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.

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.

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.

Identifying factors associated with detection of sessile gastric polyps in patients with familial adenomatous polyposis.

Background and study aims Gastric cancer (GC) is increasingly reported and a leading cause of death in patients with familial adenomatous polyposis (FAP). Identifying features in patients with FAP who harbor sessile gastric polyps, likely precursors to GC, may lead to alterations in endoscopic surveillance in those patients and allow endoscopic intervention to decrease the risk of GC. The aim of this study was to identify demographic and clinical factors in patients with FAP who harbor sessile gastric polyps. Patients and methods We retrospectively compared demographic, clinical, and endoscopic features in consecutive adult patients with FAP who presented for a surveillance endoscopy at a tertiary-care center with a FAP registry who harbor sessile gastric polyps to those without them. Sessile gastric polyps included pyloric gland adenomas, gastric adenomas, hyperplastic polyps, and fundic gland polyps with high-grade dysplasia. We also display the location of germline APC pathogenic variants in patients with and without sessile gastric polyps. Results Eighty patients with FAP were included. Their average age was 48 years and 70 % were male . Nineteen (24 %) had sessile gastric polyps. They were older ( P  < 0.03), more likely to have a family history of GC ( P  < 0.05), white mucosal patches in the proximal stomach ( P  < 0.001), and antral polyps ( P  < 0.026) compared to patients without a gastric neoplasm. No difference in Spigelman stage, extra-intestinal manifestations, or surgical history was note. 89 % of patients with a gastric neoplasm had an APC pathogenic variant 5' to codon 1309. Conclusions Specific demographic, endoscopic, and genotypic features are associated with patients with FAP who harbor sessile gastric polyps. We recommend heightened awareness of these factors when performing endoscopic surveillance of the stomach with resection of gastric neoplasia when identified.

Efficacy of endoscopic retrograde cholangiopancreatography in familial adenomatous polyposis patients after duodenectomy.

Objectives: Familial adenomatous polyposis (FAP) patients with Spigelman stage IV polyposis should be considered for prophylactic duodenectomy. Post-surgical pancreaticobiliary complications occur and may require management via endoscopic retrograde cholangiopancreatography (ERCP). We aimed to assess the success and adverse events of ERCP in FAP patients after pancreas-sparing duodenectomy (PSD) and pancreaticoduodenectomy (PD). Methods: A retrospective review of FAP patients who underwent ERCP after PSD or PD from 1992 to 2020 at a quaternary referral center was completed. The technical success of ERCP was defined as the ability to identify the anastomosis and cannulate the duct. Post-procedural adverse events were defined by bleeding, perforation, pancreatitis, or cholangitis. Clinical outcomes included the need for surgical intervention and recurrent pancreatitis after ERCP were assessed. Results: Of 84 FAP patients with duodenectomy, 12 patients with PSD and two patients with PD underwent 17 ERCPs for pancreatic indications and five for biliary indications. The technical success of ERCP in patients with PSD and a single neoampullary complex for pancreatic (n = 6) and biliary (n = 5) indications was 100% but for those with PD (n = 2) or PSD reconstruction with pancreatic divisum or separate anastomoses (n = 3), it was 0%. Surgical intervention was required in 50% of patients with technically failed ERCP after PSD (2/4) and PD (1/2). There were no adverse events. Conclusions: ERCP is expected to be therapeutically successful for biliary complications following PSD. Assessment and potential therapy for pancreatitis post-PSD are best in the setting of a single neo-ampullary complex rather than in PD or PSD with pancreatic divisum.

Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome.

BACKGROUND: Individuals with Lynch syndrome (LS) and hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. The interplay between immunosuppression, a comorbid inflammatory condition (CID), and HNPCC on cancer risk is unclear. AIM: To evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC. METHODS: Individuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were identified. We compared the proportion of patients with cancer in LS/HNPCC group with and without a CID. We also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive medications. RESULTS: A total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no CID. Cancer occurred in 84.2% with a CID compared to 76.7% without a CID (P = 0.74) with no difference in age at first cancer diagnosis 45.5 ± 14.6 vs 43.8 ± 7.1 years (P = 0.67). LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID (P = 0.54). Nine of 21 (42.9%) patients were exposed to biologics or immunomodulators for the treatment of their CID. Cancer after diagnosis of CID was seen in 7 (77.8%) of exposed individuals vs 5 (41.7%) individuals unexposed to biologics/immunomodulators (P = 0.18). All 7 exposed compared to 3/5 unexposed developed a LS specific cancer. The exposed and unexposed groups were followed for a median 10 years and 8.5 years, respectively. The hazard ratio for cancer with medication exposure was 1.59 (P = 0.43, 95%CI: 0.5-5.1). CONCLUSION: In patients with LS/HNPCC, the presence of a concurrent inflammatory condition, or use of immunosuppressive medication to treat the inflammatory condition, might not increase the rate of cancer occurrence in this limited study.

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.

Chemoprevention Considerations in Patients with Hereditary Colorectal Cancer Syndromes.

Secondary prevention of colorectal neoplasia with chemoprevention is long-studied area of research and clinical use in patients with the 2 most common hereditary colorectal cancer syndromes including Lynch syndrome and familial adenomatous polyposis. No medication is currently approved for use for the prevention of colorectal polyps or cancer in either the general population or individuals with the hereditary colorectal cancer syndromes. Emerging data in animal models and limited data in humans suggest vaccines may be the next breakthrough for neoplasia prevention in patients with hereditary colorectal cancer. Clinicians must acknowledge chemoprevention is an adjunct and does not supplant endoscopic surveillance.

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.

Safety and efficacy of sodium picosulfate, magnesium oxide, and citric acid bowel preparation in patients with baseline renal impairment or diabetes: subanalysis of a randomized, controlled trial.

BACKGROUND: Selecting a bowel preparation for patients with renal impairment or diabetes requires special consideration. We aimed to describe the effect of baseline renal impairment or diabetes on the safety, efficacy, and tolerability of low-volume sodium picosulfate, magnesium oxide, and citric acid (SPMC) ready-to-drink oral solution bowel preparation. METHODS: A post hoc secondary analysis was performed from a randomized, assessor-blinded study of SPMC oral solution bowel preparation in participants with mild or moderate baseline renal impairment or diabetes. Primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of ascending colon cleansing from the Boston Bowel Preparation Scale (BBPS), and selected results from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs), adenoma detection, and laboratory evaluations. RESULTS: Similar overall colon cleansing was demonstrated in the subgroups, with >85% of participants in any subgroup rated as responders by the AS, and >92% of participant responders by the BBPS. Most participants reported a tolerable bowel preparation, regardless of baseline renal impairment or diabetes history. Safety of SPMC oral solution was similar between all subgroups and the overall cohort. For the mild renal impairment, moderate renal impairment, and diabetes subgroups, respectively, commonly reported, drug-related AEs were nausea (2.6%, 5.3%, 1.4%) and headache (2.2%, 2.6%, 4.3%). CONCLUSIONS: Ready-to-drink SPMC oral solution demonstrated efficacious colon cleansing in patients with baseline mild/moderate renal impairment or diabetes, with a tolerable bowel preparation reported by most. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03017235.

Incidence and Management of Rectal Cuff and Anal Transitional Zone Neoplasia in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Rectal cuff and anal transitional zone neoplasia is an increasing challenge in patients with familial adenomatous polyposis who have undergone restorative proctocolectomy. Its real incidence, range of severity, and treatment efficacy are poorly documented. OBJECTIVE: We sought to document the evolution of rectal cuff and anal transitional zone neoplasia and describe its management. DESIGN: This is a retrospective cohort study collecting prospectively recorded data. SETTINGS: This study involved a hereditary colorectal cancer group in a large academic medical center. PATIENTS: All patients undergoing primary restorative proctocolectomy at this institution were included. INTERVENTIONS: Surveillance pouchoscopy and treatment of rectal cuff/anal transitional zone neoplasia were performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the presence and the severity of rectal cuff/anal transitional zone neoplasia. Excision by cautery, snare, mucosectomy, or redo pouch was evaluated. RESULTS: A total of 165 patients were included: 52% were male (86/165) with a median age at restorative proctocolectomy of 31.0 years (SD 12.8). In 117 of 165, the proctocolectomy was their first operation and, in 48 of 165, it followed a colectomy. Of the patients, 83% (137/165) had stapled anastomosis; 17% had mucosectomy with handsewn anastomosis; and 14% (23/165) were treated with sulindac at some point during their surveillance. Median follow-up was 10.1 years (interquartile range, 4.5-17.2) and the median number of pouchoscopies per patient was 4 (interquartile range, 2-8). Seventy-eight of 165 (47.3%) developed rectal cuff/anal transitional zone adenomas, more in the stapled group (52.3%; 72/137) than in the handsewn group (21.4%; 6/28; p < 0.005). Median time to adenoma was 4.5 years (interquartile range, 2.4-8.9). Three patients developed cancer under surveillance, and, in 3 other patients, cancers developed when screenings lapsed. Five patients developed symptomatic anal stenosis secondary to repeated surgeries (median, 9 procedures; range, 2-10). LIMITATIONS: There was no quality-of-life measurement in patients who developed rectal cuff/anal transitional zone neoplasia. CONCLUSIONS: Rectal cuff/anal transitional zone adenomas are more common than previously reported. Mild polyposis can be controlled endoscopically, but repeated procedures in a higher stage are associated with risk of anal stenosis. Compliance with surveillance is essential to avoid cancer. See Video Abstract at http://links.lww.com/DCR/B594. INCIDENCIA Y TRATAMIENTO DE LA NEOPLASIA DEL REMANENTE RECTAL Y DE LA ZONA DE TRANSICIN ANAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: ANTECEDENTES:La neoplasia del remanente rectal y de la zona de transición anal presenta un desafío mayor en pacientes con poliposis adenomatosa familiar tratados con una proctocolectomía restaurativa. Su incidencia real, el espectro de la gravedad y la eficacia del tratamiento están mal documentados.OBJETIVO:Buscamos documentar la evolución de la neoplasia del remanente rectal y de la zona de transición anal y describir su tratamiento.DISEÑO:Estudio de cohorte retrospectivo que recabó datos registrados prospectivamente.AMBITO:Un grupo con cáncer colorrectal hereditario de un importante centro médico académico.PACIENTES:Todos los pacientes operados por primera vez de proctocolectomía restaurativa en nuestra institución.INTERVENCIONES:Endoscopía del pouch para vigilancia y tratamiento de la neoplasia del remanente rectal / zona de transición anal.PRINCIPALES VARIABLES ANALIZADAS:La presencia y la gravedad de la neoplasia del remanente rectal / zona de transición anal. Resección con cauterio, asa, mucosectomía o rehacer el pouch.RESULTADOS:Se incluyeron un total de 165 pacientes: 52% eran hombres (86/165) con una mediana de edad al momento de la proctocolectomía restaurativa de 31,0 años (DE 12,8). En 117/165 la proctocolectomía fue su primera cirugía y en 48/165 fue posterior a una colectomía. En 83% (137/165) tenía una anastomosis con engrapadora, 17% tenía mucosectomía y anastomosis con sutura manual (HS). El 14% de los pacientes (23/165) fueron tratados con sulindac en algún momento durante su vigilancia. La mediana de seguimiento fue de 10,1 años (IQR: 4,5, 17,2) y la mediana del número de endoscopías del pouch por paciente fue de 4. (IQR: 2, 8) 78/165 (47,3%) desarrollaron adenomas en la zona de transición anal /remanente rectal, mayor en el grupo con engrapadaora (52,3%; 72/137) comparado con el grupo con sutura manual (21,4%; 6/28) (p <0,005). La mediana del tiempo hasta el adenoma fue de 4,5 años (IQR: 2,4, 8,9). Tres pacientes que se encontraban en vigilancia desarrollaron cáncer y en 3, otros cánceres se desarrollaron transcurrida la vigilancia. 5 pacientes desarrollaron estenosis anal sintomática secundaria a múltiples cirugías (mediana de 9 procedimientos; rango 2-10).LIMITACIONES:Falta de medición de la calidad de vida en pacientes que desarrollaron neoplasia del remanente rectal / zona de transición anal.CONCLUSIONES:Los adenomas de la zona de transición anal / remanente rectal son más comunes de lo reportado anteriormente. La poliposis leve se puede tratar por endoscopía, pero procedimientos repetidos en estadíos mayores se asocian con el riesgo de estenosis anal. El apego a la vigilancia es fundamental para evitar el cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B594. (Traducción-Dr. Lisbeth Alarcon-Bernes).

Association between baseline hyperplastic polyps and metachronous serrated lesions.

BACKGROUND AND AIMS: Some data suggest that individuals with numerous, <10-mm, rectosigmoid hyperplastic polyps (HPs) are at average risk for the development of metachronous advanced adenomatous neoplasia. Guidelines suggest that these individuals do not need surveillance colonoscopy and should be followed akin to individuals with a normal colonoscopy. Less is known of the risk of metachronous neoplasia because of ≥1 HPs <10 mm proximal to the sigmoid colon. We compared the risk of metachronous neoplasia between individuals with small HPs and those with normal colonoscopy, specifically addressing the impact of location and number of HPs on risk. METHODS: Colonoscopy and pathology reports from patients with ≥2 colonoscopies between 2004 and 2014 were reviewed. Exclusions included inpatients; age <40 or >75 years; and family or personal history of colorectal cancer, inflammatory bowel disease, previous colorectal surgery, or a previous colonoscopy with any adenoma, sessile serrated lesion (SSL), or HP ≥10 mm. The risk of metachronous neoplasia, including adenomas and SSLs, was compared in individuals with a normal index colonoscopy and those with <10-mm HPs stratified by location and number of HPs. RESULTS: After exclusion, 1795 patients were included. At index colonoscopy, 82% (n = 1469) had a normal examination, 12% (219) had only 1, and 6% (107) had between 2 and 9 HPs <10 mm. Compared with patients with a normal index colonoscopy, patients with a proximal (odds ratio, 3.82; 95% confidence interval, 1.77-7.53) or distal HP (odds ratio, 2.23; 95% confidence interval, 1.18-4.00) had an increased risk of metachronous SSLs but not adenomas. CONCLUSIONS: Patients with small proximal and distal HPs are at increased risk of metachronous SSLs. These preliminary findings warrant consideration during surveillance recommendations and future studies in larger cohorts.

The Prevalence and Significance of Jejunal and Duodenal Bulb Polyposis After Duodenectomy in Familial Adenomatous Polyposis: Retrospective Cohort Study.

OBJECTIVE: To evaluate the prevalence, natural history, and severity of polyposis of the duodenal bulb and jejunum after duodenectomy in patients with FAP. SUMMARY OF BACKGROUND DATA: Advanced duodenal polyposis stage in FAP requires consideration of duodenal resection to prevent cancer; pylorus-preserving approach of pancreas-sparing duodenectomy (PSD) is preferred. Post-duodenectomy data indicate polyps occur in the duodenal bulb and the post-anastomotic jejunum, but limited data exists regarding their significance. METHODS: We identified consecutive FAP patients After duodenal resection, including pancreaticoduodenectomy, PSD, or segmental duodenectomy, at Cleveland Clinic. Medical records were used to determine time to diagnosis of duodenal bulb or jejunal polyps, length of follow up, and severity of polyposis including maximal Spigelman stage (SS) of jejunal polyposis (neo-SS). RESULTS: 64 patients with FAP underwent duodenectomy and endoscopic follow up. 28% underwent pancreaticoduodenectomy, 61% PSD, and 11% segmental duodenectomy. Postoperatively, 38/64 (59%) were diagnosed with jejunal polyposis, with median time to diagnosis of 55 months and follow up time of 127 months. Jejunal polyposis was advanced in 21% (neo- SS III or IV). Fifty percent were treated endoscopically, 1 patient required surgery. Jejunal polyp-free survival after duodenectomy differed by surgery type (P = 0.008). A total of 55/64 patients underwent a pylorus-preserving procedure, and 6/55 (11%) developed duodenal bulb polyps. All bulb polyps were large (>20 mm) and found after PSD. Endoscopic resection was unsuccessful in 5 patients, but no surgical intervention was required. CONCLUSIONS: Polyposis occurs in the remaining duodenal and jejunal mucosa in the majority of patients after surgical duodenectomy. Jejunal polyposis is advanced in 1 in 5 patients, but rarely requires surgery. Endoscopic management of jejunal polyposis seems feasible but has proven difficult for duodenal bulb polyps.

Chemoprevention in familial adenomatous polyposis: past, present and future.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and temporizing the development of extracolonic disease. An ideal chemoprevention agent should have a biologically plausible mechanism of action, be safe and easily tolerated over a prolonged treatment period, and produce a durable and clinically meaningful effect. To date, no chemoprevention agent tested has fulfilled these criteria. New agents targeting novel pathways in FAP are needed. Substantial preclinical literature exists linking the molecular target of rapamycin (mTOR) pathway to FAP. A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Here, we review the prior literature on chemoprevention in FAP, discuss the rationale for rapamycin in FAP, and outline a proposed clinical trial testing rapamycin as a chemoprevention agent in patients with FAP.

Risks, Benefits, and Effects on Management for Biopsy of the Papilla in Patients With Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Ampullary and duodenal cancer are the leading causes of death in patients with familial adenomatous polyposis (FAP) after colectomy has been performed. Risk of duodenal cancer is determined based on Spigelman stage (SS) of duodenal polyposis. Guidelines recommend endoscopic surveillance of the duodenum and visualization of the papilla to stage duodenal polyposis. There is no consensus on whether biopsies should be routinely collected from duodenal papilla and findings included in SS. Additionally, there are no data on the risk of pancreatitis after biopsy collection from papilla of patients with FAP. We studied the incidence of pancreatitis after biopsy of the papilla in patients with FAP and effects of biopsy findings on SS. METHODS: We identified consecutive patients with FAP at a single center from January 2011 through December 2018 with ≥1 endoscopy with biopsy of the papilla. Patients with history of foregut surgery were excluded. We identified 273 patients with FAP who had biopsies collected from papilla over 792 EGDs, with 1-8 independent exams with biopsy per patient. We collected demographic, endoscopic, and histology data from patients and calculated SS with vs without biopsy findings. Post-procedural pancreatitis was defined by 2 of the following: abdominal pain, lipase level 3-fold the upper limit of normal, or radiography findings consistent with pancreatitis within 7 days of esophagogastroduodenoscopy (EGD). RESULTS: Pancreatitis developed in 2 patients (0.73%): 1 after biopsy of a normal-appearing papilla and 1 after biopsy of an abnormal appearing papilla. Inclusions of biopsy data increased SS in 36 patients (13.2%), with consideration of prophylactic duodenectomy for 3.3%. CONCLUSIONS: Pancreatitis after biopsy of the duodenal papilla is rare. Histology data obtained from biopsy of the papilla in patients with FAP can change SS and affect patient management.