BMPR2 as a Novel Predisposition Gene for Hereditary Colorectal Polyposis.

BACKGROUND & AIMS: Colorectal cancer (CRC) is one of the most prevalent tumors worldwide, with incidence quickly increasing (particularly in the context of early-onset cases), despite important prevention efforts, mainly in the form of population-wide screening programs. Although many cases present a clear familial component, the current list of hereditary CRC genes leaves a considerable proportion of the cases unexplained. METHODS: In this work, we used whole-exome sequencing approaches on 19 unrelated patients with unexplained colonic polyposis to identify candidate CRC predisposition genes. The candidate genes were then validated in an additional series of 365 patients. CRISPR-Cas9 models were used to validate BMPR2 as a potential candidate for CRC risk. RESULTS: We found 8 individuals carrying 6 different variants in the BMPR2 gene (approximately 2% of our cohort of patients with unexplained colonic polyposis). CRISPR-Cas9 models of 3 of these variants showed that the p.(Asn442Thrfs∗32) truncating variant completely abrogated BMP pathway function in a similar way to the BMPR2 knockout. Missense variants p.(Asn565Ser), p.(Ser967Pro) had varying effects on cell proliferation levels, with the former impairing cell control inhibition via noncanonical pathways. CONCLUSIONS: Collectively, these results support loss-of-function BMPR2 variants as candidates to be involved in CRC germline predisposition.

Development of desmoid tumours after ileorectal anastomosis versus ileal pouch-anal anastomosis in familial adenomatous polyposis.

BACKGROUND & AIMS: Desmoid tumours (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: We performed an international historical cohort study in FAP patients who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS: We analysed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The post-operative risk was significantly higher after IPAA (p < 0.01) in multivariable analysis, while approach did not significantly influence the risk. CONCLUSIONS: The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

RISK FACTORS FOR METACHRONOUS COLORECTAL CANCER OR ADVANCED LESIONS AFTER ENDOSCOPIC RESECTION OF SERRATED POLYPS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND AND AIMS: Serrated polyps (SPs) are precursors to 15-20% 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. METHODS: We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for 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 >10mm or with dysplasia. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model. RESULTS: 5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29-2·90) for advanced SP, 1·52 (0·78-2·25) for SP>10mm, 5·86 (2·16-9·56) for SP with dysplasia, 1·18 (0·77-1·60) for proximal SP, 0·52 (0·08-1·12) for >3SP, 0·50 (0·35-0·66) for non-advanced SP, and 0·44 (0·41-0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11-3·04), and vs normal colonoscopy (RR 2·92, 2·26-3·77); in SP>10mm vs <10mm (RR 2·61, 1·43-4·77), and vs normal colonoscopy (RR 3·52, 2·17-5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00-3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1-2SP. CONCLUSIONS: CRC risk is significantly higher in patients with baseline advanced SP 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 SP.

Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.

BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

BACKGROUND: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. OBJECTIVE: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. DESIGN: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). SETTING: Spanish colorectal cancer screening program. PARTICIPANTS: 3213 persons with a positive fecal immunochemical test. INTERVENTION: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. MEASUREMENTS: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. RESULTS: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. LIMITATIONS: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. CONCLUSION: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. PRIMARY FUNDING SOURCE: Medtronic.

Real-Time Computer-Aided Detection of Colorectal Neoplasia During Colonoscopy : A Systematic Review and Meta-analysis.

BACKGROUND: Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss rates, but it may increase overdiagnosis and overtreatment of nonneoplastic polyps. PURPOSE: To quantify the benefits and harms of CADe in randomized trials. DESIGN: Systematic review and meta-analysis. (PROSPERO: CRD42022293181). DATA SOURCES: Medline, Embase, and Scopus databases through February 2023. STUDY SELECTION: Randomized trials comparing CADe-assisted with standard colonoscopy for polyp and cancer detection. DATA EXTRACTION: Adenoma detection rate (proportion of patients with ≥1 adenoma), number of adenomas detected per colonoscopy, advanced adenoma (≥10 mm with high-grade dysplasia and villous histology), number of serrated lesions per colonoscopy, and adenoma miss rate were extracted as benefit outcomes. Number of polypectomies for nonneoplastic lesions and withdrawal time were extracted as harm outcomes. For each outcome, studies were pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. DATA SYNTHESIS: Twenty-one randomized trials on 18 232 patients were included. The ADR was higher in the CADe group than in the standard colonoscopy group (44.0% vs. 35.9%; relative risk, 1.24 [95% CI, 1.16 to 1.33]; low-certainty evidence), corresponding to a 55% (risk ratio, 0.45 [CI, 0.35 to 0.58]) relative reduction in miss rate (moderate-certainty evidence). More nonneoplastic polyps were removed in the CADe than the standard group (0.52 vs. 0.34 per colonoscopy; mean difference [MD], 0.18 polypectomy [CI, 0.11 to 0.26 polypectomy]; low-certainty evidence). Mean inspection time increased only marginally with CADe (MD, 0.47 minute [CI, 0.23 to 0.72 minute]; moderate-certainty evidence). LIMITATIONS: This review focused on surrogates of patient-important outcomes. Most patients, however, may consider cancer incidence and cancer-related mortality important outcomes. The effect of CADe on such patient-important outcomes remains unclear. CONCLUSION: The use of CADe for polyp detection during colonoscopy results in increased detection of adenomas but not advanced adenomas and in higher rates of unnecessary removal of nonneoplastic polyps. PRIMARY FUNDING SOURCE: European Commission Horizon 2020 Marie Sklodowska-Curie Individual Fellowship.

Colonoscopy Satisfaction and Safety Questionnaire based on patient experience (CSSQP): A valuable quality tool for all colonoscopies.

INTRODUCTION: The Colonoscopy Satisfaction and Safety Questionnaire based on Patient experience (CSSQP) was recently developed and validated within a Bowel Cancer Screening Program. We aimed to identify factor related to patient experience through the CSSQP, including all indications for colonoscopy. Indicators of satisfaction and perceived safety with colonoscopy were also assessed to compare the different centers. METHODS: Multicenter study in nine Spanish hospitals. Consecutive patients who had undergone a colonoscopy completed the CSSQP adding a novel item on bowel preparation. Factors related to patient experiences and data from non-respondents were analyzed. RESULTS: Of 2200 patients, 1753 filled out the questionnaire (response rate 79.7%, sample error 2%). Patients whose colonoscopy indication was a primary colorectal cancer screening (OR: 1.68, 95% CI: 1.15-2.44, p=0.007) or due to a +FIT (OR: 1.73, 95% CI: 1.18-2.53) reported higher satisfaction than patients with gastrointestinal symptoms. In addition, college-educated patients (OR: 2.11, 95% CI: 1.25-3.56) were more likely to report better overall satisfaction than patients with lower education level. Significant differences were observed in the majority of the CSSQP items between centers. Safety incidents were reported by 35 (2%) patients, and 176 (10%) patients reported that they received insufficient information. CONCLUSION: The CSSQP identifies several significant factors on satisfaction and perceived safety in patients referred for colonoscopy for any reason. The CSSQP also allows comparison of patient-identified colonoscopy quality indicators between centers.

Use of multi-gene panels in patients at high risk of hereditary digestive cancer: position statement of AEG, SEOM, AEGH and IMPaCT-GENÓMICA consortium. / Uso de paneles de genes en pacientes con alto riesgo de cáncer digestivo hereditario: documento de posicionamiento de la AEG, SEOM, AEGH y consorcio IMPaCT-GENÓMICA.

This position statement, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Oncología Médica, the Asociación Española de Genética Humana and the IMPaCT-Genómica Consortium aims to establish recommendations for use of multi-gene panel testing in patients at high risk of hereditary gastrointestinal and pancreatic cancer. To rate the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We reached a consensus among experts using a Delphi method. The document includes recommendations on clinical scenarios where multi-gene panel testing is recommended in colorectal cancer, polyposis syndromes, gastric and pancreatic cancer, as well as the genes to be considered in each clinical scenario. Recommendations on the evaluation of mosaicisms, counseling strategies in the absence of an index subject and, finally, constitutional analysis after identification of pathogenic tumor variants are also made.

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Rates of repeated colonoscopies to clean the colon from low-risk and high-risk adenomas: results from the EPoS trials.

OBJECTIVE: High-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large multinational polyp surveillance trial, we aimed to investigate clinical practice variation in number of colonoscopies needed to enrol patients with low-risk and high-risk adenomas in polyp surveillance. DESIGN: We retrieved data of all patients with low-risk adenomas (one or two tubular adenomas <10 mm with low-grade dysplasia) and high-risk adenomas (3-10 adenomas, ≥1 adenoma ≥10 mm, high-grade dysplasia or villous components) in the European Polyp Surveillance trials fulfilling certain logistic and methodologic criteria. We analysed variations in number of colonoscopies needed to achieve high-quality colonoscopy and enter polyp surveillance by endoscopy centre, and by endoscopists who enrolled ≥30 patients. RESULTS: The study comprised 15 581 patients from 38 endoscopy centres in five European countries; 6794 patients had low-risk and 8787 had high-risk adenomas. 961 patients (6.2%, 95% CI 5.8% to 6.6%) underwent two or more colonoscopies before surveillance began; 101 (1.5%, 95% CI 1.2% to 1.8%) in the low-risk group and 860 (9.8%, 95% CI 9.2% to 10.4%) in the high-risk group. Main reasons were poor bowel preparation (21.3%) or incomplete colonoscopy/polypectomy (14.4%) or planned second procedure (27.8%). Need of repeat colonoscopy varied between study centres ranging from 0% to 11.8% in low-risk adenoma patients and from 0% to 63.9% in high-risk adenoma patients. On the second colonoscopy, the two most common reasons for a repeat (third) colonoscopy were piecemeal resection (26.5%) and unspecified reason (23.9%). CONCLUSION: There is considerable practice variation in the number of colonoscopies performed to achieve complete polyp removal, indicating need for targeted quality improvement to reduce patient burden. TRIAL REGISTRATION NUMBER: NCT02319928.

Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of High-risk Adenomas.

BACKGROUND & AIMS: Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs). METHODS: We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I2 statistic. RESULTS: Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1-3.0) for adenomas ≥20 mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20-3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88-4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84-1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30-2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06-3.32) for ≥10mm, 6.62 (95% CI, 4.60-9.52) for HGD, 3.58 (95% CI, 2.24-5.73) for villous component, and 2.03 (95% CI, 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs. CONCLUSION: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term.

Mutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential.

BACKGROUND: Mismatch repair (MMR) deficiency is the hallmark of tumours from Lynch syndrome (LS), sporadic MLH1 hypermethylated and Lynch-like syndrome (LLS), but there is a lack of understanding of the variability in their mutational profiles based on clinical phenotypes. The aim of this study was to perform a molecular characterisation to identify novel features that can impact tumour behaviour and clinical management. METHODS: We tested 105 MMR-deficient colorectal cancer tumours (25 LS, 35 LLS and 45 sporadic) for global exome microsatellite instability, cancer mutational signatures, mutational spectrum and neoepitope load. RESULTS: Fifty-three percent of tumours showed high contribution of MMR-deficient mutational signatures, high level of global exome microsatellite instability, loss of MLH1/PMS2 protein expression and included sporadic tumours. Thirty-one percent of tumours showed weaker features of MMR deficiency, 62% lost MSH2/MSH6 expression and included 60% of LS and 44% of LLS tumours. Remarkably, 9% of all tumours lacked global exome microsatellite instability. Lastly, HLA-B07:02 could be triggering the neoantigen presentation in tumours that show the strongest contribution of MMR-deficient tumours. CONCLUSIONS: Next-generation sequencing approaches allow for a granular molecular characterisation of MMR-deficient tumours, which can be essential to properly diagnose and treat patients with these tumours in the setting of personalised medicine.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Dye-based chromoendoscopy for the detection of colorectal neoplasia: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Dye-based chromoendoscopy (DBC) could be effective in increasing the adenoma detection rate (ADR) in patients undergoing colonoscopy, but the technique is time-consuming and its uptake is limited. We aimed to assess the effect of DBC on ADR based on available randomized controlled trials (RCTs). METHODS: Four databases were searched up to April 2022 for RCTs comparing DBC with conventional colonoscopy (CC) in terms of ADR, advanced ADR, and sessile serrated adenoma detection rate as well as the mean adenomas per patient and non-neoplastic lesions. Relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes were calculated using random-effect models. The I2 test was used for quantifying heterogeneity. Risk of bias was evaluated with the Cochrane tool. RESULTS: Overall, 10 RCTs (5334 patients) were included. Indication for colonoscopy was screening or surveillance (3 studies) and mixed (7 studies). Pooled ADR was higher in the DBC group versus the CC group (95% CI, 48.1% [41.4%-54.8%] vs 39.3% [33.5%-46.4%]; RR, 1.20 [1.11-1.29]), with low heterogeneity (I2 = 29%). This effect was consistent for advanced ADR (RR, 1.21 [1.03-1.42]; I2 = .0%), sessile serrated adenomas (6.1% vs 3.5%; RR, 1.68 [1.15-2.47]; I2 = 9.8%), and mean adenomas per patient (MD, .24 [.17-.31]) overall and in the right-sided colon (MD, .28 [.14-.43]). A subgroup analysis considering only trials using high-definition white-light endoscopy reduced the heterogeneity while still showing a significant increase in adenoma detection with DBC: 51.6% (95% confidence interval [CI], 47.1%-56.1%) and 59.1% (95% CI, 54.7-63.3%), RR = 1.14 (95% CI, 1.06-1.23), P = .0004, I2 = .0%, P = .50. CONCLUSIONS: Meta-analysis of RCTs showed that DBC increases key quality parameters in colonoscopy, supporting its use in everyday clinical practice.

Definition of competence standards for optical diagnosis of diminutive colorectal polyps: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

BACKGROUND : The European Society of Gastrointestinal Endoscopy (ESGE) has developed a core curriculum for high quality optical diagnosis training for practice across Europe. The development of easy-to-measure competence standards for optical diagnosis can optimize clinical decision-making in endoscopy. This manuscript represents an official Position Statement of the ESGE aiming to define simple, safe, and easy-to-measure competence standards for endoscopists and artificial intelligence systems performing optical diagnosis of diminutive colorectal polyps (1 - 5 mm). METHODS : A panel of European experts in optical diagnosis participated in a modified Delphi process to reach consensus on Simple Optical Diagnosis Accuracy (SODA) competence standards for implementation of the optical diagnosis strategy for diminutive colorectal polyps. In order to assess the clinical benefits and harms of implementing optical diagnosis with different competence standards, a systematic literature search was performed. This was complemented with the results from a recently performed simulation study that provides guidance for setting alternative competence standards for optical diagnosis. Proposed competence standards were based on literature search and simulation study results. Competence standards were accepted if at least 80 % agreement was reached after a maximum of three voting rounds. RECOMMENDATION 1: In order to implement the leave-in-situ strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 90 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm in the rectosigmoid. Histopathology is used as the gold standard.Level of agreement 95 %. RECOMMENDATION 2: In order to implement the resect-and-discard strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 80 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm. Histopathology is used as the gold standard.Level of agreement 100 %. CONCLUSION : The developed SODA competence standards define diagnostic performance thresholds in relation to clinical consequences, for training and for use when auditing the optical diagnosis of diminutive colorectal polyps.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

Risk of Colorectal Cancer and Advanced Polyps One Year After Excision of High-Risk Adenomas.

BACKGROUND: Patients with multiple or large adenomas are considered to be high-risk for metachronous colorectal cancer. OBJECTIVE: Evaluate the risks of detecting colorectal cancer, advanced adenoma, and advanced serrated polyps at 1-year surveillance colonoscopy in patients with >5 adenomas or adenomas >20 mm. DESIGN: Descriptive, retrospective, multicentric, cohort study. We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. SETTINGS: This study included data from a multicenter cohort colorectal cancer screening program, conducted from January 2014 to December 2015, based on fecal immunochemical tests in Spain. PATIENTS: We included 2119 participants with at least 1 adenoma ≥20 mm or ≥5 adenomas of any size. MAIN OUTCOME MEASURES: We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. RESULTS: At 1 year, participants displayed 6 colorectal cancers (0.3%), 228 advanced adenomas (10.5%), and 58 advanced serrated polyps (2.7%). The adjusted analysis identified 2 factors associated with advanced neoplasia: >5 adenomas (odds ratio 1.53; 95% CI: 1.15-2.03; p = 0.004) and polyps in a proximal location (OR 1.52; 95% CI: 1.15-2.02; p = 0.004). LIMITATIONS: First, the sample size was relatively small compared to other studies with similar aims. Another limitation was the lack of a comparison group, which could have provided more practical results in terms of surveillance recommendations. CONCLUSIONS: The colorectal cancer detection rate at a 1-year colonoscopy surveillance was low among patients classified at high risk of advanced neoplasia. The risk factors for advanced neoplasia were ≥5 adenomas and proximal polyps at baseline. See Video Abstract at http://links.lww.com/DCR/B820 . RIESGO DE CNCER COLORRECTAL Y DE PLIPOS AVANZADOS UN AO DESPUS DE LA RESECCIN DE ADENOMAS DE ALTO RIESGO: ANTECEDENTES:Los pacientes con adenomas múltiples o grandes se consideran de alto riesgo para desarrollar cáncer colorrectal metacrónico.OBJETIVO:Evaluar los riesgos de detectar cáncer colorrectal, adenoma avanzado y pólipos serrados avanzados en la colonoscopia de seguimiento al año, en pacientes con un número mayor o igual a 5 adenomas o adenomas de 20 mm o más.DISEÑO:Estudio descriptivo, retrospectivo, multicéntrico, de cohortes. Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los factores de riesgo potenciales para el desarrollo de una neoplasia avanzada en el seguimiento, fueron evaluados mediante un análisis de regresión logística univariable y multivariable.AJUSTES:Este estudio incluyó datos de un programa de cribado de cáncer colorrectal de cohorte multicéntrico, realizado entre enero de 2014 y diciembre de 2015, con base en pruebas inmunoquímicas de materia fecal, en España.PACIENTES:Incluimos 2119 participantes con al menos un adenoma ≥20 mm o con cinco o más adenomas de cualquier tamaño.PRINCIPALES MEDIDAS DE RESULTADO:Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los potenciales factores de riesgo para desarrollar una neoplasia avanzada en el seguimiento, se evaluaron mediante un análisis de regresión logística univariable y multivariable.RESULTADOS:Al año se encontraron en los pacientes participantes, 6 cánceres colorrectales (0,3%), 228 adenomas avanzados (10,5%) y 58 pólipos serrados avanzados (2,7%). Mediante el análisis ajustado se identificaron dos factores asociados con el desarrollo de neoplasia avanzada: un número igual o mayor a 5 adenomas (razón de probabilidades 1,53; IC del 95%: 1,15-2,03; p = 0,004) y la presencia de pólipos en una ubicación proximal (razón de probabilidades 1,52; IC del 95%: 1,15-2,02; p = 0,004).LIMITACIONES:Primero, el tamaño de la muestra fue relativamente pequeño en comparación con otros estudios con objetivos similares. Otra limitación fue la falta de un grupo comparativo, que podría haber proporcionado resultados más prácticos, en términos de recomendaciones de vigilancia.CONCLUSIÓNES:La tasa de detección de cáncer colorrectal mediante una colonoscopia de vigilancia al año, fue baja entre los pacientes clasificados como de alto riesgo de neoplasia avanzada. Los factores de riesgo para desarrollar una neoplasia avanzada fueron; un número igual o mayor a 5 adenomas y la presencia de pólipos proximales en la colonoscopia inicial de base. Consulte Video Resumen en http://links.lww.com/DCR/B820 . ( Traducción-Eduardo Londoño-Schimmer ).

Recommendations of the Valencian Society of Digestive Pathology for the use of telemedicine and non-contact consultations. / Recomendaciones de la Sociedad Valenciana de Patología Digestiva sobre uso de consultas no presenciales y telemedicina.

The COVID-19 pandemic has meant a qualitative change in the way patients are treated in outpatient clinics. The need to take measures of social isolation as prevention for contagion by the new coronavirus has forced the use of telematic and telephone consultations in most medical and surgical units. The specialty of digestive medicine, due to the characteristics of its patients and frequent support in complementary techniques for diagnosis, is especially suitable for the use of non-contact consultations. In this document a series of recommendations are proposed that can serve as a guide for the establishment or improvement of non-face-to-face digestive medicine consultations.