The incidence of colorectal cancer (CRC) keeps rising throughout Asia but validated models for predicting advanced colorectal neoplasia (ACN) in Thai populations are absent locally. Limited colonoscopy capacity highlights the need for precolonoscopy risk stratification. This study developed and validated a Thai-specific prediction model of ACN in asymptomatic adults, aged ≥ 40 years, by utilizing routine clinical variables. A retrospective cross-sectional study was conducted at Pattani Hospital, Thailand (2020-2024). Adults aged ≥ 40 years undergoing colonoscopy were included and assigned to derivation (n = 715) and temporal validation within a single center (n = 659) cohorts. Seven clinical predictors-age, sex, body mass index, diabetes mellitus, smoking, alcohol use, and family history of CRC-were modeled using multivariable fractional-polynomial interaction (MFPI) logistic regression. Model performance was assessed using area under the receiver-operating characteristic curve (AUC), calibration-in-the-large (CITL), calibration slope, Brier score, and decision-curve analysis (DCA). Among 1374 participants, 192 (13.9%) had ACN. The model achieved AUCs of 0.76 (95% CI 0.72-0.81) in the derivation cohort and 0.67 (95% CI 0.60-0.76) in the validation cohort, with calibration slope 0.76 and CITL 0.002. Bootstrap shrinkage was 0.94. DCA demonstrated consistent net benefit across risk thresholds of 7%-65%. Using a 12% risk cutoff, one ACN was detected for every three colonoscopies, reducing colonoscopy volume by 48.4%. The Thai-specific MFPI model demonstrates good calibration, temporal validation, and clinically meaningful utility. Its application may optimize colonoscopy allocation and strengthen precision precolonoscopy risk stratification in resource-limited settings.

Blood-based circulating tumour DNA (ctDNA) tests for colorectal cancer screening: Systematic review and meta-analysis of diagnostic accuracy.

This study aimed to develop and externally validate a risk stratification model for advanced colorectal neoplasia (ACRN) based on the quantitative fecal immunochemical test (qFIT) and easily available clinical data. Data were derived from a multicenter study, comprising 3209 individuals in the development set and 1678 in the validation set. Significant risk factors for ACRN were identified using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate model performance. After point assignments based on the regression coefficients, patients in the validation set were categorized into low-, intermediate-, high-, and very-high-risk tiers. Age, sex, body mass index, habitual residence, alcohol intake, smoking, and fecal hemoglobin concentration were identified as significant risk factors for ACRN. The model demonstrated strong predictive performance (AUROC = 0.870) and good calibration (P = 0.929). The corresponding prevalence of ACRN in the low-, intermediate-, high-, and very-high-risk tiers was 1.66%, 4.50%, 28.45%, and 60.64%, respectively. Subjects in the intermediate-, high-, and very-high-risk tiers had 2.71-, 17.13-, and 36.51-fold higher risk of ACRN, respectively, compared with those in the low-risk tier. This model can effectively stratify the risk of ACRN. Individuals in the high-risk and very-high-risk groups should undergo colonoscopy promptly. Furthermore, it may help compensate for the low detection rate of FIT for advanced adenoma. This model provides clinicians with a complementary approach to CRC screening strategy and may help optimize the efficiency of screening resource allocation.

Current post-polypectomy guidelines classified 3-4 non-advanced adenomas (NAAs) as carrying an intermediate risk of metachronous advanced colorectal neoplasia (ACRN), positioned between that of 1-2 NAAs and > 4 NAAs. However, emerging evidence suggested that individuals with 3-4 NAAs may have a risk comparable to those with 1-2 NAAs. This study aimed to compare the risk of metachronous ACRN between individuals with 1-2 NAAs and 3-4 NAAs. A two-center retrospective cohort study of individuals with NAAs and subsequent surveillance colonoscopy was conducted. Cox regression models were used to compare the risk of metachronous colorectal neoplasia (CRN) and ACRN between individuals with 1-2 and 3-4 NAAs. 2955 individuals who had NAAs removed during baseline colonoscopy were included. The risk of metachronous CRN in individuals with 1-2 NAAs was significantly lower than that in those with 3-4 NAAs (adjusted HR (95% CI), 1.28(1.04-1.57)) and those with > 4 NAAs (adjusted HR (95% CI), 1.52(1.10-2.10)), while the cumulative incidence and risk of metachronous ACRN in individuals with 1-2 NAAs was comparable with that in those with 3-4 NAAs (adjusted HR (95% CI), 0.64(0.18-2.23)) and significantly lower than that in those with > 4 NAAs (adjusted HR (95% CI), 4.69(1.51-14.6)). In this observational study, the risk of metachronous ACRN after removal of 1-2 and 3-4 NAAs was comparable and lower than that observed after removal of > 4 NAAs. These findings suggest that individuals with 3-4 NAAs may have a similar risk profile to those with 1-2 NAAs. Further prospective studies are warranted to determine the optimal surveillance interval for this subgroup.

Screening colonoscopy prevents colorectal cancer (CRC) by detecting and removing premalignant lesions. Metabolic syndrome (MetS) has been proposed as an additional risk marker to refine risk stratification beyond age-based screening, but its independent association with advanced colorectal neoplasia remains uncertain. We conducted a cross-sectional analysis of asymptomatic adults undergoing screening colonoscopy in the Salzburg Colon Cancer Prevention Initiative. Analyses were limited to participants with complete-case data for the Adult Treatment Panel III (ATP III) MetS definition (N = 4891). The primary endpoint was advanced colorectal lesions, defined as advanced adenoma and/or CRC. We estimated incidence rate ratios (IRR) using Poisson regression with robust variance in unadjusted, age/sex-adjusted and fully adjusted models (demographic and lifestyle covariates). Sensitivity analyses applied the International Diabetes Federation (IDF) MetS definition and insulin resistance (HOMA-IR; binary and per doubling). In an exploratory subsample, leptin (per doubling) was evaluated, including joint models with MetS. Bayesian models (non-informative, pessimistic, sceptical priors) quantified posterior effect distributions and equivalence probabilities. Advanced lesions occurred in 389/4891 participants (7.95%) and were more frequent in ATP III MetS (9.66% vs. 6.97%; p = 0.001). In frequentist analyses, ATP III MetS was associated with advanced lesions in unadjusted models (IRR: 1.39; 95% CI, 1.15-1.68) but not after age/sex adjustment (IRR: 1.09; 95% CI, 0.90-1.32) or full adjustment (IRR: 1.06; 95% CI, 0.83-1.36). Age was the dominant predictor (fully adjusted IRR: 1.73 per decade; 95% CI, 1.53-1.95), while female sex was protective (IRR: 0.57; 95% CI, 0.44-0.73). Findings were concordant using the IDF definition (unadjusted IRR: 1.39; age/sex-adjusted 1.09; fully adjusted 1.07) and for HOMA-IR (binary: no association; per doubling: unadjusted IRR: 1.10, p = 0.052; adjusted null). In the leptin subsample (N = 602), leptin was not independently associated with advanced lesions (per doubling IRR: 0.85 unadjusted; 0.96 age/sex-adjusted; 0.95 fully adjusted) and did not materially alter MetS estimates. Bayesian analyses mirrored attenuation with adjustment; in fully adjusted models, sceptical priors yielded a posterior median IRR of 1.01 (95% CrI: 0.91-1.12) with a 92.9% probability that the MetS effect lay within ±10% of no effect. The apparent excess risk of advanced colorectal lesions in MetS is explained by age and sex. Across MetS definitions, HOMA-IR, leptin and Bayesian sensitivity analyses, MetS does not provide independent incremental information for CRC screening risk stratification beyond established demographic factors.

Artificial intelligence (AI) has emerged as a promising tool to enhance lesion detection (CADe) and characterization (CADx) during colonoscopy. However, its effectiveness in faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening remains controversial. This single-centre, randomized, parallel-group clinical trial compared conventional colonoscopy with CAD EYE™-assisted colonoscopy in FIT-positive individuals aged 50-74 years undergoing CRC screening between October 2023 and February 2025. The primary endpoints were the adenoma detection rate (ADR) and the advanced colorectal neoplasia detection rate. A total of 361 patients were analysed. ADR (61.5% with AI vs. 69.8% without AI, p = 0.097) and advanced colorectal neoplasia detection rate (37.9% vs. 36.3%, p = 0.753) did not differ significantly between groups. Similarly, detection rates stratified by lesion type, location, size or morphology, as well as the mean number of lesions per colonoscopy, were comparable between groups. Longer withdrawal time was associated with higher detection of advanced neoplasia (OR = 1.3; p < 0.001). The CADx system revealed diagnostic accuracy exceeding 85%, with greater specificity (66.7% vs. 51.9%) and positive predictive value (PPV) (92.4% vs. 89.9%) compared with endoscopist-based optical diagnosis. In FIT-positive diagnostic colonoscopies with high baseline ADRs, AI assistance did not significantly improve lesion detection. Its primary utility lies in optimizing optical characterization by increasing specificity and PPV, suggesting a potential role in reducing false positives. Further multicentre studies incorporating cost-effectiveness analyses are warranted (ClinicalTrials.gov NCT07125300).

To test whether water exchange improves advanced neoplasia detection rate (ANDR) by pooling data from four randomized controlled trials (RCTs) conducted in Taiwan with similar designs, patient populations, and endoscopists. Water exchange colonoscopy has been shown to improve adenoma detection rate (ADR) compared to air insufflation. However, its effect on ANDR, a surrogate marker for colorectal cancer risk, remains unclear due to small sample sizes in individual studies. Patient demographics, procedural outcomes, ADR, and ANDR from four RCTs comparing water exchange and air insufflation were pooled and analyzed. A total of 1048 patients were included. Baseline characteristics were similar between groups. Water exchange significantly increased overall ADR (54.0% vs. 45.7%, p = 0.007) and overall ANDR (17.9% vs. 13.4%, p = 0.047) compared to air insufflation. The difference in ANDR was mainly observed in the proximal colon (8.7% vs. 4.6%, p = 0.007). Water exchange also resulted in a shorter mean withdrawal time (12.3 vs. 12.7 min, p = 0.023) and better bowel preparation scores. Adequate water exchange technique was confirmed by a cecal aspirated-to-infused water volume ratio of 106%. Pooled analysis of four comparable RCTs showed that water exchange colonoscopy significantly improves overall and proximal colon ANDR compared to air insufflation. Further studies are needed to determine whether this translates into a reduced risk of interval colorectal cancer.

Colorectal serrated lesions (SLs) are recognized as precursors of colorectal cancer (CRC); however, their detection rates and prevalence remain inadequately defined. We aimed to assess their detection rates and estimate their prevalence in the Asia-Pacific, as well as to examine their associated factors. This was a multicenter prospective study in the Asia-Pacific. Asymptomatic individuals aged 40-74 years undergoing first-time colonoscopy for CRC screening were prospectively enrolled. To ensure precise prevalence estimates, colonoscopy procedures involved repeated proximal colon inspection using pan-chromoendoscopy with indigo carmine dye. Detection rates of proximal SLs and sessile serrated lesions (SSLs) were calculated. Mixed-effects logistic regression analyses, accounting for institution-level variability, were performed to identify factors associated with proximal SL and SSL detection. Associations between SLs and synchronous advanced colorectal neoplasia (ACN) were evaluated. Among 965 participants, detection rates of proximal SLs and SSLs were 16.1% (95% confidence interval [CI], 13.8-18.5) and 8.6% (6.9-10.6), respectively. Institutional differences affected detection of proximal SLs (adjusted median OR, 1.44; 95% CI, 1.25-1.79) and SSLs (1.34; 1.18-1.62). A family history of CRC was associated with higher SSL detection (adjusted odds ratio [OR], 2.36; 95% CI, 1.29-4.33). Detection of proximal SLs was associated with synchronous ACN (OR, 1.94; 95% CI, 1.24-3.02 and 1.90; 1.18-3.07, respectively). This multicenter study demonstrates that detection rates and estimated prevalence of SLs are higher than previously reported in the Asia-Pacific and highlights the impact of institutional differences, challenging the notion of their low regional prevalence. UMIN-CTR number, UMIN 000042890.

Background: Colorectal cancer (CRC) is a significant health concern globally, being the second leading cause of cancer-related deaths in men and a third in women within Canada with a growing trend among young adults worldwide. However, research on colorectal neoplasia in young adults, particularly in Southeast Asia, is limited. Objectives: The goal of the study is to identify risk factors associated with advanced colorectal neoplasia (ACN) in young adults and propose an evidence-based age cut-off for CRC screening. Methods: We conducted a retrospective cohort study of 130 young adult patients in the Philippines. Patient demographic and clinical variables, such as age, gender, family history of CRC, location of the lesion and type of service, were analyzed. A multivariable logistic regression model was used to determine significant predictors of ACN. Multiple predictive models were trained using three-fold cross-validation. An age cut-off was determined using the receiver operating characteristic (ROC) curve. Results: We identified age, gender, family history, and lesion location to be the significant predictors of ACN. The odds of ACN increased with age (OR [95% CI]: 1.10 [1.05, 1.16]), in females (2.62 [1.07, 6.75]), and among individuals with a family history of CRC (13.5 [3.12, 97.0]). Left-sided lesions such as lesions in the descending colon (5.78 [1.31, 29.0]) were more strongly associated with ACN than the right-sided lesions in the cecum and ascending colon. The ROC curve identified 36 years as the optimal age cut-off for ACN risk stratification. Conclusions: These findings can inform health policy to improve early detection of CRC and provide a foundation for revising the recommended age for CRC screening in young adults, particularly in the Philippines.

Incidence and Risk of Colorectal Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

Background and Objectives: Colorectal cancer (CRC) is the most common gastrointestinal malignancy in Oman and among the top three cancers nationally, with an increasing burden of early-onset CRC (EOCRC) diagnosed before age 50. Despite national CRC guidelines, the lack of an organized screening program means most cases are detected symptomatically and at advanced stages. This study evaluated age-related differences in colonoscopic findings and advanced neoplasia risk in symptomatic adults to inform early detection and screening strategy development. Materials and Methods: A cross-sectional analysis of 2041 colonoscopies performed at two national tertiary referral centers, Sultan Qaboos University Hospital and Royal Hospital, was conducted (2018-2021). Patients were categorized by age (<50 vs. ≥50 years). Outcomes included adenoma detection rate (ADR), advanced premalignant lesions (APL), colorectal cancer (CRC), and advanced colorectal neoplasia (ACRN; APL and/or CRC). Associations between presenting symptoms and ACRN were analyzed using univariable logistic regression, and diagnostic yield was estimated via number needed to scope (NNS). The cohort was predominantly symptomatic (71.9%), with 15.8% screening and 12.3% surveillance procedures. Results: Of 2041 procedures, 742 (36.3%) were in patients <50 years. ADR, APL, CRC, and ACRN were significantly higher in those ≥50 years (14.9%, 7.5%, 5.8%, and 13.3%) than in younger adults (8.5%, 3.2%, 2.7%, and 5.9%; all p < 0.01). Among younger adults, rectal bleeding (OR 2.17, 95% CI 1.15-4.08, p = 0.026) and abdominal pain (OR 2.14, 95% CI 1.15-3.98, p = 0.022) were significantly associated with ACRN. Diagnostic efficiency (NNS) was highest for loss of appetite in both age groups (4.7 in <50 vs. 2.8 in ≥50 years). Despite lower overall rates, a substantial burden of advanced neoplasia was observed in symptomatic adults <50 years (5.9% ACRN, 2.7% CRC). Conclusions: This bicenter study demonstrates clear age-related disparities in colorectal neoplasia, with a clinically important burden of advanced disease in symptomatic adults under 50 years. These findings highlight the importance of prompt colonoscopic evaluation for younger adults presenting with alarm symptoms, particularly rectal bleeding and abdominal pain, and provide evidence supporting risk-stratified diagnostic approaches. While age-related differences suggest potential value in earlier screening initiation, our predominantly symptomatic tertiary care cohort cannot directly determine optimal screening age thresholds. Prospective screening trials and cost-effectiveness analyses are needed to establish population-based detection rates and inform evidence-based screening policy development in Oman.

Colorectal cancer (CRC) has increased in adults younger than 50 years of age, particularly in the distal colon. Data examining the risk factors of advanced colorectal neoplasia in young adults as stratified by anatomic location have important implications for screening and risk modification. We conducted a cross-sectional analysis of data from New Hampshire Colonoscopy Registry participants younger than 50 years of age. We developed an average-risk equivalent sample by excluding patients with IBD, genetic syndromes, and those with indications predictive of colorectal neoplasia such as anemia or hematochezia. Our outcomes were left-sided and right-sided advanced conventional neoplasia (≥1 cm; villous or high grade dysplasia), advanced serrated neoplasia (>1 cm or with dysplasia), and having synchronous advanced neoplasia and sessile serrated polyps/lesions. We included 14,369 patients, younger than 50 years at colonoscopy. Increased risk of left-sided advanced neoplasia was observed with current smoking (odds ratio [OR] 2.14), male sex (OR 1.66), older age (OR 1.07), and higher body mass index (BMI) (OR 1.02). Right-sided advanced neoplasia was associated with smoking (OR 1.71), family history of CRC (OR 1.62), older age (OR 1.07), and higher BMI (OR 1.03). Left advanced serrated neoplasia was associated with older age (OR 1.08), and higher BMI (OR 1.05). Left-sided synchronous lesions were associated with smoking (OR 2.33), older age (OR 1.08), and higher BMI (OR 1.04). Right-sided synchronous lesions were associated with family history of CRC (OR 1.67). The lower bound of the 95% CI for each OR was ＞1. We identified modifiable risk factors including current smoking and higher BMI in young adults with right and left-sided colorectal polyps. Older age, male sex, and family history were nonmodifiable predictors. These data can help to inform screening and prevention of CRC in young adults.

US guidelines recommend surveillance colonoscopy after polyp removal, but stool testing may offer a more efficient, acceptable strategy for patients with nonadvanced lesions. We conducted exploratory analyses to evaluate the diagnostic accuracy of quantitative fecal immunochemical testing (FIT) results to diagnose advanced colorectal neoplasia in patients undergoing surveillance colonoscopy. We classified patients by previous colonoscopy findings as having low, intermediate, or high risk polyps. We compared the diagnostic performance for detecting advanced colorectal neoplasia at an optimal cutoff identified by the Youden index vs the standard cutoff of 100 ng/mL. We also estimated cumulative sensitivity and specificity for serial FIT testing in patients with nonadvanced findings. Among the 449 participants (mean ± SD age 65.4 ± 7.1, 53.2% women, and 92.7% White), the median interval between colonoscopies was 5.0 years (IQR 3.5, 5.6); adequate or better bowel prep was achieved in 89.3%, and cecal intubation in 98.4%. We detected 55 advanced precancerous lesions, but no cancers. For patients with previous nonadvanced lesions (n = 378), the optimal cutoff was 26 ng/mL. Compared with the standard cutoff, the optimal cutoff increased sensitivity (14.3%-35.7%, P < 0.01) but reduced specificity (95.5%-79.2%, P < 0.01). Estimated cumulative sensitivity across 3 rounds of FIT testing was 73.4% at the optimal cutoff vs 37.1% with the standard cutoff. Lowering the FIT hemoglobin cutoff markedly improved sensitivity for detecting advanced precancerous lesions in patients without previous advanced polyps. Serial testing could further enhance detection. FIT-based surveillance should be further evaluated as a potential strategy to prioritize, delay, or replace colonoscopy.

Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We investigated whether MAFLD or its respective subtypes were associated with the risk of advanced colorectal neoplasia (ACN), including age-specific associations. This single-centre retrospective study included 21 642 participants who underwent medical health check-ups. Participants were categorised by fatty liver disease presence (NAFLD or MAFLD). Patients with MAFLD were categorised into three subtypes: overweight-MAFLD, lean-MAFLD, and diabetes-MAFLD. The fibrosis-4 index assessed hepatic fibrotic burden. Both NAFLD and MAFLD were significantly associated with nonadvanced colorectal neoplasia risk [odds ratio (OR) = 1.19 and 1.34, respectively; P < 0.05]. In contrast, NAFLD was not significantly associated with ACN risk. Multivariate analysis showed that MAFLD was independently associated with increased ACN risk (OR = 1.20, P < 0.05). Among MAFLD subtypes, diabetes-MAFLD alone was independently associated with increased ACN risk (OR = 1.56, P < 0.05). This MAFLD-ACN association was significant only in patients aged less than or equal to 50 years (OR = 2.54 for 30-39 years and OR = 1.43 for 40-49 years, all P < 0.05). High hepatic fibrotic burden (fibrosis-4 greater than or equal to 1.3) was associated with higher ACN risk in MAFLD patients (OR = 1.31, P < 0.05). MAFLD was independently associated with an increased risk of ACN; however, this association differed according to age and MAFLD subtype. Patients with MAFLD, especially those with high fibrotic burden, underlying diabetes, or aged less than or equal to 50 years, may benefit from appropriate colorectal cancer screening.

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.

Background: Advanced colorectal neoplasia (CRN) and coronary artery disease (CAD) are major health problems with common underlying pathogenic mechanisms.This study sought to investigate the association between the presence of advanced CRN and subclinical coronary atherosclerosis through a large cohort of asymptomatic Korean individuals who voluntarily underwent colonoscopy and coronary computed tomography angiography (CCTA) as routine health screening tests.Methods: A total of 6,044 Korean individuals aged 20 years who underwent a general health examination at the Health Promotion Center of Ulsan University Hospital between January 2009 and March 2020 were retrospectively analyzed.Advanced CRN was defined as the presence of invasive cancer or adenoma with a villous component, high-grade dysplasia, and/or a size of 1 cm.Subclinical coronary atherosclerosis was evaluated by CCTA.Results: Participants with any CRN (n = 1,916, 31.7%) or advanced CRN (n = 240, 4.0%) had a higher coronary artery calcium score and a higher prevalence of any coronary, calcified, mixed, and non-calcified plaques, and obstructive CAD ( 50% diameter stenosis) on CCTA compared with participants with non-CRN (n = 4,128, 68.3%) (all P < 0.05).In the multivariable analysis to evaluate the association between CRN and CCTA findings, the advanced CRN group showed a statistically significant association with obstructive CAD (odds ratio, 1.65; 95% confidence interval, 1.09-2.50;P = 0.019).Conclusion: Asymptomatic subjects with CRN showed a higher prevalence of subclinical coronary atherosclerosis compared to those with non-CRN.Advanced CRN was independently associated with obstructive CAD on CCTA.

Abstract Background The risk of colorectal neoplasia (CRN) in inflammatory bowel disease (IBD) is slowly declining, but it is unclear whether this is attributable to benefits of colonoscopy surveillance and/or to the effect of IBD drugs. This is the first cohort addressing these questions by stratification of patients according to the risk level of CRN and adjustment for all CRN risk factors and IBD drugs. Methods The I-CARE cohort is a prospective cohort including IBD patients enrolled by 508 gastroenterologists from 15 countries between 2016 and 2019 (1). Patients provided monthly reports for up to six years including details of IBD treatment, clinical disease activity based on validated scores, colonoscopy procedures, and CRN diagnoses. Physicians yearly confirmed/completed patient’s information. CRN diagnoses were based on pathological reports. Patients were categorized as higher risk (HR) of CRN if eligible for colonoscopy surveillance or as average risk (AR) otherwise (2). Expected incidences of colorectal cancer (CRC) for country, sex and age-specific stratum were based on 2022 IARC estimates (3). The risk of CRN associated with IBD drugs was assessed using marginal structural models adjusting for baseline variables (IBD subtype and location, IBD disease duration, family history of CRC, personal history of PSC and advanced CRN, body mass index, smoking and alcohol status) and time-varying confounders (clinical activity and exposure to IBD drugs). Results Over a median follow-up of 37.0 months (IQR, 35.6-42.3) in 10,105 patients (60.4% Crohn’s disease (CD); HR group, n = 3,064), 81 patients developed CRN (CRC: n = 23; high-grade dysplasia: n = 10; low-grade dysplasia: n = 48). Standardized incidence ratio (SIR) of CRC was 1.84 (95% CI, 1.17-2.76) in the total IBD population, 0.74 (95% CI, 0.24-1.73) in the AR group and 3.12 (95% CI, 1.85-4.94) in the HR group (Table 1). Results did not differ substantially among IBD subtypes and gender. We observed a trend for chemoprevention of CRN for anti-TNFs in the total population (Figure 1), and in all subgroups (only statistically significant in CD, hazard ratio, 0.30; 95% CI, 0.11-0.76). A similar trend was observed for thiopurines at a lesser extent. Aminosalicylates had no impact on the risk, while exposure to methotrexate or vedolizumab was associated with an increased risk of CRN (hazard ratio, 3.02; 95% CI, 1.17-7.81 and 2.16; 95% CI, 1.09-4.29). Conclusion In the biologic era, patients at higher risk of CRN still have a tripled risk of CRC. In the I-CARE cohort, we showed a chemopreventive effect of anti-TNFs against CRN in CD. No protective effect was observed for other IBD treatments, including thiopurines and aminosalicylates. The effect of methotrexate and vedolizumab on CRN must be further explored.

Metabolic factors are associated with an increased risk of colorectal neoplasia, but whether metabolic factors impact individuals already considered at elevated risk of CRC due to a family or personal history of neoplasia is unknown. This study aimed to determine whether metabolic factors are associated with an increased risk of colorectal neoplasia in individuals undergoing surveillance colonoscopy in an Australian cohort. A retrospective cohort study design with a sample size of 2806 was implemented using colonoscopy and metabolic data from a hospital surveillance program. The association between self-reported metabolic factors (obesity, hypertension, type two diabetes (T2DM), dyslipidemia, and a cluster of these factors called metabolic syndrome (MetS)) and diagnosis of colorectal neoplasia, its advanced form, or histopathological subtypes at surveillance colonoscopy was analysed using logistic regression models. Metabolic factors that increased the odds of colorectal neoplasia diagnosis included obesity (adjusted odds ratio (AOR) = 1.61; 95% CI 1.06-2.44), T2DM (AOR = 1.40; 95% CI 1.09-1.80), and MetS (AOR = 1.47; 95%CI 1.10-1.99), with similar findings observed for the association with advanced colorectal neoplasia (obesity: AOR = 1.24; 95% CI 1.01-1.51; T2DM: AOR = 1.29; 95%CI 1.06-1.56; MetS: AOR = 1.45; 95% CI 1.18-1.80). These associations were driven by conventional adenomas (87% of all neoplasia) in males. No associations were observed between metabolic factors and colorectal neoplasia in females, nor for the odds of serrated polyps (p > 0.05). Obesity, T2DM and MetS were significant risk factors for the risk of conventional adenoma in a surveillance population, specifically in males. These metabolic disorders should be considered when determining the frequency of colonoscopy surveillance for males.

Colorectal cancer (CRC) is among the most prevalent malignancies, with an increasing incidence in China, posing increasing challenges to current screening strategies. This study aimed to evaluate the feasibility of a screening strategy based on the stool-based methylated Syndecan-2 gene (mSDC2) test for detecting advanced colorectal neoplasia in the Chinese population. In this multicenter randomized study, participants aged 45-80 years and identified through community screening were randomized to take either the mSDC2 test or a fecal immunochemical test (FIT), and those with positive results were referred for colonoscopy between 2020 and 2022. The primary outcome was the detection rate of advanced colorectal neoplasia, including advanced adenoma, advanced serrated polyps, and CRC. The secondary outcome was adherence to colonoscopy. Univariable and multivariable logistic regression analyses were conducted to evaluate colonoscopy adherence among participants with positive stool-based test results. A total of 44,475 eligible participants were enrolled from 189 communities (93 in the mSDC2 test group and 96 in the FIT group). In the mSDC2 test group (n = 21,854), the detection rate of advanced neoplasia was 0.53% (n = 115), including 93 (0.43%) advanced adenomas, 8 (0.04%) advanced serrated polyps, and 17 (0.08%) CRC cases. In the FIT group (n = 22,621), the detection rate of advanced neoplasia was 0.47% (n = 106), including 71 (0.31%) advanced adenomas, 9 (0.04%) advanced serrated polyps, and 29 (0.13%) CRC cases. In addition, adherence to colonoscopy was greater in the mSDC2 test group (35.6% vs. 26.4%; odds ratio: 1.59, 95% confidence interval: 1.36-1.87; P <0.001). This study revealed the effectiveness of the mSDC2 test and FIT in detecting advanced colorectal neoplasia in a large Chinese population in a real-world setting, and indicated a possible improvement in adherence to colonoscopy for the mSDC2 test. Further studies with improved comparability and longer follow-up are warranted to clarify its clinical utility. ClinicalTrials.gov, No. NCT04221854.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Colonoscopy is the gold standard for CRC screening, but its effectiveness in population-based programs requires further evaluation. We conducted a follow-up study in Xuzhou, China. Participants were recruited from 2014 to 2021, with follow-up continuing until December 2023. The study comprised two components: 1) an active follow-up to assess treatment outcomes for patients with colorectal advanced neoplasia (CAN) detected during screening; 2) a passive follow-up to compare CRC incidence and mortality between participants who underwent colonoscopy and those who refused it. The active follow-up included 196 participants, while 15,440 were included the passive follow-up (4,029 in the colonoscopy group and 11,411 in the non-colonoscopy group). 96.43% (189/196) CAN patients were actively followed. However, only 25.93% (49/189) received treatment. The CRC incidence density was 35.77 per 100,000 person-years in the colonoscopy group, which was significantly lower than the 95.50 per 100,000 in the non-colonoscopy group (IRR = 0.37, P = 0.011). 83.33% (5/6) of the CRC cases in the colonoscopy group were from the subgroup of CAN patients who did not receive treatment. There was no significant difference in CRC mortality between the two groups. Colonoscopy screening is effective in reducing the risk of CRC. However, its real-world effectiveness has been compromised by the low participation rate and the poor treatment adherence among screen-positive patients. The impact of colonoscopy screening on reducing CRC mortality remains undetermined.