Recomendaciones preanalíticas para la obtención y análisis de ADN circulante a partir de sangre periférica. Recomendación (2018) / Preanalytical recomendations for circulating DNA extraction and analysis from peripheral blood. Recommendation (2018)

El análisis de ADN circulante a partir de sangre periférica ha demostrado ser de utilidad en campos clínicos tan diferentes como la oncología, los trasplantes y el cribado prenatal. Para su incorporación al laboratorio clínico es necesario asegurar protocolos preanalíticos adecuados, reproducibles y estandarizados. En este documento se pretenden dar unas recomendaciones preanalíticas para la obtención de ADN circulante a partir de sangre periférica. Incluyen el tipo de espécimen, el tipo de tubo de extracción, el modo de centrifugación de la muestra, la extracción del ADN circulante y cuantificación, así como su conservación

Cell-free DNA analysis in peripheral blood has been shown to be useful in oncology, organ transplantation, and prenatal screening. For its introduction into the clinical laboratory, it is necessary to ensure appropriate, reproducible and standardised pre-analytical protocols are in place. The aim of this document is to provide pre-analytical recommendations for obtaining of cell free DNA from peripheral blood. These recommendations include the type of sample and extraction tube, the method of centrifugation, the method for cell free DNA extraction, and measurement and storage conditions

Recomendaciones para la optimización del uso de marcadores tumorales de utilización frecuente. Recomendación (2018) / Recommendations for the optimization of the use of frequently used tumor markers. Recommendation 2018

Este documento describe las causas de error más frecuentes en la medición de marcadores tumorales séricos proteicos en sus diferentes fases: preanalítica, analítica y postanalítica y recomendaciones para detectar y solventar problemas, así como la interpretación de los resultados de los marcadores tumorales en la práctica clínica

This document describes the most frequent causes of error in the measurement of 13 serum protein tumour markers in their different phases: preanalytical, analytical and 14 postanalytic and recommendations to detect and solve problems, as well as the 15 interpretation of the results of the Tumor Markers in clinical practice

Utilización de procalcitonina y proteína C reactiva como marcadores de infección en la neutropenia febril de pacientes sometidos a trasplante de progenitores hematopoyéticos / Use of procalcitonin and C-reactive protein as infection markers in febrile neutropenic patients undergoing haematopoietic stem cell transplant

INTRODUCCIÓN Y OBJETIVO: La neutropenia es un signo frecuente en los pacientes que van a ser sometidos a trasplante de progenitores hematopoyéticos (TPH). Una complicación importante es la infección favorecida por la inmunodepresión y el grado de neutropenia. El objetivo del estudio es evaluar la utilidad diagnóstica de la procalcitonina (PCT) y de la proteína C reactiva (PCR) en pacientes onco-hematológicos sometidos a quimioterapia y TPH para discriminar la etiología de la fiebre. PACIENTES Y MÉTODOS: Se midieron los valores de PCT y PCR en 30 episodios de neutropenia febril antes del inicio de la quimioterapia, el día de la neutropenia, el día del inicio de la fiebre y los días 1, 2, 3 y 6 postinicio de la fiebre y al fin del episodio. Los episodios fueron clasificados como 5 bacteriemias, 3 infecciones documentadas microbiológicamente, 10 infecciones clínicas y 12 fiebres de origen desconocido. RESULTADOS: Los valores medios de PCT más elevados correspondieron al grupo de pacientes con bacteriemia. Hubo diferencias estadísticamente significativas (p = 0,04) el segundo día tras el inicio de la fiebre. El punto de corte de 0,5 ng/ml mostró una sensibilidad del 66% y una especificidad del 75%. La PCR mostró diferencias estadísticamente significativas los días 1, 2 y 3 postinicio de la fiebre (p = 0,01; p = 0,003 y p = 0,002). El punto de corte de 7,5 mg/dl mostró una sensibilidad del 88% y una especificidad del 58%. CONCLUSIONES: La combinación de PCT y PCR es un método insuficiente para la detección de infección bacteriana y no puede sustituir el correcto diagnóstico clínico y microbiológico

INTRODUCTION AND OBJECTIVE: Neutropenia is a frequent sign in patients who are going to have a haematopoietic stem cell transplant (HSCT).Infection is an important complication in these patients, which is favoured by immunosuppression and the degree of neutropenia. This study aims to evaluate the diagnostic usefulness of procalcitonin (PCT) and C-reactive protein (CRP) in onco-haematological patients undergoing chemotherapy and HSCT to determine the origin of the fever. PATIENTS AND METHODS:PCT and CRP values were measured in 30 episodes of febrile neutropenia: before starting chemotherapy, appearance of neutropenia, onset of fever, days 1, 2, 3 and 6 after the onset of fever, and when the febrile episode ended. The episodes were classified as 5 bacteraemia, 3 microbiologically documented infections, 10 clinical infections, and 12 fevers of unknown origin. RESULTS: The highest PCT mean values corresponded to the group of patients with bacteraemia. Statistically significant differences (P=.04) were found on the second day after the onset of fever. The cut-off point of 0.5ng/ml showed a sensitivity of 66% and a specificity of 75%. PCR results showed statistically significant differences on days 1, 2 and 3 after the onset of fever (P=.01, P=.003, and P=.002, respectively). The cut-off point of 7.5mg/L had a sensitivity of 88% and a specificity of 58%.CONCLUSIONS:The combination of PCT and CRP is an insufficient method to detect bacterial infections and may not replace the proper clinical and microbiological diagnosis (AU)

HE4, Ca125 and ROMA algorithm for differential diagnosis between benign gynaecological diseases and ovarian cancer.

The aim of this study is to evaluate the diagnostic performance of human epididymis protein 4 (HE4), cancer antigen 125 (Ca125) and the risk of ovarian malignancy algorithm (ROMA) in discriminating ovarian cancer from other benign gynaecological diseases. Serum levels of HE4 and Ca125 were measured in 119 women with benign gynaecological diseases, 29 patients with primary ovarian cancer, 32 patients with ovarian cancer on chemotherapy treatment (18 of them with progressive disease), 6 patients treated and free of disease and 32 healthy women. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios (LR ±) were calculated. Receiver operator characteristic (ROC) curves were constructed, and the areas under the curve (AUC) were calculated. High serum levels for HE4, Ca125 and ROMA were observed in cancer patients. HE4 was elevated in 12.6 %, Ca125 in 21 % and ROMA in 9.2 % in the benign group, but HE4 was not elevated in endometriosis. The AUC values for HE4, Ca125 and ROMA were 0.92, 0.911 and 0.945 respectively. The sensitivity for discriminating ovarian cancer from benign gynaecological diseases was 86.2 % for HE4 and Ca125 and 93.1 % for ROMA. The specificity was 87.4, 78.9 and 90.7 % for HE4, Ca125 and ROMA. The overall positive likelihood ratio (LR+) was 6.84 for HE4, 4.1 for Ca125 and 10.01 for ROMA. In premenopausal women, LR + was 11.86 for HE4, 5.11 for ROMA and 2.02 for Ca125. HE4 might be significant in the differential diagnosis of ovarian cancer. HE4 seems to be superior to Ca125 in terms of diagnostic performance of all premenopausal women. ROMA could help to discriminate in cases with any doubt with a high diagnostic accuracy.

[Use of procalcitonin and C-reactive protein as infection markers in febrile neutropenic patients undergoing haematopoietic stem cell transplant]. / Utilización de procalcitonina y proteína C reactiva como marcadores de infección en la neutropenia febril de pacientes sometidos a trasplante de progenitores hematopoyéticos.

INTRODUCTION AND OBJECTIVE: Neutropenia is a frequent sign in patients who are going to have a haematopoietic stem cell transplant (HSCT). Infection is an important complication in these patients, which is favoured by immunosuppression and the degree of neutropenia. This study aims to evaluate the diagnostic usefulness of procalcitonin (PCT) and C-reactive protein (CRP) in onco-haematological patients undergoing chemotherapy and HSCT to determine the origin of the fever. PATIENTS AND METHODS: PCT and CRP values were measured in 30 episodes of febrile neutropenia: before starting chemotherapy, appearance of neutropenia, onset of fever, days 1, 2, 3 and 6 after the onset of fever, and when the febrile episode ended. The episodes were classified as 5 bacteraemia, 3 microbiologically documented infections, 10 clinical infections, and 12 fevers of unknown origin. RESULTS: The highest PCT mean values corresponded to the group of patients with bacteraemia. Statistically significant differences (P=.04) were found on the second day after the onset of fever. The cut-off point of 0.5ng/ml showed a sensitivity of 66% and a specificity of 75%. PCR results showed statistically significant differences on days 1, 2 and 3 after the onset of fever (P=.01, P=.003, and P=.002, respectively). The cut-off point of 7.5mg/L had a sensitivity of 88% and a specificity of 58%. CONCLUSIONS: The combination of PCT and CRP is an insufficient method to detect bacterial infections and may not replace the proper clinical and microbiological diagnosis.

Valor diagnóstico de la procalcitonina, la interleucina 8, la interleucina 6 y la proteína C reactiva en la detección de bacteriemia y fungemia en pacientes con cáncer / Diagnostic value of procalcitonin, interleukin 8, interleukin 6, and c-reactive protein for detecting bacteremia and fungemia in cancer patients

Introducción y objetivo La bacteriemia es una de las causas más importantes de morbimortalidad en los pacientes con cáncer. El objetivo del presente estudio es evaluar la utilidad diagnóstica de la procalcitonina (PCT), la interleucina 8 (IL-8), la interleucina 6 (IL-6) y la proteína C reactiva (PCR) en la detección de bacteriemia en pacientes con cáncer. Pacientes y métodos Se midieron los valores de PCT, IL-8, IL-6 y PCR en 2 grupos de pacientes con cáncer que presentaron fiebre: el grupo con bacteriemia verdadera y el grupo sin bacteriemia. Resultados Se estudiaron 79 síndromes febriles en 79 pacientes, 43 hombres y 36 mujeres. Cuarenta y cuatro pacientes pertenecían al grupo de bacteriemia verdadera. Se encontraron diferencias significativas al comparar los valores de PCT, IL-8 e IL-6 (p<0,001, p<0,001, p=0,002, respectivamente) entre los pacientes con bacteriemia verdadera y sin bacteriemia. Los resultados de la PCR no mostraron diferencias significativas entre los 2 grupos estudiados (p=0,23). El punto de corte para la PCT fue de 0,5ng/ml y mostró la mejor especificidad (91,4%), con una sensibilidad del 59,1%.ConclusionesEl marcador de infección que puede aportar más información en el diagnóstico de bacteriemia en pacientes con cáncer es la PCT (AU)

Background and Objective Bacteremia is one of the most important causes of morbidity and mortality in cancer patients. The aim of this study was to evaluate the diagnostic usefulness of procalcitonin (PCT), interleukin 8 (IL-8), interleukin 6 (IL-6), and C-reactive protein (CRP) in the detection of bacteremia in cancer patients. Patients and methods PCT, IL-8, IL-6, and CPR levels were measured in 2 groups of cancer patients who had fever: one group with true bacteremia and another without bacteremia. Results Seventy-nine febrile episodes were analyzed in 79 patients, 43 men and 36 women. Forty-four patients were in the true bacteremia group. Significant differences in PCT (P<0.001), IL-8 (P<0.001), and IL-6 (P=0.002) values were found between patients with and without true bacteremia. CPR results were not significantly different between the groups (P=0.23). The cut-off point for PCT was 0.5ng/mL and this parameter yielded the best specificity at 91.4%, with a sensitivity of 59.1%.ConclusionsAmong the infection markers studied, PCT provided the most information for diagnosing bacteremia in cancer patients (AU)

[Diagnostic value of procalcitonin, interleukin 8, interleukin 6, and C-reactive protein for detecting bacteremia and fungemia in cancer patients]. / Valor diagnóstico de la procalcitonina, la interleucina 8, la interleucina 6 y la proteína C reactiva en la detección de bacteriemia y fungemia en pacientes con cáncer.

BACKGROUND AND OBJECTIVE: Bacteremia is one of the most important causes of morbidity and mortality in cancer patients. The aim of this study was to evaluate the diagnostic usefulness of procalcitonin (PCT), interleukin 8 (IL-8), interleukin 6 (IL-6), and C-reactive protein (CRP) in the detection of bacteremia in cancer patients. PATIENTS AND METHODS: PCT, IL-8, IL-6, and CPR levels were measured in 2 groups of cancer patients who had fever: one group with true bacteremia and another without bacteremia. RESULTS: Seventy-nine febrile episodes were analyzed in 79 patients, 43 men and 36 women. Forty-four patients were in the true bacteremia group. Significant differences in PCT (P<0.001), IL-8 (P<0.001), and IL-6 (P=0.002) values were found between patients with and without true bacteremia. CPR results were not significantly different between the groups (P=0.23). The cut-off point for PCT was 0.5 ng/mL and this parameter yielded the best specificity at 91.4%, with a sensitivity of 59.1%. CONCLUSIONS: Among the infection markers studied, PCT provided the most information for diagnosing bacteremia in cancer patients.

La proteína S-100 como marcador tumoral en pacientes con melanoma cutáneo / S-100 protein as a tumoral marker in cutaneous melanoma patients

La proteína S100 se ha utilizado como marcador tumoral en pacientes diagnosticados de melanoma en los últimos años. Los objetivos de este estudio han sido analizar el significado de la proteína S100 en el momento del diagnóstico y evaluar su uso durante el seguimiento posterior de los pacientes. Se incluyeron 156 pacientes diagnosticados de melanoma, 58 pacientes en estadio I, 62 en estadio II, 22 en estadio III, nueve en estadio IV y en cinco pacientes en estadio I/II (18 no tratados y 138 tratados previamente). Los niveles séricos se determinaron con un ensayo inmunorradiométrico. El valor de corte fue de 0,2 µg/l. En los 18 pacientes no tratados la determinación media sérica de S100 antes del tratamiento fue de 0,235 µg/l. Estos valores fueron significativamente mayores en los pacientes con melanoma nodular y los valores medios de los estadios III y IV fueron mayores que los estadios I y II. De los 79 pacientes con dos o más determinaciones durante el seguimiento clínico se ha obtenido una sensibilidad de la proteína S100 para la detección de la progresión de la enfermedad o de la recidiva del 83,3% y una especificidad del 89,5%. Concluimos que la S100 no es eficaz para diagnosticar melanomas en estadios precoces, pero que es útil como marcador tumoral en los casos de enfermedad metastásica y en la monitorización de las respuestas a los tratamientos, y podría ser útil durante el seguimiento de los pacientes para ampliar estudios complementarios en el caso de que se positivizara (AU)