Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU / Manejo de las toxicidades digestivas secundarias al tratamiento con inhibidores de checkpoint: documento de posicionamiento de la AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.(AU)

El descubrimiento de los inhibidores de checkpoint inmunológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumento ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastrointestinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 y 40%, ésta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomendaciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia.(AU)

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy / Aplicabilidad de la escala Barcelona para valorar la calidad de la limpieza de la mucosa en la esofagogastroduodenoscopia

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. (AU)

Introducción Existen pocas escalas validadas prospectivamente para evaluar la limpieza de la mucosa esofagogastroduodenal durante la endoscopia digestiva alta (EDA). El objetivo de este estudio fue desarrollar una escala válida y reproducible para su uso en la realización de una EDA. Métodos Desarrollamos una escala de limpieza (escala Barcelona) en la que se aplicó una puntuación de 0 a 2 a cinco áreas del tracto digestivo superior (esófago, fundus, cuerpo, antro y duodeno) después de haber realizado todas las maniobras de lavado necesarias. Inicialmente, se evaluaron 125 fotos (25 de cada área) y se asignó una puntuación (de 0 a 2) a cada una por consenso entre siete endoscopistas. Posteriormente, se seleccionaron 100 de las 125 fotografías y se evaluó la variabilidad inter e intraobservador de 15 endoscopistas previamente formados utilizando las mismas imágenes en dos momentos diferentes. Resultados Se efectuaron un total de 1.500 observaciones. En 1.336/1.500 de ellas (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,83 (0,45-0,96). En la segunda evaluación, en 1.330/1.500 observaciones (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,82 (mínimo 0,45 y máximo 0,93). La variabilidad intraobservador fue de 0,89 (0,76-0,99). Conclusiones La escala de limpieza Barcelona es una medida válida y reproducible con un mínimo entrenamiento. Su uso en la práctica clínica podría ser un paso significativo para estandarizar la calidad de la EDA. (AU)

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Colonoscopy Satisfaction and Safety Questionnaire based on patient experience (CSSQP): A valuable quality tool for all colonoscopies / Cuestionario de Satisfacción y Seguridad de la Colonoscopia basado en la experiencia del Paciente (CSSQP): una valiosa herramienta de calidad para todas las colonoscopias

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 (AU)

Introducción El Cuestionario de Satisfacción y Seguridad de la Colonoscopia basado en la experiencia del Paciente (CSSQP) ha sido desarrollado y validado recientemente en pacientes del Programa de cribado de cáncer colorrectal (CCR). El objetivo del estudio fue identificar los factores relacionados con la experiencia de los pacientes a través del CSSQP, incluyendo todas las indicaciones de la colonoscopia. Además, se evaluaron los factores relacionados con la satisfacción y la seguridad del paciente con el fin de comparar diferentes departamentos. Métodos Estudio multicéntrico de nueve hospitales españoles en el que se incluyeron pacientes consecutivos que completaron el CSSQP incorporando un nuevo ítem sobre la preparación intestinal. Se analizaron los factores relacionados con la experiencia de los pacientes y los datos de los no respondedores. Resultados De 2.200 pacientes, 1.753 completaron el cuestionario (tasa de respuesta del 79,7%, error muestral del 2%). Los pacientes en los que la indicación era por cribado de CCR (OR: 1,68; IC 95%: 1,15-2,44; p=0,007) o por FIT positivo (OR: 1,73; IC 95%: 1,18-2,53) informaron mayor satisfacción que en aquellos que se solicitó la colonoscopia por síntomas gastrointestinales. Además, los pacientes con estudios universitarios (OR: 2,11; IC 95%: 1,25-3,56) informaron mayor satisfacción que aquellos con menor nivel de estudios. Se observaron diferencias significativas en la mayoría de los ítems del CSSQP entre los centros participantes. Treinta y cinco (2%) pacientes reportaron incidentes de seguridad y 176 (10%) reconocieron haber recibido información insuficiente. Conclusiones El CSSQP identifica los factores determinantes que influyen en la satisfacción y la seguridad de los pacientes a los que se les realiza colonoscopia por cualquier indicación. Además, permite comparar los indicadores de calidad de la colonoscopia desde la perspectiva del paciente entre los distintos centros (AU)

Influence of social support and stressful life events on adherence to colorectal cancer screening using faecal occult blood test in Spanish medium risk population / Influencia del apoyo social y los acontecimentos vitales estresantes en el cribado de cáncer colorrectal con sangre oculta en heces en población española de riesgo medio

Introduction Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. Five-year survival rate in Spain is 57%. The most important prognostic factor is the stage of the tumor at the diagnosis. CRC can be early diagnosed, but the adherence to screening programs is low (<50%). This study aims to ascertain the influence of social support and stressful life events on the adherence to the population screening of CRC with fecal occult blood test in Spanish average risk population. Methods Multicenter case–control study. We conducted a simple random sampling among individuals invited to participate in the colorectal cancer screening program. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors. We performed a descriptive and a bivariant analyses and a logistic regression analysis. Results Four hundred and eight patients (237 cases and 171 controls) were included. Multivariant analyses showed independent association between higher adherence to the screening program and older age (OR: 1.06; 95% CI: 1.01–1.10), stable partner (OR: 1.77, 95% CI: 1.08–2.89) and wide social network (OR: 1.68; 95% CI: 1.07–2.66). Otherwise, lower adherence was associated to perceiving barriers to participate in the program (OR: 0.92; 95% CI: 0.88–0.96). We find a statistically significant association between lower adherence and high impact stressful life events in the bivariant analyses, and the tendency was maintained (OR: 0.63, 95% CI: 0.37–1.08) in the multivariant. Conclusion Social variables decisively influence the adherence to colorectal cancer screening. The implementation of social interventions that improve social support, reduce impact of stressful life events and the design of screening programs that decrease the perceived barriers, will contribute to increase the participation on these programs. Secondary, the colorectal cancer diagnosis will be made in early-stages with the consequent mortality reduction (AU)

Introducción El cáncer colorrectal (CCR) es la segunda causa de muerte por cáncer en el mundo. La tasa de supervivencia a cinco años en España es de 57%. El factor pronóstico más importante es el estadio del tumor en el momento del diagnóstico. El CCR se puede diagnosticar precozmente, pero la adherencia a los programas de cribado es baja (< 50%). Este estudio pretende conocer la influencia del apoyo social y los acontecimientos vitales estresantes en la adherencia al cribado poblacional de CCR con sangre oculta en heces en población española de riesgo medio. Métodos Estudio multicéntrico de casos y controles. Realizamos un muestreo aleatorio simple entre los individuos invitados a participar en un programa de cribado de CCR. Analizamos variables epidemiológicas y sociales asociadas al estilo de vida y factores conductuales. Realizamos un análisis descriptivo, un análisis bivariante y una regresión logística. Resultados Se incluyeron 408 pacientes (237 casos y 171 controles). El análisis multivariante demostró una asociación independiente entre una mayor adherencia al programa de cribado y mayor edad (OR: 1,06; IC 95%: 1,01-1,10), tener pareja estable (OR: 1,77, IC 95%: 1,08-2,89) y disponer de una amplia red social (OR: 1,68; IC 95%: 1,07-2,66). Por el contrario, la menor adherencia se asoció a la percepción de barreras para participar en el cribado (OR: 0,92; IC 95%: 0,88-0,96). Encontramos una asociación estadísticamente significativa entre menor adherencia y acontecimientos vitales estresantes de alto impacto en el análisis bivariante. La tendencia se mantuvo (OR: 0,63, IC 95%: 0,37-1,08) en el análisis multivariante (AU)

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.

Influence of social support and stressful life events on adherence to colorectal cancer screening using faecal occult blood test in Spanish medium risk population.

INTRODUCTION: Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. Five-year survival rate in Spain is 57%. The most important prognostic factor is the stage of the tumor at the diagnosis. CRC can be early diagnosed, but the adherence to screening programs is low (<50%). This study aims to ascertain the influence of social support and stressful life events on the adherence to the population screening of CRC with fecal occult blood test in Spanish average risk population. METHODS: Multicenter case-control study. We conducted a simple random sampling among individuals invited to participate in the colorectal cancer screening program. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors. We performed a descriptive and a bivariant analyses and a logistic regression analysis. RESULTS: Four hundred and eight patients (237 cases and 171 controls) were included. Multivariant analyses showed independent association between higher adherence to the screening program and older age (OR: 1.06; 95% CI: 1.01-1.10), stable partner (OR: 1.77, 95% CI: 1.08-2.89) and wide social network (OR: 1.68; 95% CI: 1.07-2.66). Otherwise, lower adherence was associated to perceiving barriers to participate in the program (OR: 0.92; 95% CI: 0.88-0.96). We find a statistically significant association between lower adherence and high impact stressful life events in the bivariant analyses, and the tendency was maintained (OR: 0.63, 95% CI: 0.37-1.08) in the multivariant. CONCLUSION: Social variables decisively influence the adherence to colorectal cancer screening. The implementation of social interventions that improve social support, reduce impact of stressful life events and the design of screening programs that decrease the perceived barriers, will contribute to increase the participation on these programs. Secondary, the colorectal cancer diagnosis will be made in early-stages with the consequent mortality reduction.

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.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events (AU)

El descubrimiento de los inhibidores de checkpoint inmu nológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumen to ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastroin testinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 % y 40 %, esta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomenda ciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia. (AU)

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.

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.

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).

Impact of the COVID-19 Pandemic on the Diagnosis of Colorectal Cancer within a Population-Based Organized Screening Program.

BACKGROUND: The interruption of the activity of population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of the detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at diagnosis in a CRC screening program. METHODS: We analyzed all the invitations between 1 January 2019 and 31 December 2021. We defined the pandemic period as the period after 12 March 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically of CRC and colorectal neoplasia (CRC and/or adenoma), as well as the CRC stage at diagnosis. RESULTS: In the period analyzed, 976,187 invitations were sent (61.0% in the pandemic period), 439,687 FIT were returned (62.4% in the pandemic period) and 23,092 colonoscopies were performed (59.1% in the pandemic period). The colonoscopies were normal in 7378 subjects (32.4%) and CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly by seven months during the pandemic period (p < 0.001). In all the invitations, the delay from the invitation to the colonoscopy increased significantly by 8 days (p < 0.001). Once adjusted for the confounding variables, the participation in the screening program increased significantly (OR = 1.1; 95% CI = 1.09-1.11), with no changes in the adherence to colonoscopy (OR = 0.9; 95% CI = 0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR = 0.90; 95% CI = 0.78-1.02) or colorectal neoplasia (OR = 0.98; 95% CI = 0.92-1.03) detection. Finally, we found no differences in the CRC stage at diagnosis (p = 0.2). CONCLUSIONS: Although the interruption of the CRC screening program due to the COVID pandemic increased the delays, it did not reduce participation, adherence to colonoscopy, or the diagnostic yield of colonoscopy.

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.

Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study.

BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.

Targeted depletion of pks+ bacteria from a fecal microbiota using specific antibodies.

The pks island is one of the most prevalent pathogenicity islands among the Escherichia coli strains that colonize the colon of colorectal carcinoma (CRC) patients. This pathogenic island encodes the production of a nonribosomal polyketide-peptide named colibactin, which induces double-strand breaks in DNA molecules. Detection or even depletion of this pks-producing bacteria could help to understand the role of these strains in the context of CRC. In this work, we performed a large-scale in silico screening of the pks cluster in more than 6,000 isolates of E. coli. The results obtained reveal that not all the pks-detected strains could produce a functional genotoxin and, using antibodies against pks-specific peptides from surface cell proteins, a methodology for detection and depletion of pks+ bacteria in gut microbiotas was proposed. With our method, we were able to deplete a human gut microbiota of this pks+ strains, opening the door to strain-directed microbiota modification and intervention studies that allow us to understand the relation between these genotoxic strains and some gastrointestinal diseases. IMPORTANCE The human gut microbiome has also been hypothesized to play a crucial role in the development and progression of colorectal carcinoma (CRC). Between the microorganisms of this community, the Escherichia coli strains carrying the pks genomic island were shown to be capable of promoting colon tumorigenesis in a colorectal cancer mouse model, and their presence seems to be directly related to a distinct mutational signature in patients suffering CRC. This work proposes a novel method for the detection and depletion of pks-carrying bacteria in human gut microbiotas. In contrast to methods based on probes, this methodology allows the depletion of low-abundance bacterial strains maintaining the viability of both targeted and non-targeted fractions of the microbiota, allowing the study of the contribution of these pks-carrying strains to different diseases, such as CRC, and their role in other physiological, metabolic or immune processes.

Técnicas de imagen avanzada en la detección y caracterización de las lesiones precursoras del cáncer gástrico y del cáncer gástrico precoz / Image-enhanced endoscopy in the diagnosis of gastric premalignant conditions and gastric cancer

La detección del cáncer gástrico precoz y de sus lesiones precursoras constituye un desafío para gran parte de los endoscopistas occidentales. Los cambios morfológicos que se producen en la mucosa gástrica generalmente son sutiles y, por tanto, difíciles de visualizar. En esta revisión se analiza la utilidad de la cromoendoscopia convencional, así como de sus modalidades digitales, y de la endoscopia con magnificación para reconocer y caracterizar estas lesiones.(AU)

Diagnosis of early gastric cancer and its precancerous lesions remains a challenge for great part of western endoscopists. Changes seen in the mucosal pattern are generally subtle and hence difficult to identify. In this article, we will review the usefulness of conventional and virtual chromoendoscopy and magnification endoscopy in the recognition and classification of these lesions.(AU)