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w.vandewetering@maastrichtuniversity.nl ABSTR AC T Background and study aims Implementation of optical diagnosis of diminutive polyps may potentially increase the efficacy and cost-effectiveness of colonoscopies. To adopt such strategy in clinical practice, the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) thresholds provide the basis to be met: ≥ 90 % negative predictive value (NPV) for diagnosis of adenomatous histology and ≥ 90 % agreement on surveillance intervals. We evaluated this within the Dutch Bowel Cancer Screening Program (BCSP). Patients and methods Endoscopic and histological datawere collected from participants of the national bowel cancer screening program with an unfavorable fecal immunochemical test referred for colonoscopy between February 2014 and August 2015 at four endoscopy centers. The "resect and discard" scenario was studied, resecting diminutive polyps without histological evaluation. Agreement between optical diagnosis and histological diagnosis was measured for surveillance intervals according to Dutch, European and American post-polypectomy surveillance guideline.Results Fifteen certified endoscopists participated in this study and included 3028 diminutive polyps. In 2,330 patients both optical and histological diagnosis were available. Optical diagnosis of diminutive polyps showed NPV of 84 % (95 % CI 80-87) for adenomatous histology in the rectosigmoid. Applying the 'resect and discard' strategy resulted in 90.6 %, 91.2 %, 90.9 % agreement on surveillance intervals for the Dutch, European and American guideline respectively.Conclusion Our data representing current clinical practice in the Dutch BCSP practice on optical diagnosis of diminutive polyps showed that accuracy of predicting histology remains challenging, and risk of incorrect optical diagnosis is still significant. Therefore, it is too early to safely implement these strategies.

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OBJECTIVES:To improve colorectal cancer (CRC) survival and lower incidence rates, colonoscopy and/or fecal immunochemical test screening are widely implemented. Although candidate DNA methylation biomarkers have been published to improve or complement the fecal immunochemical test, clinical translation is limited. We describe technical and methodological problems encountered after a systematic literature search and provide recommendations to increase (clinical) value and decrease research waste in biomarker research. In addition, we present current evidence for diagnostic CRC DNA methylation biomarkers.METHODS:A systematic literature search identified 331 diagnostic DNA methylation marker studies published before November 2020 in PubMed, EMBASE, Cochrane Library, and Google Scholar. For 136 bodily fluid studies, extended data extraction was performed. STARD criteria and level of evidence were registered to assess reporting quality and strength for clinical translation.RESULTS:Our systematic literature search revealed multiple issues that hamper the development of DNA methylation biomarkers for CRC diagnosis, including methodological and technical heterogeneity and lack of validation or clinical translation. For example, clinical translation and independent validation were limited, with 100 of 434 markers (23%) studied in bodily fluids, 3 of 434 markers (0.7%) translated into clinical tests, and independent validation for 92 of 411 tissue markers (22%) and 59 of 100 bodily fluids markers (59%).DISCUSSION:This systematic literature search revealed that major requirements to develop clinically relevant diagnostic CRC DNA methylation markers are often lacking. To avoid the resulting research waste, clinical needs, intended biomarker use, and independent validation should be better considered before study design. In addition, improved reporting quality would facilitate meta-analysis, thereby increasing the level of evidence and enabling clinical translation.

(Virtual) chromoendoscopy (CE) improves the detection of small or flat colorectal polyps; however, the evidence in high-risk groups, such as patients of Lynch syndrome (LS), is low. Our aim was to identify and update the evidence for the recommendations regarding surveillance of LS patients, for which the current underlying evidence for use of (virtual) CE was explored. A systematic literature search in PubMed, EMBASE, and Cochrane library was conducted, for all studies comparing (virtual) CE with white-light endoscopy in LS patients. Studies are explained in detail, with special attention to study design, type of (virtual) CE, and timing of polypectomy. Eight studies (409 patients) were included. Five were nonrandomized back-to-back studies and three were randomized back-to-back studies (one parallel and two cross-over design). In six studies the polyps were directly removed, while in two studies polyps were removed only during the second caecal withdrawal. Five studies researched CE with indigo carmine and three studies investigated virtual CE. Due to the heterogeneity between studies, no statistical analysis could be performed. There was a large variety in study design, timing of polypectomy, different (virtual) CE techniques and the patients that were included. Based on current literature, no firm conclusions can be drawn with respect to the additional value of (virtual) CE in the surveillance of patients with LS. However, training of endoscopists in detection and removal of nonpolypoid colorectal neoplasms is crucial, as well as stricter adherence to LS surveillance guidelines in daily clinical practice. For future research, standardization in study designs is needed.