Dye-based chromoendoscopy for the detection of colorectal neoplasia: meta-analysis of randomized controlled trials

      Background and Aims

      Dye-based chromoendoscopy (DBC) could be effective in increasing the adenoma detection rate (ADR) in patients undergoing colonoscopy, but the technique is time-consuming and its uptake is limited. We aimed to assess the effect of DBC on ADR based on available randomized controlled trials (RCTs).


      Four databases were searched up to April 2022 for RCTs comparing DBC with conventional colonoscopy (CC) in terms of ADR, advanced ADR, and sessile serrated adenoma detection rate as well as the mean adenomas per patient and non-neoplastic lesions. Relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes were calculated using random-effect models. The I2 test was used for quantifying heterogeneity. Risk of bias was evaluated with the Cochrane tool.


      Overall, 10 RCTs (5334 patients) were included. Indication for colonoscopy was screening or surveillance (3 studies) and mixed (7 studies). Pooled ADR was higher in the DBC group versus the CC group (95% CI, 48.1% [41.4%-54.8%] vs 39.3% [33.5%-46.4%]; RR, 1.20 [1.11-1.29]), with low heterogeneity (I2 = 29%). This effect was consistent for advanced ADR (RR, 1.21 [1.03-1.42]; I2 = .0%), sessile serrated adenomas (6.1% vs 3.5%; RR, 1.68 [1.15-2.47]; I2 = 9.8%), and mean adenomas per patient (MD, .24 [.17-.31]) overall and in the right-sided colon (MD, .28 [.14-.43]). A subgroup analysis considering only trials using high-definition white-light endoscopy reduced the heterogeneity while still showing a significant increase in adenoma detection with DBC: 51.6% (95% confidence interval [CI], 47.1%-56.1%) and 59.1% (95% CI, 54.7-63.3%), RR = 1.14 (95% CI, 1.06-1.23), P = .0004, I2 = .0%, P = .50.


      Meta-analysis of RCTs showed that DBC increases key quality parameters in colonoscopy, supporting its use in everyday clinical practice.


      ADR (adenoma detection rate), CC (conventional colonoscopy), CE (chromoendoscopy), CRC (colorectal cancer), DBC (dye-based chromoendoscopy), MAP (mean adenomas per patient), MD (mean difference), RCT (randomized controlled trial), RR (relative risk), SSA (sessile serrated adenoma), TSA (traditional serrated adenoma)
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        • Zauber A.G.
        • Winawer S.J.
        • O’Brien M.J.
        • et al.
        Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.
        N Engl J Med. 2012; 366: 687-696
        • Kaminski M.F.
        • Regula J.
        • Kraszewska E.
        • et al.
        Quality indicators for colonoscopy and the risk of interval cancer.
        N Engl J Med. 2010; 362: 1795-1803
        • Corley D.A.
        • Jensen C.D.
        • Marks A.R.
        • et al.
        Adenoma detection rate and risk of colorectal cancer and death.
        N Engl J Med. 2014; 370: 1298-1306
        • 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.
        Endoscopy. 2017; 49: 378-397
        • Kaminski M.F.
        • Wieszczy P.
        • Rupinski M.
        • et al.
        Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death.
        Gastroenterology. 2017; 153: 98-105
        • Brown S.R.
        • Baraza W.
        • Din S.
        • et al.
        Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum.
        Cochrane Database Syst Rev. 2010; 10: CD006439
        • Bisschops R.
        • East J.E.
        • Hassan C.
        • et al.
        Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) guideline—update 2019.
        Endoscopy. 2019; 51: 1155-1179
        • Harbord M.
        • Eliakim R.
        • Bettenworth D.
        • et al.
        Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management.
        J Crohns Colitis. 2017; 11: 769-784
        • Jess T.
        • Rungoe C.
        • Peyrin-Biroulet L.
        Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies.
        Clin Gastroenterol Hepatol. 2012; 10: 639-645
        • Kiesslich R.
        • Fritsch J.
        • Holtmann M.
        • et al.
        Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis.
        Gastroenterology. 2003; 124: 880-888
        • Houwen B.B.S.L.
        • Mostafavi N.
        • Vleugels J.L.A.
        • et al.
        Dye-based chromoendoscopy in patients with Lynch syndrome: an individual patient data meta-analysis of randomized trials.
        Am J Gastroenterol. 2021; 116: 825-828
        • Thayalasekaran S.
        • Frazzoni L.
        • Antonelli G.
        • et al.
        Endoscopic technological innovations for neoplasia detection in organized colorectal cancer screening programs: a systematic review and meta-analysis.
        Gastrointest Endosc. 2020; 92: 840-847
        • Repici A.
        • Wallace M.B.
        • East J.E.
        • et al.
        Efficacy of per-oral methylene blue formulation for screening colonoscopy.
        Gastroenterology. 2019; 156: 2198-2207
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • et al.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        J Clin Epidemiol. 2009; 62: 1006-1012
        • Gupta S.
        • Lieberman D.
        • Anderson J.C.
        • et al.
        Spotlight: US Multi-Society Task Force on Colorectal Cancer recommendations for follow-up after colonoscopy and polypectomy.
        Gastroenterology. 2020; 158: 1154
        • Higgins J.P.T.
        • Altman D.G.
        • Gøtzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 18: 343
        • Higgins J.P.T.
        • Thompson S.G.
        • Deeks J.J.
        • et al.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Berkey C.S.
        • Hoaglin D.C.
        • Antczak-Bouckoms A.
        • et al.
        Meta-analysis of multiple outcomes by regression with random effects.
        Stat Med. 1998; 17: 2537-2550
        • Rosenthal R.
        • Rubin D.
        Meta-analytic procedures for combining studies with multiple effect sizes.
        Psychological Bulletin. 1986; 99: 400-406
        • Brooker J.C.
        • Saunders B.P.
        • Shah S.G.
        • et al.
        Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy: a randomized controlled trial.
        Gastrointest Endosc. 2002; 56: 333-338
        • Hurlstone D.P.
        Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy.
        Gut. 2004; 53: 376-380
        • Lapalus M.-G.
        • Helbert T.
        • Napoleon B.
        • et al.
        Does chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate?.
        Endoscopy. 2006; 38: 444-448
        • Stoffel E.M.
        • Turgeon D.K.
        • Stockwell D.H.
        • et al.
        Chromoendoscopy detects more adenomas than colonoscopy using intensive inspection without dye spraying.
        Cancer Prev Res. 2008; 1: 507-513
        • Pohl J.
        • Schneider A.
        • Vogell H.
        • et al.
        Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomised two-centre trial.
        Gut. 2011; 60: 485-490
        • Kahi C.J.
        • Anderson J.C.
        • Waxman I.
        • et al.
        High-definition chromocolonoscopy vs. high-definition white light colonoscopy for average-risk colorectal cancer screening.
        Am J Gastroenterol. 2010; 105: 1301-1307
        • Lesne A.
        • Rouquette O.
        • Touzet S.
        • et al.
        Adenoma detection with blue-water infusion colonoscopy: a randomized trial.
        Endoscopy. 2017; 49: 765-775
        • Hurt C.
        • Ramaraj R.
        • Farr A.
        • et al.
        Feasibility and economic assessment of chromocolonoscopy for detection of proximal serrated neoplasia within a population-based colorectal cancer screening programme (CONSCOP): an open-label, randomised controlled non-inferiority trial.
        Lancet Gastroenterol Hepatol. 2019; 4: 364-375
        • Le Rhun M.
        • Coron E.
        • Parlier D.
        • et al.
        High resolution colonoscopy with chromoscopy versus standard colonoscopy for the detection of colonic neoplasia: a randomized study.
        Clin Gastroenterol Hepatol. 2006; 4: 349-354
        • Murakami T.
        • Sakamoto N.
        • Nagahara A.
        Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma.
        J Gastroenterol Hepatol. 2019; 34: 1685-1695
        • Schlemper R.J.
        • Riddell R.H.
        • Kato Y.
        • et al.
        The Vienna classification of gastrointestinal epithelial neoplasia.
        Gut. 2000; 47: 251-255
        • Facciorusso A.
        • Antonino M.
        • Di Maso M.
        • et al.
        Non-polypoid colorectal neoplasms: classification, therapy and follow-up.
        World J Gastroenterol. 2015; 21: 5149-5157
        • Kaltenbach T.
        • Soetikno R.
        Endoscopic mucosal resection of non-polypoid colorectal neoplasm.
        Gastrointest Endosc Clin North Am. 2010; 20: 503-514
        • Dekker E.
        • Houwen B.B.S.L.
        • Puig I.
        • et al.
        Curriculum for optical diagnosis training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) position statement.
        Endoscopy. 2020; 52: 899-923
        • Zimmermann-Fraedrich K.
        • Pohl H.
        • Rösch T.
        • et al.
        Designs of colonoscopic adenoma detection trials: more positive results with tandem than with parallel studies—an analysis of studies on imaging techniques and mechanical devices.
        Gut. 2021; 70: 268-275
        • Bitar H.
        • Zia H.
        • Bashir M.
        • et al.
        Impact of fellowship training level on colonoscopy quality and efficiency metrics.
        Gastrointest Endosc. 2018; 88: 378-387
        • Lee T.J.W.
        • Blanks R.G.
        • Rees C.J.
        • et al.
        Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.
        Endoscopy. 2013; 45: 20-26