We review several reports on the preoperative diagnosis of malignant brain tumors by MRI or PET and present our imaging findings on this clinical entity. We document the usefulness of diffusion- and per fusion-weighted MRI and of FDG- and MET-PET scans. These imaging findings are useful not only for the diagnosis of malignant brain tumors but also for the identification of the biological characteristics of the tumor cells. We found that DWI, PWI and FDG- or MET-PET are important tools for the diagnosis of malignant brain tumors such as gliomas, malignant lymphomas, and metastatic brain tumors.

View full abstract

The role of surgery in malignant gliomas under the assistance of modern multi-modal navigation systems was retrospectively analyzed. The patients in this study included 12 with anaplastic astrocytomas and 38 with glioblastomas, all of which presented as supratentorial hemispheric tumors in adults. The navigation systems used consisted of echo-linked real time navigation, fluorescence-guided tumor detection and functional mapping with subcortical stimulation. The mean rate of tumor resection was 92% in non-eloquent areas and 88% in eloquent areas. About half of the tumors in eloquent areas were resected by 95% and more. The extensive resection used in the glioblastomas did not deteriorate these patient's postoperative KPS scores, but rather improved them. Although three patients with 100% resection of their glioblastoma survived longer than three years, extensive resection of 95% and more did not significantly prolong either the overall survival or progression-free survival compared to a tumor resection of less than 95% in glioblastomas. Median survival time (MST) in resections of 95% and more in glioblastoma was 18.5 months and MST in resections of less than 95% of the tumor was 12.6 months. The modern multi-modal navigation systems enabled the extensive resection of malignant gliomas without compromising neuronal function, but any significance of the extent of tumor resection in prognosis remains unclear.

View full abstract

Cell cycle checkpoints block the transition from one phase of the cell cycle to the next phase until all processes are completed. Defects in these checkpoint functions lead to genomic instability, which results in the development of malignant tumors. However, it has become known that a loss of checkpoint function is directly related to sensitivity to antineoplastic treatments. Most cancer cells are deficient in G1 checkpoint function and therefore fail to arrest in the G1 phase on exposure to genotoxic agents. Instead, they accumulate temporarily in the G2 phase. However, given that the G2 checkpoint is also partially impaired in cancer cells, they are unable to maintain G2 arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe or mitotic death. Mitotic catastrophe is an important mechanism for the induction of cell death in cancer cells by antineoplastic agents. Cells entering mitosis with DNA damage arrest at metaphase for more than 10hr without chromosome segregation and subsequently die directly from metaphase. This long-term metaphase arrest before catastrophic death is termed the "precatastrophic phase". We found that spindle check is activated during the precatastrophic phase. Therefore, inhibition of the spindle checkpoint function as a result of depletion of BubR1 or Mad2 by RNAi caused cells to escape from mitotic catastrophe and led to subsequent abnormal mitosis when DNA damage is induced. Our data suggest that a dysfunction of the mitotic checkpoint in cancer cells may confer resistance to DNA-damaging agents and malignant progression. In this review article, I would like to summarize how cancer cells are terminated by DNA-damaging agents and anti-mitotic drugs. Based on these findings, I would like to propose the novel mechanisms by which tumors become insensitive to those chemotherapeutic agents.

View full abstract

In the treatment of glioblastoma (GBM), postoperative radiotherapy has been recognized as standard therapy, whereas the addition of chemotherapy has been a controversial issue. A meta-analysis based on 12 randomized trials suggested only a small benefit. The recent trial by the European Organisation for Research and Therapy of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trial Group was the first study to demonstrate unequivocally that the addition of temozolomide to radiotherapy provides a statistically significant survival benefit in GBM. For anaplastic oligodendroglioma and oligoastrocytoma, two separate trials by EORTC and the Radiation Therapy Oncology Group clearly demonstrated that chemotherapy by procarbazine, lomustine, and vincristine, plus radiotherapy does not prolong survival but does increase the incidence of progression-free survival. The combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors, and no genetic subgroup could be identified that benefited with respect to survival from adjuvant PCV. In low-grade gliomas, older age, astrocytoma histology, presence of neurologic deficits, largest tumor diameter, and tumor crossing the midline were important prognostic factors for survival, and these factors can be used to identify low-risk and high-risk patients. Taken together, these evidences reported recently provide the most up-to-date treatment strategies for malignant gliomas.

View full abstract

The merging of bio-technology, nano-technology, and computer technologies has led to the creation of new advanced medical fields including gene therapy. In 2000, we started a clinical trial of the first original gene therapy for malignant glioma based on made-in-Japan technology, and confirmed the safety and effectiveness of this therapy. The results led to the founding of the Center for Genetic and Regenerative Medicine (CGRM), which is an institute to put advanced medicine into practice in our Nagoya University Hospital. In 2006, CGRM gained ISO (International Organization for Standardization) 9001: 2000 and 13485: 2003 accreditation. We are now the first academic institute in Japan to achieve ISO Certification. At CGRM we are making an effort to gain a better understanding of advanced medical services with the goal of ensuring that our patients receive the best available, safe and effective medical services.

View full abstract

Usually we use 5-aminolevulinic acid (5-ALA) and a navigation system to remove malignant gliomas. 5-ALA is converted to protoporphyrin IX (PpIX) in the body and expresses red fluorescence by the excitation of blueviolet light. As PpIX is preferentially accumulated in the tumor tissue in comparison with normal tissue, this red fluorescence becomes a good landmark for discriminating between normal and tumor tissue, especially for malignant gliomas, which have infiltrative characteristics. In this paper, we introduce operations for three different disease conditions using these modalities. One condition is an irregularly shaped malignant-transformed glioblastoma (GB)without radiation necrosis, which invaded the corpus callosum. The other two are mixed diseases of radiation necrosis and tumor recurrence of GB and pure radiation necrosis after boron neutron capture therapy and conventional X-ray irradiation. We can dissect red-fluorescence-positive tumor tissue under 5-ALA-guided microsurgery. The fence-post catheter technique using the navigation system is useful especially for the removal of necrotic tissue. Not only tumor tissue but also the gliotic plane just next to radiation necrosis sometimes show red fluorescence activity by 5-ALA administration. The most essential point of 5-ALA-guided microsurgery is to use good equipment that can provide enough operative fields even under the fluorescence mode.

View full abstract

We report a rare case of Onodi cell mucocele. The patient was a 37-year-old man who developed acute impairment of his left visual acuity without pain or abnormal findings in the ocular fundus. Bone window CT scan and MR images demonstrated a mass lesion surrounding and over the left optic canal. An emergency craniotomy revealed an Onodi cell mucocele, and its excision resulted in good visual recovery for the patient. Onodi cells are the most posterior air cells of the ethmoid sinus. They are anatomically situated over the optic canal. Onodi cell mucocele must be included in the differential diagnosis of unilateral retrobulbar optic neuropathy. Careful examination of CT scans and MR images, and prompt surgical intervention are recommended.

View full abstract