detection rate. B, Mean number of adenomas per colonoscopy. ADR, Adenoma detection rate; CI, confidence interval; HD-WLE, high-definition white-light endoscopy; IV, instrumental variable; MAC, mean number of adenomas per colonoscopy; SDC, standard-definition colonoscopy; SE, standard error.
      Figure thumbnail fx2
      Supplementary Figure 2Funnel plots for studies assessing the effect of high-definition colonoscopy on the adenoma detection rate (A) and on the mean number of adenomas per colonoscopy (B). MD, Mean difference; RR, risk ratio; SE, standard error.
      Figure thumbnail fx3
      Supplementary Figure 3Forrest plot for studies assessing the effect of high-definition colonoscopy on the mean number of advanced adenomas per colonoscopy. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; IV, instrumental variable; SDC, standard-definition colonoscopy; SE, standard error.
      Figure thumbnail fx4
      Supplementary Figure 4Forrest plot for studies assessing the effect of high-definition colonoscopy on the mean number of sessile serrated adenomas per colonoscopy. CI, Confidence interval; HD-WLE, high-definition white-light endoscopy; IV, instrumental variable; SDC, standard-definition colonoscopy; SE, standard error.

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