Sessile serrated lesions with dysplasia (SSLd) are direct precursors of colorectal carcinomas (CRCs) but pose a diagnostic challenge. We aim to explore contemporary practice leading to recommendations to improve detection of dysplasia. (i) The frequency of dysplasia in SSLs was estimated through a nationwide study of individuals undergoing colonoscopy in the Netherlands (2014-2022). Out of 186 427 SSLs, 17 456 showed dysplasia, yielding a frequency of 9.4%. (ii) A national audit evaluating diagnostic practices and interobserver variability revealed diagnostic discrepancies in 11% of SSLd cases, while ancillary immunohistochemistry (IHC) was used by only 20% of participating laboratories. (iii) The additional value of biomarkers (MLH1, p16, p53, beta-catenin and c-myc) was assessed using retrospective (n = 213) and prospective (n = 348) SSL cohorts. MLH1 emerged as the only useful biomarker for identifying dysplasia among SSLs, increasing SSLd diagnoses from 33 to 41 cases in the retrospective cohort (P = 0.008) and from 35 to 43 cases in the prospective cohort (P = 0.013). (iv) Misdiagnosis of SSLd among conventional adenomas was investigated using BRAF IHC in a cohort of 1572 advanced adenomas and was found to be very rare, occurring in only 2 cases. The diagnosis of SSLd appears to have good reproducibility among pathologists and positive diagnostic trends that are observed in recent years. MLH1 is the only IHC marker with robust clinical utility to identify SSLd that do not meet the morphologic criteria for overt dysplasia but should be used only in selected cases due to its low prevalence.

This study aimed to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) in detecting synchronous malignant lesions in the proximal colon in endoscopically obstructive left-sided colorectal cancer. All patients with a biopsy-proven left-sided endoscopically obstructive colorectal cancer who had a preoperative PET/CT scan and a postoperative total colonoscopy within 6 months after the index surgery between January 2015 and July 2024 at a comprehensive cancer center were enrolled into the study. The synchronous malignant lesions on PET/CT were confirmed with the pathologic examination of the subtotal/total colectomy specimen and postoperative total colonoscopy. The primary endpoint was to evaluate the diagnostic performance of PET/CT in detecting synchronous malignant lesions, and the second endpoint was to determine the ability of PET/CT to distinguish malignant lesions from advanced adenomas. Out of 90 patients, 50 (55.6%) were male with a mean age of 62.46±10.81 years. The obstructing malignant lesions detected on colonoscopy were located in the rectum, n=8 (8.9%), rectosigmoid junction, n=29 (32.2%), sigmoid colon, n=31 (34.4%), descending colon, n=16 (17.8%), and distal part of the transverse colon, n=6 (6.7%). Nine areas of abnormal fluorodeoxyglucose (FDG) uptake on PET/CT in the proximal part of the colon with a mean SUVmax value of 19.23 (range: 6.4-42) were identified in 6 patients. Four patients with synchronous lesions on PET/CT underwent a total colectomy. Two patients with synchronous lesions on PET/CT were treated with segmental resection with subsequent postoperative endoscopic submucosal dissection (ESD) for the synchronous lesion. The detection rate of PET/CT for synchronous malignant lesions was 4.4% (n=4) with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 100%, 94.4%, 44.4%, 100%, and 94.6%, respectively. PET/CT demonstrated a high sensitivity and a high negative predictive value in detecting synchronous malignant lesions located in the proximal colon distal to the obstructing left-sided colorectal cancer. As a result, patients underwent a single-stage surgery and were spared from an unnecessary second surgical intervention.

Pump-based chromoendoscopy is recommended for the surveillance of dysplasia associated with inflammatory bowel disease. This study was designed to compare the efficacy of pump-based pan chromoendoscopy (PCE) with white-light endoscopy (WLE) for the detection of colorectal neoplasia in patients at high risk of colorectal cancer (CRC). This randomized controlled trial prospectively recruited 366 participants who were randomly allocated in a 1:1 ratio to the WLE group and the PCE group. adenoma detection rate (ADR); secondary outcome: mean number of adenomas per procedure (MAP), sessile serrated lesion detection rate (SDR), flat adenoma detection rate (FDR), and advanced adenoma detection rate (AADR). The ADR was significantly higher with PCE (86/167, 51.5%) versus WLE (57/165, 34.5%; RR 1.49 [95% 1.15 to 1.93]: p = 0.002). The FDR and SDR were significantly higher in PCE than in WLE (50.3% vs. 32.1% RR 1.57 [95% 1.20 to 2.05] p = 0.001; 10.8% vs. 2.4% RR 4.45 [95% CI 1.54 to 12.86] p = 0.002). This study demonstrated that using a novel spraying technique with low-concentration indigo carmine during colonoscopy achieved a significantly higher detection rate for colorectal lesions. Moreover, PCE significantly increased ADR, particularly for flat adenomas and the detection rate of sessile serrated lesions. ClinicalTrials.gov identifier: NCT06596317.

Colorectal advanced adenomas (CAAs) are key colorectal cancer (CRC) precursors. While familial CRC risk is well-established, the neoplastic risk (adenoma, CAA, CRC) in first-degree relatives (FDRs) of CAA patients is unclear. This systematic review aimed to quantify this risk and identify risk-modifying factors. Per PRISMA guidelines, we systematically searched MEDLINE, EMBASE, and CENTRAL through May 2025 for observational studies comparing neoplasm risk in FDRs of CAA probands versus controls. Two reviewers independently extracted data and assessed bias (Newcastle-Ottawa Scale). A qualitative synthesis was performed due to heterogeneity. Of 421 records identified, four studies from diverse populations were included. FDRs of CAA patients had a significantly increased risk for any adenoma (OR/RR 1.33-3.29, with 95% CIs ranging from 0.96 to 5.03) and advanced neoplasia (CAA/CRC) (OR/RR 1.65-6.33, 95% CIs 1.01-43.8). CRC risk findings were inconsistent; two larger studies showed a modest risk increase (RR/OR 1.7-2.3, 95% CIs 1.01-5.09), while two smaller studies reported non-significant results. Proband age <60 years, adenoma multiplicity, and male sex of the FDR emerged as potential risk modifiers in individual studies, though evidence is limited. Regarding proband adenoma location, a distal lesion was more consistently associated with increased familial risk, although an association with proximal lesions was also reported. FDRs of CAA patients appear to have an elevated risk for colorectal adenomas, particularly CAAs, although evidence certainty is limited. Documented family history of CAA may warrant consideration as one of several factors in future risk-stratified screening approaches; however, the current evidence is insufficient to define CAA-specific screening intervals beyond existing guideline frameworks. Further research is needed to validate risk estimates and optimize screening strategies.

Fecal occult blood test (FOBT) is widely used in colorectal cancer (CRC) screening; however, its ability to predict clinically significant pathology may vary across patient populations. This study aimed to evaluate colonoscopy outcomes in FOBT-positive patients and to identify clinical factors associated with clinically significant colonoscopic findings. This retrospective single-center cohort study included 216 adult patients with positive FOBT results who underwent colonoscopy between 2018 and 2024. Demographic characteristics, hemoglobin levels, FOBT methods, colonoscopic findings, and histopathological results were analyzed. Clinically significant pathology was defined as the presence of adenoma, advanced adenoma, CRC, or inflammatory lesions. Multivariable logistic regression analysis was performed to identify factors associated with clinically significant pathology, and receiver operating characteristic analysis was used to evaluate discriminative performance. Clinically significant pathology was detected in 57.4% of patients. The most frequent findings were adenomas (28.7%), advanced adenomas (14.8%), and CRC (8.3%). Older age (≥60 years), male sex, and anemia were significantly associated with clinically significant findings. Among these variables, anemia showed the strongest association with significant pathology. Receiver operating characteristic analysis demonstrated moderate discriminative ability for individual variables, whereas a combined model incorporating age, sex, and anemia achieved the highest performance (area under the curve = 0.81). FOBT positivity was associated with a high rate of clinically significant colonoscopic findings. Older age, male sex, and anemia may help identify higher-risk patients; however, these factors should not be used to exclude any FOBT-positive patient from colonoscopy. Prospective multicenter studies are needed to validate these findings.

Colorectal cancer (CRC) screening reduces disease burden, but the comparative performance of various screening strategies remains unclear. We evaluated the performance of four screening strategies based on questionnaire-based risk assessment (QRA) and fecal immunochemical test (FIT), followed by colonoscopy. In this population-based study, 14,327 residents aged 40-74 years from 13 regions in Shandong Province, China, were invited to undergo QRA, FIT, and colonoscopy between January 2024 and December 2025. Based on test results, we constructed four strategies: QRA-only, FIT-only, parallel (QRA or FIT positive), and tandem (QRA and FIT positive) combinations. The detection rate of CRC and advanced adenoma (AA), number needed to scope (NNS), and cost per case detected were compared. In total, 4982, 1806, 5970, and 764 individuals were identified as high-risk for each strategy. The tandem strategy detected 33 CRCs (4.32%) and 199 AAs (26.03%), compared with 35 (0.71%) and 553 (11.22%) in the QRA-only strategy, 68 (3.77%) and 340 (18.86%) in the FIT-only strategy, and 70 (1.17%) and 694 (11.62%) in the parallel strategy. Across subgroups defined by older age, male, and early-stage disease, the tandem strategy consistently yielded higher detection rates. The NNS to detect one CRC was 141, 27, 86, and 24, and the corresponding costs per CRC detected were $9874.31, $2097.88, $7084.68, and $1700.71 for each strategy. The tandem strategy combining QRA and FIT demonstrated superior performance in CRC screening. In resource-constrained settings, tandem strategies that jointly integrate risk assessment and FIT may improve the allocation and utilization of screening resources.

Whether collecting one or two fecal samples for immunochemical testing (FIT) optimizes colorectal cancer screening outcomes remains unclear. We systematically searched multiple databases until October 2025 for studies directly comparing 1-FIT and 2-FIT strategies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Five studies (n = 45,888) and three economic evaluations were included. Participation was higher with 1-FIT (RR = 1.05, P < 0.0001), while 2-FIT had a higher positivity rate (RR = 0.65, P < 0.0001). Although 2-FIT detected more CRC (RR = 0.62, P = 0.02), advanced neoplasia and advanced adenoma detection were similar. The 2-FIT strategy had higher sensitivity (RR = 0.64, P = 0.04) but lower specificity (RR = 1.70, P < 0.001) than 1-FIT. A pivotal finding was that the 1-FIT strategy demonstrated a superior positive predictive value (PPV) for both advanced neoplasia (RR = 1.21, P = 0.004) and advanced adenoma (RR = 1.41, P < 0.0001), which translated into a substantially lower demand for colonoscopy (RR = 0.64, P < 0.0001) Economic evaluations consistently favored 1-FIT across different healthcare systems. Although the 2-FIT strategy improves test sensitivity, it fails to enhance advanced neoplasia detection while substantially increasing colonoscopy demand due to its reduced positive predictive value. In contrast, the 1-FIT strategy preserves screening efficacy with superior participation rates, resource utilization, and cost-effectiveness. We recommend 1-FIT as the preferred strategy in settings with constrained colonoscopy resources, while reserving 2-FIT for resource-abundant environments where maximizing sensitivity justifies the additional economic and operational costs (Scheme 1). The research protocol was prospectively registered in the PROSPERO registry, bearing the registration identifier CRD420251153202.

Large, prospective cohorts are needed to research the gut microbiome's role in colorectal cancer (CRC) risk. We evaluated the gut microbiome leveraging residual fecal immunochemical tests (FIT) from a CRC screening program in Turin, Italy, and conducted one of the largest population-based case-control studies across the adenoma-carcinoma sequence to date. We extracted DNA from residual FIT stool, used whole-genome shotgun sequencing, and included those with CRC (N = 44), advanced adenomas (N = 269), early adenomas (N = 134), and FIT-negative controls (N = 478). Alpha diversity, beta diversity, and species, gene, and pathway relative abundances were estimated. Multivariable logistic regression models were used to estimate associations of these metrics with colorectal neoplasms. Alpha diversity was mostly inversely associated with colorectal neoplasms, particularly early adenomas (OR: 0.45, 95% CI: 0.25-0.80; P = 0.01). Presence of oral pathogens, including Parvimonas micra, was associated with higher odds of CRC. Furthermore, Escherichia coli and Bacteroides fragilis were strongly associated with higher odds of all colorectal neoplasms. Several genes and pathways were associated with colorectal neoplasms. Our findings align with smaller studies of the gut microbiome and colorectal neoplasms, supporting that CRC screening programs provide opportunities to prospectively study the gut microbiome's association with cancer risk in large populations.

ABSTRACTBackgroundThe risk of colorectal cancer (CRC) after serrated polyp resection remains unclear, and current surveillance recommendations rely on limited evidence. We evaluated CRC incidence in individuals with advanced serrated lesions (ASL) detected at baseline colonoscopy and compared risk according to the most advanced lesion identified.MethodsParticipants undergoing colonoscopy within the COLONPREV trial (n = 8989) were included in this post hoc analysis. Individuals were classified according to the most advanced baseline lesion: no lesion, non‐advanced adenoma, advanced adenoma, or ASL. The primary outcome was incident CRC. Cumulative incidence and hazard ratios (HR) were estimated using Cox proportional hazard models.ResultsAt baseline colonoscopy, serrated polyps were detected in 19.8% of participants, including ASL in 2.5%. Over a mean follow‐up of 9.5 years, 44 CRC cases were diagnosed (cumulative incidence 0.49%; incidence rate 0.52 per 1000 person‐years). The 10‐year cumulative incidence was 0.27% in individuals without baseline lesions (n = 5496), 0.57% in those with non‐advanced adenomas (n = 2091), 1.23% in advanced adenomas (n = 1218), and 1.09% in ASL (n = 184). In multivariable analysis, CRC risk was increased for non‐advanced adenomas (HR 3.25, 95% CI 1.48–7.16), advanced adenomas (HR 9.77, 95% CI 4.24–22.50), and ASL (HR 6.37, 95% CI 1.42–28.54). Surveillance colonoscopy was associated with lower CRC incidence (HR 0.46, 95% CI 0.22–0.95 for one colonoscopy; HR 0.09, 95% CI 0.02–0.40 for ≥ 2 colonoscopies).ConclusionIn this screening cohort, ASL were associated with increased CRC risk in the range of advanced adenomas. These findings provide risk estimates relevant to post‐polypectomy management.Trial registration numberNCT00906997.

The incidence of early-onset colorectal cancer is rising globally. While metabolic dysregulation is a known risk, the specific contribution of lipid profiles to colorectal carcinogenesis in young adults remains unclear. Remnant cholesterol (RC) has emerged as a significant cardiovascular risk factor, but its association with young-onset colorectal neoplasia is not fully elucidated. We conducted a retrospective, cross-sectional study of 4,100 asymptomatic individuals under 50 years of age undergoing screening colonoscopy. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. We used multivariate logistic regression to assess the independent association between RC levels and the presence of young-onset adenoma (YOA) and advanced YOA. Patients with YOA had significantly higher RC levels than controls (17.65 ± 14.52 mg/dL vs. 14.69 ± 11.14 mg/dL; P< 0.001). In adjusted multivariate analysis, RC was independently associated with YOA risk (odds ratio [OR], 1.011; 95% confidence interval [CI], 1.003-1.019; P= 0.005). Notably, for advanced YOA, RC remained the only lipid parameter that retained statistical significance in the multivariable model (OR, 1.021; 95% CI, 1.004-1.038; P= 0.015), whereas traditional lipid markers were not significant. Higher RC levels were independently associated with YOA and advanced YOA in this cohort of asymptomatic individuals under 50 years of age. Among the lipid parameters examined, RC remained statistically significant in the multivariable model for advanced YOA.

In colorectal cancer (CRC) screening, colonoscopy quality is assessed by sporadic adenoma detection and withdrawal time (WT). In inflammatory bowel disease (IBD), withdrawal is more complex due to IBD-specific tasks, such as targeted biopsies, dysplasia surveillance, and segmental inflammatory activity assessment. We hypothesized that in screening-age IBD patients in endoscopic remission, the yield of sporadic adenomas would be similar to that observed in non-IBD patients. We aimed to test this hypothesis recognizing that current quality benchmarks are extrapolated from non-IBD screening despite higher CRC risk in IBD. We conducted a secondary analysis of prospectively collected colonoscopy data from a tertiary academic center. Our primary outcome was sporadic adenoma detection rate (ADR) in IBD, using non-IBD patients as a reference group. Secondary outcomes were mean WT, polyp detection rate, adenomas and polyps per colonoscopy, advanced adenoma detection rate, and sessile serrated lesion detection rate. We analyzed 1366 colonoscopies (155 IBD;1211 non-IBD). When adjusting for WT and other potential confounders, ADR was significantly lower in IBD than in non-IBD (18.6% vs 43.0%). The increase in detection per additional WT minute was markedly attenuated in IBD: the odds of detecting an adenoma increased by 16.6% per additional minute in non-IBD versus 2.7% in IBD. Achieving a 26% ADR required an estimated WT of 6.8min in non-IBD versus 28.2min in IBD. In a screening-age cohort without endoscopic IBD activity, our findings suggest that IBD-specific procedural demands limit effective inspection time, and other intrinsic characteristics of the surveillance context influence adenoma detection dynamics. Non-IBD quality thresholds may not be directly applicable to IBD, supporting the development of IBD-specific quality metrics.

Label-free vibrational spectroscopic techniques (Raman spectroscopy) combined with machine learning (ML) methodologies have huge potential for the development of screening and diagnostic tests in oncology. Traditionally, screening for colorectal cancer (CRC) has relied on immunochemical faecal occult blood (iFOBT) testing; however, this has shown to have low compliance in the Australian setting. The aim of this study was to assess the efficacy of Raman spectroscopy for the detection of CRC and potential screening for CRC. Plasma samples were analysed from a total of 370 participants; 117 CRC patients and 253 iFOBT positive control participants. 8 of the CRC patients were from the iFOBT cohort. The control cohort had either advanced adenomas (n = 81), non-advanced adenomas (n = 76), colitis (n = 2) or no evidence of disease (n = 94). The Raman spectra of these plasma samples were analysed using ML algorithms in separate training (n = 222) and validation (n = 148) cohorts. A sensitivity of 84% and specificity of 93% was achieved for the detection of CRC in the validation cohort. When analysed in subcategories, 95% of people with CRC would receive a colonoscopy and 42% of FIT positive people could potentially be spared a colonoscopy. This exploratory study demonstrated a high level of accuracy for the detection of CRC using a Raman spectroscopy-based ML model and has the potential to be used for CRC screening.

Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and chemotherapy resistance often leads to poor patient prognosis. Harmane, a natural indole alkaloid, is found in Leguminosae plants (particularly those of the Crotalaria genus), as well as in mammalian tissues and certain food products. It exhibits potential anticancer activities through multiple mechanisms in various cancers, including liver, breast, and thyroid cancers. However, the role of harmane in the treatment of CRC remains unclear. In this study, we demonstrate that harmane induces cell cycle arrest and apoptosis in CRC cells via the p53-RRM2B axis. Furthermore, at the level of the gut microbiota, harmane reshapes microbial composition, thereby contributing to its anti-tumor effects.IMPORTANCEThis study is the first to demonstrate a progressive decline of harmane levels in the gut from healthy individuals to advanced adenoma and CRC patients, suggesting its potential protective role in CRC development. We further found that harmane promotes CRC cell apoptosis via RRM2B-mediated regulation, revealing the underlying molecular mechanism. Moreover, in vivo experiments showed that harmane can modulate gut microbial composition and its derived metabolites, and fecal microbiota transplantation experiments indicated that harmane exerts anticancer effects by regulating both the gut microbiota and microbial metabolites. This study proposes a novel therapeutic strategy for CRC, highlighting the importance of incorporating gut microbiota modulation into cancer treatment.

Background/Objectives: The incidence of early-onset colorectal cancer is increasing worldwide. The fecal immunochemical test (FIT) is widely used for screening adults aged 50 and older, but its performance in younger individuals is less understood. Methods: We retrospectively analyzed 202,676 FITs from asymptomatic adults aged 18–49 between 2011 and 2025. FIT results, age categories, and follow-up colonoscopy findings were evaluated. Results: The FIT positivity rate was 4.7%. Among 1973 FIT-positive individuals who underwent colonoscopy, 5.9% had advanced adenoma or sessile serrated lesion and 1.3% had invasive cancer. A total of 143 advanced neoplasms (ANs) were detected, with prevalence increasing with age. Most ANs (79.1%) occurred in those aged 40–49. The prevalence of ANs was higher in the 45–49 than in the 40–44 age group (49.0% vs. 30.1%; OR 1.55, 95% CI 1.04–2.32) and higher in the 40–44 than in the 35–39 age group (30.1% vs. 10.5%; OR 2.20, 95% CI 1.20–4.02). Conclusions: The diagnostic performance of FIT in individuals under 50 years is comparable to that observed in the older population. Given the age-related rise in the prevalence of ANs in young adults, several countries have lowered the screening age to 45 years, and extending screening to individuals aged 40 years may be warranted.

An association between higher adenoma detection rate (ADR) at index screening colonoscopy and lower risk of metachronous advanced neoplasia (AN, defined as colorectal cancer [CRC] or advanced adenoma [AA]) has been reported. However, the relationship between ADR at both index and surveillance colonoscopy and subsequent AN is unknown. We examined the association between ADR and withdrawal time (WT) at index and surveillance colonoscopy and risk of metachronous AN at surveillance colonoscopy. We used GIQuIC, a repository of colonoscopies across the United States. Each patient has a unique ID at a participating site. Endoscopist national provider identifiers are associated with each examination. We included patients with 2 colonoscopies at least 3 years apart (index and surveillance) between 2011 and 2022 and calculated the ADR and average WT for the endoscopist performing the index and surveillance colonoscopies, respectively. We built a multivariable logistic regression model with metachronous AN as the outcome and ADR and WT as independent variables, controlling for patient age, sex, and race. We included 768,274 patients and 3,425 endoscopists. Mean patient age was 61 years and 48% were men; 66% were White, and 3% were Hispanic. Indication for index colonoscopy were screening (43.4%), surveillance (39.0%), and diagnostic (17.6%). ADR quartiles were ≤29.7%, >29.7%-37.2%, >37.2%-45.0%, and >45%. WT quartiles were ≤7.1 minutes, >7.1-8.2 minutes, >8.2-9.7 minutes, and >9.7 minutes. AN detection was lowest when low ADR endoscopists performed both index and surveillance examinations (5.4%, Table 1) and high ADR index examinations were followed by low ADR surveillance examinations (4.0%). Compared with low ADR endoscopists for both index and surveillance examinations, advanced neoplasia detection was significantly higher when both examinations performed by a high ADR endoscopist (AA 7.4%; OR [odds ratio] for AN 1.10 [1.05-1.16]) or low ADR index examinations were followed by high ADR surveillance examinations (AA 13.3%; OR for AN 1.448 [1.37-1.51]). Compared with short WT endoscopists for both examinations (AA 7.2%; CRC 0.3%), AN detection was higher when both examinations were performed by a long WT endoscopist or short WT index examinations were followed by long WT surveillance examinations (AA 7.0% P = 0.53 and 9.9%, P < 0.001) but similar CRC detection of 0.2% and 0.2% ( P 0.14). Other factors associated with finding of metachronous AN were older age (76 years and older vs 45-55 years OR 1.64; 95% CI 1.48, 1.82), male sex (Male vs female OR 1.15; 95% CI 1.10-1.19), White race compared with non-White (OR 1.10; 95% CI 1.06, 1.14), 7-10 years between examinations compared with 3-5 years between examinations (OR 1.24; 95% CI 1.11, 1.37), indication of surveillance vs screening for the index examination (OR 1.1.7; 95% CI 1.13, 1.22), AA or sessile serrated lesion finding on the index examination (OR 2.08; 95% CI 1.97, 21.9 and OR 1.23; 95% CI 1.16, 1.30 respectively). Our findings show endoscopist ADR and WT for both index and surveillance colonoscopy are associated with risk of metachronous neoplasia. Future studies on metachronous neoplasia should include both sets of quality indicators.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with outcomes critically dependent on timely diagnosis, accurate risk stratification, and individualized treatment. Traditional markers such as CEA, KRAS/NRAS, BRAF, and MSI status, while foundational, are insufficient to address the full complexity of CRC biology. Over the past decade, a new generation of biomarkers has emerged spanning liquid biopsy, stool-based methylation, genomics, epigenomics, immune profiling, microbiome analysis, radiomics, patient-derived organoids, and multiomics integration-collectively redefining how CRC is detected, classified, and treated. This narrative review synthesizes evidence from 73 human studies published between 2010 and 2024, identified through structured searches of PubMed, Embase, Web of Science, and the Cochrane Library, and quality-assessed using QUADAS-2 and Newcastle-Ottawa tools. Circulating tumor DNA (ctDNA) emerged as the most clinically validated biomarker, demonstrating superior performance in minimal residual disease (MRD) detection, recurrence prediction, and real-time therapy monitoring. Stool DNA methylation assays showed strong sensitivity for early CRC and advanced adenoma detection. Genomic markers including BRAF V600E, POLE/POLD1, HER2, and KRAS G12C now directly inform targeted therapy selection, while immune biomarkers-MSI-H, TMB, and Immunoscore-guide immunotherapy decisions and stratify prognosis beyond TNM staging. Microbiome signatures, particularly Fusobacterium nucleatum and colibactin-producing Escherichia coli, were associated with chemo resistance and tumor progression. Radiomics and AI-driven imaging models provided noninvasive assessment of nodal involvement and neo-adjuvant therapy response. Patient-derived organoids demonstrated capacity to predict individual drug sensitivity, and multiomic integration enabled refined molecular subtyping. Despite this progress, widespread clinical adoption remains limited by assay variability, lack of prospective multicenter validation, and implementation barriers including cost and infrastructure. As these technologies mature, their integration into standardized, multidisciplinary workflows will be essential to translating biomarker innovation into improved patient outcomes across all stages of CRC care.

BackgroundColorectal adenoma (CRA) is precancerous lesion of colorectal cancer (CRC). Early detection and endoscopic resection of CRA are the most effective methods for preventing CRC, yet there is a significant recurrence risk. We aim to analyze the risk factors for CRA recurrence and explore the gut microbiota characteristics in individuals with recurrent CRA, in order to provide new insights for risk stratification and intervention.MethodsWe recruited 30 participants with recurrent CRA and 15 participants without CRA recurrence. Demographic information, baseline characteristics of adenomas, and other clinical data were collected from each participant. Univariate analysis and Firth Logistic regression analysis were used to analyze the risk factors for CRA recurrence. Meanwhile, fecal samples were collected from all participants and 16s rRNA sequencing was performed to analyze the composition, structure, and taxonomic differences of the gut microbiota, as well as to predict potential functional capacities. Correlation analysis is employed to explore the associations between differential gut microbiota and functional pathways.ResultsUnivariate analysis revealed that there were statistically significant differences (p < 0.05) between the two groups in terms of age, body mass index (BMI), diabetes, smoking history, adenoma size, adenoma number, and advanced adenomas. Firth Logistic analysis indicated that adenoma number and smoking history were independent clinical risk factors for CRA recurrence. Microbiomic analysis showed no significant difference (p > 0.05) in the α-diversity and β-diversity of the gut microbiota between the two groups. Taxonomic analysis revealed the abundances of potential pathogenic bacteria such as Escherichia-Shigella and Klebsiella were significantly increased in the recurrence group, while the abundances of Bacteroides and Faecalibacterium were significantly reduced. Furthermore, Linear Discriminant Analysis Effect Size (LEfSe) analysis indicated that the non-recurrence group was enriched with genera such as Megasphaera. Functional prediction analysis suggested that pathways related to fatty acid metabolic and biosynthetic process were more active in the non-recurrence group. Correlation analysis uncovered the genera enriched in the recurrence group were positively correlated with the functional pathways of styrene degradation and fat digestion and absorption, whereas the genera with reduced abundance were positively correlated with fat digestion and absorption and MicroRNAs in cance pathways.ConclusionThis study not only elucidates the clinical risk factors for CRA recurrence but also reveals that CRA recurrence may be closely associated with the gut microbiota dysbiosis. Combining clinical risk factors with gut microbial biomarkers is expected to construct a more precise predictive model for adenoma recurrence and provide crucial theoretical support for future intervention strategies targeting the gut microbiota.

ObjectivesVisual colonoscopy is a standard method for colorectal cancer screening but carries unnecessary operative risks. This study aimed to develop a clinical prediction model to identify patients at high risk of colorectal polyps or benign conditions detectable via colonoscopy.SettingData were routinely collected during mass screenings: December 2022 at Kumpawapi Hospital, January 2023 at Nhonghan Hospital, and April 2024 at Wangsammo Hospital. All participants with positive fecal immunochemical tests were included.MethodsA retrospective delayed-type cross-sectional study was conducted. Predictors included male sex, age, family history of colorectal cancer, prior colonoscopy, smoking, alcohol use, diabetes, clinical symptoms (e.g. altered bowel habits, weight loss, decreased stool caliber), and hematocrit level. Polyps were biopsied and histologically examined. A clinical prediction model was derived using multinomial logistic regression, selecting predictors based on clinical relevance and face validity. Patients were classified into three risk groups (normal, benign, malignant). Model absolute accuracy was assessed by comparing predicted versus actual classes. Polytomous discrimination index (PDI) was evaluated.ResultsAmong 1071 patients undergoing colonoscopy, 66 (20.3%) had benign polyps, 148 (45.4%) had non-advanced adenomas, 103 (31.6%) had advanced adenomas, and 9 (2.7%) had colorectal cancer. Final predictors were male sex, age (year), family history of colorectal cancer, alcohol use, and abdominal pain. The model showed an absolute accuracy of 0.484 (95% CI, 0.454-0.513) and a PDI of 0.426 (95% CI, 0.396-0.456).ConclusionsThe model showed fair discrimination in identifying high-risk patients. This prediction rule may support shared decision-making for elective colonoscopy and help prioritize patients for urgent screening.

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.

To explore the application value of fecal Syndecan-2 gene Methylation (mSDC2) detection, combined detection of serum Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 72-4 (CA72-4) in screening of Colorectal Cancer (CRC) and precancerous lesions. A total of 196 participants were enrolled in this case-control study from March to December 2023, including 65 with CRC, 38 with advanced adenomas, 33 with non-advanced adenomas, and 60 controls. The sensitivity, specificity, and Odds Ratios (OR) for serum CEA, CA72-4, and fecal mSDC2 were evaluated. The sensitivity of fecal mSDC2 for CRC was 86.2% (56/65), with a specificity of 96.7% (58/60), with an OR of 28.9 (95% CI 8.6-97.2, p < 0.001). The sensitivity in advanced adenomas was 34.2% (13/38). Serum CEA had a sensitivity of 56.9% (37/65) and a specificity of 96.7% (58/60) for CRC, with an OR of 5.7 (95% CI 2.0-16.4, p < 0.001). Combined detection of CEA and CA72-4 had a sensitivity of 69.2% (45/65) and a specificity of 81.6% (49/60). The triple combination (mSDC2 + CEA + CA72-4) achieved a sensitivity of 96.9% (63/65) and a specificity of 78.3% (47/60) in the CRC, and a sensitivity of 50% (19/38) for advanced adenomas. The combined detection had higher sensitivity than single detection, with statistically significant differences compared to serum-based detection (p < 0.001). Combining fecal mSDC2 with serum CEA and CA72-4 increased sensitivity for CRC detection in this single-center study, at the cost of reduced specificity. Validation in larger, screening-intended cohorts with predefined thresholds is warranted.