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.

Malignancy risk in individuals with familial adenomatous polyposis receiving biologics and immunomodulators.

Clinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow up or death. Hazard ratio (HR) for cancer was computed using Cox regression model and compared by exposure status to biologic/immunomodulators. 25 individuals with FAP and a comorbid inflammatory disease were identified including 9 (36%) with IBD and 16 (64%) with rheumatic disease. 14 (56%) were exposed to a biologic and or immunomodulator. Median duration of biologic/immunomodulator exposure was 48 (2-180) months. 3 (21.4%) in the exposed group compared to 1 (9.1%) in the unexposed group developed cancer with a HR for exposure of 1.92 (CI 0.2-18.5, p = 0.57). Median duration of follow up after the diagnosis of inflammatory disease was 10 (5.5-17.0) years in the exposed and 6 (3.0-15.0) years in the unexposed group. In the exposed group, 1 patient developed gastric and 2 developed colon cancer. One unexposed patient developed medullary thyroid cancer. There is a possible trend of more cancers in the group that received biologics/immunomodulators-but given the small number of patients and p-value, there may be no difference at all. This preliminary finding warrants study in a larger cohort.

Endoscopic Findings in Patients With PTEN Hamartoma Tumor Syndrome Undergoing Surveillance.

GOALS AND BACKGROUND: Phosphatase and tensin homolog hamartoma tumor syndrome (PHTS) is an inherited disorder that increases the risk for cancer in multiple organ systems, including breast, endometrial, thyroid, and the gastrointestinal tract. Surveillance is recommended however there lacks data to describe the change in polyposis phenotype and cancer incidence over surveillance. Our aim is to describe the polyposis phenotype and cancer incidence in PHTS patients undergoing endoscopic surveillance. STUDY: PHTS patients, ages 17 through 89, who underwent at least 2 esophagogastroduodenoscopy (EGDs) or colonoscopies were identified. Number and sizes of polyps were noted, from which 5 categories were recreated. Incidence of colorectal and gastric cancer was evaluated. RESULTS: Seventy patients were included. Patients were clustered and classified into 1 of 5 categories: no polyps, few small polyps (<1 cm, < 10 polyps), few large polyps (≥1 cm, < 10 polyps), many small polyps (<1 cm, ≥10 polyps), many large polyps (≥1 cm, ≥10 polyps). There was no significant difference in polyp number or size on EGD (P=0.47 and 0.83, respectively) or colonoscopy (P=0.49 and 0.10, respectively) over the surveillance period (4.8±3.9 y for stomach and 5.6±4.4 y for colon). The average interval between endoscopies was 28±24 months for EGDs and 29±23 months for colonoscopies. A stage II transverse colon adenocarcinoma and stage IV gastric adenocarcinoma were identified. Standardized incidence rates for gastric and colon cancers were 5427 (P=0.0002) and 353 (P=0.002), respectively. CONCLUSIONS: PTHS individuals can be classified into polyposis phenotypes which do not change over an endoscopic surveillance period. Two cancers were associated with a large size polyp phenotype. Surveillance intervals should be determined by polyp size ≥1 cm and pathology.

Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.

Evaluation of Urinalysis-Based Screening for Urothelial Carcinoma in Patients With Lynch Syndrome.

BACKGROUND: Approximately 5% to 10% of patients with Lynch syndrome develop urothelial carcinoma. Current screening recommendations vary and are based on expert opinion. Practices need to be evaluated for clinical effectiveness. Our program utilizes urinalysis as a screening test, followed by additional evaluation of microscopic hematuria. OBJECTIVE: This study aimed to determine the clinical utility of a urinalysis-based screening approach for urothelial cancers in patients with Lynch syndrome. DESIGN: This is a retrospective review of a prospectively maintained cohort. SETTING: Patients with Lynch syndrome were managed at a tertiary referral center. PATIENTS: All patients with a Lynch syndrome diagnosis who had a screening urinalysis done as part of our institutional screening protocol (N = 204) were included. MAIN OUTCOME MEASURES: A single-institution hereditary colorectal cancer syndrome registry was queried for patients with Lynch syndrome who had been screened for urothelial carcinomas by urinalysis. Demographics, genotype, family history of urothelial carcinoma, urinalysis results, and subsequent screenings and final diagnosis were gathered for patients between 2008 and 2017. RESULTS: Two hundred four asymptomatic patients underwent screening by urinalysis. Nineteen patients (9.3%) had microscopic hematuria and were further evaluated with urine cytology, imaging, cystoscopy, and/or Urology consultation. None of the 19 patients with microscopic hematuria had urothelial carcinoma. During the same study period, 5 of 204 (2.4%) patients with Lynch syndrome were diagnosed with urothelial cancer, and all presented with symptoms between screening intervals. LIMITATIONS: This is a retrospective study, and not all patients underwent the same secondary evaluation. CONCLUSIONS: No urothelial carcinomas were detected by screening urinalysis in our cohort of asymptomatic patients with Lynch syndrome. False-positive testing led to extensive, mostly uninformative, workups. If urothelial cancer screening is to continue, more effective screening approaches need to be identified. See Video Abstract at http://links.lww.com/DCR/B702. EVALUACIN DEL CRIBADO BASADO EN ANLISIS DE ORINA PARA CARCINOMA UROTELIAL EN PACIENTES CON SNDROME DE LYNCH: ANTECEDENTES:Aproximadamente el 5-10% de los pacientes con síndrome de Lynch desarrollan carcinoma urotelial. Las recomendaciones actuales de detección varían y se basan en la opinión de expertos. Las prácticas deben evaluarse para determinar su eficacia clínica. Nuestro programa utiliza el análisis de orina como prueba de detección, seguido de una evaluación adicional con hematuria microscópica.OBJETIVO:Determinar la utilidad clínica desde un enfoque de cribado basado en análisis de orina, para cánceres uroteliales en pacientes con síndrome de Lynch.DISEÑO:Revisión retrospectiva de una cohorte mantenida prospectivamente.ENTORNO CLINICO:Pacientes con síndrome de Lynch atendidos en un centro de referencia terciario.PACIENTES:Criterios de inclusión fueron todos los pacientes con diagnóstico de síndrome de Lynch realizándoles un análisis de orina de detección como parte de nuestro protocolo de detección institucional (N = 204).PRINCIPALES MEDIDAS DE VALORACION:Solicitando un registro de síndrome de cáncer colorrectal hereditario de una sola institución para pacientes con síndrome de Lynch previamente evaluados para carcinomas uroteliales mediante análisis de orina. Se recopilaron para los pacientes entre 2008 y 2017, datos demográficos, genotipo, antecedentes familiares de carcinoma urotelial, resultados del análisis de orina, posteriores exámenes de detección posteriores y diagnóstico final.RESULTADOS:Doscientos cuatro pacientes asintomáticos fueron sometidos a cribado mediante análisis de orina. Diecinueve pacientes (9,3%) tenían hematuria microscópica y fueron investigados más a fondo con citología de orina, imágenes, cistoscopia y / o consulta de urología. Ninguno de los 19 pacientes con hematuria microscópica tenían carcinoma urotelial. Durante el mismo período de estudio, 5 de 204 (2,4%) pacientes con síndrome de Lynch fueron diagnosticados con cáncer urotelial y todos presentaron presentando síntomas entre los intervalos de detección.LIMITACIONES:Estudio retrospectivo y no todos los pacientes sometidos a la misma evaluación secundaria.CONCLUSIONES:No se detectaron carcinomas uroteliales mediante análisis de orina de detección en nuestra cohorte de pacientes asintomáticos con síndrome de Lynch. Las pruebas de falsos positivos. Condujeron a estudios exhaustivos y en su mayoría poco informativos. Si se desea continuar con la detección del cáncer de urotelio, es necesario identificar enfoques de detección más efectivos. Consulte Video Resumen en http://links.lww.com/DCR/B702.