Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Molecular and clinical diversity in primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Recomendaciones de tromboprofilaxis en Cirugía Mayor Ambulatoria. Documento multidisciplinar de consenso de la Asociación Española de Cirugía Mayor Ambulatoria (ASECMA) / Recommendations for thromboprophylaxis in major ambulatory surgery. Multidisciplinary consensus document of the Spanish Association for Major Ambulatory Surgery (ASECMA)

La cirugía ambulatoria presenta un incremento constante, tanto en los procedimientos que se llevan a cabo como en las unidades capacitadas para su realización. Uno de los aspectos esenciales en su desarrollo es la mejoría permanente de los cuidados prequirúrgicos que reciben los pacientes. Entre ellos, ocupa un lugar destacado la profilaxis antitrombótica y, si bien la incidencia global de la enfermedad tromboembólica venosa en este grupo de pacientes no es muy elevada, se recomienda valorar en todos los pacientes los factores de riesgo trombótico personales y los relacionados con el procedimiento quirúrgico. Según esta valoración, los pacientes se podrán estratificar en bajo o moderado/alto riesgo trombótico, recomendándose aplicar las medidas de tromboprofilaxis adecuadas en cada caso: medidas generales solas o en combinación con tromboprofilaxis farmacológica y/o mecánica. En el presente documento multidisciplinar de consenso, actualización de las recomendaciones de la Asociación Española de Cirugía Mayor Ambulatoria (ASECMA) publicadas en 2011, se establecen las recomendaciones y sugerencias específicas para cada uo de los grupos de riesgo, aplicando los niveles de evidencia hallados en la literatura (AU)

In the past decade, ambulatory surgery has experienced a continuous increase, both in the types of procedures that are performed, as in the number of units qualified for outpatient surgery. One of the essential aspects in this development is the permanent improvement in the perioperative care that patients receive. In this regard, antithrombotic prophylaxis is of outstanding importance. Although the overall incidence of venous thromboembolism in these patients is not very high, the assessment of thrombosis risk factors, both personal and procedure related, is recommended. According to this risk assessment, patients may be stratified into low, moderate or high thrombotic risk categories. Therefore, thromboprophylaxis should be tailored to that risk: general measures alone, or combined with mechanical or pharmacological thromboprophylaxis. This multidisciplinary consensus document the recommendations of the Spanish Association of Major Ambulatory Surgery (ASECMA) published in 2011, and sets out evidence-based recommendations and specific suggestions for the each risk group (AU)

Venous leg ulcer in the context of chronic venous disease.

OBJECTIVES: Chronic venous disease (CVD) is a frequent disorder with a high socioeconomic impact. Little is known about the possible differences between healed ulcer (C5 group) and active ulcer (C6 group) in terms of disease severity and quality of life (QoL). Our aim was to determine the possible differences in severity disease and QoL between the C5-C6 and C1 (control) group. METHODS: Data from a national, multicentre, observational and cross-sectional study (n = 1598) were used to compare three groups of CVD: C1 (n = 243), C5 (n = 136) and C6 (n = 70). CVD severity was assessed with the Venous Clinical Severity Score (VCSS) and QoL with the Short Form 12 Health Survey (SF-12) and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). RESULTS: Patients with active ulcers had a higher mean total VCSS than patients with healed ulcers (P < 0.05). Both SF-12 and CIVIQ-20 QoL questionnaires indicated a poorer QoL in patients with ulcers than in those with C1 (P < 0.05). Compared with the C5 group, patients with active ulcers (C6) had lower QoL scores, but the differences were not statistically significant. CONCLUSIONS: Patients with venous leg ulcers (C5-C6) are associated with high severity and poor QoL. However, the healing of a leg ulcer did not contribute to improvement of QoL.

Perfil de los pacientes con claudicación intermitente en España. Estudio VITAL / Profile of patients with intermittent claudication in Spain. The VITAL Study

Introducción: La claudicación intermitente ( CI ) es frecuente entre la población occidental, incluida la española; sin embargo, sus características no son bien conocidas. El objetivo del estudio es conocer el perfil de los pacientes españoles con CI. Material y métodos: Estudio prospectivo, observacional, transversal, multicéntrico y no aleatorizado sobre 1.641 claudicantes, divididos en 2 grupos: a) angiología y cirugía vascular (ACV) (n = 920), y b) atención primaria (MAP) (n = 721). Los pacientes fueron sometidos a un cuaderno de recogida de datos (CRD), analítica, índice tobillo/brazo (ITB), cuestionario Walking Impairment Questionaire (WIQ) y cuestionario europeo de calidad de vida (EQ-5D). Resultados: Fueron varones el 75,3%, de 68,3 ± 9,4 años, destacando sobremanera el elevado número de factores de riesgo cardiovascular y enfermedades asociadas (fundamentalmente cardiacas), más frecuente en el grupo ACV. El ITB de la serie 0,66 ± 0,19, inferior en grupo ACV (p = 0,001). Los porcentajes WIQ fueron: daños motores (48,57 ± 20,12), distancia (35,09 ± 25,73), velocidad (36,18 ± 22,83) y escaleras (41,76 ± 27,62), peores en lo relativo a los daños motores (p < 0,001) y distancia (p = 0,007) en el grupo ACV. La puntuación EQ-5D fue 0,57 ± 0,21, sin diferencias entre grupos. Conclusiones: Los pacientes españoles con CI presentan 3 características: alto riesgo cardiovascular, limitada capacidad para el ejercicio e importante reducción de la calidad de vida. Existen diferencias entre grupos, dado que los ACV tratan pacientes con enfermedad más avanzada (AU)

Introduction: Intermittent claudication (IC) is a very prevalent condition in Western countries including the population of Spain. However, little is known about the medical profile and quality of life (QoL) of the IC in Spain. Aim: To determine the clinical characteristics and QoL in a large sample of Spanish patients with IC. Material and methods: An observational, prospective, cross sectional and multicentre study was performed between October 2010 and January 2011, with 625 investigators recruiting 1,641 consecutive patients with claudication. The sample was divided into two groups: a) patients evaluated by vascular surgeons (VS) (n = 920), and b) patients evaluated by general practitioners (GP) (n = 721). Demographical and clinical characteristics, analytical findings (glucose levels and lipid metabolism) and the Ankle-Brachial Index (ABI) were recorded. Each patient included in the study also filled in two questionnaires: the Walking impairment Questionnaire (WIQ) and the European Quality of Life-5 Dimensions (EQ-5D). Results: The population mean age was 68.3 ± 9.4 years; in 75.3% of the cases the patients were males. The presence of risk cardiovascular factors (49.5% of diabetes; 76.9% of hypertension and 65.3% of dyslipemia) and comorbid conditions (in particular, cardiovascular diseases) were high. The mean ABI of the series was 0.66 ± 0.19. Patients in the VS group had more severe IC than patients from GP Group (ABI = 0.63 vs ABI = 0.71, P<0.001). WIQ scores obtained were: a) walking distance = 35.09 ± 25.73; b) walking speed = 36.18 ± 22.83, and c) stair-climbing capacity = 41.76 ± 27.62. We only found significant statistical differences in walking distance between the VS Group and GP Group. The global EQ-5D score was 0,57 ± 0,21. No significant differences were observed between the VS and GP groups (AU)

Conclusions: Spanish patients with IC showed three characteristics: high cardiovascular risk, limited ability to tolerate exercise, and reduction in the quality of their life. There are differences between groups; compared to general practitioners, vascular surgeons treated patients with more advanced disease (AU)

Quality of life in patients with chronic venous disease: influence of the socio-demographical and clinical factors.

AIM: Chronic venous disease (CVD) is a well-defined and known disorder which impact on related-health quality of life (QoL). However, individuals factors which determinate quality of life on CVD are not well defined. The purposes of this study were to describe the QoL in patients with CVD and examine socio-demographical and clinical factors which influence QoL METHODS: One thousand five hundred sixty patients with CVD were evaluated. We calculated for each patient two disease-specific severity scores: The "C" grade (clinical) of the CEAP classification and the Venous Clinical Severity Score (VCSS). Additionally, two QoL questionnaires were recorded: Short-Form Health Survey (SF-12) and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). Two multivariate logistic regression analyses (SF-12 and CIVIQ-20 model) were conducted to determine whether demographic and clinical variables were independently associated with QoL. RESULTS: Both QoL questionnaires indicated that the QoL decreased significantly (P<0.05) as the C grade of CEAP increased. Each increase of 0.10 in VCSS score represented 2% worsening in QoL as measured by CIVIQ-20. Three factors were strongly associated with poor QoL on SF-12: increasing age, prior superficial venous thrombosis (SVT) or prior deep venous thrombosis. In the specific disease CIVIQ-20 questionnaire three factors (higher age, prior SVT and higher weight) were strongly associated with decrease QoL. CONCLUSION: Increasing disease severity by VCSS is associated with reductions in QoL. Subgroup analysis indicates that there are several significant individual determinants of worsening QoL.

Premio a la Excelencia para la Sociedad Española de Angiología y Cirugía Vascular / Excellence award for Sociedad Española de Angiología y Cirugía Vascular

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Determinantes de la gravedad en la insuficiencia venosa crónica. Estudio C-VIVES / Determining factors of the severity of chronic venous insufficiency. C-VIVES study

Introducción: La evaluación de la insuficiencia venosa crónica (IVC) puede medirse mediante escalas de gravedad venosa. Sin embargo, los factores individuales que la condicionan no están bien descritos. El objetivo del estudio es conocer las características sociodemográficas y clínicas de una muestra de pacientes portadores de IVC para permitir la búsqueda de los factores que incrementan la gravedad de la misma. Material y método: Estudio promovido por la Sociedad Española de Angiología y Cirugía Vascular en colaboración con otras sociedades científicas españolas sobre 1.560 pacientes con IVC y a los que se han aplicado 2 instrumentos: clasificación clínica CEAP y Venous Clinical Severity Score (VCSS). Resultados: La distribución de pacientes por estadios clínicos fue: C0, 3,3%; C1, 15,6%; C2, 21,0%, C3, 22,9%; C4, 23,6%; C5, 8,7%; C6, 4,5%. La puntuación VCSS para toda la cohorte fue de 0,89 ± 0,53, siendo superior a la media en 4 de los 10 atributos medidos: dolor (1,59 ± 0,75), venas varicosas (1,80 ± 0,74), edema (1,40 ± 0,89), y pigmentación (1,05 ± 0,98). A mayor CEAP le corresponde mayor puntuación VCSS. En el análisis por subgrupos destacan como factores de gravedad el género, varón, edad, peso, sedentarismo, antecedentes personales y familiares de enfermedad venosa. En el análisis de regresión múltiple, los determinantes fundamentales de gravedad son: 1) edad; 2) antecedente de trombosis venosa superficial o profunda, y 3) peso del paciente. Conclusiones: Existe una relación positiva entre CEAP y VCSS. El análisis por subgrupos define factores fuertes y débiles de gravedad, que quedan clarificados mediante regresión múltiple(AU)

Introduction: Chronic venous insufficiency (CVI) can be evaluated using venous clinical severity scores. However, the individual factors that may lead to this condition have not been well described. The objective of this study is to analyse the sociodemographic and clinical characteristics of sample of patients who suffer from CVI in order determine the factors that increase the severity of their condition. Material and method: A study, promoted by the Spanish Society of Angiology and Vascular Surgery in collaboration with other scientific societies, was conducted on 1,560 patients with CVI using two measurement tools: CEAP (clinical grade, etiology, anatomy, pathophysiology) classification and Venous Clinical Severity Score (VCSS). Results: The patient distribution by clinical status (C0 to C5) was: C0: 3.3%; C1: 15.6%; C2: 21.0%, C3: 22.9%; C4: 23.6%; C5: 8.7%; C6: 4.5%. The VCSS score for the whole cohort was 0.89 ± 0.53, being greater than the mean in four of the ten measurements attributed to: pain (1.59 ± 0.75), varicose veins (1.80 ± 0.74), oedema (1.40 ± 0.89), and pigmentation (1.05 ± 0.98). A higher CEAP corresponded to a higher VCSS. In the analysis by subgroups, the risk severity factors were associated with, being male, weight, being sedentary, personal and family history of venous disease. In the multiple regression analysis, the main determining factors were: 1) age; 2) history of superficial of deep venous thrombosis; and 3) patient weight. Conclusions: There is a positive relationship between CEAP and VCSS. The analysis by sub-groups defines strong and weak factors of severity, that are made clear using multiple regression analysis(AU)

Formación médica continuada en úlceras vasculares / Continuing medical education in vascular ulcers

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Chronic venous disease in Spain: doctor-patient correlation.

AIM: The present study aimed to demonstrate how the quality of life (QoL) perceived by patients with chronic venous disease (CVD) is correlated with the severity of their disease objectively assessed by primary care physician. MATERIAL AND METHODS: A total of 1560 patients with CVD were evaluated using four measurement instruments: CEAP clinical classification, Venous Clinical Severity Score (VCSS), SF-12 Health Survey and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). Statistical correlations between these tools were analysed using Spearman's coefficient. RESULTS: Patients were distributed in C0, 58 (3.7%); C1, 243 (15.6%); C2, 328 (21.0%); C3, 357 (22.9%); C4, 368 (23.6%); C5, 136 (8.7%); and C6, 70 (4.5%). The VCSS score for the whole cohort was 0.89 ± 0.53. The correlation between CEAP and VCSS was moderately strong (r = 0.69). The overall QoL scores measured by SF and CIVIQ were 56.84 ± 19.63 and 65.11 ± 14.35, respectively. The correlation between the two QoL questionnaires was very strong (r = 0.81). The correlations of the SF and CIVIQ with the VCSS were moderately strong (r = -0.47 and -0.48). The correlations between QoL questionnaires and CEAP were moderate and lower than those with VSCC. CONCLUSIONS: While there is correlation between VCSS, CEAP, modified CIVIQ and venous ultrasound findings, subgroup analysis indicates that this correlation is driven by different components of VCSS compared with the other venous assessment tools. Patients' opinions about their disease are correlated with those assessed by primary care physicians.

Nuevos anticoagulantes orales en el tratamiento de la trombosis venosa profunda / New oral anticoagulants in the treatment of deep venous thrombosis

El tratamiento de la trombosis venosa profunda (TVP) puede cambiar con la aparición de los nuevos antitrombóticos. Actualmente existe una clara apuesta por los anticoagulantes de administración oral, inicio de actividad precoz y una diana específica y directa anti-Xa o anti-IIa. En el tratamiento de la TVP ya disponemos de resultados procedentes de dos ensayos clínicos fase iii : RE-COVER (dabigatran) y EINSTEIN-DVT/EXT (rivaroxaban). Conjuntamente existen otros dos ensayos (AMPLIFY [apixaban] y HOKUSAI [edoxabán]) muy avanzados, pero sin publicar sus resultados. A la luz de los datos disponibles se puede concluir que los nuevos anticoagulantes orales son atractivos por múltiples razones, y que sus investigaciones apoyan la idea de poder reemplazar a los anticoagulantes convencionales (heparinas de bajo molecular y antivitaminas K) en el tratamiento de la TVP. A pesar de estos prometedores resultados, cada subgrupo de pacientes (oncológicos, obesos, etc.) requerirá de nuevas investigaciones(AU)

The treatment of deep venous thrombosis (DVT) may change with the appearance of the new antithrombotics. There is currently a clear commitment to oral anticoagulant administration, starting early activity and a specific and direct anti- x a or anti- ii a target. We already have the results of two phase iii clinical trials on the treatment of DVT: RE-COVER (dabigatran) and EINSTEIN-DVT/EXT (rivaroxaban). At the same time there are another two very advanced trials (AMPLIFY [apixaban] and HOKUSAI [edoxaban]), that have not yet published their results. In the light of the available data, it can be concluded that the new oral anticoagulants are attractive for several reasons and that research supports the idea that they could replace conventional anticoagulants (low molecular weight heparins, anti-vitamin K) in the treatment of DVT. Despite these promising results, each patient sub-group (oncological, obese, etc.) will require new studies(AU)

Novedades en la enfermedad tromboembólica venosa / News on venous thromboembolic disease

Este artículo recoge las últimas novedades que se han producido en diferentes aspectos de la enfermedad tromboembólica venosa (ETEV): a) profilaxis de la ETEV en cirugía ortopédica mayor; b) profilaxis de la ETEV en pacientes médicos; c) avances terapéuticos en la embolia pulmonar; d) en la trombosis venosa superficial; y e) perspectivas de futuro en la ETEV. Se resumen las 5 ponencias desarrolladas en la II Jornada de Novedades en Tratamiento Anticoagulante (Madrid, 18 noviembre de 2011), organizada por la Fundación para el Estudio de la Enfermedad Tromboembólica en España y auspiciada por la Sociedad Española de Medicina Interna, Sociedad Española de Neumología y Cirugía Torácica, Sociedad Española de Cardiología, Sociedad Española de Trombosis y Hemostasia, y Sociedad Española de Angiología y Cirugía Vascular(AU)

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery(AU)

[News on venous thromboembolic disease]. / Novedades en la enfermedad tromboembólica venosa.

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

La trombosis venosa superficial: ¿es una enfermedad benigna? / Superficial venous thrombosis: is it a benign disease?

Nuevos conocimientos sobre la trombosis venosa superficial, aparecidos en la última década,han modificado sustancialmente el diagnóstico y tratamiento de la misma. Esta entidad, consideradaantes como una patología banal de fácil diagnóstico y sencillo tratamiento, actualmentees una patología potencialmente grave (al asociarse en muchas ocasiones a trombosis del sistemavenoso profundo y la posibilidad de embolia pulmonar), que precisa de la práctica de diferentesexploraciones complementarias (eco-doppler, estudios de trombofilia, etc.) para instaurarun tratamiento específico. En este contexto, parecen estar indicadas las heparinas de bajopeso molecular(AU)

New knowledge has come to light on superficial venous thrombosis in the last ten years, and hassubstantially changed its diagnosis and treatment. This condition, once considered a trivialdisease, easy to diagnose and with straightforward treatment, is currently a potentiallyserious disease (on often being associated with deep vein thrombosis and the possibility ofpulmonary embolism), which requires different complementary examinations (Echo-Doppler,thrombophilia studies, etc.), in order to install specifi c treatment, such as low molecular weightheparins(AU)

Estudio genético del complejo enzimático succinato deshidrogenasa en los paragangliomas carotídeos. Implicaciones diagnósticas / Genetic study of the succinate dehydrogenase enzyme complex in carotid paragangliomas: diagnostic implications

Introducción: Los paragangliomas (PG) en general y los carotídeos (PGC) en particular son tumores infrecuentes, generalmente únicos y de evolución benigna, que presentan controversias en su comportamiento biológico e historia natural. Objetivo: Correlacionar la presencia de mutaciones de los genes del complejo enzimático succinato deshidrogenasa (SDH) con la aparición de presentaciones atípicas de PG (bilaterales, multicéntricos y malignos). Pacientes y método: Estudio genético en 20 pacientes, 18 con PGC esporádico y 2 con PGC familiar; 2 pacientes presentaban localizaciones múltiples y 3 fueron de evolución maligna. Después de consentimiento informado específico, se obtuvo sangre periférica de los pacientes para realizar un estudio genómico según protocolo estándar. Resultados: Se detectaron mutaciones en 6 pacientes (30 % de la serie), repartiéndose de forma homogénea (2 por subunidad B, C o D). Las mutaciones fueron del 100 % en las formas familiares (2/2) y del 22,2 % en las esporádicas (4/18). Los 2 pacientes con PG múltiples presentaron mutaciones (SDHB y SDHC). En 2 de 3 pacientes con PG de evolución maligna se presentaron mutaciones en SDHB. En los casos familiares se estudió a 3 hijos de los pacientes, resultando positivo (SDHB) un caso. Finalmente, 3 de las 6 mutaciones descritas por nosotros no han sido referidas previamente en la literatura consultada (SDHB c.472 del A, SDHC c.A377G y SDHC c.A21G). Conclusiones: La mutación de las subunidades de SDH es responsable de la tendencia a padecer un PG tanto en las formas familiares como en las esporádicas, teniendo una importante relevancia en la presencia de formas múltiples y el pronóstico evolutivo de estos tumores(AU)

Introduction: Carotid paragangliomas (CPGs) are uncommon tumours which tend to be isolated and benign. However, there are controversies over their biological behaviour and natural history. Aim: To correlate the presence of mutations of succinate dehydrogenase (SDH) complex genes with the appearance of atypical CPGs (bilateral, multicentral and malignant). Patients and methods: We carried out mutation analyses in 18 patients with sporadic CPGs and 2 patients with familial CPGs. Two patients had multiple locations and three had a malignant outcome. After obtaining informed consent, peripheral blood was obtained to perform a genomic study according to a standard protocol. Results: We identified SHD mutations in six patients (30 %), 100 % in familial CPGs (2/2) and 22.2 % in sporadic CPGs (4/18). Both patients with multiple CPGs showed mutations in SDH (SDH subunit B and SDH subunit C). Two of three patients with CPGs and malignant outcome showed mutation in the SDH subunit B gene. In familial CPGs, we studied three children and we found a positive case (SDHB). Finally, we identified three novel SHD mutations (SDHB c.472 del A, SDHC c.A377G; and SDHC c.A21G). Conclusion: SDH mutations are responsible for the trend to suffer CPGs in both familial and sporadic forms and may play an important role in multiple CPGs and malignant PGs(AU)