Atypical and Malignant Meningiomas: Neurooncologic Management in a Brazilian cohort.

OBJECTIVE: To analyze the surgical and oncologic treatment of a Brazilian cohort of patients with grade II and III meningioma at a follow-up time of 15 years to get an overview of these patients' outcomes. METHODS: Cross-sectional study of 43 patients (26 women, 17 men; age range 20 to 83 years; average 57.72 ± 14.54) operated on from 2000 to 2014 at a single institution, with the neuropathologic diagnosis of meningioma grade II (39 patients) and grade III (4 patients). RESULTS: Radiotherapy: 24 patients (55.81%) underwent radiotherapy; the time between the surgical procedure and the beginning of radiotherapy was 5 months; 7 patients with a diagnosis of AM underwent a new surgical procedure, albeit of adjuvant therapy, because of tumor recurrence, and only 3 of them underwent radiotherapy after the first resection. Mortality: in total, 19 deaths (44.18%) were identified in this sample: 15 (38.46%) with GII and 4 (100%) with GIII. The 10-year survival was expected in 35% of GII patients and 0% of GIII patients. CONCLUSION: Surgery is still the main form of treatment and the mainstay for prolonging survival. Radiotherapy is still controversial; however, we observed its positive impact on recurrence and progression-free survival.

Clinical Outcome, Tumor Recurrence, and Causes of Death: A Long-Term Follow-Up of Surgically Treated Meningiomas.

OBJECTIVE: The medical literature still lacks information about the impact of surgery and adjuvant treatment on the life of patients with meningioma. The clinical outcome, timing of tumor recurrence, and causes of death are often overlooked. This study evaluates these data taking into account tumor localization and histologic grade. METHODS: The article is a cross-sectional study of patients operated on between 2000 and 2014 in a single institution. The series has 593 adult patients (442 females and 151 males) and follow-up of 68.8 ± 48.9 months. Imaging of 434 patients was reviewed and 379 patients/families interviewed. RESULTS: Sixty-eight deaths were related to tumor treatment/progression and 36 to other causes. After 2 years of surgery, deaths not related to tumor were 7 times more frequent than were tumor-related deaths (odds ratio, 7.1; 95% confidence interval, 2.8-19.5; P < 0.0001). Ten-year survival was expected in 85% of patients with grade I (GI) meningioma, 35% of patients with atypic (GII) meningioma, and 0% of patients with anaplastic (GIII) meningioma. Convexity tumors had about half the risk of recurrence compared with other localizations (odds ratio, 0.4; 95% confidence interval, 0.27-0.67; P = 0.0002). In GI meningioma, recurrence was neither related to death nor to impairment of independent life. All patients with GII and GIII meningioma who had recurrence died. 96.3% of interviewees reported neurologic improvement or stability after the surgery. CONCLUSIONS: Histologic grade is the most important factor for long-term survival. Complete resection has to be pursued in GII and GIII meningioma but must be carefully weighed against morbidities in GI meningioma.

Use of intraoperative MRI for resection of gliomas.

UNLABELLED: Literature has shown that extent of tumor resection has an impact on quality of life and survival of patients with gliomas. Intraoperative MRI has been used to increase resection while preserving procedure's safety. METHOD: The first five patients with gliomas operated on at the University of São Paulo using intraoperative MRI are reported. All but one patient had Karnofsky Performance Status of 100% before surgery. Presentation symptoms were progressive headache, seizures, behavior disturbance, one instance of hemianopsia, and another of hemiparesis. RESULTS: Gross total removal was achieved in two patients. Surgical resection was limited by tumor invasion of critical areas like the internal capsule or the mesencephalon in the remaining patients. CONCLUSION: Intra-operative MRI is an important tool that helps surgeons to remove glial tumors, however, knowledge of physiology and functional anatomy is still fundamental to avoid morbidity.

Cognitive impairments in patients with low grade gliomas and high grade gliomas.

OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma.

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

Massive intra and extracranial benign meningioma metastasizing to the lung and spine: the problem of meningiomas classification and iatrogenic metastasizing / Meningioma benigno intra e extracraniano com metástase para pulmão e coluna: o problema da classificação e disseminação iatrogênica

Meningioma is a common CNS tumor and metastasis in these tumours is a rare occurrence. Malignant meningiomas are more prone to metastase. However, there are frequent case reports of metastases in atypical (grade II) and even benign (grade I), which demonstrates the somehow unsatisfying prognostic power of the current classification system. We describe an extraordinary case of a patient with a massive intra and extra-cranial, benign meningioma, metastasizing to both lung and spine. Following the report we discuss 1) some of the problems of classifying meningioma, 2) massive meningiomas and 3) the possibility of intra-operative iatrogenic metastasizing. This case is unique due to its combination of different sites of metastases, massiveness, invasive growth and benign histology. Thus it ranks among those rare but not uncommon complicated courses in meningioma which is otherwise a common benign tumor. Unfortunately the existing classification-criteria do not have sufficient power to predict such complicated courses.

Meningioma é um tumor comum que raramente metastatiza, principalmente em casos de meningiomas malignos. Contudo, há casos frequentes de metástases em casos de tumores benignos ou atípicos, o que denota evidente falha no sistema atual de classificação desses tumores. Os autores descrevem o caso de um paciente com extenso meningioma benigno intra e extracraniano que metastizou para pulmões e coluna e adicionalmente discutem questões relativas a classificação e mecanismos de disseminação hematogênica.

Use of intraoperative MRI for resection of gliomas / Uso de ressonância magnética intraoperatória para ressecção de gliomas

Literature has shown that extent of tumor resection has an impact on quality of life and survival of patients with gliomas. Intraoperative MRI has been used to increase resection while preserving procedure's safety. METHOD: The first five patients with gliomas operated on at the University of São Paulo using intraoperative MRI are reported. All but one patient had Karnofsky Performance Status of 100 percent before surgery. Presentation symptoms were progressive headache, seizures, behavior disturbance, one instance of hemianopsia, and another of hemiparesis. RESULTS: Gross total removal was achieved in two patients. Surgical resection was limited by tumor invasion of critical areas like the internal capsule or the mesencephalon in the remaining patients. CONCLUSION: Intra-operative MRI is an important tool that helps surgeons to remove glial tumors, however, knowledge of physiology and functional anatomy is still fundamental to avoid morbidity.

A literatura demonstra que extensão da ressecção do tumor tem impacto na qualidade de vida e sobrevida dos pacientes com gliomas. RM intraoperatória tem sido utilizada para aumentar a área de ressecção, preservando a segurança do procedimento. MÉTODO: Os cinco primeiros pacientes com gliomas operados na Universidade de São Paulo utilizando RM intraoperatória são relatados. Quatro pacientes tinham índice de Karnofsky de 100 por cento antes da cirurgia. Primeiros sintomas foram cefaléia progressiva, convulsões, distúrbios de comportamento, um caso de hemianopsia, e outro de hemiparesia. RESULTADOS: A remoção macroscópica total foi obtida em dois pacientes. A ressecção cirúrgica foi limitada pela invasão tumoral de áreas críticas como a cápsula interna ou o mesencéfalo no restante dos pacientes. CONCLUSÃO: A RM intra-operatório é uma importante ferramenta que auxilia o cirurgião para remover os tumores gliais, porém, o conhecimento da fisiologia e anatomia funcional ainda é fundamental para evitar a morbidade.

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1 percent of glioblastoma by methylation-specific PCR and 38.8 percent by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

Cognitive impairments in patients with low grade gliomas and high grade gliomas / Comprometimentos cognitivos em pacientes com gliomas de baixo grau e gliomas de alto grau

OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

OBJETIVO: A associação entre tumores cerebrais e déficits cognitivos é bem estabelecida na literatura. No entanto, estudos sobre a cognição de pacientes com gliomas de baixo e alto grau são escassos, especialmente, em sujeitos com baixa escolaridade. Este estudo investigou o funcionamento cognitivo de uma amostra de pacientes com gliomas de baixo e alto grau antes da intervenção cirúrgica. MÉTODO: Os pacientes com glioma de baixo grau (G1, n=19) e alto grau (G2, n=8) foram avaliados quanto à memória, funções executivas, habilidades visuo-perceptivas e visuo-espaciais, nível intelectual e linguagem. RESULTADOS: Houve prejuízo significativo em G2 na memória episódica verbal e visual, funções executivas incluindo flexibilidade mental, fluência verbal nominal e categórica e velocidade de processamento de informações. G1 demonstrou apenas déficits específicos de evocação verbal e visual, flexibilidade mental e velocidade de processamento. CONCLUSÃO: Estes achados demonstraram níveis diferenciados de comprometimento nos domínios executivos e mnésticos de pacientes com gliomas de baixo e alto grau.

Metástases encefálicas: considerações sobre diagnóstico e tratamento / Brain metastasis: a critical review about diagnosis and treatment

O câncer sistêmico é a segunda maior causa de mortalidade na população adulta. Destes pacientes, 20% desenvolvem sintomas neurológicos em algum momento de sua doença. A incidência do câncer sistêmico vem crescendo com a evolução dos exames diagnósticos, melhora das terapias e ao aumento da sobrevida da população geral. Isto reflete, conseqüentemente, no aumento da incidência das metástases intracranianas o que representa, por sua vez, uma considerável fonte de morbimortalidade. Neste artigo os autores revisam os princípios de diagnóstico e conduta a cerca das metástases encefálicas.

Introdução ao estudo das craniotomias ântero-laterais e osteotomias associadas / An introduction to the study of osteotomies associated to anterolateral craniotomies

Neste artigo estão integrados conceitos elementares no aprendizado das vias de acesso ântero-laterais do crânio, de acordo com uma sistematização baseada na associação progressiva de osteotomias às craniotomias rotineiras. Um roteiro de estudos sobre estes acessos é exposto com as respectivas recomendações de leitura.

To systematize progressive association of regional osteotomies into the classical and basic anterolateralcraniotomies. The basic literature was reviewed and inicated as a direction to elementary studies about this approaches.