Antonio Soriano-Izquierdo

Novel Methylation Panel for the Early Detection of Colorectal Tumors in Stool DNA

BACKGROUND Previous studies showed that the assessment of promoter hypermethylation of a limited number of genes in tumor biopsies may identify the majority of colorectal tumors. This study aimed to assess the clinical usefulness of a panel of methylation biomarkers in stool DNA in the identification of colorectal tumors, using methylation-specific melting curve analysis (MS-MCA), a technique that simultaneously analyzes all cytosine-phosphate-guanine (CpG) residues within a promoter. MATERIALS AND METHODS The promoter methylation status of 4 tumor-related genes (RARB2, p16INK4a, MGMT, and APC) was analyzed in DNA stool samples and corresponding tissues in an initial set of 12 patients with newly diagnosed primary colorectal carcinomas and 20 patients with newly diagnosed colorectal adenomas, using methylation-specific polymerase chain reaction. Results were replicated in a set of 82 patients (20 healthy subjects, 16 patients with inflammatory bowel disease (IBD), 20 patients with adenomas, and 26 patients with carcinomas), using MS-MCA analyses. RESULTS In the initial set, >or= 1 positive methylation marker was detected in the stools of 9 of 12 patients (75%) with carcinomas and 12 of 20 patients (60%) with adenomas, with no false-positive results. Stool analyses missed 7 methylated lesions (25%). In the replication set, stool DNA testing detected 16 of 26 carcinomas (62%) and 8 of 20 adenomas (40%). The MS-MCAs missed 14 methylated tumors (37%). No aberrant methylation was evident in healthy subjects, but the RARB2 marker was positive in 2 of 15 stool samples (13%) of patients with IBD. CONCLUSION Analysis via MS-MCA of a panel of methylation markers in stool DNA may offer a good alternative in the early, noninvasive detection of colorectal tumors.

Estado actual del tratamiento de la enfermedad inflamatoria intestinal

Resumen La enfermedad inflamatoria intestinal engloba un grupo de enfermedades del tracto digestivo de etiologia todavia no bien conocida, que se caracterizan por su curso cronico y por la alternancia de periodos de actividad, de gravedad variable, con periodos de remision clinica. Durante los ultimos anos, la enfermedad inflamatoria intestinal ha sido objeto de una intensa investigacion, circunstancia que ha promovido un mejor conocimiento de sus mecanismos fisiopatogenicos. Este hecho ha permitido el desarrollo de una nueva generacion de farmacos biotecnologicos capaces de controlar a pacientes considerados previamente refractarios al tratamiento medico, reducir la dosis acumulada de corticoides, y disminuir las indicaciones de cirugia y los ingresos hospitalarios, con un incremento de la calidad de vida. Por otro lado, se ha demostrado la eficacia de determinados farmacos clasicos en la prevencion de la recurrencia tras la cirugia de la enfermedad de Crohn, asi como su utilidad en la prevencion de la displasia y el cancer colorrectal en los pacientes con enfermedad inflamatoria intestinal.

T2025 Comparative Study of Guaiac and Quantitative Immunochemical Fecal Occult Blood Test for Colorectal Neoplasia. Preliminary Results

Introduction: The low sensitivity of the fecal occult blood tests (FOBT) based on the guaiac have made to develop new immunochemical tests with an efficiency to detect advanced neoplasia (advanced adenoma and colorectal cancer) still not well established. Aim: Determine the sensitivity and specificity of a FOBT based on the guaiac (FOBTg) with a quantitative immunochemical FOBT (FOBTi) to detect advanced neoplasia. Material and methods: Patients: all individuals with a colonoscopy programmed by any cause (screening, surveillance or symptoms) were included. Individuals with personal history of inflammatory bowel diseases or colorectal cancer were excluded. During the days previous to the exploration three high sensitivity FOBTg and two FOBTi (positive test ≥100ng/ml) were completed. The sample was calculated for demonstrating the superiority of the FOBTi of 15% of sensitivity with a final sample of 700 individuals. Results We presented the results of the first 140 individuals. The colonoscopy was performed for symptoms in 66% of cases and for screening or surveillance in 34% of cases. The colonoscopy detected 16 individuals (11%) with an advanced neoplasia (2 infiltrant carcinoma and 14 advanced adenomes). Other finds were: 20 patients with non advanced adenomes, 11 with polyps not adenomatous and 4 inflammatory colitis. The colonoscopy was normal in 88 (63%) individuals. The percentage of positive test was from 3,5% (5/140) and 16,5% (23/140) for the FOBTg and FOBTi, respectively. The sensitivity, specificity, positive predictive value and negative predictive value to detect an advanced neoplasia were 12%, 97%, 40% and 89% with the FOBTg and of 62,5%, 89%, 60,8%, 81% for the FOBTi. If considered only the first immunochemical test, the sensitivity, specificity, positive predictive value and negative predictive value were 43,7%, 92,7%, 43,7%, 92,7%, respectively. Conclusion The FOBTi is very superior to the FOBTg to detect advanced neoplasia although the high number of false positives could limit its use. The utilization of one or two FOBTi should be appraised depending on the disposable endoscopic resources.