Stool Testing for Colorectal Cancer Screening

Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality and is widely recommended. However, despite the demonstrated benefits of screening and ongoing efforts to improve screening rates, a large percentage of the population remains unscreened. Noninvasive stool based tests offer great opportunity to enhance screening uptake. The evidence supporting the use of both fecal immunochemical testing (FIT) and stool DNA (sDNA) has been growing rapidly and both tests are now commercially available for use. Other stool biomarkers (eg, RNA and protein based) are also actively under study both for use independently and as adjuncts to the currently available tests. This mini review provides current, state of the art knowledge about noninvasive stool based screening. It includes a more detailed examination of those tests currently in use (ie, FIT and sDNA) but also provides an overview of stool testing options under development (ie, protein and RNA)

Refers to: Paul Enck. Not more, but less studies are warranted—If you take your meta-analysis seriously

This submission is in reply to a letter by Dr. Paul Enck regarding our recent conclusions regarding the clinical efficacy of patented probiotic, VSL#3, in Irritable Bowel Syndrome

Associations of chronic diarrhoea with non-alcoholic fatty liver disease and obesity-related disorders among US adults

Mechanisms explaining observed associations between diarrhoea and obesity or increased body mass index (BMI) are unclear. Objective: To assess associations of bowel patterns with BMI, metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD) and other obesity-related disorders. Design: We performed a cross-sectional analysis of data from adults who completed bowel health questions for the 2005 to 2010 cycles of the National Health and Nutrition Examination Surveys. Relationships were examined using multinomial logistic regression. Confounding effects of demographics, smoking, alcohol and BMI were examined by sequential modelling. Results: Among 13 413 adults, weighted prevalence rates of constipation and diarrhoea were 8.9% and 6.6%, respectively. Mean BMI was associated with bowel patterns (p<0.001), and was higher with diarrhoea (30.3 kg/m2) versus normal bowel patterns (28.6 kg/m2) and with diarrhoea versus constipation (27.8 kg/m2). NAFLD was more prevalent (ORs, 95% CI) in diarrhoea versus normal bowel patterns (OR=1.34, 95% CI 1.01 to 1.78) or constipation (OR=1.45, 95% CI 1.03, 2.03) in adjusted analyses. The higher prevalence of MS in diarrhoea versus constipation (OR=1.27, 95% CI 0.97 to 1.67) was not independent of BMI. Conclusions: These findings suggest an association between diarrhoea and NAFLD that is independent of BMI

Thinking Big About Small Adenomas: Moving Toward "Precision Surveillance"

Quality metrics and technological advances for colonoscopy are contributing to detection of more diminutive and small adenomas, increasing the proportion of persons undergoing surveillance for non-advanced neoplasia. In this issue, Kim and colleagues report surveillance colonoscopy findings in average-risk Koreans who had one or more adenomas on a first screening colonoscopy and found a similar risk of metachronous advanced neoplasia between those with 1-2 non-advanced adenoma (the "low-risk adenoma" group) and those with 3 or more small adenomas. The validity, generalizability, and clinical implications of the findings are considered along with recent similar studies. In sum, these studies support expanding the low-risk subgroup to include up to four diminutive tubular adenomas and perhaps persons with up to four small tubular adenomas. They also prompt consideration of "precision surveillance" that considers features of not just the polyps, but of the patient and endoscopist

Adherence to Surveillance Guidelines in Nondysplastic Barrett’s Esophagus

Introduction: Surveillance patterns in Barrett's esophagus (BE) are not well characterized. Guidelines published between 2002 and 2008 recommended surveillance esophagogastroduodenoscopy (sEGD) at 3-year intervals for nondysplastic BE (NDBE). We assessed guideline adherence in incident NDBE in a Veterans Affairs (VA)-based study. Methods: At a single VA center, we identified incident cases of biopsy-confirmed NDBE between January, 2006 and December, 2008. We excluded patients aged 76 years and above and those who developed BE-associated dysplasia or cancer during follow-up. All sEGDs through October, 2014 were documented. Our primary criteria classified cases as guideline adherent if a sEGD was performed within 6 months of each expected 3-year surveillance interval; in cases with >=2 sEGDs, 1 sEGD >6 months, and <=1 year outside an interval was allowed if the average interval was between 2.5 and 3.5 years. Comorbidity, primary care encounters, presence of long-segment BE (LSBE), endoscopist recommendations, and Charlson comorbidity index (CCI) were assessed. Results: We identified 110 patients (96.4% male, 93.6% white) with mean age 58.9+/-8.5 years at index EGD. Median follow-up was 6.7 years (range, 3.7 to 8.6). Thirty-three (30.0%) cases were guideline adherent; 77 (70.0%) cases were nonadherent, including 52 (47.3%) with irregular surveillance and 25 (22.7%) with no surveillance. Forty cases (14 adherent) had 1 sEGD, 36 (18 adherent) had 2, 8 (1 adherent) had 3, and 1 nonadherent case had 4. Adherent cases were significantly older (61.5 vs. 57.9 y, P=0.04), and tended to have more LSBE (33.3% vs. 20.8%, P=0.16). There were no differences between adherent and nonadherent cases in annual primary care encounters (72.7% vs. 66.2%, P=0.66), CCI>=4 (15.2% vs. 15.6%, P=0.95), biopsy-positive sEGDs (75.8% vs. 76.6%, P=0.92), and any recommendation for subsequent surveillance (81.8% vs. 77.9%, P=0.65). A logistic regression model using age, CCI, and LSBE showed an independent association between adherence and older age (P=0.03). Conclusions: In a single-center VA cohort, sEGD of NDBE was mostly nonadherent to guidelines. Adherent cases were older at baseline with a trend toward more LSBE. A larger study is needed to identify medical and social factors associated with adherence or nonadherence to surveillance

Patient Understanding of Benefits, Risks, and Alternatives to Screening Colonoscopy

While several tests and strategies are recommended for colorectal cancer (CRC) screening, studies suggest that primary care providers often recommend colonoscopy without providing information about its risks or alternatives. These observations raise concerns about the quality of informed consent for screening colonoscopy

Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis

Background & Aims Colorectal cancer (CRC) incidence and mortality are higher in black vs white populations. The reasons for these disparities are not clear, yet some guidelines recommend screening black persons for CRC starting at ages 40–45 years. We performed a systematic review and meta-analysis to compare the prevalence of advanced adenomas (AAs) and advanced, precancerous colorectal neoplasms (ACNs) between asymptomatic black and white screen-eligible adults. Methods We searched Ovid MEDLINE, PubMed, Embase, and the Cochrane Library to identify articles (published from 1946 through June 2017) that reported prevalence values of AA or ACN in average-risk black and white individuals undergoing screening colonoscopy. Two authors independently assessed study quality and risk for bias using a modified validated quality assessment instrument. Following the PRISMA guidelines, 2 authors independently abstracted descriptive and quantitative data from each study. We performed a random effects meta-analysis to determine risk differences and odds ratios (ORs). Results From 1653 articles, we identified 9 studies for analysis, comprising 302,128 individuals. Six of the 9 studies were of high methodological quality, had a low risk for bias, and were included in the meta-analysis. In these 9 studies, the overall prevalence values for AA and ACN did not differ significantly between back (6.57%) and white screened individuals (6.20%; OR, 1.03; 95% CI, 0.81–1.30). Among a subgroup of 5 studies, the prevalence of proximal AA and ACN was significantly higher in black (3.30%) than in white screened individuals (2.42%; OR, 1.20; 95% CI, 1.12–1.30). Excluding the largest study did not affect overall prevalence (OR, 0.99; CI, 0.73–1.34) but eliminated the difference in prevalence of proximal AA or ACN (OR, 1.48; 95% CI, 0.87–2.52). Conclusions In a meta-analysis, we found the overall prevalence of AA and ACN did not differ significantly between average-risk black and white persons, indicating that the age at which to begin CRC screening need not differ based on race

Performance Characteristics of Fecal Immunochemical Tests for Colorectal Cancer and Advanced Adenomatous Polyps: A Systematic Review and Meta-analysis

Background: Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas. Purpose: To summarize performance characteristics of FITs for CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy (reference standard) and to identify factors affecting these characteristics. Data Sources: Ovid MEDLINE, PubMed, Embase, and the Cochrane Library from inception through October 2018; reference lists of studies and reviews. Study Selection: Two reviewers independently screened records to identify published English-language prospective or retrospective observational studies that evaluated FIT sensitivity and specificity for colonoscopic findings in asymptomatic, average-risk adults. Data Extraction: Two authors independently extracted data and evaluated study quality. Data Synthesis: Thirty-one studies (120 255 participants; 18 FITs) were included; all were judged to have low to moderate risk of bias. Performance characteristics depended on the threshold for a positive result. A threshold of 10 µg/g resulted in sensitivity of 0.91 (95% CI, 0.84 to 0.95) and a negative likelihood ratio of 0.10 (CI, 0.06 to 0.19) for CRC, whereas a threshold of greater than 20 µg/g resulted in specificity of 0.95 (CI, 0.94 to 0.96) and a positive likelihood ratio of 15.49 (CI, 9.82 to 22.39). For advanced adenomas, sensitivity was 0.40 (CI, 0.33 to 0.47) and the negative likelihood ratio was 0.67 (CI, 0.57 to 0.78) at 10 µg/g, and specificity was 0.95 (CI, 0.94 to 0.96) and the positive likelihood ratio was 5.86 (CI, 3.77 to 8.97) at greater than 20 µg/g. Studies had low to high heterogeneity, depending on the threshold. Although several FITs had adequate performance, sensitivity and specificity for CRC for 1 qualitative FIT were 0.90 and 0.91, respectively, at its single threshold of 10 µg/g; positive and negative likelihood ratios were 10.13 and 0.11, respectively. Comparison of 3 FITs at 3 thresholds was inconclusive: CIs overlapped, and the comparisons were across rather than within studies. Limitations: Only English-language studies were included. Incomplete reporting limited quality assessment of some evidence. Performance characteristics are for 1-time rather than serial testing. Conclusion: Single-application FITs have moderate to high sensitivity and specificity for CRC, depending on the positivity threshold. Sensitivity of 1-time testing for advanced adenomas is low, regardless of the threshold

A risk prediction tool for colorectal cancer screening: a qualitative study of patient and provider facilitators and barriers

Background: Despite proven effectiveness of colorectal cancer (CRC) screening, at least 35% of screen-eligible adults are not current with screening. Decision aids and risk prediction tools may help increase uptake, adherence, and efficiency of CRC screening by presenting lower-risk patients with options less invasive than colonoscopy. The purpose of this qualitative study was to determine patient and provider perceptions of facilitators and barriers to use of a risk prediction tool for advanced colorectal neoplasia (CRC and advanced, precancerous polyps), to maximize its chances of successful clinical implementation. Methods: We conducted qualitative, semi-structured interviews with patients aged 50-75 years who were not current with CRC screening, and primary care providers (PCPs) at an academic and a U.S. Department of Veterans Affairs Medical Center in the Midwest from October 2016 through March 2017. Participants were asked about their current experiences discussing CRC screening, then were shown the risk tool and asked about its acceptability, barriers, facilitators, and whether they would use it to guide their choice of a screening test. The constant comparative method guided analysis. Results: Thirty patients and PCPs participated. Among facilitators were the tool's potential to increase screening uptake, reduce patient risk, improve resource allocation, and facilitate discussion about CRC screening. PCP-identified barriers included concerns about the tool's accuracy, consistency with guidelines, and time constraints. Conclusions: Patients and PCPs found the risk prediction tool useful, with potential to increase uptake, safety, and efficiency of CRC screening, indicating potential acceptability and feasibility of implementation into clinical practice