The highest cancer risks in familial adenomatous polyposis (FAP) include colorectal, duodenal, and thyroid for which surveillance is recommended. Nearly all patients with FAP have gastric fundic gland polyposis (FGP), but gastric cancers are rarely reported with a similar incidence as the general population. We describe a recent, sudden increase in the incidence of gastric cancer in FAP. Seven of the ten cases were diagnosed in the last 20 months. Comparing our population to the SEER database for gastric cancer, the standardized incidence ratio is 140. All cases arose in patients with a carpeting of FGP and associated with large mounds of proximal gastric polyps. Nearly all patients were under upper endoscopic surveillance. This is a concerning observation and reflects a change in the phenotypic presentation of FAP in Western patients.
IMPORTANCE Research demonstrates adenoma detection rate (ADR) and proximal sessile serrated polyp detection rate (pSSPDR) are associated with endoscopist characteristics including sex, specialty, and years in practice. However, many studies have not adjusted for other risk factors associated with colonic neoplasia.OBJECTIVE To assess the association between endoscopist characteristics and polyp detection after adjusting the factors included in previous studies as well as other factors.DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted in the Cleveland Clinic health system with data from individuals undergoing screening colonoscopies between January 2015 and June 2017. The study analyzed data using methods from previous studies that have demonstrated significant associations between endoscopist characteristics and ADR or pSSPDR. Multilevel mixed-effects logistic regression was performed to examine 7 endoscopist characteristics associated with ADRs and pSSPDRs after controlling for patient demographic, clinical, and colonoscopy-associated factors.EXPOSURES Seven characteristics of endoscopists performing colonoscopy. MAIN OUTCOMES AND MEASURESThe ADR and pSSPDR, with a hypothesis created after data collection began.RESULTS A total of 16 089 colonoscopies were performed in 16 089 patients by 56 clinicians. Of these, 8339 patients were male (51.8%), and the median (range) age of the cohort was 59 (52-66) years. Analyzing the data by the methods used in 4 previous studies yielded an association between endoscopist and polyp detection; surgeons (OR, 0.49 [95% CI, 0.28-0.83]) and nongastroenterologists (OR, 0.50 [95% CI 0.29-0.85]) had reduced odds of pSSPDR, which was similar to results in previous studies. In a multilevel mixed-effects logistic regression analysis, ADR was not significantly associated with any endoscopist characteristic, and pSSPDR was only associated with years in practice (odds ratio, 0.86 [95% CI, 0.83-0.89] per increment of 10 years; P < .001) and number of annual colonoscopies performed (odds ratio, 1.05 [95% CI, 1.01-1.09] per 50 colonoscopies/year; P = .02). CONCLUSIONS AND RELEVANCEThe differences in ADRs that were associated with 7 of 7 endoscopist characteristics and differences in pSSPDRs that were associated with 5 of 7 endoscopist characteristics in previous studies may have been associated with residual confounding, because they were not replicated in this analysis. Therefore, these characteristics should not influence the choice of endoscopist for colorectal cancer screening. However, clinicians further from their training and those with lower colonoscopy volumes have lower adjusted pSSPDRs and may need additional training to help increase pSSPDRs.
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.
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 TRANSICIóN 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)
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