Detection of serrated lesions in proximal colon by simulated sigmoidoscopy vs faecal immunochemical testing in a multicentre, pragmatic, randomised controlled trial.
ABSTRACT: Background:The diagnostic yield of the faecal immunochemical test and sigmoidoscopy in detecting proximal serrated polyps in a colorectal cancer screening programme has not been fully assessed. Aim:We determined the detection rate of proximal serrated polyps by simulated sigmoidoscopy and faecal immunochemical test compared with total colonoscopy in a population-based, multicentre, nationwide, randomised controlled trial (ColonPrev study). Methods:Sigmoidoscopy yield was simulated based on the UK-Flexible Sigmoidoscopy Trial for total colonoscopy referral. Definitions were: proximal serrated polyp (proximal serrated polyp): sessile serrated polyp or hyperplastic polyp of any size and proximal at-risk serrated polyp (at-risk proximal serrated polyp): sessile serrated polyp of any size or hyperplastic polyp???10?mm, both located proximally to the splenic flexure. Results:A total of 10,611 individuals underwent faecal immunochemical test and 5059 underwent total colonoscopy and were evaluated by simulated sigmoidoscopy. Sigmoidoscopy and faecal immunochemical test were less accurate in detecting proximal serrated polyps (odds ratio: 0.13; 95% confidence interval: 0.10-0.18 and 0.13; 0.09-0.18, p?
Project description:<h4>Background & aims</h4>Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance.<h4>Methods</h4>We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (?10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (?10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors.<h4>Results</h4>After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38).<h4>Conclusions</h4>These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.
Project description:BACKGROUND:It is unknown whether narrow-band imaging (NBI) could be more effective than high-definition white-light endoscopy (HD-WLE) in detecting serrated lesions in patients with prior serrated lesions >?5?mm not completely fulfilling serrated polyposis syndrome (SPS) criteria. METHODS:We conducted a randomized, cross-over trial in consecutive patients with prior detection of at least one serrated polyp ?10?mm or???3 serrated polyps larger than 5?mm, both proximal to the sigmoid colon. Five experienced endoscopists performed same-day tandem colonoscopies, with the order being randomized 1:1 to NBI-HD-WLE or HD-WLE-NBI. All tandem colonoscopies were performed by the same endoscopist. RESULTS:We included 41 patients. Baseline characteristics were similar in the two cohorts: NBI-HD-WLE (n?=?21) and HD-WLE-NBI (n?=?20). No differences were observed in the serrated lesion detection rate of NBI versus HD-WLE: 47.4% versus 51.9% (OR 0.84, 95% CI: 0.37-1.91) for the first and second withdrawal, respectively. Equally, no differences were found in the polyp miss rate of NBI versus HD-WLE: 21.3% versus 26.1% (OR 0.77, 95% CI: 0.43-1.38). Follow-up colonoscopy in nine patients (22%) allowed them to be reclassified as having SPS. CONCLUSIONS:In patients with previous serrated lesions, the serrated lesion detection rate was similar with NBI and HD-WLE. A shorter surveillance colonoscopy interval increases the detection of missed serrated polyps and could change the diagnosis of SPS in approximately one in every five patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT02406547, registered on April 2, 2015.
Project description:BACKGROUND:Serrated polyps are important colorectal cancer precursors that are variably detected during colonoscopy. We measured serrated polyp detection rate (SPDR) in a large, multicenter, cross-sectional study of colonoscopy quality to identify drivers of SPDR variation. METHODS:Colonoscopy and pathology reports were collected for a 2-year period (10/2013-9/2015) from four sites across the United States. Data from reports, including size, location, and histology of polyps, were abstracted using a validated natural language processing algorithm. SPDR was defined as the proportion of colonoscopies with ??1 serrated polyp (not including hyperplastic polyps). Multivariable logistic regression was performed to determine endoscopist characteristics associated with serrated polyp detection. RESULTS:A total of 104?618 colonoscopies were performed by 201 endoscopists who varied with respect to specialty (86?% were gastroenterologists), sex (18?% female), years in practice (range 1?-?51), and number of colonoscopies performed during the study period (range 30?-?2654). The overall mean SPDR was 5.1?% (SD 3.8?%, range 0?-?18.8?%). In multivariable analysis, gastroenterology specialty training (odds ratio [OR] 1.89, 95?% confidence interval [CI] 1.33?-?2.70), fewer years in practice (??9 years vs. ??27 years: OR 1.52, 95?%CI 1.14?-?2.04)], and higher procedure volumes (highest vs. lowest quartile: OR 1.77, 95?%CI 1.27?-?2.46)] were independently associated with serrated polyp detection. CONCLUSIONS:Gastroenterology specialization, more recent completion of training, and greater procedure volume are associated with serrated polyp detection. These findings imply that both repetition and training are likely to be important contributors to adequate detection of these important cancer precursors. Additional efforts to improve SPDR are needed.
Project description:BACKGROUND:Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. METHODS:We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. RESULTS:Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. CONCLUSIONS:PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.
Project description:These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address:Which patients should commence surveillance post-polypectomy and post-cancer resection?What is the appropriate surveillance interval?When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10?mm in size or containing any grade of dysplasia, or an adenoma of at least 10?mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant.two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10?mm in size or containing any grade of dysplasia, or an adenoma of at least 10?mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either:two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10?mm in size or containing any grade of dysplasia, or an adenoma of at least 10?mm in size or containing high-grade dysplasia); or five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1?year clearance colonoscopy, then a surveillance colonoscopy after 3 more years.
Project description:OBJECTIVE:Evaluate effectiveness, harms and burdens of faecal blood testing, sigmoidoscopy and colonoscopy screening for colorectal cancer over 15 years. DESIGN:We performed an update of a Cochrane systematic review, and performed network meta-analysis comparing randomised trials evaluating colorectal cancer screening with guaiac faecal occult blood test (gFOBT) (annual, biennial), faecal immunochemical test (FIT) (annual, biennial), sigmoidoscopy (once-only) or colonoscopy (once-only) in a healthy population, aged 50-79 years. We conducted subgroup analysis on sex. Follow-up >5 years was required for analysis of colorectal cancer incidence and mortality. RESULTS:12 randomised trials proved eligible. Compared with no-screening, we found high certainty evidence for sigmoidoscopy screening slightly reducing colorectal cancer incidence (relative risk (RR) 0.76; 95% confidence interval (CI 0.70 to 0.83) and mortality (RR 0.74; 95% CI 0.69 to 0.80), while gFOBT screening had little or no difference on colorectal cancer incidence, but slightly reduced colorectal cancer mortality (annual: RR 0.69; 95% CI 0.56 to 0.86, biennial: RR 0.88; 95% CI 0.82 to 0.93). No screening test reduced mortality nor incidence by more than six per 1000 screened over 15 years. Sigmoidoscopy had a greater effect in men, for both colorectal cancer incidence (women: RR 0.86; 95% CI 0.81 to 0.92, men: RR 0.75, 95% CI 0.71 to 0.79), and mortality (women: RR 0.85; 95% CI 0.71 to 0.96, men: RR 0.67; 95% CI 0.61 to 0.75) (moderate certainty). CONCLUSIONS:In a 15-year perspective, sigmoidoscopy reduces colorectal cancer incidence, while sigmoidoscopy, annual and biennial gFOBT all reduce colorectal cancer mortality. Sigmoidoscopy may reduce colorectal cancer incidence and mortality more in men than in women. PROSPERO REGISTRATION NUMBER:CRD42018093401.
Project description:Measures shown to improve the adenoma detection during colonoscopy (excellent bowel preparation, cecal intubation, cap fitted colonoscope to examine behind folds, patient position change to optimize colon distention, trained endoscopy team focusing on detection of subtle flat lesions, and incorporation of optimum endoscopic examination with adequate withdrawal time) are applicable to clinical practice and, if incorporated are projected to facilitate comprehensive colonoscopy screening program for colon cancer prevention. To determine adenoma and serrated polyp detection rate under conditions designed to optimize quality parameters for comprehensive screening colonoscopy. Retrospective analysis of data obtained from a comprehensive colon cancer screening program designed to optimize quality parameters. Academic medical center. Three hundred and forty-three patients between the ages of 50 years and 75 years who underwent first screening colonoscopy between 2009 and 2011 among 535 consecutive patients undergoing colonoscopy. Comprehensive colonoscopy screening program was utilized to screen all patients. Cecal intubation was successful in 98.8% of patients. The Boston Bowel Preparation Scale for quality of colonoscopy was 8.97 (95% confidence interval [CI]; 8.94, 9.00). The rate of adenoma detection was 60% and serrated lesion (defined as serrated adenomas or hyperplastic polyps proximal to the splenic flexure) detection was 23%. The rate of precancerous lesion detection (adenomas and serrated lesions) was 66%. The mean number of adenomas per screening procedure was 1.4 (1.2, 1.6) and the mean number of precancerous lesions (adenomas or serrated lesions) per screening procedure was 1.6 (1.4, 1.8). Retrospective study and single endoscopist experience. A comprehensive colonoscopy screening program results in high-quality screening with high detection of adenomas, advanced adenomas, serrated adenomas, and multiple adenomas.
Project description:BACKGROUND:To improve patients' comprehension of bowel preparation instructions before colonoscopy, enhanced patient education (EPE) such as cartoon pictures or other visual aids, phone calls, mobile apps, multimedia education and social media apps have been proposed. However, it is uncertain whether EPE can increase the detection rate of colonic polyps and adenomas. OBJECTIVE:This meta-analysis aimed to evaluate the efficacy of EPE in detecting colonic polyps and adenomas. METHODS:We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from their inception to June 2019 for the identification of trials comparing the EPE with standard patient education for outpatients undergoing colonoscopy. We used a random effects model to calculate summary estimates of the polyp detection rate (defined as the number of patients with at least one polyp divided by the total number of patients undergoing selective colonoscopy), adenoma detection rate (defined as the number of patients with at least one adenoma divided by the total number of patients undergoing selective colonoscopy), advanced adenoma detection rate (defined as the number of patients with at least one advanced adenoma divided by the total number of patients undergoing selective colonoscopy), sessile serrated adenoma detection rate (defined as the number of patients with at least one sessile serrated adenoma divided by the total number of patients undergoing selective colonoscopy), cancer detection rate (defined as the number of patients with at least one cancer divided by the total number of patients undergoing selective colonoscopy), or adenoma detection rate - plus (defined as the number of additional adenomas found after the first adenoma per colonoscopy). Moreover, we conducted trial sequential analysis (TSA) to determine the robustness of summary estimates of all primary outcomes. RESULTS:We included 10 randomized controlled trials enrolling 4560 participants for analysis. The meta-analysis suggested that EPE was associated with an increased polyp detection rate (9 trials; 3781 participants; risk ratio [RR] 1.19, 95% CI 1.05-1.35; P<.05; I2=42%) and adenoma detection rate (5 trials; 2133 participants; RR 1.37, 95% CI 1.15-1.64; P<.001; I2=0%), which were established by TSA. Pooled result from the inverse-variance model illustrated an increase in the sessile serrated adenoma detection rate (3 trials; 1248 participants; odds ratio 1.76, 95% CI 1.22-2.53; P<.05; I2=0%). One trial suggested an increase in the adenoma detection rate - plus (RR 4.39, 95% CI 2.91-6.61; P<.001). Pooled estimates from 3 (1649 participants) and 2 trials (1375 participants) generated no evidence of statistical difference for the advanced adenoma detection rate and cancer detection rate, respectively. CONCLUSIONS:The current evidence indicates that EPE should be recommended to instruct bowel preparation in patients undergoing colonoscopy because it can increase the polyp detection rate, adenoma detection rate, and sessile serrated adenoma detection rate. However, further trials are warranted to determine the efficacy of EPE for advanced adenoma detection rate, adenoma detection rate - plus, and cancer detection rate because of limited data.
Project description:We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type.
Project description:Background:Organised programmes for colorectal cancer screening demand a high burden of medical and economic resources. The preferred methods are the faecal immunochemical test and primary colonoscopy. Objective:The purpose of this study was to perform an economic analysis and comparison between these tests in Europe. Methods:We used a Markov cost-utility analysis from a societal perspective comparing biennial faecal immunochemical test or colonoscopy every 10 years screening versus non-screening in Portugal. The population was screened, aged from 50-74 years, and efficacy was evaluated in quality-adjusted life years. For the base-case scenario, the faecal immunochemical test cost was €3 with 50% acceptance and colonoscopy cost was €397 with 38% acceptance. The threshold was set at €39,760/quality-adjusted life years and the primary outcome was the incremental cost-effectiveness ratio. Results:Screening by biennial faecal immunochemical test and primary colonoscopy every 10 years resulted in incremental utilities of 0.00151 quality-adjusted life years and 0.00185 quality-adjusted life years at additional costs of €4 and €191, respectively. The faecal immunochemical test was the most cost-effective option providing an incremental cost-effectiveness ratio of €2694/quality-adjusted life years versus €103,633/quality-adjusted life years for colonoscopy. Colonoscopy capacity would have to increase 1.3% for a faecal immunochemical test programme or 31% for colonoscopy. Conclusion:Biennial faecal immunochemical test screening is better than colonoscopy as it is cost-effective, allows more individuals to get screened, and provides a more rational use of the endoscopic capacity available.