Faculty Bibliography

The multitarget stool DNA test with fecal immunochemical test (sDNA-FIT) is recommended by all major US guidelines as an option for colorectal cancer screening. It is approved by the Food and Drug Administration for use in average-risk individuals aged 45 years and older. The sDNA-FIT tests for 11 biomarkers, including point mutations in KRAS, aberrant methylation in NDRG4 and BMP3, and human hemoglobin. Patients collect a stool sample at home, send it to the manufacturer's laboratory within 1 day, and the result is reported in approximately 2 weeks. Compared with FIT, sDNA-FIT has higher sensitivity but lower specificity for colorectal cancer, which translates to a higher false-positive rate. A unique feature of sDNA-FIT is the manufacturer's comprehensive patient navigation system, which operates 24 hours a day and provides active outreach for patient education and reminders in the first month after a test is ordered. Retesting is recommended every 1-3 years, although the optimal testing interval has not yet been determined empirically. The cost of sDNA-FIT is $681 without insurance, but Medicare and most private insurers cover it with no copay or deductible.

Colorectal cancer screening incorporates various testing modalities. Factors including effectiveness, harms, cost, screening interval, patient preferences, and test availability should be considered when determining which test to use. Fecal occult blood testing and endoscopic screening have the most robust evidence, while newer blood- and imaging-based techniques require further evaluation. In this review, we compare the effectiveness, harms, and costs of the various screening strategies.

INTRODUCTION/BACKGROUND:The Veterans Health Administration introduced a clinical reminder system in 2018 to help address process gaps in colorectal cancer screening, including the diagnostic evaluation of positive fecal immunochemical test (FIT) results. We conducted a qualitative study to explore the differences between facilities who performed in the top vs bottom decile for follow-up colonoscopy. METHODS:Seventeen semi-structured interviews with gastroenterology (GI) providers and staff were conducted at 9 high-performing and 8 low-performing sites. RESULTS:We identified 2 domains, current practices and perceived barriers, and most findings were described by both high- and low-performing sites. Findings exclusive to 1 group mainly pertained to current practices, especially arranging colonoscopy for FIT positive patients. We observed only 1 difference in the perceived barriers domain, which pertained to primary care providers. DISCUSSION/CONCLUSIONS:These results suggest that what primarily distinguishes high- and low-performing sites is not a difference in barriers, but rather in the GI clinical care process. Developing and disseminating patient education materials about the importance of diagnostic colonoscopy, eliminating in-person pre-colonoscopy visits when clinically appropriate, and involving GI in missed colonoscopy appointments and outside referrals should all be considered to increase follow-up colonoscopy rates. Our study illustrates the challenges of performing a timely colonoscopy after a positive FIT result and provides insights on improving the clinical care process for patients who are at substantially increased risk for colorectal cancer.

BACKGROUND:Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS), of 141 variants. METHODS:Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3,486 cases and 3,890 controls aged less than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS:Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per standard deviation of ERS = 1.14, 95% confidence interval [CI] = 1.08, 1.20; odds ratio per standard deviation of PRS = 1.59, 95% CI = 1.51, 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615, 0.647). Based on absolute risks, we can expect 26 excess cases per 10,000 men and 21 per 10,000 women, among those scoring at the 90th percentile for both risk scores. CONCLUSIONS:Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.

BACKGROUND:Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer (CRC); however, it remains unclear if the association varies by screening status, time, and other factors. METHODS:We therefore evaluated these questions in UK Biobank. Multivariable-adjusted Hazard Ratios (HRs) and 95% Confidence Intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS:No association was observed between use of glucosamine and risk of CRC overall (HR: 0.94; 95% CI: 0.85-1.04). However, the association varied by screening status (p-interaction:0.05), with an inverse association observed only among never-screened individuals (HR: 0.86; 95% CI: 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008, HR: 0.80; 95% CI: 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of non-steroidal anti-inflammatory drugs. CONCLUSIONS:While there was no association between glucosamine use and CRC overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of US cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009. In line with this, we observed an inverse association limited to early follow-up in those surveyed 2006-2008, before screening was widely implemented. IMPACT/CONCLUSIONS:These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.

BACKGROUND & AIMS/OBJECTIVE:Colorectal cancer (CRC) incidence has decreased overall in the last several decades, but it has increased among younger adults. Prior studies have characterized this phenomenon in the United States (U.S.) using only a small subset of cases. We describe CRC incidence trends using high-quality data from 92% of the U.S. population, with an emphasis on those younger than 50 years. METHODS:We obtained 2001 to 2016 data from the U.S. Cancer Statistics database and analyzed CRC incidence for all age groups, with a focus on individuals diagnosed at ages 20 to 49 years (early-onset CRC). We compared incidence trends stratified by age, as well as by race/ethnicity, sex, region, anatomic site, and stage at diagnosis. RESULTS:We observed 191,659 cases of early-onset and 1,097,765 cases of late-onset CRC during the study period. Overall, CRC incidence increased in every age group from 20 to 54 years. Whites were the only racial group with a consistent increase in incidence across all younger ages, with the steepest rise seen after 2012. Hispanics also experienced smaller increases in incidence in most of the younger age groups. Asians/Pacific Islanders and blacks saw no increase in incidence in any age group in 2016, but blacks continued to have the highest incidence of CRC for every age group. Greater increase in early-onset CRC incidence was observed for males, left-sided tumors, and regional and distant disease. CONCLUSIONS:Early-onset CRC incidence increased overall from 2001 to 2016, but the trends were markedly different for whites, blacks, Asians/Pacific Islanders, and Hispanics. These results may inform future research on the risk factors underlying early-onset CRC.

Introduction: Digestive laboratory abnormalities related to COVID-19 have been previously described, but most reports came from single centers and findings have been conflicting. We conducted a multi-center study using data from three large urban VA centers (New York Harbor VA, New Orleans VA and Detroit VA) to examine the association between demographics and digestive laboratory values with mortality on index hospitalization among individuals diagnosed with COVID-19.
Method(s): We manually extracted data on individuals hospitalized for COVID-19 between December 2019 and June 2020 at the three facilities. For this analysis, data on demographics and seven digestive laboratory values (highest AST, ALT, alkaline phosphatase, total bilirubin, and INR during admission, as well as lowest hemoglobin and platelets) were analyzed in relation to index hospitalization mortality. We performed descriptive statistics and conducted a multivariable logistic regression model.
Result(s): Out of a total of 390 individuals who were hospitalized with COVID-19, 168 (43%) died and 222 survived. The median age of patients who died was higher than those who survived (75 vs. 69 years). The vast majority (94%) of patients were male. Black patients accounted for a higher proportion of those who died than those who survived (61% vs. 55%), whereas the opposite was true for Whites (26% vs. 31%) and Hispanics (9% vs. 12%). In the multivariable model (Table), mortality was associated with older age (OR 1.07, 95% CI 1.03-1.10), higher BMI (OR 1.05, 95% CI 1.01-1.10), higher AST (OR 1.01, 95% CI 1.004-1.02), lower ALT (OR 0.99, 95% CI 0.98-0.996), higher alkaline phosphatase (OR 1.02, 95% CI 1.01-1.02), and lower hemoglobin (OR 0.83, 95% CI 0.72-0.97).
Conclusion(s): In this multicenter VA study of patients hospitalized with COVID-19 during the first half of 2020, overall mortality was 43%. For mortality during index hospitalization, we observed a positive association with age, BMI, AST, and alkaline phosphatase, and an inverse association with ALT and hemoglobin. Every 1 unit increase in hemoglobin was associated with 17% decreased odds of death. These findings suggest that commonly used digestive laboratory tests have prognostic significance for COVID-related survival

Importance/UNASSIGNED:Gastric cancer is one of the most common cancers, with a high mortality-to-incidence ratio. It is uncertain whether developed nations may encounter an increasing burden of gastric cancer in young adults, as occurs for other cancers. Objectives/UNASSIGNED:To evaluate the incidence and mortality of gastric cancer and compare the global incidence trends between younger (<40 years) and older (≥40 years) populations. Design, Setting, and Participants/UNASSIGNED:This population-based cohort study analyzed data from global and national cancer registries, including data from 1980 to 2018, with at least 15 calendar years of incidence and mortality data. Data on age-standardized incidence and mortality rates of gastric cancer among 48 countries were retrieved from the Surveillance, Epidemiology, and End Results Program, the National Cancer Institute, the Nordic Cancer Registries, and the World Health Organization Mortality Database. The 10-year incidence trend of gastric cancer was assessed by age and sex. The 2018 GLOBOCAN database was used for reporting the global incidence and mortality of gastric cancer, the most recent data available at the time of analysis. Analyses were performed between January 10, 2020, and March 20, 2020. Main Outcomes and Measures/UNASSIGNED:The average annual percent change (AAPC) of the incidence and mortality trends as evaluated by joinpoint regression analysis. Results/UNASSIGNED:A total of 1 033 701 new cases of gastric cancer and 782 685 related deaths were reported in 2018. Overall, the incidence of gastric cancer decreased in 29 countries, and mortality decreased in 41 countries. The age-standardized incidence of gastric cancer decreased from a range of 2.6 to 59.1 in 1980 to a range of 2.5 to 56.8 in 2018 per 100 000 persons. The overall age-standardized mortality rate changed from a range of 1.3 to 25.8 in 1980 to a range of 1.5 to 18.5 in 2018 per 100 000 persons, but increasing mortality was observed in Thailand (female: AAPC, 5.30; 95% CI, 4.38-6.23; P < .001; male: AAPC, 3.92; 95% CI, 2.14-5.74; P < .001). The incidence of gastric cancer decreased in most regions among individuals 40 years or older and increased in populations younger than 40 years in several countries, including Sweden (male: AAPC, 13.92; 95% CI, 7.16-21.11; P = .001), Ecuador (female: AAPC, 6.05; 95% CI, 1.40-10.92; P = .02), and the UK (male: AAPC, 4.27; 95% CI, 0.15-8.55; P = .04; female: AAPC, 3.60; 95% CI, 3.59-3.61; P < .001). Conclusions and Relevance/UNASSIGNED:In this population-based cohort study, an increasing incidence of gastric cancer was observed in younger individuals in some countries, highlighting the need for more preventive strategies in younger populations. Future research should explore the reasons for these epidemiologic trends.

BACKGROUND AND AIMS:Whether patients with cirrhosis have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which infection and cirrhosis increase the risk of adverse patient outcomes remain unclear. APPROACH AND RESULTS:We identified 88,747 patients tested for SARS-CoV-2 between March 1, 2020, and May 14, 2020, in the Veterans Affairs (VA) national health care system, including 75,315 with no cirrhosis-SARS-CoV-2-negative (C0-S0), 9,826 with no cirrhosis-SARS-CoV-2-positive (C0-S1), 3,301 with cirrhosis-SARS-CoV-2-negative (C1-S0), and 305 with cirrhosis-SARS-CoV-2-positive (C1-S1). Patients were followed through June 22, 2020. Hospitalization, mechanical ventilation, and death were modeled in time-to-event analyses using Cox proportional hazards regression. Patients with cirrhosis were less likely to test positive than patients without cirrhosis (8.5% vs. 11.5%; adjusted odds ratio, 0.83; 95% CI, 0.69-0.99). Thirty-day mortality and ventilation rates increased progressively from C0-S0 (2.3% and 1.6%) to C1-S0 (5.2% and 3.6%) to C0-S1 (10.6% and 6.5%) and to C1-S1 (17.1% and 13.0%). Among patients with cirrhosis, those who tested positive for SARS-CoV-2 were 4.1 times more likely to undergo mechanical ventilation (adjusted hazard ratio [aHR], 4.12; 95% CI, 2.79-6.10) and 3.5 times more likely to die (aHR, 3.54; 95% CI, 2.55-4.90) than those who tested negative. Among patients with SARS-CoV-2 infection, those with cirrhosis were more likely to be hospitalized (aHR, 1.37; 95% CI, 1.12-1.66), undergo ventilation (aHR, 1.61; 95% CI, 1.05-2.46) or die (aHR, 1.65; 95% CI, 1.18-2.30) than patients without cirrhosis. Among patients with cirrhosis and SARS-CoV-2 infection, the most important predictors of mortality were advanced age, cirrhosis decompensation, and high Model for End-Stage Liver Disease score. CONCLUSIONS:SARS-CoV-2 infection was associated with a 3.5-fold increase in mortality in patients with cirrhosis. Cirrhosis was associated with a 1.7-fold increase in mortality in patients with SARS-CoV-2 infection.