Utilización de las zonas de entrada seguras para el abordaje de lesiones intrínsecas de tronco cerebral en adultos / Use of safe entry zones for the approach of intrinsic brainstem lesions in adults

Introducción: Las "zonas de entrada seguras" (ZES) al tronco cerebral describen accesos destinados a preservar estructuras críticas. La mayoría de las publicaciones son descripciones anatómicas; existiendo pocas sobre su aplicación. En este escenario, nuestro trabajo puede sumar información para el manejo quirúrgico en casos seleccionados. Material y Métodos: De una serie de 13 pacientes, se presentan 9 que no eran candidatos para biopsia estereotáctica y recibieron microcirugía. Las localizaciones fueron: mesencéfalo (3), tectum (1), protuberancia (2) y bulbo (3). Cinco pacientes tuvieron KPS => 70; y 4, KPS <70. Diferentes ZES fueron utilizadas según la topografía lesional. El grado de resección se basó en la biopsia intraoperatoria y el monitoreo neurofisiológico. Resultados: Los hallazgos patológicos fueron: astrocitoma pilocítico (1), glioma de bajo grado (1), hemangioblastoma (1), subependimoma (1), disgerminoma (1), y lesiones pseudotumorales (3 cavernomas y 1 pseudotumor inflamatorio). El grado de resección fue completo (4), subtotal (3), y biopsia fue considerada suficiente en (2). Un paciente falleció en el postoperatorio. Discusión: Las lesiones del tronco cerebral son infrecuentes en adultos. Las controversias surgen cuando se balancean los beneficios de obtener diagnóstico histopatológico y los riesgos potenciales de procedimientos invasivos. La amplia variedad de hallazgos en esta localización exige una precisa definición histopatológica, que no solamente determinará la terapéutica adecuada, sino que advierte sobre las consecuencias potencialmente catastróficas de los tratamientos empíricos. Las ZES ofrecen un acceso posible y seguro, aunque es más realista considerarlas como áreas para abordar lesiones intrínsecas con baja morbilidad más que como zonas completamente seguras

Introduction: The "safe entry zones" (SEZ) to the brainstem are special entrances described to preserve critical structures. Most publications correspond to anatomic research; few papers report their application in surgery. In this scenario, our report could add information to the surgical management in selected cases. Material and Methods: Out of a series of 13 patients, 9 were non-candidates for stereotactic biopsy and received microsurgery. Localizations of the lesions were: mesencephalus (3), tectal plate (1), pons (2) and medulla oblongata (3). Five patients had KPS => 70; 4, KPS <70. Different SEZ were used according to lesional topography. The extent of resection were based on the frozen pathology findings and neurophysiological monitoring. Results: A variety of pathological findings were found: low-grade glioma (1); pilocytic astrocytoma (1); hemangioblastoma (1); subependimoma (1); disgerminoma (1); pseudotumoral lesions (cavernomas 3 and inflammatory pseudotumor 1). The extent of resection was complete (4), subtotal (3), and biopsy was considered sufficient in 2 cases. One patient died 96-hours-postoperative due to brainstem edema. Discussion: Brainstem structural lesions are uncommon in adults. Controversies arise regarding the need of histologic diagnosis, weighing benefits of a reliable diagnosis and the potential disadvantages of the invasive procedures. The accurate histopathological definition could not only determine an adequate therapy, but also can prevent the disastrous consequences of empiric treatments. The SEZ provides a feasible and safe access, although it is more realistic to consider them as areas to approach intrinsec lesions with less morbidity than to consider them as completely safe entrances

Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models–using both xenografted material and genetically engineered mice–will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models–using both xenografted material and genetically engineered mice–will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

Gamma Knife Radiosurgery for Brainstem Metastasis

OBJECTIVE: Brainstem metastases are rarely operable and generally unresponsive to conventional radiation therapy or chemotherapy. Recently, Gamma Knife Radiosurgery (GKRS) was used as feasible treatment option for brainstem metastasis. The present study evaluated our experience of brainstem metastasis which was treated with GKRS. METHODS: Between November 1992 and June 2010, 32 patients (23 men and 9 women, mean age 56.1 years, range 39-73) were treated with GKRS for brainstem metastases. There were metastatic lesions in pons in 23, the midbrain in 6, and the medulla oblongata in 3 patients, respectively. The primary tumor site was lung in 21, breast in 3, kidney in 2 and other locations in 6 patients. The mean tumor volume was 1,517 mm3 (range, 9-6,000), and the mean marginal dose was 15.9 Gy (range, 6-23). Magnetic Resonance Imaging (MRI) was obtained every 2-3 months following GKRS. Follow-up MRI was possible in 24 patients at a mean follow-up duration of 12.0 months (range, 1-45). Kaplan-Meier survival analysis was used to evaluate the prognostic factors. RESULTS: Follow-up MRI showed tumor disappearance in 6, tumor shrinkage in 14, no change in tumor size in 1, and tumor growth in 3 patients, which translated into a local tumor control rate of 87.5% (21 of 24 tumors). The mean progression free survival was 12.2 months (range, 2-45) after GKRS. Nine patients were alive at the completion of the study, and the overall mean survival time after GKRS was 7.7 months (range, 1-22). One patient with metastatic melanoma experienced intratumoral hemorrhage during the follow-up period. Survival was found to be associated with score of more than 70 on Karnofsky performance status and low recursive partitioning analysis class (class 1 or 2), in terms of favorable prognostic factors. CONCLUSION: GKRS was found to be safe and effective for management of brainstem metastasis. The integral clinical status of patient seems to be important in determining the overall survival time.

Unusual dissemination patterns of low-grade astrocytomas in childhood

CONTEXT: Low-grade astrocytomas are intracerebral lesions of relatively high frequency in the under-18 pediatric population. They often present indolent behaviour, and complete surgical resection is the choice treatment. In cases where the surgery is not possible, chemotherapy and radiotherapy may be used. Medical reports do not recommend examination of the spinal cord at diagnosis or during treatment, since the risk of dissemination of the lesion to the spine is minimal according to medical experience. We describe here four cases of children with low-grade astrocytoma with aggressive dissemination to the neuroaxis.

CONTEXTO: Gliomas de baixo grau de malignidade são lesões intracerebrais relativamente freqüentes na população pediátrica menor de 18 anos de idade. Eles freqüentemente são indolentes em seu comportamento e a ressecção cirúrgica completa é o tratmento de eleição. Nos casos em que a cirurgia não é possível, a quimioterapia e a radioterapia podem ser utilizadas. Relatos da literatura não recomendam a avaliação radiológica da coluna espinhal ao diagnóstico ou durante o tratamento, desde que o risco de disseminação destas lesões para a coluna é considerado mínimo. Descrevemos aqui quatro casos de crianças com gliomas de baixo grau de malignidade com disseminação agressiva para o neuroeixo.