The overall age-adjusted incidence rate of brain tumors in Japan was reported to be 14.1 (11.6 for males, 16.4 for females) per 100,000 population per year and it is almost the same as that in the United States (19.3 per 100,000). The most common tumors in both Japan and the USA are meningiomas, gliomas, pituitary adenomas, neurinomas and primary CNS lymphomas. Gliomas are the most common malignant brain tumors and the new incidence of gliomas are supposed to be about 4,000-5,000 patients per year. Gliomas are rare cancers and the prognoses of grade 2/3 gliomas have improved for 40 years, however, the prognosis of glioblastoma has remained poor and a 5-year overall survival rate is still under 10% and as such it is the worst prognostic cancer. The standard therapy for grade 2 gliomas is maximal resection + single radiation therapy (RT) and for grade 3/4 malignant gliomas it is maximal resection+RT+temozolomide (TMZ), but these protocols are still controversial. One of the reasons that gliomas continue to have poor prognoses is that there are few chemotherapeutic agents against them. Neurosurgeons and neuro-oncologists have to know the evidence of the treatments for gliomas and we have to attend many clinical trials around the world in order to improve the prognoses of malignant gliomas.

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Intracranial gliomas can be clearly revealed based on the preoperative neuroimaging, an intraoperative investigation of frozen or smear sections of the biopsy sample, and detailed postoperative evaluation of the resected tissue using various histopathological, immunohistochemical, and molecular methods. In the majority of cases advanced MRI techniques permit us to establish an accurate diagnosis of the parenchymal brain tumor, however, differentiation of the lesion with cerebral infarction and demyelination disease may be problematic, especially if aggressive surgical resection is under consideration. In such cases functional and metabolic neuroimaging, such as proton MR spectroscopy and positron emission tomography (PET) with methionine, may be extremely useful adjuncts providing valuable diagnostic information. It should be emphasized, that stereotactic biopsy of the brain lesion can be accompanied by sampling errors. In our series the diagnostic accuracy through biopsy in cases of low-grade gliomas was less than 50%. Molecular evaluation of the tissue specimen may be helpful to arrive at a precise diagnosis based on the tissue samples. Intraoperative neuronavigation, which is routinely used in our practice, affords a surgeon precise orientation in the surgical field and tremendously improves the possibilities for aggressive tumor resection. While the available neuronavigation devices may be based on different technical principles and have different tools for data visualization, the optical tracking and display on a PC screen seems to be the most common options. Recently, novel techniques, which permit fusion of the functional data obtained with tractography, the visualized eloquent cortex, and or metabolic information provided by PET, have become available and significantly increase the number of surgical opportunities for aggressive and safe brain turner resections. Nevertheless, understanding and recognizing the possible navigation errors is very important. Particularly, the effect of brain shift can result in 4-8 mm mislocalization errors, which should be compensated for by intraoperative MRI, CT, or ultrasound. Further development of neuronavigation techniques and the creation of preoperative three-dimensional simulation devices for detailed planning of the surgical procedure may result in significant breakthroughs in the surgical management of gliomas.

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With the introduction of temozolomide (TMZ), a drug treatment for malignant gliomas has been developed and the importance of chemotherapy has been validated. Nonetheless, these tumors are still incurable, and many issues remain to be solved. Recent advances in tumor genetics have enabled us to better predict each patient's prognosis, and, especially in the TMZ era, methylation of the O^6-methylguanine-DNA methyltransferase (MGMT) promoter has been thoroughly investigated. This DNA repair enzyme catalyzes the O^6-methylguanine that TMZ creates and theoretically promotes TMZ resistance, and clinical studies have revealed that MGMT-proficient gliomas indeed showed a poorer prognosis. Thus many studies were carried out in an effort to inhibit MGMT in gliomas and to overcome TMZ resistance, but unfortunately, none have yielded a successful result, which leads to the conclusion that TMZ-resistance is not promoted solely by MGMT. Since medical treatment for malignant gliomas using DNA damaging agents could show limited efficacy, a new concept of molecular-targeted therapy has been developed. However, clinical studies using various molecular-targeted compounds did not make remarkable improvement in patients' prognosis either. New problems that have emerged from various clinical studies are discussed in this text to open novel prospects for medical treatment of malignant gliomas.

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The prognosis of patients with malignant gliomas is still poor, and the dominant pattern of failure after conventional treatment is "local". Therefore, intensive treatment targeting the regional tumor is required to improve the survival of patients. Recent innovations in irradiation techniques, such as stereotactic radiosurgery/therapy (SRS SRT),3 dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT), have made it possible to deliver a higher dose to the target without increasing the dose to the surrounding normal structures. The dose-escalation trials using these advanced irradiation techniques revealed that high-dose irradiation with a dose of 90 Gy or more improved the control of the local region. However, these trials also revealed that local control alone did not contribute to better patient survival. To achieve better patient survival, a multimodal treatment is required to control not only regional tumor cells but also infiltrating tumor cells and freed cells in the cerebrospinal fluid. High-dose irradiation by advanced radiotherapy may play a significant role to control the regional tumor in these multimodal treatments. Radiation injury is still a serious problem especially in the long survivors, despite the accurate delivery of doses afforded by advanced radiotherapy. Target delineation based upon precise information concerning the extent of tumor cells is required to limit brain damage after irradiation. However, conventional imaging modalities such as MRI and CT do not fill the requirements, but biological imaging such as amino-acid PET is expected to provide the necessary information to accurately delineate the target. Bevacizumab is an antibody against the vascular endothelial growth factor (VEGF). This agent is used in the treatment of patients with several cancers, but it is also known to have a significant effect on radiation necrosis. The establishment of a treatment for radiation necrosis will further improve the safety of high-dose irradiation. In the future, advanced radiotherapy is expected to play an increasingly important role in the multimodal treatment of patients with malignant gliomas.

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Technologic advances in genetic analysis have yielded information on the genetics of glioma from various fields of research. The development of DNA-microarray and DNA-Chip and other instruments for genetic analysis facilitated a comprehensive approach to the detection of genetic alterations. In 2008, The Cancer Genome Atlas (TCGA) on glioblastoma (GBM) was published in the journal Nature. It was found that anomalies in 3 signal pathways contributed importantly to the pathogenesis of GBM. Furthermore, GBM was divided into 4 subtypes based on the expression of genes and on clinical factors such as the therapeutic response. Among genetic alterations in gliomas, 1p/19q loss of heterozygosity is frequently found in oligodendrogliomas and appears to be a good predictive factor. Since the detection in 2008 of Isocitrate dehydrogenase-1/2 (IDH1/2) gene mutations in gliomas, the IDH1/2 gene has been subjected to genetic analysis in laboratories around the world. The IDH1 mutation, thought to be an early event in gliomagenesis, was found in 60〜80% of WHO grade 2/3 gliomas and is now thought to be a good prognostic factor. In piloycytic astrocytoma, the genetic alteration of proto-oncogen B-Raf kinase (BRAF) has been reported. BRAF is a signal molecule in the Mitogen-activated protein (MAP) kinase pathway and other genetic alterations in this signal have also been documented. Consequently, MAP kinase pathway activation is considered to play a central role in the tumorigenesis of pilocytic astrocytomas.

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In this paper, we selected three representative disorders among pediatric gliomas and reviewed standard treatments for these diseases. Optic pathway/hypothalamic astrocytoma : The formation of this rare disease is involved with BRAF mutation as well as cerebellar pilocytic astrocytoma. Radical resection is not recommended as initial therapy due to high morbidity. Despite its good tumor control, radiotherapy is not a standard therapy due to neuroendocrine and neurocognitive dysfunction. Several papers have reported the effectiveness of platinum-based chemotherapy, which is a useful for induction therapy. Ependymal tumors : Recent progress in molecular analyses has suggested that some markers might be used for staging ependymoma. While total resection is considered to be strongly correlated with patients'survival, the majority of recurrence occurs in the primary site. Despite many clinical trials, chemotherapeutic agents were not found to be effective for this disease. Since whole brain radiation cannot prevent dissemination, local radiation is recommended for adjuvant therapy. Brain stem gliomas : The prognosis of this disease is still dismal, and median survival time is within 1 year. Although clinical trials have been conducted to assess the efficacy of chemotherapy prior to, concomitantly with, or after radiotherapy, an effective regimen has not yet been established. Therefore, only conventional local radiotherapy is the standard regimen for this disease. A new therapeutic approach, such as convection-enhanced drug delivery, would be required for improved outcomes in patients with this disease.

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Objective : The aim of the present study was to investigate the efficacy of topiramate (TPM) for the treatment of neurosurgical disease with localization-related epilepsy. Methods : TPM was administered as an add-on drug for patients who presented refractory seizures despite trying two or three antiepileptic drugs. A total of 27 patients with refractory localization-related epilepsy were enrolled in the study. Results : TPM was administered for at least 12 months. Fourteen patients attained seizure free status, 2 patients had a reduction of seizure frequency of more than 50%. The remaining 11 patients discontinued TPM because of adverse effects or insufficient efficacy. Among the 16 patients whose seizures were well-controlled without adverse effects, 11 patients (63.8%) took TPM at a dosage of less than 100 mg/day a smaller than recommended amount. On the contrary, 11 patients who were intolerable to the adverse effects of TPM, such as headache, dizziness or fainting withdrew from TPM administration, in spite of careful initial titration from a small dose. Conclusions : Seizure control was achieved with a lower dose of TPM than recommended for neurosurgical patients with localization-related refractory epilepsy.

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A 44-year-old man suffering from a hearing impairment was admitted to our institution. An artriovenous malformation (AVM) located at the pineal region was revealed by magnetic resonance imaging (MRI) studies. We performed surgical resection through the infratentorial supracerebellar (ITSC) approach with the patient in a sitting position. Complete resection was confirmed by intraoperative angiography. Air embolism was successfully avoided by monitoring the intra-ventricular air bubbles using transesophageal ultrasonography. He was discharged from our clinic without any neurological deficits. Histopathological study revealed that the specimen included neuronal cells arranging in a lobular fashion, which was typical for the pineal body. The ITSC approach with the patient in a sitting position might be one of the most effective approaches in surgical resection of pineal AVMs.

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We report three rare cases of spontaneous regression of meningiomas. The cases were comprised of three elderly male patients ranging in age from 72 to 79 years old. The tumors were located at the parasagittal region, the middle fossa and the olfactory groove. The tumor volumes were calculated using Cavalieri's Principle: V=4/3×π×a/2×b/2×c/2 (where a, b, and c represent the diameters in three dimensions). These three tumors regressed in size without any intervention and went from 6.1cm^3 to 1.1cm^3 (reduction rate 82%) during 4.5 years in case 1, from 7.2 cm^3 to 3.4 cm^3 (53%) during 6 years in case 2, and from 16.0 cm^3 to 4.0 cm^3 (75%) during 6.5 years in case 3. A closely watched follow-up period is a useful therapeutic option for elderly patients with asymptomatic meningioma.

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