Abstract INTRODUCTION Though several factors are known to influence on long-term cognitive function in children with brain tumor, the impact of tumor localization to specific cognitive function was not well known. Here we investigated the influence of local brain resection by surgery on postoperative cognitive outcome in school-aged children. METHODS Participants were seven pediatric patients who underwent craniotomy for tumor resection in our hospital (mean age, 13.9 years). Their diagnosis were WHO grade 1 or 2 glioma (n=6) and hemangioma (n=1). Tumor were mainly located in following regions; frontal, n=2; parietal, n=2; temporal, n=3 (These lesions included hippocampus or were located very close to it). Temporal assessments for cognitive function of several functional domains were performed according to tumor location until post-op 1 year. Based on MRI, we estimated cognitive dysfunctions and compared them to observational symptoms. RESULTS Preoperative cognitive function was normal in all patients. Cognitive dysfunctions estimated from resected area were as follows (cumulative total number); memory or working memory disorder, n=4; visuospatial cognitive disorder, n=3; disorder of processing speed, n=2; facial or topographical agnosia, n=2; Gerstman syndrome, n=1. Just after surgery, cognitive function was declined in two functional domains of two patients, which were only 16.7% of estimated deficit from resected region. They recovered completely until 3 months postoperatively, and returned to school without any deficits. CONCLUSIONS In pediatric lower-grade tumor, focal cognitive symptom was unlikely to be induced by local resection.
Abstract BACKGROUND Glioblastoma (GBM) represents the most aggressive and frequent type of primary malignant brain tumors with a dismal clinical outcome. Though adjuvant temozolomide (TMZ) chemotherapy followed by surgical resection can extend patient`s post-operative survival, a considerable number of GBM cases are refractory to TMZ. Novel therapeutic agents that can overcome chemoresistance against TMZ are urgent. Drug repositioning is a process of identifying new indications for existing drugs and provides potential possibilities to discover new drugs. In this study, we explored novel anti-glioma agents which enhances the effect of TMZ with the strategy of drug repositioning. METHODS Drug library which contains 1300 diverse chemical compounds was screened using 2 kinds of glioma stem cell (GSC) lines to select novel therapeutic candidate. The effect of candidate drug on the proliferation of GSCs was estimated by sphere formation assay. To evaluate its efficacy against glioma cell biology, proliferation assay, matrigel invasion assay were performed. To clarify the mechanism of drug effects, we investigated target molecules by gelatin zymography and western blot. RESULTS Acyl CoA synthetase inhibitor named 2-fluoropalmitic acid (2-FPA) was selected as a novel candidate. 2-FPA suppressed proliferation of glioma cell lines by single administration and/or combination with TMZ. The sphere formation of GSCs was suppressed by combination therapy. Combination therapy enhanced TMZ effect. 2-FPA also suppressed invasion of glioma cell lines in a dose dependent manner. 2-FPA suppressed MMP-2 activity and phosphorylation of STAT3. CONCLUSION 2-FPA was identified as a novel potential therapeutic agent against GBM.
Controversy remains over whether the cancer stem cell (CSC) theory applies to all tumors. To determine whether cells within a highly aggressive solid tumor are stochastically or hierarchically organized, we combined a reporter system where the nucleostemin (NS) promoter drives GFP expression (termed NS-GFP) with a mouse brain tumor model induced by retroviral Ras expression on a p16(Ink4a)/p19(Arf)-deficient background. The NS-GFP system allowed us to monitor the differentiation process of normal neural stem/precursor cells by analyzing GFP fluorescence intensity. In tumor-bearing mice, despite the very high frequency of tumorigenic cells, we successfully identified the NS-GFP(+) cells as tumor-initiating cells (T-ICs). The clonal studies conclusively established that phenotypical heterogeneity can exist among the cells comprising a genetically homogeneous tumor, suggesting that this aggressive brain tumor follows the CSC model. Detailed analyses of the NS-GFP(+) brain tumor cells revealed that T-ICs showed activation of the receptor tyrosine kinase c-Met, which functions in tumor invasiveness. Thus, the NS-GFP system provides a powerful tool to elucidate stem cell biology in normal and malignant tissues.
Implantation of carmustine-impregnated wafers (Gliadel®) into the tumor resection cavity has demonstrated a survival benefit for patients with malignant glioma. However, some precautions should be taken regarding Gliadel implantation. We report a case of a 63-year-old man with glioblastoma who was implanted with Gliadel after a left temporal lobe tumor had been removed, and who later developed vasospasm of the lenticulostriate artery close to the implanted Gliadel, leading to serious cerebral infarction. Therefore, the implantation of Gliadel in cases where important vessels run close to the resection cavity should be considered with great caution.
Abstract Brain mapping during awake craniotomy for gliomas can help preserve neurological functions, including maintenance of central and peripheral vision. However, the consecutive changes in the visual field remain unknown. We retrospectively assessed 14 patients who underwent awake craniotomy for gliomas infiltrating into the optic radiation. Cortico-subcortical direct electrical stimulation (DES) was intraoperatively applied until transient visual symptoms were elicited and recorded. The visual fields were examined consecutively in the preoperative period and postoperative subacute and chronic periods. To evaluate the anatomo-functional validity of the recordings, all DES-elicited points were overlaid onto a three-dimensional template that included the optic radiation, using voxel-based morphometry (VBM) mapping. All patients experienced visual symptoms that were classified as phosphenes, blurred vision, or hallucinations during DES, and surgical resection was limited to within the functional boundaries. In VBM, almost all the subcortical positive mapping points overlapped with the surface of the optic radiation, and the distribution of sites that induced visual phenomena in the upper or lower visual fields could be differentiated in the anatomical space. We observed no postoperative visual deficit in four patients (29%), time-dependent improvements in five out of eight patients that presented transient quadrantanopia or partial visual defect (36% out of 57%), and permanent hemianopsia (14%) in two patients with occipital lesions. Intraoperative DES that identifies and preserves optic radiation in awake craniotomy for gliomas is a reliable and effective technique to avoid permanent deficit, but has a low success rate in patients with occipital involvement.
Stereotactic brain biopsy using a navigation system is minimally invasive because it can be performed under local anesthesia. However, there are problems due to the localization and accessibility of the tumor and instability of the airway under sedation. This study aimed to examine the differences in safety and surgical time between the supine and lateral position.This study included 25 cases which underwent navigation-guided brain biopsies from May 2015 to March 2018 in the Kanazawa University Hospital. We compared tumor localization, operation time, standby time, intraoperative difficulties, and final diagnosis acquisition rates between the supine and lateral positions. Puncture sites were then examined by visualizing all biopsy trajectories simultaneously on a three-dimensional cerebral template.Biopsies of the tumor in all cerebrum lobes were possible in the lateral position. There were no significant differences in operating time or standby time between the supine and lateral positions. One case in the spine position required sedation by an anesthesiologist due to body movement, but there were no difficulties in any cases of lateral positioning. The final diagnosis acquisition rate was 100% in all cases. In the lateral position, stable breathing was maintained because the head and the trunk axes remined in the same line.Stereotactic brain biopsy in the lateral position can be safer and more useful than in the supine position under local anesthesia.
