Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas

'Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations (AU)

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

Prognostic significance of sentinel node biopsy status in cutaneous melanoma: a 21-years prospective study from a single institution.

AIM: To analyze the accuracy of the sentinel lymphatic node biopsy (SLNB) and to investigate predictive factors for sentinel node (SN) status and prognostic factors for recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with melanoma. MATERIAL AND METHODS: Between June 1997 and June 2017, 440 consecutive patients, who underwent SLNB by a single surgical team, were prospectively included. Descriptive and survival analysis were performed. RESULTS: 119 of 440 patients (26%) had positive SN. SLNB's false-negative rate was 6.3%. Breslow thickness, Clark´s level, ulceration and histological subtype were statistically significant predictive factors of SN metastases. In a multivariate analysis, positive SN (HR = 2.21, p = 0.01), deeper Breslow thickness (HR = 2.05, p = 0.013), male gender (RR = 2.05, p = 0.02), and higher Clark's level (HR = 2.30, p = 0.043) were significantly associated with decreased RFS; and positive SN (HR = 2.58, p < 0.001), deeper Breslow thickness (HR = 2.57, p = 0.006) and male gender (HR = 1.93, p = 0.006) were associated with lower DSS. CONCLUSION: SLNB is a reliable and reproducible procedure with high sensitivity (93.7%). Positive SN metastases, Breslow thickness and male gender were statistically associated with poorer outcomes. Male gender was an independent prognostic factor of tumor thickness or SN status.

Utility of PET/CT in patients with stage I-III melanoma.

PURPOSE: To study the utility of positron emission tomography with computerized tomography (PET/CT) in patients with a stage I-III melanoma. PATIENTS AND METHODS: PET/CT findings from all patients with a stage I-III melanoma attended at our hospital from September 2011 to November 2015 were reviewed. RESULTS: Data from 83 patients with a stage I-III melanoma, 39 patients with a positive sentinel lymph node biopsy (SLNB) and 35 patients with locoregional recurrences were analyzed. Sensitivity of PET/CT in clinical stage I-III patients was 5%, with a 14% of false positives. In patients with a positive SLNB, PET/CT previous to complete lymph node dissection had a 23% of false negatives. In patients with clinical locoregional recurrences, PET/CT findings revealed asymptomatic visceral distant metastasis in 25.7%. CONCLUSIONS: PET/CT has a significant rate of false positive and negative results in patients with a stage I-III melanoma. Utility in patients with nodal locoregional recurrences seems higher than in patients with skin metastases.

Why do patients with thick melanoma have different outcomes? A retrospective epidemiological and survival analysis

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Adecuación de ranelato de estroncio tras alertas de farmacovigilancia en un área de gestión sanitaria / Suitability of strontium ranelate in a health care management area after drug surveillance alert

OBJETIVO: Analizar el impacto de una estrategia de adecuación de ranelato de estroncio tras la emisión de recomendaciones, en base a las notas de farmacovigilancia emitidas por la Agencia Española de Medicamentos y Productos Sanitarios, así como el grado de aceptación. DISEÑO: Estudio prospectivo de intervención desde abril de 2012 a noviembre de 2014. Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. PARTICIPANTES: Pacientes con prescripción activa de ranelato de estroncio. INTERVENCIONES: Se realizó en cuatro fases, ligada a la emisión de notas de farmacovigilancia sobre ranelato de estroncio por la Agencia Española de Medicamentos y Productos Sanitarios, listados de pacientes y recomendaciones de adecuación. MEDICIONES PRINCIPALES: Adecuación del tratamiento con ranelato de estroncio y grado de aceptación de las recomendaciones por los facultativos. RESULTADOS: Desde el inicio del estudio, con 182 pacientes incluidos, hasta el comienzo de la revisión de la adecuación por farmacia, se produjo una reducción del 87,9%. La prescripción de ranelato de estroncio era inadecuada en 16 pacientes de los 22; 11 por no cumplir criterios de tratamiento, tres por no haber tenido tratamiento previo con otros medicamentos para prevención de fracturas y dos por contraindicación. El grado de aceptación de las recomendaciones fue del 87,5%, produciéndose en diez pacientes la suspensión de ranelato de estroncio y en cuatro, el cambio a alendrónico o alendrónico/colecalciferol. CONCLUSIONES: El número de pacientes con prescripción de ranelato de estroncio ha disminuido considerablemente. Las intervenciones dirigidas a la revisión de la adecuación del tratamiento, en base a las alertas de farmacovigilancia han sido efectivas

OBJECTIVE: To analyse the impact of a strategy on the suitability of strontium ranelate, and its level of acceptance, after issuing recommendations based on drug surveillance alerts issued by the Spanish Medicines and Medical Devices Agency. DESIGN: A prospective interventional study conducted from April 2012 to November 2014. SETTING: South Seville Health Management Area. PARTICIPANTS: Patients currently prescribed with strontium ranelate. INTERVENTIONS: The study consisted of four phases linked to the issue of drug surveillance alerts on strontium ranelate by the Spanish Medicines and Medical Devices Agency, listed by patients and suitability recommendations. MAIN MEASUREMENTS: Suitability of strontium ranelate treatment and the level of acceptance by physicians. RESULTS: There was a reduction of 87.9% in prescriptions from the beginning of the study, with 182 patients included, until the review of the suitability of the drug began. The prescribing of strontium ranelate was unsuitable in 16 out of the 22 patients remaining; 11 of which were due not meeting the treatment criteria, 3 for not having had previous treatments with other drugs for the prevention of fractures, and 2 due to contraindications. The level of acceptance of the recommendations was 87.5%, leading to the stopping of strontium ranelate in 10 patients, and the changing to alendronate or alendronate/cholecalciferol in another four PATIENTS: CONCLUSIONS: The number of patients prescribed strontium ranelate has decreased considerably. The interventions directed at reviewing the suitability of this treatment, based on the drug surveillance alerts, have been effective

[Suitability of strontium ranelate in a health care management area after drug surveillance alerts]. / Adecuación de ranelato de estroncio tras alertas de farmacovigilancia en un área de gestión sanitaria.

OBJECTIVE: To analyse the impact of a strategy on the suitability of strontium ranelate, and its level of acceptance, after issuing recommendations based on drug surveillance alerts issued by the Spanish Medicines and Medical Devices Agency. DESIGN: A prospective interventional study conducted from April 2012 to November 2014. SETTING: South Seville Health Management Area. PARTICIPANTS: Patients currently prescribed with strontium ranelate. INTERVENTIONS: The study consisted of four phases linked to the issue of drug surveillance alerts on strontium ranelate by the Spanish Medicines and Medical Devices Agency, listed by patients and suitability recommendations. MAIN MEASUREMENTS: Suitability of strontium ranelate treatment and the level of acceptance by physicians. RESULTS: There was a reduction of 87.9% in prescriptions from the beginning of the study, with 182 patients included, until the review of the suitability of the drug began. The prescribing of strontium ranelate was unsuitable in 16 out of the 22 patients remaining; 11 of which were due not meeting the treatment criteria, 3 for not having had previous treatments with other drugs for the prevention of fractures, and 2 due to contraindications. The level of acceptance of the recommendations was 87.5%, leading to the stopping of strontium ranelate in 10 patients, and the changing to alendronate or alendronate/cholecalciferol in another four patients. CONCLUSIONS: The number of patients prescribed strontium ranelate has decreased considerably. The interventions directed at reviewing the suitability of this treatment, based on the drug surveillance alerts, have been effective.

Absceso retroperitoneal secundario a espondilodiscitis tuberculosa simulando una hernia inguinal incarcerada.

Tuberculosis is the commonest cause of spinal infection worldwide (9-46%). Tuberculosis spondylodiscitis causes multifocal thoracic and lumbar spinal disease, and big paraspinal and psoas abscesses. It is more frequent in people under 40 who had previous tuberculosis infection and from countries where the illness is endemic. Clinic is non-specific and sub-acute. We report the clinical case of a 29-year-old patient who suffered from pericardic tuberculosis in her childhood and who presents a bilateral retroperitoneal abscess due to tuberculosis spondylodiscitis. Her clinical debut began with left inguinal pain and an irreducible mass at this level that simulated an incarcerated inguinal hernia, which is why surgery was indicated. Due to discrepancies between intraoperative findings and the initial diagnosis, the diagnosis and treatment strategy were changed. The purpose of this case report is to emphasize the challenge that the diagnosis of this pathology represents, due to low incidence in our environment and poor clinical features, which results in late diagnosis and late management.

Influence of adding etravirine on complexity index and patients' perceived complexity.

WHAT IS KNOWN AND OBJECTIVE: Adherence to highly active antiretroviral treatment (HAART) is an important predictive factor of treatment outcome. Medication regimen complexity can be one of the main causes of non-adherence. Thus, treatment simplification is a key strategy in the development of antiretroviral therapy. The aim of this study was to determine the influence of adding etravirine on complexity index and patients' perceived complexity of their treatment regimen. METHODS: We conducted a prospective two-centre observational study. Patients on etravirine-based therapy, for at least 6 months, who came personally to pharmacy departments for a drug refill from February to July 2012 were included. Data were collected for the current etravirine-based HAART and for the previous HAART without etravirine. The main variables were complexity index and patients' perceived complexity. We also evaluated the adherence during the 6 months before and after the introduction of etravirine into HAART. The complexity index was based on a score which takes into account the number of pills per day, the dosing schedule, the dosage form and any specific instructions linked to use of the drug. To evaluate the patients' perceived complexity of their current and previous HAART, patients were asked to assign a mark on a visual analogue scale ranging from 0 (minimum) to 10 (maximum). We assessed the differences in the variables collected between the current and previous antiretroviral therapy. Finally, we carried out a correlation analysis between the complexity index and the patients' perceived complexity. RESULTS AND DISCUSSION: Eighty patients were included. The complexity index was significantly reduced after the addition of etravirine to HAART (P = 0·035). Perceived complexity was also reduced (P = 0·015). After the introduction of the drug, the proportion of adherent patients increased from 65% to 81·3% (P = 0·002). The correlation between the complexity index and the patients' perceived complexity was positive (r = 0·594). The correlation increased (r = 0·696) when the difference between the complexity index before and after the introduction of etravirine in HAART grew. WHAT IS NEW AND CONCLUSION: The addition of etravirine to HAART results in a significant reduction in complexity index and patients' perceived complexity of their therapy. These changes were associated with better adherence to treatment.

Improvement of a method for the sequential determination of 210Pb, 226Ra, and uranium isotopes by LSC and alpha-particle spectrometry.

In a previous paper the authors proposed a sequential method for the determination of isotopes of uranium, thorium, radium, and lead from environmental samples using alpha-particle spectrometry and LSC techniques. Although the radiochemical yields were suitable when the assays were performed on synthetic samples, application to real environmental samples caused a major decrease in the radiochemical yield, especially for uranium in inorganic samples (soils). A modification of the procedure is described that overcomes this drawback.

[The assessment of sedation in the critically ill child on mechanical ventilation during tracheal suction]. / Valoración de la sedación en el niño crítico con ventilación mecánica durante la aspiración endotraqueal.

OBJECTIVES: To compare the changes in clinical sedation scales, bispectral index (BIS) and physiological variables occurring during tracheal suction in critically ill children. DESIGN: Prospective, observational study in critically ill children on mechanical ventilation. BIS value, heart rate (HR), systolic blood pressure (SPB), diastolic blood pressure (DBP), modified Ramsay sedation scale score and the dose of sedative drugs were recorded before and 3 minutes after every tracheal suction. RESULTS: A total of 83 tracheal suctions were analyzed from 46 children, 1 month to 15 years of age. Most of the children (92%) were receiving continuous infusions of fentanyl and midazolam, and 45.7% of them were receiving vecuronium. The increase in BIS, SPB and DBP values were small but statistically significant (BIS, from 51.8 to 57.3; SBP, from 92.9 to 103.1 mmHg; DBP, from 51.8 to 58.9 mmHg). There was poor correlation between the BIS, HR, SBP and DBP values before and after suction. A total of 87% of patients maintained the same Ramsay score values. CONCLUSIONS: Tracheal suction produces a slight increase in the BIS and the BP in critically ill children who are receiving sedation by continuous infusion. Most children with adequate sedation do not need any other drugs before the tracheal suction. Physiological variables have no correlation with sedation scales or BIS values during the tracheal suction.

Valoración de la sedación en el niño crítico con ventilación mecánica durante la aspiración endotraqueal / The assessment of sedation in the critically ill child on mechanical ventilation during tracheal suction

Objetivo: valorar el cambio en el grado de sedación producido por la aspiración endotraqueal en niños críticos y comparar las modificaciones en las escalas clínicas, el índice biespectral (BIS) y las variables fisiológicas. Material y métodos: estudio prospectivo observacional en niños ingresados en la unidad de cuidados intensivos sometidos a ventilación mecánica. Se recogieron, antes de cada aspiración endotraqueal y 3min después, los valores del BIS, la frecuencia cardíaca (FC), la presión arterial sistólica (PAS), la presión arterial diastólica (PAD), la puntuación en la escala clínica de Ramsay y la dosis de fármacos sedantes. Resultados: se analizaron 83 aspiraciones endotraqueales realizadas en 46 niños entre 1 mes y 15 años de edad. El 92% de los niños recibían tratamiento con fentanilo y midazolam en perfusión continua y un 45,7%, con vecuronio. Los valores de BIS, PAS y PAD aumentaron ligeramente con la aspiración de forma estadísticamente significativa (BIS, 51,8 frente a 57,3; PAS, 92,9 frente a 103,1 mmHg; PAD, 51,8 frente a 58,9 mmHg). No hubo buena correlación entre los valores de BIS y FC, PAS y PAD. En el 87% de los pacientes se mantuvo la misma puntuación en la escala de Ramsay. Conclusiones: la aspiración endotraqueal produce un ligero aumento del BIS y la presión arterial, en los niños críticos que reciben sedoanalgesia en perfusión continua. Ni las escalas clínicas ni el BIS son capaces de predecir los cambios en el grado de sedación producidos por la aspiración. La mayoría de los niños con una sedación adecuada no precisan medicación sedoanalgésica previa a la aspiración endotraqueal. Las variables fisiológicas no se correlacionan con el BIS ni las escalas clínicas de sedación (AU)

Objectives: To compare the changes in clinical sedation scales, bispectral index (BIS) and physiological variables occurring during tracheal suction in critically ill children. Design: Prospective, observational study in critically ill children on mechanical ventilation. BIS value, heart rate (HR), systolic blood pressure (SPB), diastolic blood pressure (DBP), modified Ramsay sedation scale score and the dose of sedative drugs were recorded before and 3 minutes after every tracheal suction. Results: A total of 83 tracheal suctions were analyzed from 46 children, 1 month to 15 years of age. Most of the children (92%) were receiving continuous infusions of fentanyl and midazolam, and 45.7% of them were receiving vecuronium. The increase in BIS, SPB and DBP values were small but statistically significant (BIS, from 51.8 to 57.3; SBP, from 92.9 to 103.1 mmHg; DBP, from 51.8 to 58.9 mmHg). There was poor correlation between the BIS, HR, SBP and DBP values before and after suction. A total of 87% of patients maintained the same Ramsay score values. Conclusions: Tracheal suction produces a slight increase in the BIS and the BP in critically ill children who are receiving sedation by continuous infusion. Most children with adequate sedation do not need any other drugs before the tracheal suction. Physiological variables have no correlation with sedation scales or BIS values during the tracheal suction (AU)

Mononucleosis infecciosa de evolución tórpida / Indolent infectious mononucleosis

Se presenta el caso de una paciente de 14 años, diagnosticada de mononucleosis infecciosa, con una importante hipertrofia del sistema reticuloendotelial, con hepatosplenomegalia de más de 16 cm, una importante afectación de las enzimas hepáticas e hipertrofia de los ganglios cervicales. A pesar de estas manifestaciones, prácticamente no presentó ningún tipo de sintomatología clínica. La paciente evolucionó clínica yanalíticamente a la normalidad en cuatro semanas; sin embargo, persistió la afectación del sistema reticuloendotelial con hipertrofia adenoidea y hepatomegalia durante 10 meses

The authors report the case of a 14-year-old girl. diagnosed as having infectious mononucleosis. She presented severe hypertrophy of the reticuloendothelial system, with hepatosplenomegaly of more than 16 cm, marked changes in liver enzymes and hypertrophy of the cervical Iymph nodes. Despite these signs, she presented practically no clinical symptomatology. Four weeks later, the clinical and analytical findings were normal; however, the reticuloendothelial system involvement persisted, with adenoid hypertrophy and hepatomegaly that lasted for 10 months

[Evaluation of primary care treatment of oncology patients with opiates]. / Evaluación del tratamiento con opiáceos en pacientes oncológicos en atención primaria.

OBJECTIVES: To evaluate how adequately pain in terminal cancer patients is managed by morphine taken orally. DESIGN: A descriptive, retrospective study, from January 1993 to March 1994. SETTING: Primary care. Four primary care teams of the 10th Health Area of Madrid. PATIENTS: 37 patients with terminal cancer who took morphine under the supervision of primary care doctors. MEASUREMENTS AND MAIN RESULTS: Average age was 64.6 +/- 14. The most common site of the primary tumour was lungs (n = 6), colon (n = 4) and stomach (n = 4). All the patients received conventional analgesics at first and 82% went on to weak opiates before progressing to morphine. Half the patients began with an oral solution of morphine and the other half with long-acting tablets. Increases in the doses of morphine were correct in 62% of cases. 41% of the patients took antiemetics and 55% laxatives. 82% of the bone and 100% of the brain metastases were correctly treated. CONCLUSIONS: In general, primary care doctors in our area correctly handle pain caused by terminal cancer. The most significant errors are to do with increases in doses of morphine and with the associated use of laxatives. These can easily be rectified so that our patients' quality of life can be improved.