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 ).

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.

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.

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.

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.

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.

Surveillance for pathology associated with cancer on endoscopy (SPACE): criteria to identify high-risk gastric polyps in familial adenomatous polyposis.

BACKGROUND AND AIMS: Gastric cancer is an extracolonic manifestation of familial adenomatous polyposis (FAP) and is associated with high-risk gastric polyps. There are no known endoscopic criteria to identify these high-risk polyps. Our aim was to develop endoscopic criteria to identify high-risk polyps on endoscopy in FAP. METHODS: We prospectively collected 150 gastric polyps in consecutive patients undergoing surveillance EGD at the Cleveland Clinic. Pictures were taken of each polyp under narrow-band imaging and high-definition white light. In an exploratory phase, 5 endoscopists developed consensus criteria using the images to distinguish high-risk (pyloric gland adenoma, tubular adenoma, hyperplastic) from low-risk (fundic gland with low-grade or no dysplasia) polyps. In the assessment phase, endoscopists were blinded to polyp pathology and used the criteria to predict the individual polyp risk category. To measure diagnostic accuracy, we reported the mean sensitivity, specificity, and interrater agreement (κ). RESULTS: Consensus criteria were developed based on 16 low-risk and 9 high-risk polyps. The final 149 polyps consisted of 128 low-risk and 22 high-risk polyps (1 polyp was excluded from analysis). Using the criteria, the 5 endoscopists distinguished high- from low-risk polyps with a mean sensitivity and specificity of 79% (16.3%) and 78.8% (10.8%), respectively. The κ coefficient was .45, indicating moderate agreement. CONCLUSIONS: We developed endoscopic criteria to distinguish between high- and low-risk polyps associated with gastric cancer in FAP. The criteria provide guidance to endoscopists in targeting high-risk polyps while surveying the stomach of patients with proximal gastric polyposis.

Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis.

BACKGROUND AND AIMS: The greatest known risk factor for duodenal cancer in familial adenomatous polyposis (FAP) is Spigelman stage (SS) IV duodenal polyposis. Endoscopic surveillance is recommended in FAP patients with SS 0 to IV, and prophylactic duodenectomy should be considered in SS IV. Cancer occurs in patients without SS IV polyposis. We assessed the relationship of SS and other factors with duodenal cancer in FAP. METHODS: We performed a case-control study on 18 FAP patients with duodenal cancer and 85 randomly selected FAP control subjects with similar age characteristics. Demographic, clinical, and endoscopic features were compared using univariate and logistic regression analyses to assess factors associated with duodenal cancer. RESULTS: Fifty-three percent of cases had no SS IV history. SS components positively associated with cancer included duodenal polyp size (77% vs 47%, P = .015), and high-grade dysplasia (HGD; 29% vs 6%, P = .003) but not polyp number or histology. In the papilla, the frequency of tubulovillous or villous histology (80% vs 22%, P < .001) and HGD (30% vs 4%, P = .010) was greater in cases than control subjects. CONCLUSIONS: SS IV polyposis was absent in half of FAP patients with duodenal cancer. Only 2 of 4 SS components (large duodenal polyp size and HGD) were positively associated with duodenal cancer. Advanced pathology of the papilla appears to be an important feature. Revision of SS to emphasize these findings should be considered to better estimate cancer risk.

Endoscopic and histologic features associated with gastric cancer in familial adenomatous polyposis.

BACKGROUND AND AIMS: Gastric cancer (GC) is a newly described cancer risk in Western patients with familial adenomatous polyposis (FAP). Little is known about clinical, endoscopic, and pathologic features associated with FAP-related GC. We compared these features in FAP patients with and without GC. METHODS: FAP patients were identified through the David G. Jagelman Inherited Colorectal Cancer Registries Cologene database. FAP patients with GC and randomly selected FAP patients without GC who had undergone at least 2 EGDs were analyzed. Demographic, clinical, endoscopic, and pathologic features were compared. RESULTS: Ten FAP patients with GC were identified, and 40 age-matched FAP control subjects were selected. No demographic differences were noted between patients and control subjects. All GC cases arose in the proximal stomach among gastric polyposis, with only 2 endoscopically visible. The prevalence of gastric polyposis was similar (100% vs 93%). Endoscopic features associated with GC included a carpeting of gastric polyps (100% vs 22.5%), solitary polyps >20 mm (100% vs 0%), and a polypoid mound of polyps (80% vs 0%; all P < .001). GC patients had a higher prevalence of gastric adenomas (30% vs 5%, P = .048) and polyps with high-grade dysplasia, including fundic gland polyps (50% vs 10%, P = .01) and pyloric gland adenomas (20% vs 0%, P = .037). CONCLUSIONS: We identified endoscopic features and advanced pathology present in the stomachs of Western patients with FAP who developed GC. Upper GI surveillance in FAP should include the stomach and awareness of features associated with GC. Optimal approaches to treatment of gastric polyposis and methods of identification of early GC precursors in FAP are needed.

Mental Health Symptoms in Patients With Familial Adenomatous Polyposis: An Observational Study.

BACKGROUND: Almost all patients with familial adenomatous polyposis undergo abdominal surgery with a risk of disease and surgery-related complications. This, the familial nature of the syndrome, and its wide-ranging manifestations make patients prone to mental health symptoms. If this is true, patients need appropriate evaluation and treatment. OBJECTIVE: The purpose of this study was to record the experience of mental health symptoms in a group of unselected patients with FAP. DESIGN: We conducted an observational study using an anonymized mental health symptom survey for patients affected with familial adenomatous polyposis. SETTINGS: The study was conducted using the Hereditary Colorectal Cancer Registry in a tertiary referral center. PATIENTS: Patients affected with familial adenomatous polyposis were included. MAIN OUTCOME MEASURES: Results of the mental health survey were measured. RESULTS: Seventy nine of 100 patients completed the survey; 57 endorsed ≥1 psychosocial symptom (72.2%). with a mean of 4 per patient. Nine patients (11.4%) met all 4 of the American Psychiatric Association diagnostic criteria for posttraumatic stress disorder, and 8 (10.1%) endorsed partial posttraumatic stress disorder criteria (3/4 symptoms). Patients who met all of the criteria for posttraumatic stress disorder had an average of 9.3 psychosocial symptoms each compared with 8.3 for those who met 3 of 4 and 2.2 for those who met <3. Six patients endorsed suicidal thoughts, all of whom met 3 or 4 of the criteria for posttraumatic stress disorder. LIMITATIONS: The study was limited by its referral bias toward severe cases and relatively small number of patients. Because of the limitations of an anonymous self-administered screening, no mental health diagnoses have been given. CONCLUSIONS: Patients with familial adenomatous polyposis are at risk for mental health symptoms, which can be multiple and severe. Some patients need professional counseling. A correlation between familial adenomatous polyposis patients with posttraumatic stress disorder and suicidal ideation is important. See Video Abstract at http://links.lww.com/DCR/A995. SÍNTOMAS PSICOPATOLÓGICOS EN PACIENTES CON PÓLIPOSIS ADENOMATOSO FAMILIAR: UN ESTUDIO OBSERVACIONAL: Un mayoría de pacientes con póliposis adenomatoso familiar (PAF) se someten a cirugía abdominal con los riesgos de enfermedad propria y complicaciones relacionadas a cirugía. Estos factores, la relación familiar del síndrome y sus manifestaciones altamente variables hacen que los pacientes sean propensos a psicopatologías. Si estas consideraciones son validas, los pacientes requieren evaluación y tratamiento adecuado. OBJETIVO: Documentar la experiencia de los síntomas psicopatológicos en un grupo de pacientes no seleccionados con PAF. DISEÑO:: Estudio observacional utilizando una encuesta anónima de síntomas psicopatológicos en pacientes afectados con póliposis adenomatoso familiar. AMBIENTE CLINICO: Registro de cáncer colorrectal hereditario en un centro de referencia de tercer nivel. PACIENTES: Individuos afectados con póliposis adenomatoso familiar. OBJETIVOS PRINCIPALES A VALORACIÓN:: Resultados de la encuesta de salud mental. RESULTADOS: Setenta y nueve de 100 pacientes completaron la encuesta; 57 afirmaron uno o más síntomas psicosociales (72,2%) con un promedio de 4 por paciente. 9 (11,4%) pacientes cumplieron con los 4 criterios de diagnóstico de la Asociación Estadounidense de Psiquiatría para el trastorno por estrés postraumático, y 8 (10,1%) llenaron los criterios del trastorno de estrés postraumático parcial (3/4 síntomas). Los pacientes que cumplieron con todos los criterios para el trastorno por estrés postraumático tuvieron un promedio de 9.3 síntomas psicosociales cada uno, en comparación con 8.3 para los que cumplieron con 3/4 y 2.2 para los que cumplieron con <3. 6 pacientes afirmaron pensamientos de suicidio, todos los cuales cumplieron con 3 o 4 de los criterios para el trastorno por estrés postraumático. LIMITACIONES: Sesgo de referencia hacia casos graves, y un número relativamente pequeño de pacientes. Debido a las limitaciones de un examen anónimo auto administrado, no se confirmaron diagnósticos de psicopatología. CONCLUSIONES: Los pacientes con póliposis adenomatoso familiar tienen riesgo de síntomas de salud mental alterada que pueden ser múltiples y graves. Algunos pacientes necesitan asesoramiento profesional. La correlación entre los pacientes con póliposis adenomatoso familiar con trastorno por estrés postraumático y ideación suicida es importante. Vea el Resumen del Video en http://links.lww.com/DCR/A995.

Web-Based Model for Predicting Time to Surgery in Young Patients with Familial Adenomatous Polyposis: An Internally Validated Study.

INTRODUCTION: The timing of prophylactic colorectal surgery in patients with familial adenomatous polyposis (FAP) is based on the immediacy of the colorectal cancer risk. The ability to predict the need for surgery may help patients and their families plan in the context of life events and CRC risk. We created a model to predict the likelihood of surgery within 2 and 5 years of first colonoscopy at our institution. METHODS: A single institution hereditary colorectal syndrome (Cologene™) database was interrogated for all patients with FAP having a deleterious APC mutation. Patients with first colonoscopy after age 30 and before year 2000 were excluded. Cox regression analysis was done to assess multiple factors associated with surgery, followed by stepwise Cox regression analysis to select an optimal model. Receiver operator curve (ROC) analysis was performed to assess the model. RESULTS: A total of 211 (53% female) patients were included. Forty-five percent underwent surgery after an average of 3.8 years of surveillance. The final model was created based on initial clinical characteristics (age, gender, BMI, family history of desmoids, genotype-phenotype correlation), initial colonoscopic characteristics (number of polyps, polyp size, presence of high-grade dysplasia); and on clinical events (chemoprevention and polypectomy). AUC was 0.87 and 0.84 to predict surgery within 2 and 5 years, respectively. The final model can be accessed at this website: http://app.calculoid.com/#/calculator/29638 . CONCLUSION: This web-based tool allows clinicians to stratify patients' likelihood of colorectal surgery within 2 and 5 years of their initial examination, based on clinical and endoscopic features, and using the philosophy of care guiding practice at this institution.

Natural history of colonic polyposis in young patients with familial adenomatous polyposis.

BACKGROUND AND AIMS: Proctocolectomy prevents colorectal cancer in familial adenomatous polyposis (FAP). Colorectal polyp progression is one of the indications for surgery. No data exist regarding the natural history of colorectal polyposis in young patients with FAP. This study examined the rate of polyposis progression and factors associated with it. METHODS: Patients with FAP <30 years old who had undergone ≥2 colonoscopies since 2000 were identified. Rate of polyposis progression was calculated by review of polyp counts obtained from baseline and last colonoscopy, accounting for any polyps removed during the observation period. Endoscopic and non-endoscopic factors affecting the rate of polyposis progression were evaluated. Multivariate analysis was performed to identify factors associated with rate of polyposis progression. RESULTS: One hundred sixty-eight patients (52% female; median age, 13.5 years) were included. Median rate of polyposis progression was 25.4 polyps/year (interquartile range, 9.5-69.8). Highest median rate of polyposis progression (89 polyps/year) was associated with mutation in codon 1309. The rate of polyposis progression was independently associated with the location of mutation in the adenomatous polyposis coli gene, the number of polyps at the initial colonoscopy, and exposure to chemoprevention. Of the 39.9% of patients who underwent surgery, an increase in polyp number was the most common indication (53.7%). CONCLUSIONS: The rate of polyposis progression in young patients with FAP varies with a median of about 25 new polyps per year. Progression is associated with distinct factors, which can be used in discussion with patients regarding the need for and timing of prophylactic colorectal surgery.

Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by abnormal vascular structures that may present as epistaxis, telangiectasias, and/or arteriovenous malformations. The genes associated with HHT (ACVRL1, ENG, and SMAD4) are members of the TGFß pathway. Other syndromes associated with abnormalities in TGFß signaling include Marfan syndrome, Loeys-Dietz syndrome and related disorders. These disorders have aortic disease as a prominent finding. While there are case reports of patients with HHT and aortopathy (dilatation/aneurysm, dissection, and rupture), this has not been systematically investigated. We conducted a retrospective chart review to determine the prevalence of aortopathy in an HHT cohort. Patients from a single institution were identified who met the Curacao Criteria for a clinical diagnosis of HHT and/or had a mutation in ACVRL1, ENG, or SMAD4 and underwent echocardiogram. Two-dimensional echocardiograms were reviewed by a single pediatric cardiologist, and data were collected on demographics, genotype, HHT features, aortic root measurements, past medical history, and family history. Z scores and nomograms were utilized to identify abnormal results. Twenty-six patients from 15 families (one ACVRL1, four ENG, eight SMAD4, and two clinical diagnoses) were included in the analysis. Aortopathy was found in 6/26 (23%) patients; all had SMAD4 mutations. In our cohort, 6/16 (38%) SMAD4 mutation carriers had evidence of aortopathy. These data suggest that aortopathy could be part of the spectrum of SMAD4-induced HHT manifestations. Routine aortic imaging, including measurements of the aorta, should be considered in patients with SMAD4 mutations to allow for appropriate medical and surgical recommendations.

Desmoids and genotype in familial adenomatous polyposis.

BACKGROUND: Desmoid disease can be a serious, life-threatening complication of familial adenomatous polyposis. The ability to predict patients at increased desmoid risk is important, but a convincing genotype-phenotype correlation for desmoid formation has not yet been described. PURPOSE: The aim of this study is to assess the relationship between desmoid disease and genotype in patients with familial adenomatous polyposis. DESIGN: This is a cohort study. PATIENTS: All patients with familial adenomatous polyposis and a documented pathogenic APC mutation in themselves or a first-degree relative were selected. MAIN OUTCOMES MEASURES: The comparison of genotype and the presence, stage, and site of desmoid disease are the primary end points of this study. RESULTS: Three hundred twenty-three patients from 219 families were identified. Mutations spanned the length of the gene, from codon 213 to codon 2051. Desmoid disease was diagnosed in 77 patients from 68 families. Desmoid disease was found in 14.9% of patients with a mutation 5' of codon 400, 23.2% of patients with a mutation from codon 401 to 1400, and in 37.1% of those with a mutation 3' of 1400. All patients with 5' mutations had stage I or II abdominal desmoid disease, and all tumors were stable or shrinking. Twelve percent of patients who had desmoid disease with mutations between codons 400 and 1400 had stage III or IV desmoid disease, and 5 of 42 (12%) tumors were growing at the time of the study. There had been 2 desmoid-related deaths. Almost half (44%) of patients who had desmoid disease with mutations 3' of codon 1400 had stage III or IV disease. Three of 14 tumors were growing (21%), and there were 4 desmoid-related deaths. LIMITATIONS: This study was conducted at a tertiary referral center, and there was no systematic surveillance for desmoids. CONCLUSION: Desmoid disease occurs in patients who have familial adenomatous polyposis with almost any APC mutation, although there is an increased propensity in those with a 3' mutation. The incidence and severity of the desmoid disease are related to the site of the mutation.

Desmoid tumors do not prevent proctectomy following abdominal colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis.

BACKGROUND: Elective proctocolectomy has been recommended for patients at high risk of desmoids based on the possibility that cancer in a retained rectum may be unresectable because of desmoid disease. There are no data to support the reality of this concern. OBJECTIVE: The aim of this study was to see how often proctectomy was prevented by desmoids. DESIGN: This retrospective, descriptive, database study was augmented by chart review. SETTING: This study was conducted at a hereditary colorectal cancer clinic in a tertiary referral center. PATIENTS: Those presenting for proctectomy after colectomy and ileorectal anastomosis for familial adenomatous polyposis were selected. INTERVENTIONS: Patients underwent a proctectomy. MAIN OUTCOME MEASURES: The primary outcomes measured were the rate of proctectomy, rate of IPAA, and the incidence of desmoid disease. RESULTS: Sixty- seven patients, 34 men and 33 women, underwent an operation with the intent of performing proctectomy. Mean age at surgery was 39.7 years, an average of 175 months from ileorectal anastomosis. Indications for proctectomy were uncontrollable adenomas in 56, cancer in 8, and high-grade dysplasia in 3. Proctectomy was always possible. Ileal pouch-anal anastomosis was planned in 62 patients; 54 had this operation. Desmoid disease was found in 26 patients (38.8%) and influenced surgery in 13 cases, stopping pouch-anal anastomosis in 8. One patient had no resection, 2 had a pouch-low rectal anastomosis, and 5 had proctectomy and ileostomy. Proctectomy and ileostomy was planned in 5 patients and performed in all. LIMITATIONS: This is a retrospective review from a single institution. CONCLUSION: The fear of an unresectable rectum or an impossible pouch-anal anastomosis should not be an indication for proctectomy in patients with low rectal polyp counts but a high risk for desmoid disease.

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.

Hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas complicating familial adenomatous polyposis: two cases and review of the literature.

Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and extracolonic tumors. Adenocarcinoma of the pancreas and hepatocellular carcinoma are rare in FAP. In this case series, we describe a mother and daughter with FAP who developed a hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas, respectively.

The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome.

BACKGROUND: Juvenile polyposis syndrome is a dominant GI polyposis syndrome defined by ≥ 5 GI juvenile polyps or ≥ 1 juvenile polyps with a family history of juvenile polyposis. Mutations in BMPR1A or SMAD4 are found in 50% of individuals. Hereditary hemorrhagic telangiectasia is a dominant disorder characterized by epistaxis, visceral arteriovenous malformations, and telangiectasias. Hereditary hemorrhagic telangiectasia is diagnosed when ≥ 3 criteria including clinical manifestations or a family history, are present. A juvenile polyposis-hereditary hemorrhagic telangiectasia overlap syndrome has previously been reported in 22% of patients with juvenile polyposis due to a SMAD4 mutation. OBJECTIVE: Our objective was to determine the prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia by Curacao criteria in our juvenile polyposis SMAD4 patients. DESIGN, PATIENTS, AND SETTING: This was a cohort study of juvenile polyposis patients in our inherited colon cancer registries. Hereditary hemorrhagic telangiectasia manifestations were obtained from medical records, patient contact, and/or prospective hereditary hemorrhagic telangiectasia screening. The Curacao criteria was used for diagnosis of hereditary hemorrhagic telangiectasia (≥ 3 criteria diagnostic; 2 criteria suspect of). MAIN OUTCOME MEASURES: Prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia in juvenile polyposis SMAD4 patients. RESULTS: Forty-one juvenile polyposis families were identified. Genetic testing was available for individuals within 18 families. SMAD4 mutations were found in 21 relatives in 9 families. Eighty-one percent of SMAD4 patients had hereditary hemorrhagic telangiectasia and 14% were suspected of having hereditary hemorrhagic telangiectasia. Epistaxis and asthma are the most common symptoms in our overlap patients. Symptomatic and subclinical arteriovenous malformations were noted near universally. LIMITATIONS: There was a single, tertiary referral center. CONCLUSIONS: Nearly all juvenile polyposis SMAD4 patients have the overlap syndrome. The clinical implications and need for hereditary hemorrhagic telangiectasia screening are important factors for genetic testing in juvenile polyposis. Health care providers must be cognizant of the juvenile polyposis-hereditary hemorrhagic telangiectasia overlap syndrome and the implications for management of these patients.

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.

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.