Computer-aided detection software (CADe) has shown promising results in real-time polyp detection, but a limited head-to-head comparison of the available CADe systems has been performed. Moreover, such systems have not been compared to endoscopists using standardized videos. This study aims to compare the performance of three CADe systems in detecting polyps, employing a novel standardized methodology.

Videos from 300 colonoscopies conducted at Oslo University Hospital were analyzed. Short video clips (20-45 s) presenting normal mucosa or polyps were randomly selected. These videos were then streamed through each CADe system from Medtronic, Olympus, and Augere Medical. Each system featured diverse configurations, resulting in a total of six software settings. Sensitivity and false positivity (FP) were assessed by comparing the CADe systems to both the mean of the systems and pairwise between them. Furthermore, the systems' performance was compared to the performance of five endoscopists.

CADe systems' sensitivity ranged between 84.9% and 98.7%, with statistically significant differences observed between the systems, both in comparison to the mean and to each other. FP rates ranged between 1.2% and 5.6%, also differing statistically significantly between the systems. The CADe systems achieving the highest sensitivity also exhibited the highest FP. Statistically significant differences in the alert delay were observed between different CADe systems and endoscopists.

This study highlights significant differences between commercially available CADe software regarding sensitivity and FP, but a superior performance compared to endoscopists. The software with the highest sensitivity also exhibited the highest FP, highlighting the need for further refinement.

In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)?

Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient.

Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30 000 participants and a companion microsimulation study simulating 10 year follow-up for 100 000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance.

For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation).

An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation UNDERSTANDING THE RECOMMENDATION: The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens-including more frequent surveillance colonoscopies-are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use.The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate.

This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ.

Colorectal cancer (CRC) can evolve from colorectal adenomas, which can be further classified into non-advanced adenomas (NAAs) and advanced adenomas (AAs) based on their clinical characteristics. Their prognoses are vastly different, with patients with NAAs having significantly lower recurrence and CRC-related mortality rates than those with AA or CRC. Although serum metabolomics has shown promise for the early diagnosis of CRC, the differences in serum metabolite composition between NAA and AA still need to be further elucidated. This study aimed to explore the mechanism of CRC occurrence and development based on the unique serum metabolic fingerprints of different stages of CRC and to discover a new non-invasive diagnostic method based on serum metabolomics. A clinical CRC progression cohort containing healthy control (NC; n = 40), NAA (n = 40), AA (n = 40), and CRC (n = 22) groups was constructed, and untargeted metabolomic analysis based on liquid chromatography/mass spectrometry was performed to analyze the serum metabolite characteristics of each group. A semi-quantitative analysis of intergroup metabolite differences was conducted, focusing on specific metabolites that differed in the NAA and AA groups. Finally, variable metabolites were selected based on least absolute shrinkage and selection operator (LASSO) regression analysis, and receiver operating characteristic curves were plotted to evaluate the efficacy of the serum metabolite-based diagnostic model in distinguishing NC/NAA populations from AA/CRC populations. Metabolomic analysis revealed significant differences in the composition of metabolites in the NC and NAA groups compared to the CRC group, whereas the serum metabolites of the AA group were similar to those of the CRC group. The levels of 33 metabolites were significantly different in the serum of AA/CRC patients compared to that of NAA patients, and their functions included glycerophospholipid, sphingolipid, and caffeine metabolism. LASSO regression analysis identified 57 differential metabolite variables between the NC/NAA and AA/CRC groups. The diagnostic model constructed using the random forest algorithm had the best discrimination effect, with areas under the curve of 1.000 (95% confidence interval [CI] 1.000-1.000) and 0.685 (95% CI 0.540-0.830) for the training and testing sets, respectively. The composition of serum metabolites is specific to the different stages of CRC development. The serum metabolite composition of patients with AAs was similar to that of patients with CRC. Auxiliary diagnostic measures based on serum metabolites have the potential to guide the follow-up and treatment of patients with adenoma.

Colorectal cancer progresses through a well-defined adenoma-carcinoma sequence (ACS), which is pivotal for early detection and intervention. While ACS-based surveillance has been instrumental, its reliance on tissue sampling limits accurate staging. Liquid biopsies, including circulating tumor DNA (ctDNA) and extracellular RNA, have emerged as non-invasive alternatives, yet they primarily detect genetic alterations or passive RNA release rather than active biological processes. Thus, there is a need for biomarkers that reflect real-time immune responses and tumor-microenvironment interactions during ACS progression. This study aimed to identify circulating RNA biomarkers associated with ACS by analyzing blood samples from 160 individuals across five groups: colorectal cancer, advanced adenoma, non-advanced adenoma, symptomatic non-disease control, and healthy control. RNA sequencing coupled with gene ontology and protein-protein interaction analyses identified stage-specific circulating transcripts. Notably, IFI27 was linked to the symptomatic non-disease control group, DEFA4 to the non-advanced adenoma group, MPO to the advanced adenoma group, and CD177 to the colorectal cancer group. These findings suggest that colorectal-cancer-related circulating RNA markers reflect host immune responses during ACS progression, supporting their potential role in early detection and non-invasive diagnoses. By addressing critical gaps in early colorectal cancer detection, this study advances the utility of circulating RNA biomarkers and liquid biopsies in colorectal cancer screening and clinical management.

Recent studies suggest the role of gut microbes in bile acid metabolism in the development and progression of colorectal cancer. However, the surveys of the association between fecal bile acid concentrations and colorectal cancer (CRC) have been inconsistent. We searched online to identify relevant cross-sectional and case-control studies published online in the major English language databases (Medline, Embase, Web of Science, AMED, and CINAHL) up to January 1, 2024. We selected studies according to inclusion and exclusion criteria and extracted data from them. RevMan 5.3 was used to perform the meta-analyses. In CRC risk meta-analysis, the effect size of CA (cholic acid), CDCA (chenodeoxycholic acid), DCA (deoxycholic acid), and UDCA (ursodeoxycholic acid) were significantly higher (CA: standardized mean difference [SMD] = 0.41, 95% confidence interval [CI]: 0.5-0.76, P = 0.02; CDCA: SMD = 0.35, 95% CI: 0.09-0.62, P = 0.009; DCA: SMD = 0.33,95% CI: 0.03-0.64, P = 0.03; UDCA: SMD = 0.46, 95% CI: 0.14-0.78, P = 0.005), and the combined effect size was significantly higher in the high-risk than the low-risk CRC group (SMD = 0.36, 95% CI: 0.21-0.51, P < 0.00001). In the CRC incidence meta-analysis, the effect sizes of CA and CDCA were significantly higher (CA: SMD = 0.42, 95% CI: 0.04-0.80, P = 0.03; CDCA: SMD = 0.61, 95% CI: 0.26-0.96, P = 0.00079), and their combined effect size was also significantly higher in the high-risk compared to low-risk CRC group (SMD = 0.39, 95% CI: 0.09-0.68, P = 0.01). Only one cross-sectional study suggested a higher concentration of CDCA, DCA, and UDCA in the stool of the CRC high-risk group than the low-risk group. These findings indicate that higher fecal concentrations of bile acid may be associated with a higher risk/incidence of CRC.

Artificial intelligence (AI) is increasingly used to improve adenoma detection during colonoscopy. This meta-analysis aimed to provide an updated evaluation of computer-aided detection (CADe) systems and their impact on key colonoscopy quality indicators.

We searched the EMBASE, PubMed, and MEDLINE databases from inception until February 15, 2024, for randomized control trials (RCTs) comparing the performance of CADe systems with routine unassisted colonoscopy in the detection of colorectal adenomas.

Twenty-eight RCTs were selected for inclusion involving 23,861 participants. Random-effects meta-analysis demonstrated a 20% increase in adenoma detection rate (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.14-1.27; P < .01) and 55% decrease in adenoma miss rate (RR, 0.45; 95% CI, 0.37-0.54; P < .01) with AI-assisted colonoscopy. Subgroup analyses involving only expert endoscopists demonstrated a similar effect size (RR, 1.19; 95% CI, 1.11-1.27; P < .001), with similar findings seen in analysis of differing CADe systems and healthcare settings. CADe use also significantly increased adenomas per colonoscopy (weighted mean difference, 0.21; 95% CI, 0.14-0.29; P < .01), primarily because of increased diminutive lesion detection, with no significant difference seen in detection of advanced adenomas. Sessile serrated lesion detection (RR, 1.10; 95% CI, 0.93-1.30; P = .27) and miss rates (RR, 0.44; 95% CI, 0.16-1.19; P = .11) were similar. There was an average 0.15-minute prolongation of withdrawal time with AI-assisted colonoscopy (weighted mean difference, 0.15; 95% CI, 0.04-0.25; P = .01) and a 39% increase in the rate of non-neoplastic resection (RR, 1.39; 95% CI, 1.23-1.57; P < .001).

AI-assisted colonoscopy significantly improved adenoma detection but not sessile serrated lesion detection irrespective of endoscopist experience, system type, or healthcare setting.

Data of long-term follow up for large non pedunculated colorectal polyps (LNPCPs) ≥4 cm removed with piecemeal wide field endoscopic mucosal resection (PWF-EMR) are limited. We primarily evaluated the recurrence rates and secondarily the rates of post colonoscopic polypectomy colorectal cancer (PCPCRC) on a long-term basis.

We retrospectively reviewed a prospectively-stored electronic database of all patients who underwent PWF-EMR for LNPCPs at the Venizeleion General Hospital, between 2009 and 2020. Eligible patients were those with LNPCPs ≥4 cm, deemed completely removed by endoscopic means and followed-up for a minimum of 36 months with at least two surveillance colonoscopies, the first one (SC1) (4-6) months after the initial PWF-EMR procedure and the second one (SC2) after (12-18) months. In 2023, all cases were checked for PCPCRC development.

Residual/early recurrent tissue was detected in 44 (31 %) cases among the 142 (82 males, 60 females) assessed during SC1. Late recurrent tissue was detected in 9 (6.6 %) cases among the 137 surveyed during SC2. Investigation did not reveal any case of PCPCRC .

This historical cohort shows that the PWF-EMR for LNPCPs ≥4 cm is a safe and definitive removal method while it is not associated with the appearance of PCPCRC.

Early detection for colorectal cancer (CRC) can enhance the patient prognosis. We aimed to validate the combined multi-gene detection in plasma of Septin9, SDC2, KCNQ5, and IKZF1 for early diagnosing of CRC in this prospective study.

Overall, 124 participants including 45 CRC patients, 8 advanced adenoma patients, 34 small polyp patients, and 37 normal controls who underwent colonoscopy were enrolled. The carcinoembryonic antigen (CEA) test and methylation tests for Septin9, SDC2, KCNQ5, and IKZF1 were performed. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were utilized to evaluate the diagnostic value of each biomarker. Additionally, the association between the positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed.

The positive detection rate of multi-gene methylation in CRC patients was 86.67%, for stage I and stage II patients, the positive rates were 90.91% and 87.50%, both of which were significantly higher than CEA, which had rates of 55.56%, 18.18% and 56.25% for the corresponding stages. In patients with advanced adenomas and small polyps, the positive rates for the four-gene combined test were 62.50% and 52.94%, respectively, which were markedly higher than the CEA rates of 12.50% and 14.71%. AUC of the ROC curve indicated that the diagnostic value of the multi-gene test for CRC was superior to that of any single gene. Correlation analysis revealed that the positive rate of the test was not affected by patients' clinicopathological characteristics.

A combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 test has the potential for early diagnosis of CRC patients, advanced adenoma patients, and small polyp patients.

For the early detection of colorectal cancer, it is important to identify the premalignant lesions to prevent cancer development. Non-invasive testing methods such as the faecal immunochemical test are well established for the screening and triage of patients with suspected colorectal cancer but are not routinely used for polyps. Additionally, the role of volatile organic compounds has been tested for cancer detection. The aim of this review was to determine the diagnostic accuracy of the faecal immunochemical test and volatile organic compounds in detecting colorectal polyps.

Original articles with diagnostic test accuracy measures for both the faecal immunochemical test and volatile organic compounds for advanced adenomas were included. Four databases including Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Web of Science were searched. The quality assessment tool for diagnostic accuracy study was used to assess the risk of bias and applicability. Meta-analysis was performed using RStudio® and the combined faecal immunochemical test-volatile organic compounds sensitivity and specificity were computed.

Twenty-two faecal immunochemical tests and 12 volatile organic compound-related articles were included in the systematic review whilst 18 faecal immunochemical tests and eight volatile organic compound-related studies qualified for the meta-analysis. The estimated pooled sensitivity and specificity of the faecal immunochemical test to diagnose advanced adenoma(s) were 36% (95% c.i. 30 to 41) and 89% (95% c.i. 86 to 91) respectively, with an area under the curve of 0.65, whilst volatile organic compounds pooled sensitivity and specificity was 83% (95% c.i. 70 to 91) and 76% (95% c.i. 60 to 87) respectively, with an area under the curve of 0.84. The combined faecal immunochemical test-volatile organic compounds increased the sensitivity to 89% with a specificity of 67%.

Faecal immunochemical testing has a higher specificity but poor sensitivity for detecting advanced adenomas, while volatile organic compound analysis is more sensitive. The combination of both tests enhances the detection rate of advanced adenomas.

Despite reports indicating that polyps proximal to the splenic flexure have higher rates of metachronous colorectal adenocarcinoma (CRC), the role of adenoma location on surveillance recommendations remains unclear. This study aimed to analyze the association between index polyp location and postcolonoscopy CRC among participants of the Minnesota Colon Cancer Control Study.

The Minnesota Colon Cancer Control Study randomized 46,551 patients 50-80 years to usual care, annual, or biennial screening with fecal occult-blood testing. Screening was performed between 1976 and 1992. Positive fecal occult-blood testing was followed by colonoscopy. We analyzed participants whose colonoscopy revealed at least 1 adenoma. Patients were divided into those with at least 1 lesion proximal to the splenic flexure and those without.

Of 2,295 patients, 815 had proximal adenomas. The majority were men; mean age = 62 years at randomization, and 69 years at index polyp. There was a high rate of advanced adenomas: 44% ≥ 1 polyp ≥1 cm, 35% with villous histology, and 5% high-grade dysplasia. At 20 years, 87 patients had a CRC diagnosis, and the estimated cumulative incidence of CRC was 4.3%. Proximal adenomas had a higher risk of developing a postcolonoscopy CRC (subdistribution hazard ratio = 1.63, 95% confidence interval = 1.05-2.53, P = 0.03), which was attenuated after adjusting for polyp multiplicity in sensitivity analyses (subdistribution hazard ratio = 1.56, 95% confidence interval = 0.96-2.53, P = 0.07).

Although patients with proximal adenomas were found to have higher hazards of postcolonoscopy CRC, adjusting for polyp multiplicity attenuated the strength of association. Further research is warranted to determine whether polyp location should be factored in the determination of appropriate surveillance intervals.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.

We utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.

Eight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.

In summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.

United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.g., age and sex), 19 lifestyle and environmental risk factors, and a polygenic risk score for colorectal cancer. Ten-year absolute cancer risks for each diagnostic colonoscopy finding (advanced adenomas [N = 2,446], ≥3 non-advanced adenomas [N = 483], 1-2 non-advanced adenomas [N = 4,400], and no adenoma [N = 7,183]) were used as implicit risk thresholds for recommended surveillance intervals.

The area under the curve for the model including colonoscopy findings, baseline characteristics, and polygenic risk score was 0.658. Applying the equal management of equal risks framework, 28.2% of individuals with no adenoma and 42.7% of those with 1-2 non-advanced adenomas would be considered high risk and assigned a significantly shorter surveillance interval than currently recommended. Among individuals who developed cancer within 10 years, 52.4% with no adenoma and 48.3% with 1-2 non-advanced adenomas would have been considered high risk and assigned a shorter surveillance interval.

Using a personalized risk-based model has the potential to identify individuals with no adenoma or 1-2 non-advanced adenomas, who are higher risk and may benefit from shorter surveillance intervals.

Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening.

To estimate the clinical and economic impacts of novel CRC screening tests.

Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer).

Published data.

Average-risk persons.

Ages 45 to 100 years.

Health sector.

Novel versus established CRC screening tests.

Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs.

For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective.

Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT's impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT's uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up.

Longitudinal test-specific participation patterns are unknown.

First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives.

The Gorrindo Family Fund.

Background/Objectives: Colorectal cancer (CRC) frequently co-occurs with intestinal system diseases (ISDs), yet their molecular interplay remains poorly understood. We employed a comprehensive bioinformatics approach to elucidate shared genetic signatures and pathways between CRC and ISDs. Methods: We systematically analyzed 12 microarray and RNA-seq datasets encompassing 989 samples across seven ISDs and CRC. Differentially expressed genes (DEGs) were identified using Limma and DESeq2. Functional enrichment analysis was performed using clusterProfiler. Protein-protein interaction networks were constructed via STRING and visualized with Cytoscape to identify hub genes. Clinical significance of shared genes was further assessed through survival analysis and validated by immunohistochemistry staining of 30 paired CRC-normal tissue samples. Results: Integrating bioinformatics and machine learning approaches, we uncovered 160 shared DEGs (87 upregulated, 73 downregulated), which predominantly enriched cell metabolism, immune homeostasis, gut-brain communication, and inflammation pathways. Network analysis revealed nine key hub proteins linking CRC and ISDs, with seven upregulated (CD44, MYC, IL17A, CXCL1, FCGR3A, SPP1, and IL1A) and two downregulated (CXCL12 and CCL5). Survival analysis demonstrated the prognostic potential of these shared genes, while immunohistochemistry confirmed their differential expression in CRC tissues. Conclusions: Our findings unveil potential biomarkers and therapeutic targets, providing insights into ISD-influenced CRC progression and offering a robust foundation for improved diagnostic and treatment strategies in ISD-associated CRC.

Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma-carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741-114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741-114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741-114379093 as a promising biomarker and therapeutic target for CRC management.

Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines.

Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines.

During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37).

CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.

Colorectal cancer (CRC) screening has been proven to reduce both mortality and the incidence of this disease. Most CRC screening programs are based on fecal immunochemical tests (FITs), which have a low participation rate. Searching for blood protein biomarkers can lead to the development of a more accepted screening test. The aim of this systematic review was to compare the diagnostic potential of the most promising serum protein biomarkers. A systematic review based on PRISMA guidelines was conducted in the PubMed and Web of Science databases between January 2010 and December 2023. Studies assessing blood protein biomarkers for CRC screening were included. The sensitivity, specificity, and area under the ROC curve of each biomarker were collected. Among 4685 screened studies, 94 were considered for analysis. Most of them were case-control studies, leading to an overestimation of the performance of candidate biomarkers. The performance of no protein biomarker or combination of biomarkers appears to match that of the FIT. Studies with a suitable design and population, testing new assay techniques, or based on algorithms combining FIT with serum tests are needed.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide, mostly arising from adenomatous polyps. Mounting evidence has demonstrated that changes in the gut microbiome play key roles in CRC progression, while quite few studies focused on the altered microbiota architecture of advanced adenoma (AA), a crucial precancerous stage of CRC. Thus, we aimed to investigate the microbial profiles of AA patients.

Fecal samples were collected from 26 AA patients and 26 age- and sex-matched normal controls (NC), and analyzed by shotgun metagenomic sequencing.

Gut microbial dysbiosis was observed in AA patients with lower alpha diversity. Advanced adenoma was characterized by an increased Bacillota/Bacteroidota ratio and higher Pseudomonadota levels compared to normal individuals. Linear discriminant analysis effect size (LEfSe) analysis was performed and identified 14 microbiota with significantly different abundance levels between AA and NC groups. Functional analysis revealed that tryptophan metabolism was upregulated in AA. Correspondingly, the expressions of gut microbes implicated in tryptophan metabolism also changed, including Akkermansia muciniphila, Bacteroides ovatus, Clostridium sporogenes, and Limosilactobacillus reuteri. The microbial network suggested that AA exhibited decreased correlation complexity, with Escherichia coli and Enterobacteriaceae unclassified harboring the strongest connectivity. A diagnostic model consisting of 3 microbial species was established based on random forest, yielding an area under the curve (AUC) of 0.799.

Our study profiled the alterations of the gut microbiome in AA patients, which may enrich the knowledge of microbial signatures along with colorectal tumorigenesis and provide promising biomarkers for AA diagnosis.

Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting.

This population-based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow-up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high-grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40-1.83), villous histology (HR 1.91, 95% CI 1.59-2.28), size ≥10 mm (HR 1.12, 95% CI 1.02-1.23), proximal location (HR 1.12, 95% CI 1.02-1.23), two or more adenomas (HR 1.28, 95% CI 1.16-1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42-1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high-grade dysplasia (HR 2.49, 95% CI 1.92-3.24) were an independent risk factor for metachronous CRC.

Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)-based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable.

Although inflammatory bowel disease (IBD) and colorectal polyps are considered as significant risk factors of colorectal cancer (CRC), the molecular mechanism associated with colorectal carcinogenesis is still explored. Unlike sporadic CRC, local persistent inflammation in IBD induces genetic and epigenetic alterations, leading to tumor development. Moreover, cumulative data indicate that colorectal polyps display a significant malignant potential. In this context, our study aimed to investigate the clinicopathological features of CRC associated with IBD and/or colorectal neoplastic polyps in a retrospective group of CRC cases. The clinical data and histopathological features of CRC cases have been collected from our files. Immunohistochemical examination of mismatch repair (MMR) proteins has been performed in a selected case. The study group comprised 40 patients, 72.5% men and 27.5% women, with a median age of 64.73±9.09 years. Out of the cases with double association, 62.5% of CRC cases displayed colorectal polyps, while 32.5% of patients were diagnosed with both CRC and IBD, which encompassed both ulcerative colitis (UC) and Crohn's disease (CD). Two patients included in our study group exhibited a triple association of IBD, colorectal polyps, and CRC, one of them showing defective MMR (dMMR) phenotype. Although our results provide significant data on the relationship between IBD, colorectal polyps, and colorectal carcinogenesis, future cohort studies are needed to improve our understanding on the complex mechanism of colorectal carcinogenesis, ultimately guiding improved prevention, diagnosis, and treatment strategies for these patients.

Serrated polyps (SPs) are precursors to 15% to 20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps.

We systematically searched PubMed, Embase, and Cochrane for cohort studies, case-control studies, and clinical trials from inception to December 31, 2023, of CRC or advanced polyps (advanced adenoma [AA] or advanced SP) incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those ≥10 mm or with dysplasia. CRC and advanced polyp incidence per 1000 person-years were estimated. We performed a meta-analysis by calculating pooled relative risks (RRs) using a random-effects model.

A total of 5903 studies were reviewed, and 14 were included with 493,949 patients (mean age, 59.5 years; 55% men). The mean follow-up was 4.9 years. CRC incidence per 1000 person-years was 2.09 (95% confidence interval [CI], 1.29-2.90) for advanced SPs, 1.52 (95% CI, 0.78-2.25) for SPs of ≥10 mm, 5.86 (95% CI, 2.16-9.56) for SPs with dysplasia, 1.18 (95% CI, 0.77-1.60) for proximal SPs, 0.52 (95% CI, 0.08-1.12) for ≥3 SPs, 0.50 (95% CI, 0.35-0.66) for nonadvanced SPs, and 0.44 (95% CI, 0.41-0.46) for normal colonoscopy findings. Metachronous CRC risk was higher in advanced SPs versus nonadvanced SPs (RR, 1.84; 95% CI, 1.11-3.04) and versus normal colonoscopy findings (RR, 2.92; 95% CI, 2.26-3.77), in SPs of ≥10 mm versus <10 mm (RR, 2.61; 95% CI, 1.43-4.77) and versus normal colonoscopy findings (RR: 3.52; 95% CI, 2.17-5.69); and in SPs with dysplasia versus normal colonoscopy findings (RR: 2.71; 95% CI, 2.00-3.67). No increase in CRC or advanced polyp risk was found in patients with proximal versus distal SPs, nor in ≥3 SPs versus 1 or 2 SPs.

CRC risk is significantly higher in patients with baseline advanced SPs after 4.9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SPs.

Surveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals for surveillance remain unclear.

We prospectively followed 156 699 participants who had undergone a colonoscopy from 2007 to 2017 in a large integrated healthcare system. Using multivariable Cox proportional hazards regression we estimated the subsequent risk of CRC and high-risk polyps, respectively, according to index colonoscopy polyps, colonoscopy quality measures, patient characteristics and the use of surveillance colonoscopy.

After a median follow-up of 5.3 years, we documented 309 CRC and 3053 high-risk polyp cases. Compared with participants with no polyps at index colonoscopy, those with high-risk adenomas and high-risk serrated polyps had a consistently higher risk of CRC during follow-up, with the highest risk observed at 3 years after polypectomy (multivariable HR 5.44 (95% CI 3.56 to 8.29) and 8.35 (95% CI 4.20 to 16.59), respectively). Recurrence of high-risk polyps showed a similar risk distribution. The use of surveillance colonoscopy was associated with lower risk of CRC, with an HR of 0.61 (95% CI 0.39 to 0.98) among patients with high-risk polyps and 0.57 (95% CI 0.35 to 0.92) among low-risk polyps. Among 1548 patients who had high-risk polyps at both index and surveillance colonoscopies, 65% had their index polyps in the proximal colon and 30% had index and interval polyps in the same segments.

Patients with high-risk polyp findings were at higher risk of subsequent CRC and high-risk polyps and may benefit from early surveillance within 3 years. The subsite distribution of the index and recurrent high-risk polyps suggests the contribution of incomplete resection and missed lesions to the development of interval neoplasia.

Combined endoscopic and laparoscopic surgery (CELS) has been used to resect colon polyps since the 1990s. These colon-sparing techniques, however, have not yet been widely adopted. With the evolution of technology in both diagnosing and treating colon cancer, colorectal surgeons should strive for a diverse and complete armamentarium through which they can best serve their patients. In this article, we hope to provide clarity on CELS by discussing three topics: (1) the history and fruition of CELS; (2) the techniques involved in CELS; and (3) the utility of CELS within different clinical scenarios. Our goal is to educate readers and stimulate consideration of CELS in select patients who might benefit greatly from these techniques.

The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC).

Screening for colorectal lesions.

14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set.

In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001).

Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.

To investigate the effect of different working periods on missed diagnoses in patients with colorectal polyps in colonoscopy.

We conducted a retrospective analysis of patients who were diagnosed with colorectal polyps during colonoscopy in an outpatient department between July and December 2022. These patients were subsequently hospitalized for resection during this period. Patients with missed diagnoses were those who had newly discovered polyps in a second colonoscopy. The working periods were categorized as work, near the end of work, and delayed work, respectively, in the morning and afternoon.

A total of 482 patients were included, and the miss rate of diagnosis was 48.1% (232/482), mainly in the transverse colon (25%), and the ascending colon (23%). Patient age was a risk factor for the miss rate of diagnosis (OR = 1.025, 95%CI: 1.009-1.042, P = 0.003) and was also associated with the number of polyps detected for the first colonoscopy (χ2 = 18.196, P = 0.001). The different working periods had no statistical effect on the missed rate of diagnosis (χ2 = 1.998, P = 0.849). However, there was an increasing trend in miss rates towards the end of work and delayed work periods, both in the morning and afternoon. The highest miss rate (60.0%) was observed during delayed work in the afternoon. Additionally, poor bowel preparation was significantly more common during delayed work in the afternoon.

The increasing trend in miss rates towards the end of work and delayed work periods deserves clinical attention. Endoscopists cannot always stay in good condition under heavy workloads.

The 2020 United States Multi-Society Task Force on Colorectal Cancer guidelines for surveillance after colonoscopy with polypectomy introduced significant changes in surveillance intervals. We sought to identify rates of adherence to these new guidelines at an academic medical center.

Average-risk screening colonoscopies where 1 to 4 polyps <10 mm were removed between January 1, 2020, and June 30, 2021 were included. To determine predictors of nonadherence, a multivariable logistic regression analysis was conducted and included patient and procedure-related variables. Bayesian changepoint analysis was applied to identify timing of change in adherence. Multinomial logistic regression was used to identify predictors of variability within the guidelines.

One thousand twenty-six procedures were analyzed. Adherence to the guidelines was 85%. In procedures with 1 to 2 polyps, increasing size (odds ratio [OR] 0.84 per mm; 95% confidence interval [CI]: 0.75-0.93) and a mixture of tubular adenomas (TA) and hyperplastic polyps (OR 0.35; 95% CI: 0.21-0.59) were associated with nonadherence. Among procedures with 1 to 2 TAs, age (OR 0.86 per 5-year increase; 95% CI: 0.75-0.99), increasing size (OR 0.86 per mm; 95% CI: 0.75-0.99) and polyp number (OR 0.54; 95% CI: 0.33-0.90) were associated with nonadherence. Changepoint analysis identified a potential changepoint on September 2, 2020 (95% credible interval April 2, 2020-February 22, 2020). Larger TAs were less likely to receive a 10-year recommendation (OR 0.61, 95% CI 0.5-0.75).

Adherence rates to the 2020 surveillance guidelines were high with a potential changepoint identified on 2/9/20. Deviation from guidelines was associated with patient and procedure related variables.

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.

The colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The hazard of developing a tumor is deeply associated with the number and size of adenomas and their subtype. Adenomatous polyps are histologically categorized as follows: approximately 80-90% are tubular, 5-15% are villous, and 5-10% are tubular/villous. Given the higher risk of a malignant transformation observed in tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at an improved risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma; in particular, intestinal cells first acquire loss-of-function mutations in the APC gene that induce the formation of adenomas.

Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, and BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 were affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors.

In this study, both the APC gene and protein were less expressed in the colon tumor compared to the adjacent colonic mucosa. Conversely, the activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed the literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlines that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered.

This is the first study analyzing the difference in expression of the Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes with the use of APC and β-catenin as biomarkers.

Piecemeal endoscopic mucosal resection (pEMR) is the best approach to resect large lateral spreading tumors (LST, > 20 mm width). However, it is associated with early recurrence (ER) and late recurrence (LR). This study aims to assess the risk factors associated with ER and LR and to validate different predictive scores (SMSA, SERT, and BCM) in identifying the risk of ER and LR after LST resected by pEMR in a European cohort.

Retrospective observational cohort study, based on a prospectively collected database, of large LST submitted to pEMR.

A total of 108 patients were included in the study and the incidence rates of ER and LR were 22 % and 8 %, respectively. The lesion's size, SERT, and BCM scores were independent predictor factors of ER (p-value < 0.05), while the lesion's site and BCM score were independent predictor factors of LR (p-value < 0.05). For the prediction of ER, the SERT score (cut-off > 1) presented the highest AUROC (0.758 vs 0.697 from BCM and 0.647 from SMSA). Regarding LR, the BCM model (cut-off > 2) presented the highest AUROC (0.817 vs 0.708 from SERT and 0.691 from SMSA).

We present the first external validation of the three scores mentioned in an European cohort. SERT and BCM scores had an acceptable performance in predicting ER and LR. However, the BCM model was the only score that proved to be an independent predictor of both ER and LR, proving to be valuable for both applications.

False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists.

The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome.

Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403).

The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

CRC is going to be an important issue in Middle East countries. Also, the main parts of this cancer develop from benign adenomas.

To understand the recurrence rate of colorectal polyps among average-risk subjects.

In a prospective study, the average-risk patients with colorectal adenoma were enrolled in this study based on inclusion criteria. The patients were consulted annually by an expert gastroenterologist. A control colonoscopy was programmed after three years of follow-up. It was not an obligation to follow our program, and each patient could exit the study at any time. The patient who developed one of the exclusion criteria was also withdrawn from the study by the gastroenterologist of this study.

237 patients were enrolled in this study. Of them, 102 patients completed their 3-year follow-up. Among these participants, 62 (60.8%) were male and 40 (39.2%) were female, with a mean age of 57.05 ± 12.87 years. Additionally, 20 (19.6%) subjects had adenomatous polyps at the end of the study. Patients with recurrent colorectal polyps tend to be raised in large ones with a tubulovillous morphology. The polyps were more commonly located in the sigmoid colon, rectum. Furthermore, high-grade dysplasia was recorded in 5 patients. Tubulovillous polyp had higher chance of recurrence than patients with tubular polyp.

We believe the colonoscopy screening needs to be set up in regions previously considered low-risk for CRC. Also, it may be valuable to control colonoscopy for less than three years in patients with dysplasia.

Colonoscopy surveillance guidelines categorize individuals as high or low risk for future colorectal cancer (CRC) based primarily on their prior polyp characteristics, but this approach is imprecise, and consideration of other risk factors may improve postpolypectomy risk stratification.

Among patients who underwent a baseline colonoscopy with removal of a conventional adenoma in 2004-2016, we compared the performance for postpolypectomy CRC risk prediction (through 2020) of a comprehensive model featuring patient age, diabetes diagnosis, and baseline colonoscopy indication and prior polyp findings (i.e., adenoma with advanced histology, polyp size ≥10 mm, and sessile serrated adenoma or traditional serrated adenoma) with a polyp model featuring only polyp findings. Models were developed using Cox regression. Performance was assessed using area under the receiver operating characteristic curve (AUC) and calibration by the Hosmer-Lemeshow goodness-of-fit test.

Among 95,001 patients randomly divided 70:30 into model development (n = 66,500) and internal validation cohorts (n = 28,501), 495 CRC were subsequently diagnosed; 354 in the development cohort and 141 in the validation cohort. Models demonstrated adequate calibration, and the comprehensive model demonstrated superior predictive performance to the polyp model in the development cohort (AUC 0.71, 95% confidence interval [CI] 0.68-0.74 vs AUC 0.61, 95% CI 0.58-0.64, respectively) and validation cohort (AUC 0.70, 95% CI 0.65-0.75 vs AUC 0.62, 95% CI 0.57-0.67, respectively).

A comprehensive CRC risk prediction model featuring patient age, diabetes diagnosis, and baseline colonoscopy indication and polyp findings was more accurate at predicting postpolypectomy CRC diagnosis than a model based on polyp findings alone.

Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs).

We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables.

Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28).

CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.