Risk of Proctectomy After Ileorectal Anastomosis in Familial Adenomatous Polyposis in the Modern Era.

BACKGROUND: Prophylactic surgery for familial adenomatous polyposis has evolved over several decades. Restorative proctocolectomy with IPAA provides an alternative to total abdominal colectomy with ileorectal anastomosis. We have previously shown that the rate of proctectomy and rectal cancer after total abdominal colectomy with ileorectal anastomosis in the "pre-pouch era" was 32% and 13%, respectively. OBJECTIVE: To determine the rate of proctectomy and rectal cancer among familial adenomatous polyposis patients and relative rectal sparing (fewer than 20 rectal polyps) selected for total abdominal colectomy with ileorectal anastomosis in the modern era. DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution with a hereditary colorectal cancer registry. PATIENTS: Patients with familial adenomatous polyposis who underwent total abdominal colectomy with ileorectal anastomosis between 1993 and 2020. MAIN OUTCOME MEASURES: Incidence of proctectomy for any indication and rectal cancer. RESULTS: A total of 197 patients with a median age of 24 years (range, 10-67) were included. The median follow-up after total abdominal colectomy with ileorectal anastomosis was 13 years (interquartile range, 6-17). Sixteen patients (8%) underwent proctectomy. Indications included rectal cancer in 6 patients (3%; 2 stage I and 4 stage III), polyps with high-grade dysplasia in 4 (2%), progressive polyp burden in 3 (1.5%), defecatory dysfunction in 2 (1%), and anastomotic leak in 1 (0.5%). Among 30 patients (18%) with 20 or more rectal polyps at the time of total abdominal colectomy with ileorectal anastomosis, 8 patients (26%) underwent proctectomy and 3 patients developed rectal cancer (10%). Among 134 patients (82%) with fewer than 20 polyps, 8 patients (6%) underwent proctectomy and 3 patients developed rectal cancer (2%). Number of rectal polyps at the time of total abdominal colectomy with ileorectal anastomosis was associated with the likelihood of proctectomy (OR 1.1, p < 0.001) but not incident rectal cancer ( p = 0.3). LIMITATION: Retrospective data collection. CONCLUSIONS: Patients with familial adenomatous polyposis selected for total abdominal colectomy with ileorectal anastomosis by rectal polyp number have low rates of proctectomy and rectal cancer compared to historical controls. With appropriate selection criteria and surveillance, total abdominal colectomy with ileorectal anastomosis remains an important and safe treatment option for patients with familial adenomatous polyposis. See Video Abstract . RIESGO DE PROCTECTOMA DESPUS DE ANASTOMOSIS ILEORRECTAL EN POLIPOSIS ADENOMATOSA FAMILIAR EN LA ERA MODERNA: ANTECEDENTES:La cirugía profiláctica para la poliposis adenomatosa familiar (PAF) ha evolucionado durante varias décadas. La proctocolectomía restauradora con anastomosis anal con bolsa ileal (IPAA) proporciona una alternativa a la colectomía abdominal total con anastomosis ileorrectal (TAC/IRA). Anteriormente hemos demostrado que la tasa de proctectomía y cáncer de recto después de TAC/IRA en la era "pre-bolsa" era del 32% y el 13%, respectivamente.OBJETIVO:Determinar la tasa de proctectomía y cáncer de recto entre pacientes con PAF y pacientes con preservación rectal relativa (<20 pólipos rectales) seleccionados para TAC/IRA en la era moderna.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Institución única de atención terciaria con un registro de cáncer colorrectal hereditario.PACIENTES:Pacientes con PAF que se sometieron a TAC/IRA entre 1993 y 2020.MEDIDAS DE RESULTADO PRINCIPALES:Incidencia de proctectomía por cualquier indicación y cáncer de recto.RESULTADOS:Se incluyeron 197 pacientes con una mediana de edad de 24 años (rango 10-67). La mediana de seguimiento tras TAC/IRA fue de 13 años (RIC 6-17). 16 pacientes (8%) fueron sometidos a proctectomía. Las indicaciones incluyeron cáncer de recto en 6 (3%) (2 en estadio I y 4 en estadio III); pólipos con displasia de alto grado en 4 (2%); carga progresiva de pólipos en 3 (1,5%), disfunción defecatoria en 2 (1%); y fuga anastomótica en 1 (0,5%). Entre 30 pacientes (18%) con ≥20 pólipos rectales en el momento de TAC/IRA, 8 pacientes (26%) se sometieron a proctectomía y 3 pacientes desarrollaron cáncer de recto (10%). Entre 134 pacientes (82%) con <20 pólipos, 8 pacientes (6%) se sometieron a proctectomía y 3 pacientes desarrollaron cáncer de recto (2%). El número de pólipos rectales en el momento de TAC/IRA se asoció con la probabilidad de proctectomía (OR 1,1, p <0,001), pero no con la incidencia de cáncer de recto (p = 0,3).LIMITACIÓN:Recopilación de datos retrospectivos.CONCLUSIÓN:Los pacientes con PAF seleccionados para TAC/IRA por el número de pólipos rectales tienen tasas bajas de proctectomía y cáncer de recto en comparación con los controles históricos. Con criterios de selección y vigilancia adecuados, TAC/IRA sigue siendo una opción de tratamiento importante y segura para los pacientes con PAF. (Pre-proofed version ).

Risk Factors Associated with Advanced Colorectal Neoplasia in Adults Younger than Age 45.

BACKGROUND: Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified. AIM: To identify factors associated with advanced colorectal neoplasia in adults aged <45 years. METHOD: Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia. RESULTS: In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10 mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10 mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6 y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5 kg/m 2 ), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P <0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P <0.0001), age (OR increase by 1.06 per year, P <0.0001), male gender (OR 1.476, P <0.0001), family history of CRC (OR 3.91, P <0.0001), aspirin use (1.31, P =0.035), and diabetes (OR 2.106, P 0.001). CONCLUSION: Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings.

Metachronous Colorectal Neoplasia in Young Adults With Advanced Neoplasia Undergoing Colonoscopy: A Comparison of Risk by Age <45 Years Versus 45 to 49 Years.

BACKGROUND: The risk of metachronous advanced colorectal neoplasia (mACRN) in young adults with advanced lesions at baseline colonoscopy is not well defined. AIMS: To examine the risk for (mACRN) in adults <50 years old who had advanced neoplasia (AN) at baseline colonoscopy and determine factors associated with mACRN in these patients. METHOD: Patients 18 to 49 years of age with ≥1 AN [tubular adenoma (TA) ≥10 mm or with villous features or high-grade dysplasia (HGD), sessile serrated lesion (SSL) ≥10 mm or with dysplasia, traditional serrated adenoma (TSA)] on baseline colonoscopy between 2011 and 2021 who had surveillance colonoscopy >6 months after their baseline examination were included. Outcomes were assessed based on age at baseline colonoscopy, <45 years versus 45 to 49 years, and by follow-up colonoscopy findings: (1) normal, (2) nonadvanced neoplasia (NAN), and (3) AN. RESULTS: Three hundred sixty-six patients with AN underwent ≥1 surveillance colonoscopy: 310 (84.7%) <45 years versus 56 (15.3%) 45 to 49 years. The mean follow-up time was longer for the <45-year-olds versus the 45 to 49-year-olds (43±26.4 vs. 28.4±12.8 mo respectively, P<0.001). The absolute risk of mACRN was 13.5% in the <45 age group versus 16.1% in the 45 to 49 age group, P=0.28. The 3-year cumulative incidence rates of mACRN were comparable for patients <45 and 45 to 49 years old: 10% (95% CI: 10% to 42%) versus 20% (95% CI: 7% to 15%), P=0.065. BMI was the only risk factor associated with mACRN OR 1.045 [95% CI (1.001 to 1.09)]. CONCLUSIONS: In our cohort of patients <50 years old with AN at baseline, mACRN occurred at a similar rate to that reported by guidelines in 50 years and older, suggesting that current recommended post polypectomy surveillance is appropriate for this age group. BMI was independently associated with mACRN. Future studies should examine how weight management in patients with high BMI mitigates the recurrence of advanced neoplasia.

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis.

IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate. OBJECTIVE: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP. DESIGN, SETTING AND PARTICIPANTS: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres. EXPOSURES: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months. MAIN OUTCOMES AND MEASURES: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy). RESULTS: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention. CONCLUSION: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis. TRIAL REGISTRATION NUMBER: NCT02961374.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis.

BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown. METHODS: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease. RESULTS: A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups. CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).

AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.

Impact of Clinical and Endoscopic Features on the Development of Metachronous Colorectal Advanced Serrated Lesions.

BACKGROUND AND AIMS: High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs. METHODS: In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%-32%) for SSL ≥10 mm, 17% (95% CI, 3.5%-29%) for HP ≥10 mm, 21% (95% CI, 0%-42%) for 3-4 SSLs <10 mm, 18% (95% CI, 0%-38%) for TSA, and 27% (95% CI, 3.6%-45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL. CONCLUSIONS: Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3-5 years for patients with baseline HP ≥10 mm or 3-4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL.

Accuracy of ChatGPT in Common Gastrointestinal Diseases: Impact for Patients and Providers.

Since its release in 2022, Chat Generative Pre-Trained Transformer (ChatGPT) became the most rapidly expanding consumer software application in history,1 and its role in medicine is underscored by its potential to enhance patient education and physician-patient communication. Previous studies in gastroenterology and hepatology have focused primarily on the earlier Generative Pre-Trained Transformer 3 (GPT-3) model, with none investigating ChatGPT's ability to generate supportive references for its responses, or its applicability as a physician educational tool.2-6 Our study evaluated the accuracy of the more recent ChatGPT, powered by GPT-4, in addressing frequently asked questions by patients on irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonoscopy and colorectal cancer (CRC) screening, questions on CRC screening from a physician perspective, and reference generation and suitability.

The Natural History of Asymptomatic Gallstones: A Longitudinal Study and Prediction Model.

BACKGROUND & AIMS: Despite the high prevalence of asymptomatic gallstones (AGs), there are limited data on their natural history. We aimed to determine the rate of symptom development in a contemporary population, determine factors associated with progression to symptomatic gallstones (SGs), and develop a clinical prediction model. METHODS: We used a retrospective cohort design. The time to first SG was shown using Kaplan-Meier curves. Multivariable competing risk (death) regression analysis was used to identify variables associated with SGs. A prediction model for the development of SGs after 10 years was generated and calibration curves were plotted. Participants were patients with AGs based on ultrasound or computed tomography from the general medical population. RESULTS: From 1996 to 2016, 22,257 patients (51% female) with AGs were identified; 14.5% developed SG with a median follow-up period of 4.6 years. The cumulative incidence was 10.1% (±0.22%) at 5 years, 21.5% (±0.39%) at 10 years, and 32.6% (±0.83%) at 15 years. In a multivariable model, the strongest predictors of developing SGs were female gender (hazard ratio [HR], 1.50; 95% CI, 1.39-1.61), younger age (HR per 5 years, 1.15; 95% CI, 1.14-1.16), multiple stones (HR, 2.42; 95% CI, 2.25-2.61), gallbladder polyps (HR, 2.55; 95% CI, 2.14-3.05), large stones (HR, 2.03; 95% CI, 1.80-2.29), and chronic hemolytic anemia (HR, 1.90; 95% CI, 1.33-2.72). The model showed good discrimination (C-statistic, 0.70) and calibration. CONCLUSIONS: In general medical patients with AGs, symptoms developed at approximately 2% per year. A predictive model with good calibration could be used to inform patients of their risk of SGs.

Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer.

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.

The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Frequency of endoscopic photodocumentation of large colorectal polyps.

BACKGROUND AND AIMS: Colonoscopy quality affects colorectal cancer (CRC) incidence and mortality. The U.S. Multi-Society Task Force on Colorectal Cancer strongly recommends photodocumentation (PD) of lesions ≥10 mm in size (ie, large polyps [LPs]) pre-resection and suggests PD postresection to enhance the quality of colonoscopy. No studies have assessed the frequency of LP PD. We evaluated the frequency of and factors associated with PD of LPs. METHODS: Reports from endoscopists performing ≥50 colonoscopies with LP resection between 2016 and 2021 were reviewed. The frequency of LP PD pre-resection and post-resection and factors associated with PD were collected. A composite score of 2 quality metrics (PD of completeness of examination and bowel preparation quality) was created. Endoscopists were divided into 2 tiers based on the frequency of the score on all included examinations: Tier 1, ≥95% of examinations; and Tier 2, <95% of examinations. Univariate and multivariate analyses were used to assess factors associated with PD. RESULTS: A total of 1322 colonoscopies, 1693 LPs, and 25 endoscopists were included in this study. PD of LPs occurred in 1392 (82%) pre-resection and in 878 (52%) post-resection. Factors associated with pre-resection PD include endoscopist subspecialty (colorectal surgery vs gastroenterology: odds ratio [OR], .12; 95% confidence interval [CI], .04-.42); >1 LP on examination (2 vs 1 LP: OR, .41 [95% CI, .27-.61]; and ≥3 vs 1 LP: OR, .41 [95% CI, .24-.70]), and longer withdrawal time (OR, 1.02; 95% CI, 1.01-1.04). CONCLUSIONS: We provide the first data on PD of LP pre-resection and post-resection, which can inform future benchmarking in this area. The implications of PD on metachronous advanced neoplasia need to be studied.

Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better assess this, we conducted a systematic review and meta-analysis. METHODS: MEDLINE, Embase, and Scopus databases were searched for the key words juvenile polyposis syndrome, juvenile polyps, stomach cancer, GC, SMAD4, BMPR1A, hamartomatous polyposis syndrome, hamartomas, and hereditary cancers for studies reporting upper GI manifestations in JPS. The primary outcome was the reported occurrence of GC in JPS. We then compared GC occurrence based on the presence or absence of pathogenic germline variants (PGVs) and in untested patients. RESULTS: Eleven studies including 637 patients were included. The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8-5.2; I2 = 12.3%) at a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC in patients with SMAD4 PGV was 10.1% (95% CI, 3.2-16.8%; I2 = 54.7%). GC was reported in only 1 BMPR1A PGV carrier and was not reported in patients without an identifiable PGV. In patients with prior germline testing, the risk of GC was higher in SMAD4 PGV carriers (odds ratio, 11.6; 95% CI, 4.6-29.4; I2 = 18.3%) compared with patients without SMAD4 PGV. In JPS patients with unknown status of germline testing, pooled occurrence of GC was 7.5% (95% CI, 0-15.5). There was an overall moderate risk of bias in the studies. CONCLUSIONS: GC is highest in SMAD4-associated JPS and was not reported in patients without identifiable PGVs. The value of GC surveillance in BMPR1A PGV carriers and JPS patients without an identifiable PGV is questionable. Germline testing should be performed in all JPS patients to inform GC risk discussion and utility of surveillance.

Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. METHODS: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. RESULTS: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). CONCLUSIONS: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

The Cumulative Incidence and Progression of Ileal Pouch Adenomas in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Patients with familial adenomatous polyposis who have undergone restorative proctocolectomy can develop adenomas in the pouch. OBJECTIVE: To review experience with pouch surveillance and create a classification system for polyposis severity. DESIGN: A retrospective review of patients undergoing IPAA and follow-up at 1 institution. SETTING: A center for hereditary colorectal cancer within a quaternary referral center. PATIENTS: All patients undergoing IPAA and followed endoscopically after surgery by the center. INTERVENTIONS: Yearly pouchoscopy and treatment of polyps as required. MAIN OUTCOME MEASURES: Primary outcome measure was incidence and severity of pouch neoplasia and its changes with time. METHODS: A retrospective study of patients who had a restorative proctocolectomy for familial adenomatous polyposis at Cleveland Clinic. Severity of polyposis was classified on the basis of size, number, and histology. RESULTS: One hundred sixty-five patients were analyzed. The median age at IPAA was 31 years and 52% were male. The median follow-up was 10.1 years; the median number of pouchoscopies per patient was 4. The median interval between pouchoscopies was 21.9 months. Overall, the incidence of pouch adenomas was found in 47 patients (28.5%). The median time from pouch to first pouch adenoma diagnosis was 10.3 years. The estimated cumulative incidence rates of pouch adenoma at 5, 10, 15, 20, and 30 years after IPAA were 5.9%, 21.7%, 40%, 54.8%, and 69.9%, respectively. At the first diagnosis of pouch adenoma, 25 patients had stage 1, 10 had stage 2, 8 had stage 3, and 4 had stage 4. Twenty of 47 patients progressed to a higher stage. No patient developed cancer. LIMITATIONS: Genotype was not available for all patients. CONCLUSIONS: There is an increasing incidence of pouch neoplasia after restorative proctocolectomy, reaching a plateau at 25 years. The polyposis is usually mild but sometimes increases in severity. LA INCIDENCIA ACUMULADA Y LA PROGRESIN DE LOS ADENOMAS DE LA BOLSA ILEAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: ANTECEDENTES:Los pacientes con poliposis adenomatosa familiar que se han sometido a una proctocolectomía restauradora pueden desarrollar adenomas en la bolsa.OBJETIVO:Revisamos nuestra experiencia con la vigilancia de la bolsa y creamos un sistema de clasificación para la gravedad de la poliposis.DISEÑO:Una revisión retrospectiva de pacientes sometidos a anastomosis de bolsa ileoanal y seguimiento en una institución.ESCENARIO:Un centro para el cáncer colorrectal hereditario dentro de un centro de referencia cuaternarioPACIENTES:Todos los pacientes sometidos a anastomosis reservorio ileoanal y seguidos por vía endoscópica tras la cirugía por el centro.INTERVENCIONES:Bolsascopia anual y tratamiento de pólipos según sea necesarioPRINCIPALES MEDIDAS DE RESULTADO:Primaria: Incidencia y gravedad de la neoplasia del reservorio y sus cambios con el tiempo.MÉTODOS:Un estudio retrospectivo de pacientes que se sometieron a una proctocolectomía restauradora por poliposis adenomatosa familiar en la Clínica Cleveland. La gravedad de la poliposis se clasificó según el tamaño, el número y la histología.RESULTADOS:Se analizaron 165 pacientes. La mediana de edad del IPAA fue de 31 años y el 52% eran hombres. La mediana de seguimiento fue de 10,1 años; número medio de reservorioscopias por paciente = 4. El intervalo medio entre reservorioscopias fue de 21,9 meses. Incidencia global de adenomas de reservorio = 47/165 (28,5%). Tiempo mediano desde el reservorio hasta el primer diagnóstico de adenoma en reservorio = 10,3 años. La tasa de incidencia acumulada estimada de adenoma de bolsa a los 5, 10, 15, 20, y 30 años después de la IPAA es del 5,9%, 21,7%, 40%, 54,8%, y 69,9%, respectivamente. En el primer diagnóstico de adenoma de la bolsa, 25 pacientes tenían estadio 1, 10 estadio 2, 8 estadio 3 y 4 estadio 4. 20/47 pacientes progresaron a un estadio superior Ningún paciente desarrolló cáncer.LIMITACIONES:Genotipo no disponible para todos los pacientesCONCLUSIONES:Hay una incidencia creciente de neoplasia de la bolsa después de la proctocolectomía restauradora, alcanzando una meseta a los 25 años. La poliposis suele ser leve, pero a veces aumenta en severidad. (Traducción-Dr. Yesenia Rojas-Khalil ).

Colorectal Cancer Risk and Recommendations for Colorectal Cancer Surveillance in Adult Survivors of Childhood Cancer.

While many organizations have published guidance on the approach to colorectal cancer (CRC) screening in average-risk and certain high-risk groups, adult survivors of childhood cancer (ASCC) who have a heightened risk of CRC are rarely included as a target group for enhanced CRC surveillance. The population of ASCC continues to grow due to increasingly effective cancer therapies and improved survival. With this increased survival comes an increased risk for subsequent malignant neoplasms, including CRC. Since there is little published guidance for CRC surveillance in ASCC and limited awareness of increased CRC risk among both physicians and patients, the objectives of our paper are to review the incidence of and risk factors for colorectal neoplasia in ASCC, describe the clinical phenotypes of colorectal neoplasia in ASCC, review published surveillance strategies based on consensus-based survivorship guidelines, and outline areas for future research to optimize surveillance strategies.

The Approach to Performance of Quality Upper Endoscopy in Lynch Syndrome (QUELS): An International Expert Statement.

Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limited. Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage UGI cancers. On the basis of the emerging favorable evidence derived from EGD surveillance programs, the 2022 National Comprehensive Cancer Network (NCCN) Guidelines for LS recommend UGI surveillance with EGD starting between age 30 and 40 years with repeat EGDs every 2 to 4 years, preferably in conjunction with colonoscopy, in all patients with a germline pathogenic variant (PV) in MLH1, MSH2, EPCAM, and MSH6 and, because of the lack of data, consideration in PMS2. Standardization of the approach to performing EGD surveillance in LS and reporting clinically actionable findings is requisite for both improving quality and understanding the cost efficiency and outcomes of patients undergoing EGD as a surveillance tool. Accordingly, the primary objective of this Quality of Upper Endoscopy in Lynch Syndrome (QUELS) statement is to articulate a framework for standardizing the approach to performing and reporting EGD findings in patients with LS by introducing emerging quality metrics. The recommendations presented herein were developed from available evidence and consensus-based expert opinion and provide a practical approach for clinicians applying EGD surveillance in accordance with the most recent and existing LS guidelines.

Upper Gastrointestinal Neoplasia and Worrisome Thyroid Nodules are Common in Colonic Polyposis of Unknown Etiology (CPUE).

BACKGROUND: Colonic polyposis of unknown etiology (CPUE) is defined as ≥10 cumulative colonic adenomas without a detectable germline pathogenic variant. Surveillance for patients with >100 adenomas is recommended, similar to patients with familial adenomatous polyposis. The utility of extra-colonic screening in patients with 10 to <100 adenomas is not well established. METHODS: All CPUE patients seen at our center between 2003 and 2022 were included. Patients were categorized based on the range of cumulative colorectal adenoma count: 10 to 19, 20 to 99, and ≥100. RESULTS: In all, 150 patients were identified of which 20(13.3%) had 10 to 19 cumulative adenomas, 79(52.7%) had 20 to 99 adenomas, and 51(34.0%) had ≥100 adenomas. Compared with patients with 10 to 19 and 20 to 99, patients with ≥100 adenomas were younger (mean 51 vs. 52 vs. 42 y, respectively). Of patients who underwent esophagogastroduodenoscopy, duodenal adenomas were found in 33.3%, 10.1%, and 38% in the 3 groups, respectively, P=0.002. Ampullary adenomas were significantly more common in the ≥100 adenoma group (14.8%, P=0.019) compared with 8.3% and 2.9% in the 10 to 19 and 20 to 99 groups, respectively. Thyroid nodules ≥1 cm were not detected in patients with 10 to 19 adenomas but were found in 23.3% and 14.3% of patients with 20 to 99 and ≥100 adenomas, respectively (P=0.254). CONCLUSION: In our cohort, duodenal and gastric adenomas occurred in CPUE patients with adenoma count 10 to ≥100 at a relatively high proportion. We recommend a baseline esophagogastroduodenoscopy in all patients with CPUE. While clinically significant thyroid nodules were not detected in patients with 10 to 19 adenomas, they occurred in about one-fifth of the patients with ≥20 adenomas, indicating that thyroid ultrasound is prudent.