Surgical and postsurgical management of abdominal paragangliomas and pheochromocytomas.

PURPOSE: To describe our current protocol for surgical and postsurgical management of abdominal paragangliomas (PGLs) and pheochromocytomas, with a special focus on multidisciplinary management in centres with experience. METHODS: The physicians involved in the management of patients with abdominal PGLs and pheochromocytomas of our hospital reviewed systematically current knowledge on the surgical management of abdominal PGLs and pheochromocytomas. RESULTS: Currently, surgery is considered the treatment of choice for abdominal PGLs and pheochromocytomas. The choice of surgical approach is determined based on the location of the lesion, size, patient́s body habitus and the likelihood of malignancy. Laparoscopic surgery is usually considered the gold standard approach for pheochromocytomas, but open access should be considered in invasive and/or potentially malignant tumours >8-10 cm and for abdominal PGLs. Postsurgical management of pheochromocytomas and PGLs includes close hemodynamic monitoring and treatment of postsurgical complications, the pathological study of the surgical specimen, reassessment of hormonal and/or radiological status and planning of follow-up based on the risk of recurrence and malignancy. CONCLUSION: Surgery represents the treatment of choice of most abdominal PGLs and pheochromocytomas. Optimal postsurgical evaluation, including hemodynamic, pathological, hormonal, and radiological evaluation, should be performed by a multidisciplinary team specializing in PGL/pheochromocytoma management.

Manejo quirúrgico y posquirúrgico de paragangliomas abdominales y feocromocitomas / Surgical and postsurgical management of abdominal paragangliomas and pheochromocytomas

Objetivo Describir nuestro protocolo actual para el manejo quirúrgico y posquirúrgico de los paragangliomas abdominales (PGL) y los feocromocitomas, con especial atención en el manejo multidisciplinar en centros con experiencia. Métodos Los facultativos implicados en el tratamiento de pacientes con PGL abdominales y feocromocitomas de nuestro hospital revisaron sistemáticamente la evidencia científica actualmente disponible sobre el tratamiento quirúrgico de los PGL abdominales y feocromocitomas. Resultados La cirugía se considera el tratamiento de primera elección para los PGL abdominales y feocromocitomas. La decisión sobre el tipo de abordaje quirúrgico se basa en la localización y el tamaño de la lesión, la constitución corporal del paciente y la probabilidad estimada de malignidad. La cirugía laparoscópica suele considerarse el abordaje de referencia para los feocromocitomas, pero en los tumores invasivos y/o potencialmente malignos de más de 8-10 cm y en los PGL abdominales debe considerarse el abordaje abierto. El tratamiento posquirúrgico de los feocromocitomas y los PGL incluye una monitorización hemodinámica estrecha, el tratamiento de las complicaciones posoperatorias, el estudio patológico de la muestra quirúrgica, la reevaluación del estado hormonal y/o radiológico y la planificación del seguimiento en función del riesgo de recurrencia y malignidad. Conclusión La cirugía representa el tratamiento de elección de la mayoría de los PGL abdominales y feocromocitomas. La evaluación posoperatoria óptima, que incluye la evaluación hemodinámica, patológica, hormonal y radiológica, debe ser realizada por un equipo multidisciplinar especializado en el tratamiento de PGL/feocromocitomas (AU)

Purpose To describe our current protocol for surgical and postsurgical management of abdominal paragangliomas (PGLs) and pheochromocytomas, with a special focus on multidisciplinary management in centres with experience. Methods The physicians involved in the management of patients with abdominal PGLs and pheochromocytomas of our hospital reviewed systematically current knowledge on the surgical management of abdominal PGLs and pheochromocytomas. Results Currently, surgery is considered the treatment of choice for abdominal PGLs and pheochromocytomas. The choice of surgical approach is determined based on the location of the lesion, size, patient́s body habitus and the likelihood of malignancy. Laparoscopic surgery is usually considered the gold standard approach for pheochromocytomas, but open access should be considered in invasive and/or potentially malignant tumours > 8-10 cm and for abdominal PGLs. Postsurgical management of pheochromocytomas and PGLs includes close hemodynamic monitoring and treatment of postsurgical complications, the pathological study of the surgical specimen, reassessment of hormonal and/or radiological status and planning of follow-up based on the risk of recurrence and malignancy. Conclusion Surgery represents the treatment of choice of most abdominal PGLs and pheochromocytomas. Optimal postsurgical evaluation, including hemodynamic, pathological, hormonal, and radiological evaluation, should be performed by a multidisciplinary team specializing in PGL/pheochromocytoma management (AU)

[Literature review in the diagnosis and treatment of malignant pheochromocytomas and paragangliomas.] / Revisión bibliográfica en el diagnóstico y el tratamiento de los feocromocitomas y paragangliomas malignos.

OBJECTIVE: Perform a review on the diagnosis and treatment of pheochromocytomas and malignant paragangliomas. MATERIAL AND METHOD: A search was conducted in PubMed and Google Scholar of articles or clinical guides that referred to the diagnosis and treatment of these tumors. RESULTS: For the diagnosis of malignancy, a histological confirmation of a pheochromocytoma or paraganglioma should be provided, plus the presence of metastasis confirmed by images. Methanephrines are recommended over other biochemical determinations. For staging, PET-CT with 18F-FDG or 18F-DOPA is preferred because of its greater sensitivity than conventional images. The 123I-MIBG scan should be requested when radiotherapy with 131I-MIBG is planned.For treatment, control of adrenergic symptoms through the use of α-blockers is recommended. Active surveillance was an option in selected patients with slowly progressive tumors. Surgical treatment improved OS (148 months vs 36 months p=<0.01). Therapy with 131I-MIBG was indicated in patients with positive scintigraphy, reporting a global survival of 50% at 5 years with variable tumor responses. Chemotherapy was proposed in rapidly progressive disease, reporting a median overall survival of 6 years. Ablative therapies should be considered when there is a limited number of lesions, to achieve local tumor control and reduce the symptoms of excess catecholamines. External radiation therapy at high doses would be effective for patients with local symptoms due to their tumor burden. Prospective multi-institutional clinical trials are needed to determine the true benefits of molecular therapies in these patients. CONCLUSIONS: We recommend a multidisciplinary approach in centers of high complexity to be able to offer the entire diagnostic - therapeutic arsenal available so far that they improve the survival and quality of life of these patients.

OBJETIVO: Realizar una revisión en el diagnóstico y el tratamiento de los feocromocitomas y los paragangliomas malignos. MATERIAL Y MÉTODO: Se realizó una búsqueda en PubMed y Google Académico de artículos o guías clínicas que se referían al diagnóstico y el tratamiento de estos tumores. RESULTADOS: Para el diagnóstico de malignidad se debe contar con una confirmación histologica de un feocromocitoma o paraganglioma más la presencia de metástasis confirmada por imágenes. Las metanefrinas se recomiendan sobre otras determinaciones bioquímicas. Para la estadificación se prefiere al PET-TC con 18F-FDG o 18F-DOPA por su mayor sensibilidad que las imágenes convencionales. La gammagrafía con 123I-MIBG se debería solicitar cuando se planea la radioterapia con 131I- MIBG. Para el tratamiento se recomienda el control de los síntomas adrenérgicos mediante el uso de α-bloqueantes. La vigilancia activa fue una opción en pacientes seleccionados con tumores lentamente progresivos. El tratamiento quirúrgico mejoró la SG (148 meses vs 36 meses p=<0,01). La terapia con 131 I-MIBG fue indicada en pacientes con gammagrafía positiva, informando una sobrevida global de 50% a 5 años con respuestas tumorales variables. La quimioterapia se propuso en enfermedad rápidamente progresiva, informando una medianade sobrevida global de 6 años. Las terapias ablativas se deben considerar cuando hay un número limitado de lesiones, para lograr el control local del tumor y reducir los síntomas del exceso de catecolaminas. La radioterapia externa a dosis altas sería eficaz para pacientes con síntomas locales por su carga tumoral. Se necesitan ensayos clínicos multiinstitucionales prospectivos para determinar los verdaderos beneficios de las terapias moleculares en estos pacientes. CONCLUSIONES: Aconsejamos un enfoque multidisciplinario en centros de alta complejidad para poder ofrecer todo el arsenal diagnóstico - terapéutico disponible hasta el momento que mejoren la sobrevida y la calidadd e vida de estos pacientes.

[Diagnostic approach of pheochromocytomas and paragangliomas]. / Enfoque diagnóstico de feocromocitomas y paragangliomas.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours associated with high morbidity and mortality. Recognizing the clinical presentation is the first step for diagnosis. Biochemical studies may determine an excess of catecholamines and their metabolites. However, the available tests offer varying diagnosis precision. Computed tomography and magnetic resonance are highly sensitive for locating these tumours. Functional tests are reserved for when metastatic and multifocal disease are suspected. One third of the patients have a germline mutation and many genes are involved in the development of these tumours.

Fundamentos moleculares de la enfermedad de von Hippel Lindau / Molecular bases of von Hipperl Lindau's disease

La enfermedad de von Hippel Lindau es una rara entidad genética que se caracteriza por la predisposición al cáncer, especialmente angiomas de la retina, hemangioblastomas del sistema nervioso central y carcinoma renal de células claras. Los productos del gen presentan un mecanismo de acción peculiar, pues está relacionado con los procesos de adaptación del organismo a la hipoxia. En este trabajo se presenta una panorámica actualizada de esta enfermedad, con énfasis en los aspectos moleculares (AU)

The von Hippel Lindau's disease is uncommon genetic entity characterized by a predisposition to cancer, specially the retina angiomas, hemangioblastomas of central nervous system and the clear cells renal carcinoma. Gene products have a typical action mechanism since it is related to organism adaptation processes to hypoxia. In present paper an updated panorama of this disease emphasizing in molecular processes (AU)

Fundamentos moleculares de la enfermedad de von Hippel Lindau / Molecular bases of von Hipperl Lindau's disease

La enfermedad de von Hippel Lindau es una rara entidad genética que se caracteriza por la predisposición al cáncer, especialmente angiomas de la retina, hemangioblastomas del sistema nervioso central y carcinoma renal de células claras. Los productos del gen presentan un mecanismo de acción peculiar, pues está relacionado con los procesos de adaptación del organismo a la hipoxia. En este trabajo se presenta una panorámica actualizada de esta enfermedad, con énfasis en los aspectos moleculares

The von Hippel Lindau's disease is uncommon genetic entity characterized by a predisposition to cancer, specially the retina angiomas, hemangioblastomas of central nervous system and the clear cells renal carcinoma. Gene products have a typical action mechanism since it is related to organism adaptation processes to hypoxia. In present paper an updated panorama of this disease emphasizing in molecular processes

Aspectos clínicos, diagnóstico e manejo dos tumores que produzem catecolaminas: feocromocitomas e paragangliomas / Clinical aspects, diagnosis and management of catecolamin-producing tumors: pheocromocitomas and paragangiomas

Os feocromocitomas e paragangliomas são tumores raros, originários de células cromafins. Os primeiros localizam-se na medula suprarrenal e os últimos podem ser encontrados em qualquer local ao longo das cadeias simpática sou parassimpáticas do sistema nervoso autônomo. Constituem causa potencialmente curável de hipertensão arterial. Usualmente, secretam catecolaminas, incluindo-se dopamina, adrenalina e noradrenalina, responsáveis pela tríade semiológica clássica de manifestações: episódios paroxísticos de cefaléia, diaforese e palpitação. No entanto, a apresentação clínica é muito variável, e um grande número de pacientes pode ser oligo- ou assintomático, sugerindo que a parte significativa dos casos não é diagnosticada. Alta suspeição, uso racional de exames laboratoriais e métodos de imagem apropriados dão o diagnóstico anatômico e funcional preciso. Este artigo traz uma revisão sobre as recomendações mais atuais para abordagem desses tumores endócrinos.

Pheocromocytomas and paragangliomas are rare tumors, originated from chromaffim cells. The first ones are located in the suprarrenal medulla, and the others are found somewhere along the sympathetic and parasympathetic chains from the autonomous neural system. They constitute a potentially curable cause of arterial hypertension. Usually, they secrete cathecolamines, including dopamine, epinephrine and norepinephrine, which are responsible for the classic triad of manifestations: paroxysms of cephaleia, diaphoresis and palpitations. However, clinical presentation is very heterogeneous and a significant number of patients are oligo- or assymptomatic, suggesting that the majority of these cases may not be detected. High suspicion, rational use of laboratorial exams and appropriate imaging methods lead to accurate functional and anatomical diagnosis. The present article brings a revision about the most recent recommendations for management of these endocrine tumors.