Despite recent advances in various therapeutic modalities for treating malignant gliomas, these tumors are still hardly curable, and the development of the new therapies is warranted in the field of chemotherapy and radiotherapy. In this context, many therapeutic compounds have been investigated, and, especially, drug treatment using molecular targeting compounds has attracted considerable attention amongst neuro-oncologists. Since previous studies have elucidated that malignant gliomas show an up-regulation of various growth factor receptor-related activities, many clinical studies using compounds targeting those receptors have been conducted. However, the development of effective molecular targeting therapy for malignant gliomas is limited by a relative lack of understanding of the biology of glioma cells. Thus, laboratory investigation including an animal tumor model is indispensible in designing a better therapeutic approach for these tumors. On the other hand, genetic analysis of gliomas has led to the discovery of prognostic markers. Recent clinical studies focusing on genetic markers has revealed the importance of the methylation status of the O^6-methylguanine-DNA methyltransferase promoter and mutational status of isocitrate dehydrogenase 1 as prognostic factors of gliomas, leading to the idea that genetic analysis could help in selecting cases with a favorable treatment response and, possibly, individualization of the treatment. In this text, recent advances in glioma biology are reviewed to help better understand the problems and future prospects in the treatment of these tumors.

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Malignant gliomas, the most common type of primary brain tumors, are classified as grade III/IV on the basis of histopathological and clinical criteria established by the World Health Organization. Especially, grade IV tumors (glioblastoma) still show poor outcomes in spite of aggressive treatment strategies. In 2006, a new chemotherapeutic drug, temozolomide (TMZ), was certified by the National Ministry of Health and Welfare in Japan. Since then, it has become one of the first-line therapeutic tools for the treatment of malignant gliomas. However, its clinical outcomes depend on O^6-methylguanine-DNA methyltransferase (MGMT) status, and MGMT modification is one of the key factors to obtain greater clinical benefits in the future. IFN-β exhibits pleiotropic biological effects and has been widely used either alone or in combination with other antitumor agents in the treatment of malignant gliomas. In the treatment of malignant gliomas, IFN-β can act as a drug sensitizer, enhancing toxicity against various neoplasms when administered in combination with nitrosourea. Recently, it has been demonstrated that IFN-β markedly enhanced chemosensitivity to TMZ in an in vitro study of human glioma cells; this suggested that one of its major mechanisms is the down-regulation of MGMT transcription via p53 induction. This study suggested that IFN-β and TMZ combination therapy might further improve the clinical outcome in malignant glioma as compared to TMZ plus radiation therapy. The phase I clinical study has already been done and revealed that this combination therapy caused minimal toxicity. In order to evaluate the clinical effectiveness of combination of IFN-β and TMZ, we are conducting a clinical study the namely Integrated Japanese Multicenter Clinical Trial: A Phase II Study of Interferon-β and Temozolomide for Glioma in Combination with Radiotherapy (INTEGRA Study). The results of this clinical study will be expected in the near feature.

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The prognosis of patients with malignant glioma has been improved recently, mainly due to availability of advanced intraoperative technologies for aggressive and safe tumor resection, as well as introduction of temozolomide as a highly effective drug for postoperative chemotherapy. Their use along with contemporary radiotherapy constitutes the basis of the present cutting-edge management of these tumors. Other modern therapeutic options directed on the improvement of patients' survival are currently evaluated in various clinical trials. Particularly, several kinds of immunotherapy using EGFRvIII, WT1, or autologous formalin-fixed vaccine are under investigation as well as new vectors of recombinant herpes virus and oncolytic virus for gene therapy. Additionally, various local therapies directed on the improvement of the tumor growth control have been developed, such as slow-release wafers and convection-enhanced delivery of chemotherapeutic drugs, brachytherapy, photodynamic therapy, highly focused ultrasound, etc. It can be expected that in the future combined treatment based on the synergistic biological and biophysical effects of various therapeutic modalities on the pathological tissue will be translated in further improvement of the clinical outcome of patients with malignant gliomas. Moreover, newly developed treatment approaches with the use of stem cells, seem very promising.

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BNCT has a unique concept for cell biological targeting. BNCT is a binary approach composed of a boron compound and a neutron beam. If we can accumulate boron compounds selectively to tumor tissue, neutron α reaction will occur only within the tumor cells, which is followed by tumor cell death with minimal hazardous effects for normal tissues. We introduce here the indication, clinical results of BNCT for newly diagnosed GBM and recurrent malignant meningiomas. For deep-seated tumors, instilling air into the tumor cavity is useful to obtain deeper neutron flux penetration. In addition, we also introduce how to treat radiation necrosis in the brain. Surgical removal of the necrotic foci and some medical treatments such as anticoagulants and bevacizumab, anti-VEGF antibody, are useful for this treatment.

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We can conclude that awake surgery has brought "logic" to glioma surgery. Before the introduction of awake surgery, the glioma surgery tended to be subjective, depend on the experienced surgeon's craftsmanship, and difficult to be evaluated. That is why glioma surgery was not and could not be discussed enthusiastically, until recently. Combination intraoperative functional brain mapping/monitoring techniques under an awake condition with neuronavigation systems and intraoperative magnetic resonance imaging has changed the glioma surgery into an objective, universal, and evaluable procedure, resulted to improved the treatment outcome of gliomas, contributed to the investigation of brain function, and helped develop neuroanesthesiology.

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After co-registration of functional MRI with finger tapping tasks for corticospinal tract tractography, the results were imported to a neuronavigation system (functional neuronavigation). Cortical and subcortical stimulation with 5-train electric pulses was then used to identify the motor system. Functional neuronavigation was a reliable and practical technique for preservation of the motor function in glioma surgery

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We report a case where a thread of cotton pledgets was left behind after a craniotomy. A 61-year-old woman presented with sudden onset vomiting and consciousness disturbance. Computed tomography demonstrated a massive intracerebral hemorrhage in the left frontal lobe, which had collapsed into the lateral ventricle. The hematoma was removed successfully. However post-operative skull X-ray and computed tomography revealed an abnormal linear structure. Immediately, a second operation was performed and a thread of cotton pledgets was removed. The thread fell from the cotton pledgets during the first craniotomy. The radiography contrasting nature of the thread made it easy to find this thread later. In order to prevent such an occurance, it is important that we use cotton pledgets with radiography contrasting thread, count the used cottons and take a skull X-ray at the end of the operation.

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We report a case of a cystic lesion mimicking an arachnoid cyst, which developed to a large cystic space-occupying lesion with peritumoral cysts. A 56-year-old man who had been experiencing mild weakness in the right hand and mental lethargy over a period of 1 month was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a round cystic tumor with large peritumoral cysts in the left frontal lobe. The cystic tumor contained a solid component, which appeared to be attached to the cyst wall just under the dura matter. Eight years before the admission, the tumor was misdiagnosed as an arachnoid cyst by the evaluation via plain CT scan. During surgery, a cystic tumor with the solid component was totally removed and the peritumoral cyst walls were subtotally resected. Histological examination indicated that the tumor was a microcystic meningioma and that the wall of the peritumoral cyst was a degenerated arachnoid membrane. This case suggests that cystic meningiomas may be mistaken for arachnoid cysts. The diagnosis of arachnoid cysts on the basis of plain CT images may be problematic, and knowledge of this variability during the differential diagnosis of an arachnoid cyst can help avoid diagnostic pitfalls. Thus, MRI with gadolinium enhancement appears to have diagnostic value in the cases of cystic meningiomas resembling arachnoid cysts.

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