Effect of the SARS-CoV-2 pandemic on colorectal cancer diagnosis and prognosis.

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.

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 / Use of multi-gene panels in patients at high risk of hereditary digestive cancer: position statement of AEG, SEOM, AEGH and IMPaCT-GENÓMICA consortium

Este documento de posicionamiento, auspiciado por la Asociación Española de Gastroenterología, la Sociedad Española de Oncología Médica, la Asociación Española de Genética Humana y el consorcio IMPaCT-Genómica, tiene como objetivo realizar recomendaciones para el uso de paneles de genes en la evaluación de individuos con alto riesgo de cáncer digestivo hereditario. Para medir la calidad de la evidencia y los niveles de recomendación se ha utilizado la metodología basada en el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Se obtuvo el consenso entre expertos mediante un método Delphi. El documento incluye recomendaciones sobre escenarios clínicos en los que se recomienda el uso de paneles de genes en cáncer colorrectal, síndromes polipósicos, cáncer gástrico y pancreático, así como los genes de los paneles a ser considerados en cada una de estas situaciones clínicas. También se establecen recomendaciones sobre la evaluación de mosaicismos, las estrategias de asesoramiento ante la ausencia de sujeto índice y, finalmente, el análisis constitucional tras identificación de variantes patogénicas tumorales. (AU)

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. (AU)

Psychological burden and quality of life in newly diagnosed inflammatory bowel disease patients.

Objective: Psychological factors, such as stress, anxiety, and depression, are frequently related to inflammatory bowel disease (IBD). However, few studies have examined these factors in patients newly diagnosed with IBD. The aim of the present study was to test the psychological burden in patients with a recent diagnosis of IBD and the factors related to this psychological burden. Methods: We performed a prospective, multi-center, observational study in patients with a new diagnosis of IBD (≤6 months). The patients were recruited from four different Spanish hospitals. Clinical and demographic characteristics were collected. Patients were evaluated using the Hospital Anxiety and Depression Scale and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ-32). The Scale of Stress Perceived by the Disease was used to assess stressful life events. Results: We included 156 patients newly diagnosed with IBD [69 women; 80 Crohn's disease (CD) and 76 ulcerative colitis (UC)], with a mean age of 42.3 (SD 16.21) years. A total of 37.2% of patients had symptoms of anxiety and 17.3% had symptoms of depression. Quality of life was affected in 30.1% of patients. Factors related to anxiety in early IBD were being a woman and having CD. The only factor related to depression was the presence of comorbidity. Being a woman and having suffered previous stressful life events were factors related to impaired quality of life. Conclusion: Anxiety, depression, and impaired quality of life are frequent in patients with a recent diagnosis of IBD. This psychological burden is greater in women.

Incidence, characteristics, and predictive factors of post-colonoscopy colorectal cancer.

BACKGROUND: Post-colonoscopy colorectal cancer (PCCRC) is colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is found. OBJECTIVE: As PCCRC has become an important quality indicator, we determined its rates, characteristics, and index colonoscopy-related predictive factors. METHODS: We carried out a multicenter, observational, retrospective study between 2015 and 2018. Rates were calculated for PCCRC developing up to 10 years after colonoscopy. PCCRC was categorized according to the most plausible explanation using World Endoscopy Organization methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date, indication, endoscopist, and hospital. RESULTS: One hundred seven PCCRC and 2508 detected CRC were diagnosed among 101,524 colonoscopy (0.1%), leading to rates of 0.4%, 2.2%, 3.1%, and 4.1% at 1, 3, 5, and 10 years, respectively. PCCRC was in right (42.4%), left (41.4%), and transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, and 11.2% stage IV. Twenty point three percent were classified as incomplete resection, 5.4% as unresected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. The median time from colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC. CONCLUSIONS: In our population, 4.1% of CRC cases were PCCRC. Most of these lesions were in right colon and attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

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.

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.

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.

Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection.

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions.

Quantification of rare somatic single nucleotide variants by droplet digital PCR using SuperSelective primers.

Somatic single-nucleotide variants (SNVs) occur every time a cell divides, appearing even in healthy tissues at low frequencies. These mutations may accumulate as neutral variants during aging, or eventually, promote the development of neoplasia. Here, we present the SP-ddPCR, a droplet digital PCR (ddPCR) based approach that utilizes customized SuperSelective primers aiming at quantifying the proportion of rare SNVs. For that purpose, we selected five potentially pathogenic variants identified by whole-exome sequencing (WES) occurring at low variant allele frequency (VAF) in at-risk colon healthy mucosa of patients diagnosed with colorectal cancer or advanced adenoma. Additionally, two APC SNVs detected in two cancer lesions were added to the study for WES-VAF validation. SuperSelective primers were designed to quantify SNVs at low VAFs both in silico and in clinical samples. In addition to the two APC SNVs in colonic lesions, SP-ddPCR confirmed the presence of three out of five selected SNVs in the normal colonic mucosa with allelic frequencies ≤ 5%. Moreover, SP-ddPCR showed the presence of two potentially pathogenic variants in the distal normal mucosa of patients with colorectal carcinoma. In summary, SP-ddPCR offers a rapid and feasible methodology to validate next-generation sequencing data and accurately quantify rare SNVs, thus providing a potential tool for diagnosis and stratification of at-risk patients based on their mutational profiling.

Long-term results after EUS gallbladder drainage in high-surgical-risk patients with acute cholecystitis: A 3-year follow-up registry.

Background and study aims Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has become the favorite drainage option for high surgical-risk patients with acute cholecystitis. However, data on long-term outcomes regarding efficacy and security over 1 year are scarce. Patients and methods We performed a retrospective review of a prospectively maintained database to analyze the 3-year long-term outcomes of EUS-GBD with lumen apposing metal stents (LAMS) in high-surgical-risk patients with acute cholecystitis. Results Fifty patients with acute cholecystitis who underwent EUS-GBD with LAMS and 3-year follow-up or until death were included in this study. No endoscopic revisions were scheduled unless an adverse event (AE) or suspected LAMS dysfunction occurred. AEs occurred in 18%, 20%, and 26% of patients in the first, second, and third years, respectively. Thirteen patients developed at least one AE, and six presented with a second AE during follow-up. Recurrence of cholecystitis occurred in two patients (4%). Seven stent migrations (14%) occurred but all were asymptomatic. Symptomatic LAMS-related AEs (LAMS-RAEs) (37.5%) were related to gastric location of the stent compared with duodenal location (66.7% vs. 12.5%, P = 0.03). No stent-related bleeding or stent-related mortality was observed. Conclusions EUS-GBD with LAMS without scheduled removal is an effective and safe long-term treatment in high-surgical-risk patients with acute cholecystitis. Late LAMS-RAEs tend to be more asymptomatic over time. Symptomatic LAMS-RAEs are associated with gastric location, and overall, AEs tend to recur.

Cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective international cohort study.

Background and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers. Patients and methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intraprocedural and post-procedural AEs. Results In total, 133 CSPs were performed in 39 patients with FAP (1-18 per session). Median adenoma size was 10 mm (interquartile range 8-15 mm), ranging from 5 to 40 mm; 27 adenomas were ≥20 mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in three polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleeds, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas. Conclusions CSP for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery.

Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas.

BACKGROUND: Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC. RESULTS: First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test. CONCLUSIONS: Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

Surveillance after colorectal polyp resection.

Post-polypectomy surveillance has proven to reduce colorectal cancer (CRC) incidence in patients with high-risk polyps, but it implies a major burden on colonoscopy units. Therefore, it should be targeted to individuals with a higher risk. Different societies have published guidelines on surveillance after resection of polyps, with notable discrepancies among them, and many recommendations come from low-quality evidence based on surrogate measures, such as risk of advanced adenoma, and not CRC risk. In this review, we aimed to summarize the evidence supporting post-polypectomy surveillance, compare the recently updated major guidelines, and discuss the existing discrepancies on this topic. Briefly, patients with adenomas ≥10 mm or high-grade dysplasia and patients with serrated polyps ≥10 mm or dysplasia are generally considered to have an increased risk of metachronous CRC and require surveillance, whereas the indication of surveillance is not clearly established in patients without these high-risk features.

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).

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.

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.

Adherence to Mediterranean diet and its association with multiple colonic polyps of unknown origin: a case-control study.

Introduction: Multiple colonic polyps do not have a genetic origin in most patients, and the cause of this phenotype remains elusive. Environmental factors, such as diet, could be related to this phenotype. Our aim was to investigate the relationship between the adherence to Mediterranean diet and multiple colonic polyps of unknown origin. Methods: A case-control pilot study was carried out with a sample of 38 individuals, including 23 cases with more than 10 adenomatous or serrated polyps from the national multicenter project EPIPOLIP and 15 healthy controls with normal colonoscopy. A validated Spanish version of the MEDAS questionnaire was administered to cases and controls. Results: Adherence to Mediterranean diet was higher in controls than in patients with multiple colonic polyps (MEDAS score: 8.6 ± 1.4 vs. 7.0 ± 1.6; p = 0.01). Optimal overall adherence to the Mediterranean diet pattern was significantly higher among the controls than among cases (MEDAS score >9: 46% vs. 13%; OR 0.17; 95% CI 0.03-0.83). Non-optimal adherence to the Mediterranean diet acts as a risk factor for developing colorectal cancer derived from colorectal polyps. Conclusion: Our results suggest that environmental factors play a role in the pathogenesis of this phenotype.

Personalized endoscopic surveillance and intervention protocols for patients with familial adenomatous polyposis: the European FAP Consortium strategy.

Background and study aims Patients with familial adenomatous polyposis (FAP) undergo colectomy and lifelong endoscopic surveillance to prevent colorectal, duodenal and gastric cancer. Endoscopy has advanced significantly in recent years, including both detection technology as well as treatment options. For the lower gastrointestinal tract, current guidelines do not provide clear recommendations for surveillance intervals. Furthermore, the Spigelman staging system for duodenal polyposis has its limitations. We present a newly developed personalized endoscopic surveillance strategy for the lower and upper gastrointestinal tract, aiming to improve the care for patients with FAP. We aim to inform centers caring for FAP patients and encourage the discussion on optimizing endoscopic surveillance and treatment in this high-risk population. Methods The European FAP Consortium, consisting of endoscopists with expertise in FAP, collaboratively developed new surveillance protocols. The proposed strategy was consensus-based and a result of several consortium meetings, discussing current evidence and limitations of existing systems. This strategy provides clear indications for endoscopic polypectomy in the rectum, pouch, duodenum and stomach and defines new criteria for surveillance intervals. This strategy will be evaluated in a 5-year prospective study in nine FAP expert centers in Europe. Results We present a newly developed personalized endoscopic surveillance and endoscopic treatment strategy for patients with FAP aiming to prevent cancer, optimize endoscopic resources and limit the number of surgical interventions. Following this new strategy, prospectively collected data in a large cohort of patients will inform us on the efficacy and safety of the proposed approaches.

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.