Gliomas malignos: biología molecular y detalles oncogenéticos / Wicked gliomas: molecular biology and oncogenetics detail

RESUMEN La biología de los gliomas malignos se asocia con el balance de la expresión de las proteínas que controlan de manera positiva o negativa el ciclo celular, la proliferación, la motilidad, la neoformación vascular y el reconocimiento del sistema inmune. La frecuencia de las alteraciones genéticas que están presentes en GBM2 y GBM1 son diferentes así como la edad de los pacientes en la que se presentan. Mientras que los GBM1 suelen aparecer en edades más tardías, alrededor de los 60-70 años, los GBM2 suelen presentarse en edades más tempranas, 40-50 años. En la génesis del glioblastoma existen alteraciones moleculares a nivel de genes supresores de tumores, oncogenes y genes reparadores de ADN (AU).

ABSTRACT The glioblastoma it is the primary wicked tumor of the central nervous system more common in adults and it invariably associates to a bad presage. The biology of the wicked gliomas associates with the balance of the expression of the proteins that they control of positive way or negative the cellular cycle, the proliferation, the motility, the vascular neoformation and the recognition of the immune system. The frequency of the genetic alterations that they are present in GBM2 and GBM1 is different. While the GBM1 usually appears in later ages, around the 60-70 years, the GBM2 usually presents in earlier ages, 40-50 years. In the genesis of the glioblastoma exist molecular alterations at level of suppressive genes of tumors (GST), oncogenes and reparative genes of DNA (AU).

Mortalidad por tumores cerebrales malignos durante los primeros 30 días de la cirugía / Mortality from malignant brain tumors within the first 30 days after surgery

Introducción: las complicaciones neurológicas en la cirugía de los gliomas de alto grado están relacionadas con problemas en localización y exposición, extensión de la resección y la manera en que se manipulan los tejidos. Hay factores secundarios que contribuyen a la evolución desfavorable y la muerte precoz de un paciente. Objetivos: establecer la relación que existe entre la mortalidad en los primeros 30 días y diferentes factores de riesgo e identificar causas de muerte. Métodos: fueron operados 131 pacientes en el Servicio de nNeurocirugía del Hospital Calixto García desde enero de 2005 a enero de 2010, con el diagnóstico de gliomas de alto grado. De ellos, 14 fallecieron en los primeros 30 días. Variables principales utilizadas: edad, localización tumoral, grado de resección quirúrgica y causas de la muerte. Se aplicó la prueba chi cuadrado de independencia con un nivel de significación de 0,05 para evaluar relación entre variables. Resultados: la mortalidad perioperatoria fue del 10,7 por ciento. El riesgo fue mayor en el sexo masculino; discretamente mayor en los mayores de 60 años. No estuvo relacionado con la localización del tumor. Operar con signos de enclavamiento cerebral, incrementó al máximo la probabilidad de fallecer en el primer mes. La resección parcial en relación con la total y con la biopsia mostró mayor probabilidad de mortalidad. No hubo muerte transoperatoria. Conclusiones: los factores que influyeron principalmente en la evolución desfavorable fueron: la baja puntuación en la escala de Karnofskyy una resección limitada, igual o menor que 50 por ciento en una craneotomía(AU)

Introduction: The neurological complications found in the high gradegliomas surgery are primarily related with location, exposure and extension of the resection and with the way of handling tissues. There are secondary factors that contribute to the unfavorable progression and even the early death of patients that suffers this disease. Objectives: To set the relationship between mortality within the first 30 days after surgery and the different risk factors, and to identify the causes of death. Methods: One hundred and thirty one patients diagnosed with high gradegliomas were operated on in the neurosurgery service of Calixto García hospital from January 2005 through January 2010. Fourteen of them died within the first thirty days. The study variables were age, tumor location, degree of surgical resection and causes of death. Chi-square test of independence with significance level of 0.05 was applied to evaluate the association among the variables. Results: The perioperative mortality rate was 10.7 percent. The risk of death was higher in males; slightly higher in those over 60 years and unrelated to the tumor location. If patients are operated on with signs of brain herniation, they are more likely to die in the first month. Partial compared to total resection and to biopsy showed higher mortality probabilities. There was no intraoperative death. Conclusions: The low scoring in the Karnofsky Scale, and a partial resection equal or smaller than 50 percent in a craniotomy were the influential factors in an unfavorable outcome of disease(AU)

Treatment of recurrent glioblastoma with intra-arterial BCNU [1, 3-bis (2-chloroethyl)-1-nitrosourea] / Tratamento do glioblastoma recorrente com BCNU [1, 3-bis (2-chloroethyl)-1-nitrosourea] intra arterial

Contemporary therapies for patients with glioblastomas remain marginally efficient, and recurrence following surgery, radiation therapy and adjuvant chemotherapy is practically universal. The major obstacles to the successful use of chemotherapy for CNS tumors are the drug delivery to the tumor site and the infusion of chemotherapeutic agents directly into the arterial supply of a tumor. The latter could provide a pharmacokinetic advantage by enhancing drug delivery to the tumor. Sixteen patients with recurrent unilateral glioblastomas treated with intra-arterial BCNU were evaluated retrospectively. During the infusion, eleven patients referred pain in the ipsilateral eye, five patients were nauseated, three reported headache, one patient presented mental confusion, while two presented focal signs. There were two deaths during the course of therapy. Four patients achieved temporary clinical improvement, seven showed disease stability, and three presented clinical deterioration. The median total survival time was 87.9 weeks. Unilateral vision loss and focal signs were observed as delayed complications of this treatment. This study has confirmed previous reports indicating that arterial chemotherapy is clearly not curative, and presents serious toxicity. Only through a randomized prospective study performed in a large series of patients can the questions concerning survival period increment be answered properly.

Os tratamentos atuais para pacientes com glioblastoma permanecem pouco eficientes e a recorrência, acompanhando cirurgia, radioterapia e quimioterapia, é a regra geral. O maior obstáculo para o sucesso da quimioterapia para os tumores do SNC é a disponibilização da droga no sitio do tumor sendo que a infusão do agente quimioterápico diretamente na trama arterial da lesão pode proporcionar vantagens por maior liberação da substância diretamente no tumor. Estudamos retrospectivamente dezesseis pacientes com glioblastomas recorrentes, unilaterais, que foram tratados com BCNU intra-arterial; durante a infusão, onze pacientes sentiram dor no olho ipsilateral, cinco ficaram nauseados, três queixaram-se de cefaléia, um apresentou confusão mental e dois apresentaram sinais focais. Ocorreram duas mortes durante a terapia. Quatro pacientes apresentaram melhora clinica temporária, sete apresentaram estabilização e três apresentaram deterioração. A média de sobrevida total foi de 87,9 semanas. Perda da visão unilateral e sinais focais foram complicações tardias. Este estudo confirmou trabalhos anteriores indicando que a quimioterapia intra-arterial claramente não é curativa, séria toxicidade pode ocorrer e somente um estudo prospectivo e randomizado, realizado em uma serie maior de pacientes, poderá responder questões sobre o aumento do tempo de sobrevida de forma adequada.