RESUMEN
Background: Pancreatic cancer remains one of the most devastating malignancies due to the absence of techniques for early diagnosis and the lack of target therapeutic options for advanced disease. Next Generation Sequencing (NGS) generates high throughput and valuable genetic information when evaluating circulating tumor DNA (ctDNA); however clinical utility of liquid biopsy in pancreatic cancer has not been demonstrated yet. The aim of this study was to evaluate whether results from a Next Generation Sequencing panel on plasma samples from pancreatic cancer patients could have a clinical significance. Methods: From December 2016 to January 2020, plasma samples from 27 patients with pancreatic ductal adenocarcinoma at two different tertiary Spanish Hospitals underwent ctDNA testing using a commercial NGS panel of 65 genes. Clinical data were available for these patients. VarsSome Clinical software was used to analyse NGS data and establish pathogenicity. Results: Evaluable NGS results were obtained in 18 out of the 27 plasma samples. Somatic pathogenic mutations were found mainly in KRAS, BRCA2, FLT3 and HNF1A, genes. Pathogenic mutations were detected in 50% of plasma samples from patient diagnosed at stages III-IV samples. FLT3 mutations were observed in 22.22% of samples which constitute a novel result in the field. Conclusions: Liquid biopsy using NGS is a valuable tool but still not sensitive or specific enough to provide clinical utility in pancreatic cancer patients.(AU)
Introducción: El cáncer de páncreas es uno de los cánceres más devastadores debido a la falta de métodos que permitan un diagnóstico temprano y la ausencia de opciones terapéuticas en enfermedad avanzada. La técnica de secuenciación de nueva generación o Next Generation Sequencing (NGS) proporciona importantes resultados de alto rendimiento de información genética en muestras de DNA circulante tumoral (ctDNA); sin embargo, la utilidad clínica de la biopsia líquida en cáncer de páncreas no ha sido demostrado todavía. El objetivo de este estudio fue evaluar si los resultados de un panel de secuenciación de nueva generación en muestras de plasma de pacientes con cáncer de páncreas podría tener un significado clínico. Métodos: Empleando un panel comercial de NGS con 65 genes se evaluaron 27 muestras de plasma de pacientes con cáncer de páncreas recogidas entre diciembre del 2016 y enero del 2020 en 2 hospitales españoles. En el estudio se disponía de datos clínicos correspondientes a los pacientes. Se empleó el software VarSome Clinical para analizar resultados y establecer patogenicidad de las variantes. Resultados: Se obtuvieron resultados evaluables en 18 de las 27 muestras de plasma. Se encontraron mutaciones patogénicas en los genes KRAS, BRCA2, FLT3 y HNF1A. El 50% de los pacientes diagnosticados en estadios ii-iv presentaron alteraciones patogénicas en plasma. Se observaron mutaciones en FLT3 en el 22,22% de las muestras, lo cual es un resultado novedoso. Conclusiones: La NGS en biopsia líquida es una herramienta valiosa pero todavía no sensible ni específica para proporcionar utilidad clínica en pacientes con cáncer de páncreas.(AU)
Asunto(s)
Humanos , Neoplasias Pancreáticas , Biopsia Líquida , Mutación , Privacidad Genética , Virulencia , Gastroenterología , Enfermedades GastrointestinalesRESUMEN
BACKGROUND: Pancreatic cancer remains one of the most devastating malignancies due to the absence of techniques for early diagnosis and the lack of target therapeutic options for advanced disease. Next Generation Sequencing (NGS) generates high throughput and valuable genetic information when evaluating circulating tumor DNA (ctDNA); however clinical utility of liquid biopsy in pancreatic cancer has not been demonstrated yet. The aim of this study was to evaluate whether results from a Next Generation Sequencing panel on plasma samples from pancreatic cancer patients could have a clinical significance. METHODS: From December 2016 to January 2020, plasma samples from 27 patients with pancreatic ductal adenocarcinoma at two different tertiary Spanish Hospitals underwent ctDNA testing using a commercial NGS panel of 65 genes. Clinical data were available for these patients. VarsSome Clinical software was used to analyse NGS data and establish pathogenicity. RESULTS: Evaluable NGS results were obtained in 18 out of the 27 plasma samples. Somatic pathogenic mutations were found mainly in KRAS, BRCA2, FLT3 and HNF1A, genes. Pathogenic mutations were detected in 50% of plasma samples from patient diagnosed at stages III-IV samples. FLT3 mutations were observed in 22.22% of samples which constitute a novel result in the field. CONCLUSIONS: Liquid biopsy using NGS is a valuable tool but still not sensitive or specific enough to provide clinical utility in pancreatic cancer patients.
Asunto(s)
ADN Tumoral Circulante , Neoplasias Pancreáticas , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias PancreáticasRESUMEN
CA19-9 serum has been suggested as a marker of unresectability but different cut-off levels have been published. A cut-off of 500 U/ml is currently considered in an international consensus as biological criteria of borderline resectable pancreatic adenocarcinoma. To evaluate whether serum CA19-9 threshold of 500 U/ml could be adequate predictor of resectability in pancreatic adenocarcinoma. Multicenter, observational, prospective study performed in Spain including 203 patients diagnosed with pancreatic adenocarcinoma. 43 (21.2%) cases were resectable and 160 (78.8%) unresectable. Among the 176 preoperative CA19-9 available values, 98 (58.3%) were ≤ 500 U/ml and 73 (42.7%) > 500 U/ml. Resectability rate in those patients with CA19-9 ≤ 500 U/ml was 60% while it was found to be 18% when CA19-9 > 500 U/ml. Statistical model to predict resectability based on CA19-9 provide an AUC of 0.6618 (95% CI 0.53-0.83) when only CA19-9 values > 500 U/ml are studied. Serum levels of CA19-9 higher than 500 U/ml are indicative of unresectable disease, however reduced sensitivity and specificity lead to a limited clinical applicability for resectability.
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Adenocarcinoma/sangre , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Neoplasias Pancreáticas/sangre , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Prospectivos , Curva ROC , EspañaRESUMEN
We report a case of acute esophageal necrosis whose initial symptom was sudden dysphagia and was completely resolved in 72 hours.
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Enfermedades del Esófago/diagnóstico por imagen , Esófago/diagnóstico por imagen , Enfermedad Aguda , Anciano de 80 o más Años , Trastornos de Deglución , Enfermedades del Esófago/tratamiento farmacológico , Enfermedades del Esófago/patología , Esófago/patología , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Membrana Mucosa/patología , NecrosisRESUMEN
No disponible
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Humanos , Masculino , Anciano de 80 o más Años , Necrosis/complicaciones , Necrosis/patología , Necrosis , Esófago/patología , Esófago , Trastornos de Deglución/complicaciones , Trastornos de Deglución/etiología , Gastroscopía/métodos , Endoscopía/métodos , Patología/métodos , Factores de Riesgo , Enfermedades Cardiovasculares/complicacionesRESUMEN
INTRODUCCIÓN: La influencia de la experiencia acumulada del médico que interpreta cápsulas endoscópicas sobre su capacidad diagnóstica es discutida. OBJETIVO: Determinar si existen diferencias en el valor predictivo negativo de las cápsulas endoscópicas informadas por los mismos endoscopistas a lo largo del tiempo. MÉTODOS: Revisamos las 900 primeras cápsulas endoscópicas realizadas por tres gastroenterólogos expertos en endoscopia durante 8 años. Se dividieron en 3 grupos de 300 cápsulas cada uno. El grupo 1 fue la suma de las tres primeras centenas informadas por cada uno, el grupo 2 la suma de las tres segundas centenas y el grupo 3 la suma de las tres terceras centenas. Se hizo un seguimiento mínimo de 28 meses a los casos con exploración normal. RESULTADOS: Aunque se consideraron normales el 18% de las cápsulas del grupo 1, el 19,3% de las del grupo 2 y el 15,6% de las del grupo 3, solo fue posible seguir y finalmente analizar a 34 enfermos en el grupo 1, a 38 en el 2 y a 36 en el 3. Sobre estos casos, el valor predictivo negativo fue del 88,2% en el grupo 1, del 89,5% en el grupo 2 y del 97% en el grupo 3 (p > 0,05). CONCLUSIÓN: El valor predictivo negativo de la cápsula endoscópica, aunque con tendencia a aumentar, se mantiene alto y sin diferencias significativas desde las 100 primeras exploraciones si los médicos que la interpretan son expertos en endoscopia convencional y tienen formación específica previa
INTRODUCTION: The impact of the accumulated experience of the capsule endoscopy (CE) reader on the accuracy of this test is discussed. AIM: To determine whether the negative predictive value of CE findings changes along the learning curve. METHODS: We reviewed the first 900 CE read by 3 gastroenterologists experienced in endoscopy over 8 years. These 900 CE were divided into 3 groups (300 CE each): group 1 consisted of the sum of the first 100 CE read by each of the 3 endoscopists; group 2, the sum of the second 100 and groups 3, the sum of the third 100. Patients with normal CE were monitored for at least 28 months to estimate the negative predictive value. RESULTS: A total of 54 (18%) CE in group 1, 58 (19.3%) in group 2 and 47 (15.6%) in group 3 were normal, although only 34 patients in group 1, 38 in group 2 and 36 in group 3 with normal CE completed follow up and were eventually studied. The negative predictive value was 88.2% in group 1, 89.5% in group 2 and 97% in group 3 (P > .05). CONCLUSION: The negative predictive value tended to increase, but remained high and did not change significantly after the first 100 when readers are experienced in conventional endoscopy and have preliminary specific training
Asunto(s)
Humanos , Endoscopía Capsular/estadística & datos numéricos , Endoscopios en Cápsulas/estadística & datos numéricos , Enfermedades Intestinales/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Valor Predictivo de las Pruebas , Interpretación de Imagen Asistida por Computador/métodos , Curva de Aprendizaje , Endoscopía Capsular/educación , Intestino DelgadoRESUMEN
INTRODUCTION: The impact of the accumulated experience of the capsule endoscopy (CE) reader on the accuracy of this test is discussed. AIM: To determine whether the negative predictive value of CE findings changes along the learning curve. METHODS: We reviewed the first 900 CE read by 3 gastroenterologists experienced in endoscopy over 8 years. These 900 CE were divided into 3 groups (300 CE each): group 1 consisted of the sum of the first 100 CE read by each of the 3 endoscopists; group 2, the sum of the second 100 and groups 3, the sum of the third 100. Patients with normal CE were monitored for at least 28 months to estimate the negative predictive value. RESULTS: A total of 54 (18%) CE in group 1, 58 (19.3%) in group 2 and 47 (15.6%) in group 3 were normal, although only 34 patients in group 1, 38 in group 2 and 36 in group 3 with normal CE completed follow up and were eventually studied. The negative predictive value was 88.2% in group 1, 89.5% in group 2 and 97% in group 3 (P>.05). CONCLUSION: The negative predictive value tended to increase, but remained high and did not change significantly after the first 100 when readers are experienced in conventional endoscopy and have preliminary specific training.
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Endoscopía Capsular , Gastroenterología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Competencia Clínica , Femenino , Humanos , Curva de Aprendizaje , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) has been proposed as the hepatic manifestation of the metabolic syndrom (Ms), with insulin resistance (IR) as the common pathophysiological mechanism. METHODS: We included 145 patients with NAFLD proven liver biopsy. NAS-score was employed to grading NAFLD. We determined anthropometric measurements, basal blood pression (BP), biochemical measurements including high lipoprotein cholesterol (HDL-Chol), low-density lipoprotein cholesterol (LDL-Chol), triglycerides and leptin levels, homeostasis model assessment index (HOMA-IR), and abdominal ultrasound scan (US) was performed. Diagnosis of Ms was performed based on ATP III criteria. RESULTS: Average age was 43.6 + 11.2 years old and the mean body mass index (BMI) was 39 ± 10.7 kg/m2. Sex distribution was: females 66 and males 79. Forty patients (27.5%) presented a NAS score > = 5. Waist circumference (p = 0.007), systolic and diastolic BP (p = 0.002 and p = 0.003 respectively), (HOMA-IR) (p = 5. Independent factors associated to NAS-score > = 5 were Ms and BMI > 30. Leptin levels were higher in patients with advanced fibrosis (≥ F2) compared to patients with mild fibrosis (F0-F1) (75.5 + 50.2 ng/ml vs - 39.7 + 38.4 ng/ml respectively; p = 0.002). CONCLUSION: Presence of Ms and obesity (BMI >30) are the principal independent factors associated to NASH (NAS score > = 5). Leptin levels and BMI are higher in patients with advanced fibrosis.
La esteatohepatitis no alcoholica (EHNA) se ha propuesto como la manifestacion hepatica del sindrome metabolico (SM), con la resistencia a la insulina (IR) como mecanismo fisiopatologico comun. Métodos: se incluyeron 145 pacientes con biopsia hepatica con enfermedad por higado graso no alcoholica. NAS-score se utilizo para graduar la EHNA. Se realizaron las siguientes determinaciones; antropometria, presion arterial basal (BP), LDL colesterol, HDL colesterol, trigliceridos, leptina, resistencia a la insulina (HOMA- IR) y ecografia abdominal. El diagnostico de sindrome metabolico se realizo en base a los criterios del ATP III. Resultados: la edad fue 43,6 + 11,2 anos y la media de indice de masa corporal (IMC) 39 + 10.7 kg/ m2 (66 mujeres y 79 varones). Cuarenta pacientes (27,5%) presentaron una puntuacion NAS> = 5. La circunferencia de la cintura (p = 0,007), la presion arterial sistolica y diastolica (p = 0,002 y p = 0,003, respectivamente, la resistencia a la insulina (HOMA-IR) (p = 5. Los factores independientes asociados a NAS-score > = 5 fueron el SM y el IMC > 30. Los niveles de leptina fueron mayores en pacientes con fibrosis avanzada (≥ F2) en comparacion con los pacientes con fibrosis leve (F0-F1) (75,5 + 50,2 ng / ml frente a 39,7 + 38,4 ng / ml, respectivamente; p = 0.002). Conclusión: la presencia de SM y obesidad (IMC> 30) son los principales factores independientes asociados a la EHNA (puntuacion NAS> = 5). Los niveles de leptina y el IMC son mayores en los pacientes con fibrosis avanzada.
Asunto(s)
Síndrome Metabólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Adulto , Biopsia , Índice de Masa Corporal , Femenino , Humanos , Lípidos/sangre , Hígado/patología , Masculino , Síndrome Metabólico/diagnóstico por imagen , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/complicaciones , Valor Predictivo de las Pruebas , UltrasonografíaRESUMEN
Non-alcoholic fatty liver disease (NAFLD) has been proposed as the hepatic manifestation of the metabolic syndrom (Ms), with insulin resistance (IR) as the common pathophysiological mechanism. Methods: we included 145 patients with NAFLD proven liver biopsy. NAS-score was employed to grading NAFLD. We determined anthropometric measurements, basal blood pression (BP), biochemical measurements including high lipoprotein cholesterol (HDL-Chol), low-density lipoprotein cholesterol (LDL-Chol), triglycerides and leptin levels, homeostasis model assessment index (HOMAIR), and abdominal ultrasound scan (US) was performed. Diagnosis of Ms was performed based on ATP III criteria. Results: average age was 43.6 + 11.2 years old and the mean body mass index (BMI) was 39 ± 10.7 kg/m2 . Sex distribution was: females 66 and males 79. Forty patients (27.5%) presented a NAS score > = 5. Waist circumference (p = 0.007), systolic and diastolic BP (p = 0.002 and p = 0.003 respectively), (HOMA-IR) (p = 5. Independent factors associated to NAS-score > = 5 were Ms and BMI > 30. Leptin levels were higher in patients with advanced fibrosis (≥ F2) compared to patients with mild fibrosis (F0-F1) (75.5 + 50.2 ng/ml vs - 39.7 + 38.4 ng/ml respectively; p = 0.002). Conclusion: presence of Ms and obesity (BMI >30) are the principal independent factors associated to NASH (NAS score > = 5). Leptin levels and BMI are higher in patients with advanced fibrosis (AU)
La esteatohepatitis no alcohólica (EHNA) se ha propuesto como la manifestación hepática del síndrome metabólico (SM), con la resistencia a la insulina (IR) como mecanismo fisiopatológico común. Métodos: se incluyeron 145 pacientes con biopsia hepática con enfermedad por hígado graso no alcohólica. NAS-score se utilizó para graduar la EHNA. Se realizaron las siguientes determinaciones; antropometría, presión arterial basal (BP), LDL colesterol, HDL colesterol, triglicéridos, leptina, resistencia a la insulina (HOMA-IR) y ecografía abdominal. El diagnóstico de síndrome metabólico se realizó en base a los criterios del ATP III. Resultados: la edad fue 43,6 + 11,2 años y la media de índice de masa corporal (IMC) 39 + 10.7 kg/ m2 (66 mujeres y 79 varones). Cuarenta pacientes (27,5%) presentaron una puntuación NAS> = 5. La circunferencia de la cintura (p = 0,007), la presión arterial sistólica y diastólica (p = 0,002 y p = 0,003, respectivamente, la resistencia a la insulina (HOMA-IR) (p = 5. Los factores independientes asociados a NAS-score > = 5 fueron el SM y el IMC > 30. Los niveles de leptina fueron mayores en pacientes con fibrosis avanzada (≥ F2) en comparación con los pacientes con fibrosis leve (F0-F1) (75,5 + 50,2 ng / ml frente a 39,7 + 38,4 ng / ml, respectivamente; p = 0.002). Conclusión: la presencia de SM y obesidad (IMC> 30) son los principales factores independientes asociados a la EHNA (puntuación NAS> = 5). Los niveles de leptina y el IMC son mayores en los pacientes con fibrosis avanzada (AU)
