Faculty Bibliography

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.

BACKGROUND/UNASSIGNED:Colorectal cancer (CRC) poses a major health challenge worldwide, specifically in developing countries, where late-stage diagnoses lead to substantial mortality rates. This study aims to evaluate CRC knowledge and screening behaviors in Pakistan while identifying barriers that hinder CRC screening uptake. MATERIALS AND METHODS/UNASSIGNED:In this cross-sectional study, a paper questionnaire was distributed to patients and companions in hospitals across all provinces in Pakistan between March 2022 and December 2023. RESULTS/UNASSIGNED:Out of 5,244 participants (68.7% male), only 23.2% claimed knowledge of CRC, while 31.5% had some awareness of it. Merely 20.1% believed CRC to be common in Pakistan. Only 6.6% of those aged 50 and above had undergone CRC screening, with 59.7% reporting no prior screening. Notably, 35.9% expressed interest in colonoscopy at age 45 for CRC screening. Screening intentions were lower in younger, female participants, and residents from Balochistan compared to their counterparts. Widowed/divorced individuals showed higher intentions than married ones. Several barriers, including a lack of screening facilities and fear of results, negatively impacted screening intentions. CONCLUSION/UNASSIGNED:Colorectal cancer awareness and screening uptake remain critically low in Pakistan, with significant barriers including a lack of knowledge, physician recommendation, and access to screening facilities. Sociodemographic factors such as age, gender, education, and region significantly influenced screening intentions. Targeted awareness efforts and improved healthcare provider engagement are essential to enhance CRC screening rates and reduce the disease burden. HOW TO CITE THIS ARTICLE/UNASSIGNED:. Colorectal Cancer Screening Knowledge and Associated Willingness and Barriers to Screening in Nationwide Pakistan Cohort. Euroasian J Hepato-Gastroenterol 2025;15(2):156-163.

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/UNASSIGNED:Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality, emphasizing the need for effective later-line therapies. Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR)1-3 inhibitor, has emerged as a promising option for refractory mCRC. This systematic review and meta-analysis evaluates its efficacy and safety, both as monotherapy and in combination with programmed death-1 (PD-1) inhibitors. METHODS/UNASSIGNED:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across PubMed, Embase, Online Vendor of International Databases (OVID), Cochrane Library, and ClinicalTrials.gov (2010-2025). Included studies were randomized controlled trials (RCTs) or real-world data on fruquintinib in mCRC after at least two prior therapies. Real-world evidence was included to complement RCT findings, as it captures broader populations, treatment patterns, and outcomes not fully reflected in controlled trial settings. Primary outcomes were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Pooled hazard ratios (HRs) and event rates were calculated using a random-effects model. RESULTS/UNASSIGNED:. 4.0%, P=0.04). In cross-study comparisons, monotherapy appeared to yield numerically longer PFS, although this was not based on head-to-head trials. AEs occurred in 86.7%, with grade ≥3 in 30.9%, most often hypertension (8.1%) and hand-foot skin reaction (5.8%). High heterogeneity was observed for several outcomes including AEs and DCR. CONCLUSIONS/UNASSIGNED:Fruquintinib significantly improves PFS and disease control in refractory mCRC with manageable toxicity. Limitations include heterogeneity across studies, with most conducted in predominantly Chinese cohorts. Further studies should explore optimal combination strategies and biomarker-based selection.

INTRODUCTION/BACKGROUND:Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. METHODS:We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC-IBD cohort) and PSC without IBD (PSC non-IBD cohort), and were matched with patients without a history of PSC or IBD (non-PSC/non-IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan-Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time-to-event rates at daily time intervals. RESULTS:PSC patients without IBD were at increased risk of CRC compared to the non-PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6-6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78-11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2-12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3-15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. DISCUSSION/CONCLUSIONS:Our findings provide real-world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.

BACKGROUND:Colorectal cancer (CRC) is the fourth most common and second deadliest cancer in the US. Screening is effective at reducing CRC incidence and mortality, but rates of screening remain suboptimal. There are no sensitive machine learning models for accurately identifying individuals at risk for colorectal cancer or precancerous polyps. OBJECTIVES/OBJECTIVE:The aim of our study was to develop and validate a novel machine learning model that uses multimodal Electronic Health Record (EHR) data, including the most recent complete blood count (CBC), basic metabolic panel (BMP), ICD codes, and medications, to estimate a patient's likelihood of having CRC or an advanced precancerous lesion. METHODS:We developed ColAI, an L1-regularized logistic regression model trained on 1-year trailing EHR data, to predict CRC or advanced adenoma at screening colonoscopy. Labs are treated as continuous variables, while ICD codes and medications are represented as binary indicators of presence. ColAI was trained using 87,825 screening colonoscopies and validated using 21,957 independent colonoscopies between August 1, 2020, and March 31, 2024, from the NYU Langone Health system. RESULTS:ColAI achieved an AUROC of 0.93 for CRC and 0.98 for CRC or advanced adenoma. Performance remained consistent across different hospitals and time periods within NYU Langone, demonstrating strong generalizability. Performance also remained consistent between first and follow-up colonoscopies, decreasing concern for selection bias. CONCLUSIONS:ColAI accurately identifies patients at elevated risk for CRC using only routine EHR data. It has the potential to enhance targeted outreach to high-risk, unscreened individuals and improve early cancer detection at the population level.