Clinical utility of one versus two faecal immunochemical test samples in the detection of advanced colorectal neoplasia in symptomatic patients.

BACKGROUND: The utility of faecal immunochemical tests (FIT) in assessment of symptomatic patients with lower gastrointestinal symptoms has not been well explored. The aims of this study were to evaluate the diagnostic yield for advanced colorectal neoplasia (ACRN) in symptomatic patients using the first of two FIT samples (FIT/1) and the higher concentration of two FIT samples (FIT/max). METHODS: Samples from two consecutive bowel motions from 208 symptomatic patients who required colonoscopy were analysed using the HM-JACKarc analyser (Kyowa Medex Co., Ltd., Tokyo, Japan). Patients were categorised into two groups: patients with any ACRN and individuals with other diagnoses or normal colonoscopy. RESULTS: Colonoscopy detected ACRN in 29 patients. In these patients, FIT/1 and FIT/max were significantly higher than in patients with low-risk adenoma (p=0.006 and p=0.024), other findings (p=0.002 and p=0.002) and normal colonoscopy (p<0.001 and p<0.001). The areas under the curves (AUC) of FIT/1 and FIT/max were 0.71 and 0.69, respectively. Undetectable FIT/1 rules out 96.6% of ACRN and the specificity was 10.6%. Increasing the FIT/1 cut-off to 10 µg Hb/g faeces, sensitivity and specificity were 34.5% and 87.2%, respectively. Similar results were obtained using FIT/max with 20 µg Hb/g faeces cut-off, providing a sensitivity and specificity of 34.5% and 85.6%, respectively. CONCLUSIONS: Undetectable FIT is a good strategy to rule-out ACRN in symptomatic patients. The diagnostic yield of collecting two samples for FIT can be achieved with one sample, but a lower faecal haemoglobin concentrations (f-Hb) cut-off is required.

Aplicación de la secuenciación masiva de nueva generación al diagnóstico molecular de la hipercolesterolemia familiar / Applicability of next generation sequencing to the molecular diagnosis of familial hypercholesterolemia

Introducción: La hipercolesterolemia familiar es una enfermedad autosómica dominante que cursa con niveles plasmáticos elevados de colesterol unido a lipoproteínas de baja densidad. La presencia de esta alteración en el metabolismo lipídico se asocia a un aumento del riesgo cardiovascular en los pacientes que la padecen, siendo de gran importancia la realización de un diagnóstico genético para ofrecer un tratamiento adecuado y disminuir la morbimortalidad. El objetivo de este trabajo es describir la aplicación de la secuenciación de nueva generación al diagnóstico genético de la hipercolesterolemia familiar, en comparación con la secuenciación Sanger, la técnica convencional usada hasta el momento. Material y métodos: Se analizaron 110 muestras de sangre venosa periférica procedente de pacientes que presentaban cuadro clínico de hipercolesterolemia familiar mediante secuenciación de nueva generación, utilizando un panel comercial que permite la identificación de mutaciones en los genes LDLR, APOB, PCSK9 yLDLRAP1 (SEQPRO Lipo, Progenika) con la tecnología GS JUNIOR 454 (Roche). Resultados: Aplicando esta tecnología fue posible secuenciar los genes asociados a la hipercolesterolemia familiar descritos hasta el momento en grupos de hasta 20 pacientes simultáneamente. Se detectaron un total de 35 mutaciones en las 110 muestras analizadas, localizándose el 94,29% en el gen LDLR. Todas las mutaciones identificadas fueron confirmadas mediante el método de secuenciación Sanger. Conclusiones: La utilización de la secuenciación masiva de nueva generación permite la realización de un diagnóstico genético más rápido y un análisis molecular más eficiente de los genes implicados en la hipercolesterolemia familiar con una fiabilidad similar a la técnica convencional Sanger (AU)

Introduction: Familial hypercholesterolemia is an autosomal dominant disorder that causes increased levels of cholesterol associated with low density lipoproteins in plasma. The presence of altered lipid metabolism in these patients increases their level of risk of suffering from a cardiovascular disease. The certainty of having this genetic disorder by making a timely and precise molecular diagnostic is crucial for the appropriate treatment and the reduction of the disease morbidity-mortality. The aim of this work is to describe the applicability of next generation sequencing technology to the genetic diagnosis of familial hypercholesterolemia and compare this novel method with the conventional Sanger sequencing method. Material and methods: A next generation sequencing commercial panel (SEQPRO Lipo, Progenika) was used to analyze 110 peripheral venous blood samples from patients with familial hypercholesterolemia. This enables the assessment of mutations in genes associated with the disease (e.g. LDLR, APOB, PCSK9 and LDLRAP1)with the GS JUNIOR 454 technology (Roche). Results: Application of next generation sequencing enables the sequencing of the genes involved in the familial hypercholesterolemias, described so far, in groups of 20 patients simultaneously. Using this novel technology, a total of 35 mutations were detected in the 110 analysed samples, with 94.29% being located in the LDLR gene. Mutations were confirmed by Sanger sequencing. Conclusion: Next generation sequencing enables a quick genetic diagnosis and a more efficient molecular analysis of all genes described so far to be involved in familial hypercholesterolemia, with similar reliability to that of conventional Sanger sequencing (AU)