Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is recognized increasingly as a multisystem disorder. We evaluated the use of immunoglobulin (Ig)G4 immunostaining of pancreatic and extrapancreatic biopsy specimens to make a definitive diagnosis of AIP. METHODS: Seventeen biopsy specimens and 3 gallbladder resections were assessed from 11 patients with clinical and radiologic features of AIP. Biopsy specimens from pancreas, liver, colon, stomach, duodenum, bone marrow, salivary gland, and kidney were analyzed morphologically, immunostained for IgG4-positive plasma cells, and compared with controls. RESULTS: Positive IgG4 immunostaining enabled a definitive diagnosis in 10 of 11 (91%) AIP patients. In both pancreatic and extrapancreatic tissues, high levels of IgG4 immunostaining (>10 IgG4-positive plasma cells/high-power field) were found in 17 of 20 (85%) specimens from AIP patients compared with 1 of 175 (0.6%) specimens from controls (P < .05). Positive extrapancreatic IgG4 immunostaining was found in 8 of 11 (73%) patients, including all those with diagnostic features in the pancreas. Increased tissue IgG4 was found irrespective of serum IgG4 level. CONCLUSIONS: The finding of IgG4 immunostaining within a range of clinically involved tissues supports the hypothesis that AIP is a multisystem disease. Positive IgG4 immunostaining in extrapancreatic tissues may allow a definitive diagnosis of AIP to be made in those with evidence of pancreatic disease, without the necessity of pancreatic biopsy or surgical exploration. Immunostaining of involved tissue for IgG4 may be particularly useful when AIP is suspected clinically but the serum IgG4 level is normal.

Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series.

OBJECTIVE: Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression. METHODS: Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted. RESULTS: Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 mumol/L to 11 mumol/L (P= 0.001), and ALT from 97 IU/L to 39 IU/L (P= 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well. CONCLUSIONS: Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.