Faculty Bibliography

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:Measurement of colorectal polyps is typically performed via visual estimation, which is prone to bias. Studies have evaluated the accuracy of visual estimation and utility of assistive tools, but results have been mixed. This study aims to clarify the accuracy of visual estimation as a measurement tool, and the benefits of artificial intelligence. METHODS:MEDLINE and Embase were searched through October 2024. Extraction and quality assessment were performed independently by two authors. The primary outcome was the pooled absolute mean difference in size between visual estimation and control. Secondary outcomes included subgroup analysis of expert vs trainee status, accuracy of artificial intelligence, study origin (East vs. West), comparator type, definition of accuracy, polyp size, direction of estimation, and image type. RESULTS:35 studies with 42,964 polyp measurements were included in our analysis. All studies were of high quality and there was no evidence of publication bias. The pooled absolute mean difference from comparator was 1.68mm (CI 1.21-2.15) with high variability explained by differences in the comparator, the direction of estimation, image type, and size of the polyp. Overall accuracy was 60% with high variability as well, with increased accuracy with video displayed over photos. Artificial intelligence improved accuracy with an odds ratio of 7.46. CONCLUSION/CONCLUSIONS:Visual estimation is an inaccurate and imprecise way to measure colorectal polyps. Further research is needed to determine the impact on clinical outcomes related to colorectal cancer. Investment in new technology to aid in polyp measurement is an important next step.

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.

BACKGROUND/UNASSIGNED:Several patient and tumor characteristics impact the prognosis of non-metastatic colon cancer. Among those, tumor location is believed to be a significant factor, as proximal lesions are associated with lower overall survival (OS) in modern cohorts. We aimed to validate these findings in a cohort of patients from the Minnesota Colon Cancer Control Study who underwent curative colectomy. METHODS/UNASSIGNED:From 1976 to 1992, 46,551 patients aged 50-80 years were randomized to usual care, annual, or biennial screening with fecal occult blood testing (FOBT). Positive FOBT was followed by colonoscopy. We analyzed participants whose colonoscopy revealed colon adenocarcinoma to estimate the impact of tumor laterality on survival after adjustment for demographic and clinicopathologic characteristics. Proximal tumors were defined as those between the cecum and the splenic flexure. RESULTS/UNASSIGNED:Of 1,486 patients, 796 met inclusion criteria; 57% had proximal cancers. After adjustment, there was no significant difference between proximal and distal tumors in disease-specific mortality [subdistribution hazard ratio (SHR) =0.94, 95% confidence interval (CI): 0.70-1.3], but proximal tumors had lower rates of death from any cause [hazard ratio (HR) =0.9, 95% CI: 0.77-1.00]. CONCLUSIONS/UNASSIGNED:Although lacking granular data, these findings from the pre-modern chemotherapy era raise questions about the generalizability of the association between side of origin and prognosis identified in contemporary, treatment-based trials.

With nearly 60 million Americans aged 65 and older, gastrointestinal (GI) conditions are a leading cause of healthcare utilization in this population. Despite this, older adults remain underrepresented in GI clinical trials and research, limiting evidence-based care. This review highlights three pivotal studies addressing this gap: (1) proton pump inhibitors, which are commonly used to treat gastroesophageal reflux disease, are not associated with the later development of dementia; (2) undertreatment of chronic inflammation among older adults with inflammatory bowel disease is associated with a higher rate of adverse events compared to treatment with anti-TNF therapy, a biologic agent; (3) the majority (85%) of surveillance colonoscopies among older adults with a life expectancy of ≥ 10 years did not yield colorectal cancer, advanced dysplasia, or ≥ 3 polyps.

Description Colorectal cancer (CRC) is a leading cause of morbidity and cancer-related mortality in the US. Despite multiple screening options, adherence to CRC screening in the US remains suboptimal and there are racial, ethnic and geographic disparities in CRC screening rates and outcomes. Advances in diagnostic technology have allowed for development and validation of blood tests for CRC screening. In this clinical practice update, our aims were to review the current evidence on blood tests, and the potential implications for CRC screening. We leveraged published modelling studies to understand the optimal test performance characteristics, interval, and uptake that would be needed for blood tests to achieve comparable effectiveness to that of currently available stool tests and screening colonoscopy.

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.

IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.

BACKGROUND & AIMS/OBJECTIVE:This study assessed the economic and health impact of colorectal cancer (CRC) screening programs for average-risk individuals aged 45 years and older. METHODS:A 10-year Markov model simulated disease progression, comparing multitarget stool RNA test (mt-sRNA, ColoSense), two mt-sDNA tests (Cologuard and Cologuard Plus), a blood-based test (cfDNA, Shield), and a fecal immunochemical test (FIT). Clinical inputs leveraged age-weighted sensitivity and specificity from independent studies. Outcomes were compared with a colonoscopy-based program and no screening. Model calibration and validation used previously reported Cancer Intervention Surveillance Modeling Network (CISNET) models. RESULTS:Among molecular tests, mt-sRNA detected the most advanced adenomas, referred the most individuals to surveillance, and prevented the highest number of CRC cases and deaths. At real-world adherence of 60%, mt-sRNA reduced CRC cases and deaths by 1% and 14% compared with FIT; by 21% and 19% compared with mt-sDNA; by 28% and 23% compared with mt-sDNA+; and by 80% and 86% compared with cfDNA. For all adherence levels, FIT ($25/test) was the most cost-effective strategy. For triennial molecular tests ($509/test), mt-sRNA was the most cost-effective strategy. Relative to the mt-sRNA program, the cost to prevent a CRC case was 30% (mt-sDNA), 45% (mt-sDNA+), and 642% (cfDNA) more expensive. Relative to the mt-sRNA program, the cost to prevent a CRC death was 30% (mt-sDNA), 41% (mt-sDNA+), and 1040% (cfDNA) more expensive. CONCLUSIONS:FIT was the most cost-effective strategy for preventing CRC cases and deaths. At real-world adherence of 60%, mt-sRNA demonstrated the greatest clinical benefit and was more cost-effective than other molecular strategies.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.