Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Growing evidence suggests that the gut microbiome plays a role in carcinogenesis for early-onset colorectal cancer (EOCRC). The novel Ring Finger Protein 213 (RNF213) gene has broad antimicrobial properties. Our study aimed to compare RNF213 mutation rates in EOCRC and late-onset colorectal cancer using data from the cBioPortal for Cancer Genomics. METHODS:All participants from the cBioPortal with CRC samples that profiled the RNF213 gene were included. Multivariable logistic regression was used to assess the association between EOCRC and primary tumor RNF213 mutation. Cox proportional hazards models were used to evaluate the influence of RNF213 mutation on all-cause mortality risk. All tests were two-sided. RESULTS:OR 1.61, 95% CI 0.72, 3.22). There was no significant difference in all-cause mortality risk by RNF213 mutation status. CONCLUSIONS:Primary tumor mutations in exon 29 of the RNF213 gene are associated with significantly increased odds of EOCRC diagnosis in a multicohort sample of participants with CRC. Future studies of germline and precancerous RNF213 mutations are needed to elucidate its possible role in EOCRC tumorigenesis.

Despite advances in endoscopic techniques, many colorectal surgeries in the United States are still performed for non-malignant colorectal polyps (NMCRPs). This study evaluated trends, demographic variations, and outcomes of surgeries for NMCRPs among all colorectal surgeries over the past decade. Using the TriNetX nationwide database, we identified adults (≥ 18 years of age) who underwent colectomy or proctectomy for NMCRPs or colorectal cancer between 2013 and 2023. We evaluated the proportion of surgeries performed for NMCRPs, stratified by demographic factors, and compared postoperative adverse events (AEs) between NMCRP and colorectal cancer surgeries. Among 136,721 surgeries, 52,480 (38.4%) were for NMCRPs. The proportion of NMCRP surgeries decreased from 59% in 2013 to 33% in 2023, with the most significant decline between 2013 and 2016. Black individuals showed the highest decrease. Compared with colorectal cancer surgeries, NMCRP surgeries were associated with significantly lower risks of wound, infectious, urinary, pulmonary, gastrointestinal, and cardiac AEs. Although the proportion of NMCRP surgeries has declined, ongoing efforts in education and training are needed to further reduce unnecessary surgeries and improve patient outcomes.

BACKGROUND:The American College of Gastroenterology (ACG) assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS:A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across five key areas (endoscopy, practice management clinical applications, training and education, IBD and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Non-consensus items were revised and re-voted electronically. RESULTS:A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection (CADe) improving adenoma detection rate and miss rate in controlled studies, with mixed "real-world" impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias via heterogeneous datasets. Outside endoscopy, ambient AI scribes, NLP-enabled coding, workflow optimization, and prior authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid "deskilling". In IBD and hepatology, AI could help improve diagnostic accuracy, help predict risk for disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. CONCLUSIONS:This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in GI, liver, and endoscopy care.

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.