The authors have recently performed a fluorescence-guided tumor resection procedure by using high-dose fluorescein sodium without any special surgical microscopes for the intraoperative visualization of glioblastoma multiforme (GBM), and they report on the actual procedure and clinicopathological findings. Thirty-two patients with GBMs underwent tumor resection during which this fluorescence-guided procedure was used. Fluorescein sodium (20 mg/kg) was intravenously injected after dural opening at the craniotomy site. The tumor was stained almost homogeneously yellow and the color was intense enough to be readily perceived for resection. The center of the solid lesion was stained a deep yellow and surrounded by a transition zone that was faintly stained. The colored lesion was clearly distinguishable from the unstained zone outside the GBM, particularly in the white matter. Both the deeply and faintly stained regions included endothelial proliferation and dense tumor cells. In the unstained region, less dense tumor cells were consistently revealed; however, no endothelial proliferation could be seen. Gross-total resection (GTR) was successful in 84.4% of the patients who received an injection of fluorescein sodium, which accounted for 100% of those in whom all the visible yellow color (both the deeply and faintly stained regions) was judged to have been resected during operation. Gross-total resection was performed in 100% of the patients who underwent the fluorescence-guided procedure and assigned to Stage I, a GBM stage in which, as a therapeutic policy, the tumor should be resected as radically as possible. The GTR rates in patients who received fluorescein sodium were significantly higher than those in patients who did not (73 patients with GBMs who underwent tumor resection without the fluorescence-guided procedure). Although the extent of surgery was revealed to be one of the significant and independent prognostic factors for GBM, the fluorescein sodium-guided resection procedure was not a significant or independent prognostic factor in this series. This surgical procedure does not require any special surgical microscopic equipment and is simple, safe, useful, readily accomplished, and universally available for resection of GBMs. Its efficacy simplifies the surgical procedure of navigating the stained lesion from the unstained area to achieve GTR of GBMs, which can be demonstrated on magnetic resonance images.

BACKGROUND AND PURPOSE:Positron-emission tomography (PET) is a useful tool in oncology. The aim of this study was to assess the metabolic activity of gliomas using 11 C-methionine (MET), [ 18 F] fluorodeoxyglucose (FDG), and 11 C-choline (CHO) PET and to explore the correlation between the metabolic activity and histopathologic features.

Glioblastoma is the most deadly brain tumor type and is characterized by a severe and high rate of angiogenesis, remaining an incurable disease in the majority of cases. Mechanistic understanding of glioblastoma initiation and progression is complicated by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell or tissue of origin. To determine these mechanisms, mouse models that recapitulate the molecular and histological characteristics of glioblastoma are required. Unlike in other malignancies, viral-mediated mouse models of glioblastoma rather than chemically induced mouse models have been developed because of its sensitivity to viruses. Based on recent molecular analyses reported for human glioblastoma, this review critically evaluates genetically engineered, xenograft, allograft, viral-mediated, and chemically induced mouse models of glioblastoma. Further, we focus on the clinical value of these models by examining their contributions to studies of glioblastoma prevention, tumorigenesis, and chemoresistance.

The aim of this study is to assess the different metabolic activities characteristic of glioma recurrence and radiation necrosis (RN) and to explore the diagnostic accuracy for differentiation of the two conditions using 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). Fifty patients with lesions suggestive of recurrent glioma by magnetic resonance imaging (MRI) underwent MET, CHO, and FDG-PET. All patients who had previously been treated with radiotherapy for malignant glioma were subjected to open surgery and pathological diagnosis (17 recurrent grade 3- gliomas (Gr.3s) comprising 7 anaplastic astrocytomas (AAs) and 10 anaplastic oligodendrogliomas (AOs), 17 recurrent glioblastomas (Gr.4s), and 16 RNs). We measured the PET/Gd volume ratio, the PET/Gd overlap ratio, and the lesion/normal brain uptake ratio (L/N ratio) and determined the optimal index of each PET scan. The PET/Gd volume ratio and the PET/Gd overlap ratio for RN were significantly lower than those of glioma recurrence only with MET-PET (P < 0.05). The L/N ratio of RN was significantly lower than that of Gr.4 with all PET imaging (P < 0.001) and was significantly lower than that of Gr.3, especially for AO, only with MET-PET images (P < 0.005). Receiver operating characteristic (ROC) analysis showed that the area under the curve of MET, CHO, and FDG was 92.5, 81.4, and 77.4, respectively. MET L/N ratio of greater than 2.51 provided the best sensitivity and specificity for establishing glioma recurrence (91.2% and 87.5%, respectively). These results demonstrated that MET-PET was superior to both CHO and FDG-PET for diagnostic accuracy in distinguishing glioma recurrence from RN.

A retrospective analysis of 32 patients with tuberculum sellae meningiomas who underwent surgery via a unilateral pterional approach was performed. A selective extradural anterior clinoidectomy (SEAC) technique was added in 20 patients. All patients had visual dysfunction preoperatively. Macroscopically complete removal with Simpson grade II was performed in 28 patients (87.5%). The postoperative visual function improved in 25 (78.1%), did not change in 3 (9.4%), and worsened in 4 patients (12.5%). The SEAC technique was effective, especially for removal of the tumour extending into the sellae/pituitary stalk (9 patients), the optic canal (4 patients) and hypothalamus (4 patients) with preservation of the visual and endocrinological function. These results were superior to those of surgery without SEAC technique. This technique is therefore recommended for complete resection of the tuberculum sellae meningiomas extending to the surrounding anatomical structures as the SEAC procedure reduces the risk of intraoperative optic nerve injury considerably.

We investigated morphological and metabolic changes of radiation necrosis (RN) of the brain following bevacizumab (BEV) treatment by using neuroimaging. Nine patients with symptomatic RN, who had already been treated with radiation therapy for malignant brain tumors (6 glioblastomas, 1 anaplastic oligodendroglioma, and 2 metastatic brain tumors), were enrolled in this prospective clinical study. RN diagnosis was neuroradiologically determined with Gd-enhanced MRI and 11C-methionine positron emission tomography (MET-PET). RN clinical and radiological changes in MRI, magnetic resonance spectroscopy (MRS) and PET were assessed following BEV therapy. Karnofsky performance status scores improved in seven patients (77.8 %). Both volumes of the Gd-enhanced area and FLAIR-high area from MRI decreased in all patients after BEV therapy and the mean size reduction rates of the lesions were 80.0 and 65.0 %, respectively. MRS, which was performed in three patients, showed a significant reduction in Cho/Cr ratio after BEV therapy. Lesion/normal tissue (L/N) ratios in MET- and 11C-choline positron emission tomography (CHO-PET) decreased in 8 (89 %) and 9 patients (100 %), respectively, and the mean L/N ratio reduction rates were 24.4 and 60.7 %, respectively. BEV-related adverse effects of grade 1 or 2 (anemia, neutropenia and lymphocytopenia) occurred in three patients. These results demonstrated that BEV therapy improved RN both clinically and radiologically. BEV therapeutic mechanisms on RN have been suggested to be related not only to the effect on vascular permeability reduction by repairing the blood-brain barrier, but also to the effect on suppression of tissue biological activity, such as immunoreactions and inflammation.

The objective of this study was to investigate the factors that potentially lead to brain radionecrosis (RN) after micromultileaf collimator-based stereotactic radiosurgery (SRS) for brain metastases. We retrospectively evaluated 131 lesions with a minimum follow-up of 6 months, 43.5% of which received prior whole-brain radiotherapy (WBRT). The three-tiered location grade (LG) was defined, as follows, for each target by considering mainly the depth from the brain surface: grade 1 (superficial), involving the region at a depth of ≤5 mm from the brain surface; grade 2 (deep), located at a depth of >5 mm from the brain surface; and grade 3 (central), located in the brainstem, cerebellar peduncle, diencephalon, or basal ganglion. The predictive factors for RN, including high-dose irradiated isodose volumes (IIDVs) and LG, were evaluated by univariate and multivariate analysis. Symptomatic RN (S-RN) and asymptomatic RN (A-RN) were observed in 8.4% and 6.9% of cases, respectively. Multivariate analysis indicated that the significant factors for both types of RN were LG, V12 Gy, and V22 Gy in all cases; V22 Gy and LG for the non-WBRT cases; and V15 Gy and LG for the WBRT cases. For the non-WBRT cases, the cutoff values of V22 Gy were 2.62 and 2.14 cm(3) for S-RN and both RN, respectively. For the WBRT cases, the cutoff values of V15 Gy were 5.61 and 5.20 cm(3) for S-RN and both RN, respectively. In addition to the IIDV data, LG helps predict the risk of RN. High-dose IIDV, V22 Gy, was also significantly correlated with RN, particularly for patients treated with SRS alone.

BACKGROUND AND PURPOSE:The relationship of 11 C-methionine (MET) uptake and tumor activity in low-grade gliomas (those meeting the criteria for World Health Organization [WHO] grade II gliomas) remains uncertain. The aim of this study was to compare MET uptake in low-grade gliomas and to analyze whether MET positron-emission tomography (PET) can estimate tumor viability and provide evidence of malignant transformation.