Endoscopic screening for identification of signet ring cell gastric cancer foci in carriers of germline pathogenic variants in CDH1.

To determine the preoperative detection of signet ring cancer cells (SRC) on upper endoscopy (EGD) in patients with CDH1 pathogenic variant (PV) undergoing gastrectomy. To evaluate the development of advanced diffuse gastric cancer (DGC) in patients choosing surveillance. Guidelines recommend prophylactic total gastrectomy (pTG) in CDH1 PV carriers with family history of DGC between 18 and 40 years. Annual EGD with biopsies according to established protocols is recommended in carriers with no SRC and no family history of DGC, with consideration of pTG. Retrospective analysis of asymptomatic patients with CDH1 PVs with ≥ 1 surveillance EGD. Outcomes included pre-operative EGD detection of SRC, surgical stage, and progression to advanced DGC in those electing surveillance with EGD. 48 patients with CDH1 PVs who had ≥ 1 EGD were included. 24/ 48 (50%) underwent gastrectomy, including pTG in 7 patients. SRCC were detected on gastrectomy specimen in 21/24 (87.5%). SRCs were identified by EGD in 17/21 patients who had SRCC on gastrectomy specimens (sensitivity 81%, 17/21). All cancers were stage pT1a. The remaining 17 patients (50% with a family history of gastric cancer) continue in annual EGD surveillance with a median follow-up of 34.6 months. No SRCC or advanced DGC have been diagnosed. No CDH1 PV carriers without SRCC on random biopsies followed in an endoscopic program developed advanced DGC over a median follow up of 3 years. In the short term, EGD surveillance might be a safe alternative to immediate pTG in experienced hands in referral centers.

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.

Sessile serrated polyp detection rates after fecal immunochemical test or multitarget stool DNA test: Systematic review and meta-analysis.

Background and study aims Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for sessile serrated polyp (SSP) detection. We performed a meta-analysis to evaluate the performance of FIT and FIT-DNA testing for SSP detection rate (SSPDR) in patients undergoing colonoscopy for follow up of positive noninvasive tests. Methods A comprehensive literature search of multiple databases (until September 2022) was performed to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA tests. The outcome was overall colonoscopy detection of any SSPs and advanced serrated polyps (ASP: SSP ≥ 10 mm and/or dysplasia). Results Included were 482,405 patients (52.4% females) with a mean age of 62.3 ± 4.4 years from 23 studies. The pooled SSPDR for all positive stool-based tests was 5.3% and higher for FIT-DNA (15.0%, 95% confidence interval [CI] 8.3-25.7) versus FIT (4.1%, 95% CI 3.0-5.6; P = 0.0002). The overall pooled ASP detection rate was 1.4% (95% CI 0.81-2.3) and higher for FIT-DNA (3.8 %, 95% CI 1.7-8.6) compared with FIT (0.71%, 95% CI 0.36-1.4; P <0.01). SSPDR with FIT-DNA was also significantly higher than FIT when the FIT cutoff was >10 ug/g and in FIT-positive patients in studies conducted in North America ( P <0.05). Conclusions FIT-DNA outperformed FIT in both SSP and ASP detection including FIT with a lower threshold cutoff of >10 ug/g. Further comparative studies are needed to assess the impact of our findings on colorectal cancer reduction.

How to do a laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers syndrome.

We demonstrate the technical details of laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers Syndrome. A 'clean sweep' reduces the risk for future recurrences but was previously performed with an open technique. A minimally invasive approach is safe, reduces bowel trauma and has good postoperative outcomes.

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.

Compound heterozygous MSH3 germline variants and associated tumor somatic DNA mismatch repair dysfunction.

We describe here an individual from a fourth family with germline compound heterozygous MSH3 germline variants and its observed biological consequences. The patient was initially diagnosed with invasive moderately-differentiated adenocarcinoma of the colon at the age of 43. Germline multigene panel testing revealed a pathogenic variant MSH3 c.2436-1 G > A and a variant of (initial) uncertain significance MSH3 c.3265 A > T (p.Lys1089*). Germline genetic testing of family members confirm the variants are in trans with the c.2436-1 G > A variant of paternal and the c.3265 A > T variant of maternal origin. Tumor DNA exhibits low levels of microsatellite instability and elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). Tissue immunohistochemical staining for MSH3 demonstrated variant MSH3 protein is present in the cytoplasm and cell membrane but not in the nucleus of normal and tumor epithelial cells. Furthermore, variant MSH3 is accompanied by loss of nuclear MSH6 and a reduced level of nuclear MSH2 in some tumor cells, suggesting that the variant MSH3 protein may inhibit binding of MSH6 to MSH2.

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 ).

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.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

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.

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.