Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Most colorectal cancer (CRC) screening tests, including fecal immunochemical (FIT) and multitarget stool DNA tests, require patients to scrape a stool sample at home before mailing it to a central lab. This requirement not only deters screening adherence but can also introduce risks of human error, environmental exposure, and transit-related issues. The multitarget stool RNA test (mt-sRNA), which comprises a FIT component and an RNA molecular component, is the only FDA-approved stool-based test for the detection of both CRC and advanced adenomas (AA) that does not require patients to perform an at-home FIT. Instead, trained technicians complete the FIT in the laboratory after the sample is received. This study evaluates the comparability of at-home and in-laboratory FIT in relation to mt-sRNA test performance. METHODS:To assess comparability between the 2 FIT methods, banked residual stool samples from the mt-sRNA test pivotal clinical trial (CRC-PREVENT) were used. As part of clinical trial requirements, subjects were required to collect a stool sample using the mt-sRNA collection kit and complete an at-home FIT swab before shipping the sample back to the laboratory. Patients were subsequently required to complete a screening colonoscopy. Residual stool was sampled using the in-laboratory FIT. Both FIT collection methods (at-home and in-laboratory) were analyzed identically. FIT results were compared with each other and with colonoscopy, to assess concordance, sensitivity, and specificity. RESULTS:A total of 1079 stool samples were tested using both at-home and in-laboratory FIT methods. Overall concordance was 93%. Among 20 CRC cases, the sensitivity for both methods was 75% (n=15). For 231 AA cases, sensitivity for the at-home and in-laboratory FIT was 33% and 38%, respectively. Positive percent agreement (PPA) for colorectal neoplasia was 87%. Among 791 subjects with negative findings, specificity for the at-home and in-laboratory FIT was 94% and 95%, respectively. For subjects with negative findings, the negative percent agreement (NPA) was 98%. When incorporating the in-laboratory FIT into the mt-sRNA test, method-calibrated CRC and AA sensitivities were 94% and 48%, respectively. Method-calibrated specificity for no lesions on colonoscopy was 90%. CONCLUSIONS:Our findings suggest that in-laboratory FIT performance may enhance the diagnostic accuracy of the mt-sRNA test. The in-laboratory method may also reduce inadequate sampling and improve patient ease of use.

BACKGROUND:Protocols for standardized assessment of complete colorectal polyp resection are lacking. This may contribute to divergent quality standards and hinder reliable comparison of incomplete resection rates (IRRs) across resection devices, techniques, endoscopists and institutions. To inform the development of such protocols, we aimed to review available methods. METHODS:We systematically searched the MEDLINE, Embase, Web of Science, and Cochrane Library databases from inception to July 30, 2024. Studies describing the use or validation of methods for assessing completeness of polyp resections were included. Studies using recurrence detected at follow-up or histopathological resection specimen margin assessment as outcome measure were excluded, unless used as a reference standard for evaluation of other methods. RESULTS:Forty-five eligible studies were identified. Methods proposed to assist in visual confirmation of complete resection included the use of image enhancement techniques (n=6), artificial intelligence (n=1), and resection defect diameter (n=1). Methods for measuring IRRs based on a histopathological reference standard involved biopsy sampling (n=29) and extended margin resection (n=8). IRR measurement protocols differed in terms of factors such as location and number of biopsies (1-8), and widths of extended resections (1-3 mm). IRRs exceeding 10% were observed for all polyp size categories and almost all resection techniques, with considerable variability in IRRs reported across studies (biopsy sampling: 0-24.2%; extended resection: 0-61.1%). CONCLUSIONS:Different methods are available to assist in visual confirmation of complete resection and measuring IRRs, with considerable variability in their application. This review highlights the need for standardized assessment of complete colorectal polyp resection.

The performance of a CRC screening blood test was validated in a prospective, multicenter, observational study (PREEMPT CRC). The composition of the clinical study population can impact performance measures, potentially affecting the generalizability of the observed outcomes. We conducted a prespecified post-stratification adjustment analysis in which PREEMPT CRC performance values were adjusted to US Census age and sex distribution. The PREEMPT CRC evaluable cohort had a higher proportion of younger individuals and females than the census population. Compared to observed values, census adjustment demonstrated nominally higher CRC sensitivity (81.1% [95% confidence interval or CI, 71.3-88.1%] vs 79.2% [95% CI, 68.4-86.9%]) and advanced precancerous lesion sensitivity (13.7% [95% CI, 12.4-15.0%] vs 12.5% [95% CI, 11.3-13.8%]), with lower advanced colorectal neoplasia specificity (90.4% [95% CI, 90.0-90.7%) vs 91.5% [95% CI, 91.2-91.9%]). Negative and positive predictive values were consistent across age groups, highlighting consistent clinical interpretability of test results regardless of patient age.

INTRODUCTION/BACKGROUND:Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently associated with inflammatory bowel disease (IBD). While both conditions independently increase cancer risk, the comparative burden of cancer in patients with coexisting IBD and PSC (IBD-PSC), isolated IBD, and isolated PSC remains inadequately defined. METHODS:We conducted a retrospective cohort study using the TriNetX nationwide electronic health records database. Patients with IBD-PSC were compared to individuals with isolated IBD and isolated PSC. Propensity score matching (PSM) was employed to balance key baseline characteristics across groups. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated for intestinal and extraintestinal malignancies across three pairwise comparisons: IBD-PSC vs isolated IBD, IBD-PSC vs isolated PSC, and isolated PSC vs isolated IBD. RESULTS:After matching, 4,187 patients were included in each of the IBD-PSC and isolated IBD groups. IBD-PSC was associated with increased risks of colorectal cancer (aHR 4.01, 95% CI: 2.79-5.75, p < 0.001), cholangiocarcinoma (aHR 27.54, 95% CI: 15.05-50.38, p < 0.001), liver cancer (aHR 13.41, 95% CI: 7.42-24.26, p < 0.001), pancreatic cancer (aHR 2.37, 95% CI: 1.18-4.76, p = 0.013), and gallbladder cancer (aHR 36.26, 95% CI: 4.94-266.23, p < 0.001). Compared to isolated PSC, IBD-PSC had higher risks of colorectal (aHR 5.72, 95% CI: 3.17-10.31, p < 0.001) and gallbladder cancer (aHR 4.14, 95% CI: 1.69-10.14, p = 0.001). CONCLUSION/CONCLUSIONS:IBD-PSC is associated with substantially elevated risks of both intestinal and extraintestinal malignancies compared to isolated IBD or PSC. These findings highlight the synergistic oncogenic potential of coexisting IBD and PSC and underscore the need for tailored surveillance and early detection strategies in this high-risk population.

INTRODUCTION/BACKGROUND:Colorectal cancer (CRC) is the fourth most common cancer in the USA and second leading cause of cancer deaths. While screening rates have increased and mortality rates have declined, disparities persist. This study investigates the screening rates and mortality correlation over 25 years. METHODS:We analyzed trends in age-adjusted CRC screening and mortality rates (AAMRs) for adults aged ≥ 50 using BRFSS and CDC WONDER databases, respectively. Correlation analysis between CRC screening rates and AAMRs and projected AAMRs at 100% screening rates were calculated using Jamovi and R software. RESULTS:CRC screening rates increased from 41.5% in 1999 to 76.3% in 2023. Non-Hispanic Whites recorded the highest rates (80.1%), while American Indians or Alaskan Natives (AI/AN) had a low screening rate of 48.65% in 2023. Non-insured individuals had a screening rate of 33.02%, while insured recorded 78.13% in 2023. AAMRs of CRC declined significantly over time, from 69.3% to 40.7% per 100,000 (1999-2024). AAMRs demonstrated a strong inverse correlation (- 0.885) with screening rates. Correlation analysis revealed stronger associations between screening and mortality for NH Whites and African Americans (AA) populations (- 0.824 and - 1.19, respectively). The projected AAMR at 100% screening was 18.91 (95% CI 17.92-19.91), versus 40.4 at 76.3% in 2023. CONCLUSION/CONCLUSIONS:CRC screening increased over the past 25 years, achieving 76.3% in 2023, correlating with decrease in AAMRs. Disparities persist across races and different socioeconomic groups. At 100% screening rates, projected AAMR is 18.919. Equity-focused interventions are needed to further increase CRC screening rates.

BACKGROUND:The benefits of achieving endoscopic remission among older adults with inflammatory bowel disease (IBD) who have mild persistent disease activity are unknown. METHODS:This was a retrospective study of adults ≥ 60 with IBD who had mild or no disease activity on endoscopy from January 1, 2018-January 1, 2023. The primary outcome was a composite of major IBD-specific adverse events (hospitalizations, surgery, and prescription of corticosteroids for IBD-related symptoms) within 1 year of endoscopic assessment. Our secondary outcome was a composite of 1-year morbidity-related events (mortality, all-cause hospitalization, infection requiring antibiotics, venous thromboembolism, cardiovascular events, and osteoporotic fractures). We also assessed outcomes at 5 years. RESULTS:Among 504 patients, 192 (38.1%) had mild endoscopic disease and 312 (61.9%) were in endoscopic remission, with a median disease duration of 11 years. On multivariable analysis, mild endoscopic disease activity increased the odds of a 1-year adverse IBD-specific outcome (aOR 4.16, 95% CI 2.10-8.24), with similar results at 5 years. Furthermore, mild endoscopic disease was associated with increased odds of experiencing an adverse morbidity-related outcome within 1 year as compared to endoscopic remission (aOR 1.56, 95% CI 1.01-2.43). CONCLUSIONS:Among older adults with prevalent IBD, mild endoscopic disease activity, as compared to endoscopic remission, was associated with increased odds of adverse IBD-specific and morbidity-related outcomes at 1 year, with this risk persisting for IBD-specific outcomes at 5 years. These findings highlight the importance of achieving endoscopic remission, which may confer both short- and longer-term benefits in this population.

BACKGROUND:Emerging blood tests may improve colorectal cancer (CRC) screening uptake and outcomes but are less sensitive for advanced precancerous lesions than some currently recommended tests. We examine whether these tests meet expectations for U.S. Preventive Services Task Force (USPSTF) recommendation. METHODS:A decision-analytic model that informed USPSTF was replicated and used to estimate the lifetime benefits (averted CRC cases & deaths, life-years gained [LYG]), burdens (required screening tests & colonoscopies), and harms (colonoscopy-related complications) for annual, biennial or triennial blood testing through age 45-75 years vs a benchmark of recommended and contemporary stool-based strategies, with colonoscopy screening as the reference. Base-case analyses assumed 100% adherence. Sensitivity analyses evaluated more realistic scenarios. RESULTS:Among benchmark strategies, colonoscopy screening had the most benefit, with an estimated 30 CRC deaths averted, 356 LYG, 4270 colonoscopies required and 15 complications per 1000 adults; stool-based strategies resulted in 81-88% of LYG for colonoscopy, 6829-19,476 screening tests, 1523-1880 colonoscopies, and 9-10 complications. By comparison, annual blood testing resulted in 85-87% of LYG for colonoscopy and an intermediate number of screenings, colonoscopies and complications. Biennial and triennial blood testing provided 57-72% of LYG for colonoscopy but resulted in net population benefit under plausible scenarios for increased utilization vs existing strategies. CONCLUSIONS:The estimated benefits, burdens and harms of annual blood testing are within the range of current CRC screening strategies. Biennial and triennial testing should also be considered for recommendation given potential for increased utilization and net population benefit.

BACKGROUND AND AIMS/OBJECTIVE:There is limited information regarding performance of fecal immunochemical test (FIT) in post-polypectomy surveillance, or for screening individuals with a family history of CRC . We conducted a systematic review to assess current evidence regarding diagnostic performance of one time FIT in increased risk populations. METHODS:A comprehensive search of multiple databases was conducted to assess studies reporting performance of a one-time FIT as screening or surveillance tool in individuals at increased risk of CRC. RESULTS:We identified three studies reporting on 8817 individuals with personal history of polyps who underwent FIT testing. For CRC detection, one time FIT showed sensitivity ranging from 27.6% to 100.0% and specificity ranging from 55.9% to 94.1% with variable test thresholds and index polyp histology. We identified 12 studies reporting on 5525 individuals with family history of CRC. One time FIT showed a sensitivity ranging from 25.0% to 100.0% and specificity ranging from 83.1% to 92.0% , with variable test thresholds and family history characteristics. CONCLUSION/CONCLUSIONS:Current evidence is limited to adequately assess diagnostic performance of FIT in individuals with family history of CRC, or as follow up after polypectomy.

OBJECTIVES/OBJECTIVE:Post-colonoscopy colorectal cancer (PCCRC) represents an important real-world colonoscopy quality indicator. Using a national database, we evaluated predictors of PCCRC in fecal immunochemical test (FIT)-positive individuals, determined the PCCRC 3-year rate (PCCRC-3y), and performed a root cause analysis (RCA). METHODS:This retrospective cohort study evaluated FIT-positive patients who underwent colonoscopy from January 2015 to July 2022. Data was collected from the Veterans Affairs (VA) national database. PCCRC was defined as CRC detected ≥6 months after colonoscopy. CRC was identified using SNOMED codes and the VA Cancer Registry. The World Endoscopy Organization methodology was used to perform the RCA and calculate the PCCRC-3y rate. RESULTS:We identified 132 PCCRCs among 52,167 FIT-positive individuals. The PCCRC-3y rate was 6.4% (95% CI, 5.0-7.7%). PCCRC locations were proximal colon (43.2%), distal colon (34.8%), and rectum (22%). Root causes were likely new CRC (17.4%), missed lesions with adequate (31.2%) or inadequate (9.8%) examination, incomplete polyp resection (22%), and detected but unresected lesions (19.7%). 16.7% of patients with PCCRC had poor bowel preparation on index colonoscopy. The cecal intubation rate was 88.6% and rectal retroflexion rate was 84.5%. In 14.4% of cases, recommended surveillance intervals did not adhere to established guidelines. Independent predictors of PCCRC were ages 70-79 (HR 7.86; 95% CI, 1.08-57.39), age ≥80 (HR 10.18; 95% CI, 1.06-97.98), tubulovillous adenoma (HR 3.98; 95% CI, 2.52-6.29), and adenoma with high-grade dysplasia (HR 10.15; 95% CI, 5.91-17.42). CONCLUSIONS:Among FIT-positive individuals, the PCCRC-3y rate was 6.4%, with missed lesions and incomplete resection as key contributors. These findings provide useful information on quality metrics in FIT-based CRC screening programs.