Glioblastoma (GBM) is a major malignant brain tumor developing in adult brain white matter, characterized by rapid growth and invasion. GBM cells spread into the contralateral hemisphere, even during ...early tumor development. However, after complete resection of tumor mass, GBM commonly recurs around the tumor removal cavity, suggesting that a microenvironment at the tumor border provides chemo-radioresistance to GBM cells. Thus, clarification of the tumor border microenvironment is critical for improving prognosis in GBM patients. MicroRNA (miRNA) expression in samples from the tumor, tumor border, and peripheral region far from tumor mass was compared, and five miRNAs showing characteristically higher expression in the tumor border were identified, with the top three related to oligodendrocyte differentiation. Pathologically, oligodendrocyte lineage cells increased in the border, but were rare in tumors. Macrophages/microglia also colocalized in the border area. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, suggesting that OPCs and macrophages/microglia constitute a special microenvironment for GBM cells at the tumor border. The supportive function of OPCs for GBM cells has not been discussed previously. OPCs are indispensable for GBM cells to establish special niches for chemo-radioresistance outside the tumor mass.
A recent study reported on mutations in the active site of the isocitrate dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected resulted in an amino acid exchange at ...position 132. We analyzed the genomic region spanning wild‐type R132 of IDH1 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene, homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the present study, R172 mutation of the IDH2 gene was detected in one anaplastic astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%), anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%), and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of the IDH1 or IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are genetically distinct entities from other glial tumors. (Cancer Sci 2009; 100: 1996–1998)
•Definite N40-P40 phase reversal in the tibial-SEP was identified, indicating the presence of the ‘medial central sulcus’ in the medial cortex.•The ‘medial central sulcus’ is shallow and located ...slightly anterior to the medial end of the central sulcus lacking their connection in appearance.•The leg motor area was predominantly located in the posterior two-thirds between the vertical lines passing through the anterior commissure (VCA) and the posterior commissure (VCP) in the paracentral lobule.
The exact location of the leg motor area is still in debate due to the lack of landmarks such as ‘precentral knob’ in the medial cortex. This study tried to identify the leg motor area based on intraoperative neurophysiological data and neuroimaging techniques.
Intraoperative data of somatosensory evoked potential (SEP) elicited by tibial nerve stimulation and motor evoked potential (MEP) of the leg muscles induced by direct cortical stimulation were recorded using subdural electrodes placed in the medial cortex. We displayed the neurophysiological data on the individual MR images and the MNI52.
Definite N40-P40 phase reversal was observed with the shallow grooves in the medial cortex in 5 cases. Leg MEP was successfully obtained in all 12 cases preserving the leg motor function. Superimposed SEP and leg MEP data on the MNI152 indicated the leg motor area was predominantly located in the posterior two-thirds between the vertical lines passing through the anterior commissure and the posterior commissure (VCP).
Our study revealed the location of the leg motor area and the presence of the ‘medial central sulcus’ in the medial cortex.
The VCP can be useful landmark to identify the sensorimotor border in the medial cortex.
The parietooccipital fissure is an anatomical landmark that divides the temporal, occipital, and parietal lobes. More than 40% of gliomas are located in these three lobes, and the temporal lobe is ...the most common location. The parietooccipital fissure is located just posterior to the medial temporal lobe, but little is known about the clinical significance of this fissure in gliomas. The authors investigated the anatomical correlations between the parietooccipital fissure and posterior medial temporal gliomas to reveal the radiological features and unique invasion patterns of these gliomas.
The authors retrospectively reviewed records of all posterior medial temporal glioma patients treated at their institutions and examined the parietooccipital fissure. To clarify how the surrounding structures were invaded in each case, the authors categorized tumor invasion as being toward the parietal lobe, occipital lobe, isthmus of the cingulate gyrus, insula/basal ganglia, or splenium of the corpus callosum. DSI Studio was used to visualize the fiber tractography running through the posterior medial temporal lobe.
Twenty-four patients with posterior medial temporal gliomas were identified. All patients presented with a parietooccipital fissure as an uninterrupted straight sulcus and as the posterior border of the tumor. Invasion direction was toward the parietal lobe in 13 patients, the occipital lobe in 4 patients, the isthmus of the cingulate gyrus in 19 patients, the insula/basal ganglia in 3 patients, and the splenium of the corpus callosum in 8 patients. Although the isthmus of the cingulate gyrus and the occipital lobe are located just posterior to the posterior medial temporal lobe, there was a significantly greater preponderance of invasion toward the isthmus of the cingulate gyrus than toward the occipital lobe (p = 0.00030, McNemar test). Based on Schramm's classification for the medial temporal tumors, 4 patients had type A and 20 patients had type D tumors. The parietooccipital fissure determined the posterior border of the tumors, resulting in a unique and identical radiological feature. Diffusion spectrum imaging (DSI) tractography indicated that the fibers running through the posterior medial temporal lobe toward the occipital lobe had to detour laterally around the bottom of the parietooccipital fissure.
Posterior medial temporal gliomas present identical invasion patterns, resulting in unique radiological features that are strongly affected by the parietooccipital fissure. The parietooccipital fissure is a key anatomical landmark for understanding the complex infiltrating architecture of posterior medial temporal gliomas.
Handling surgical microscopes with one hand requires force, especially when gripping the operating handle (OH) to swing the optic axis toward the surgeon and when moving it laterally or medially. ...These physical issues may be attributable to the non-ergonomic handling of the OH. To optimize the ease of OH handling, we applied ergonomic criteria to the positioning of the OH, i.e. holding the OH at as little ulnar deviation as possible and at abduction to strengthen the grip and ease arm rotation. Of eight male surgeons holding the OH of a mechanically counterbalanced surgical microscope, the OPMI Neuro/NC4 (Carl Zeiss AG), in ergonomics-based positions, six experienced reduced fatigue in the upper extremity. All reported that their hold on the microscope was firm when it unexpectedly became unbalanced. Ergonomics-based OH positioning, i.e. placing the involved muscles in the optimal length-tension relationship, may generate sufficient force for moving the microscope efficiently and reduce arm fatigue.
Background
Postoperative motor deficits are among the worst morbidities of glioma surgery. We aim to investigate factors associated with postoperative motor deficits in patients with frontoparietal ...opercular gliomas.
Methods
Thirty-four patients with frontoparietal opercular gliomas were retrospectively investigated. We examined the postoperative ischemic changes and locations obtained from MRI.
Results
Twenty-one patients (62%) presented postoperative ischemic changes. Postoperative MRI was featured with ischemic changes, all located at the subcortical area of the resection cavity. Six patients had postoperative motor deficits, whereas 28 patients did not. Compared to those without motor deficits, those with motor deficits were associated with old age, pre- and postcentral gyri resection, and postcentral gyrus resection (
P
= 0.023, 0,024, and 0.0060, respectively). A merged image of the resected cavity and T1-weighted brain atlas of the Montreal Neurological Institute showed that a critical area for postoperative motor deficits is the origin of the long insular arteries (LIAs) and the postcentral gyrus. Detail anatomical architecture created by the Human Connectome Project database and T2-weighted images showed that the subcortical area of the operculum of the postcentral gyrus is where the medullary arteries supply, and the motor pathways originated from the precentral gyrus run.
Conclusions
We verified that the origin of the LIAs could damage the descending motor pathways during the resection of frontoparietal opercular gliomas. Also, we identified that motor pathways run the subcortical area of the operculum of the postcentral gyrus, indicating that the postcentral gyrus is an unrecognized area of damaging the descending motor pathways.
To retrospectively assess the apparent diffusion coefficient (ADC) for prediction of malignancy and prognosis of malignant astrocytic tumors.
The institutional review board approved this study and ...did not require patient informed consent. Findings from 37 consecutive patients (21 men, 16 women; mean age, 43 years) with pathologically proved malignant astrocytic tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs) were retrospectively evaluated. The minimum ADC value of each tumor was preoperatively determined from several regions of interest defined in the tumor, preferably with avoidance of cystic or necrotic components, on ADC maps derived from isotropic diffusion-weighted images. Surgical intervention, followed by radiation therapy, was undertaken in all cases according to hospital protocol. Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation, was also determined. The patients were classified into two groups, progressive and stable, according to the 2-year observation after the initial treatment. Correlation analysis (Pearson product moment correlation), Student t test, Welch test, receiver operating characteristic analysis, and Kaplan-Meier method with log-rank test were used for statistical evaluation.
There was a significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P < .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001, Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(-1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(-1) for minimum ADC for differentiation of patients with a favorable prognosis from those with a poor prognosis provided the best combination of sensitivity (79%) and specificity (81%) (receiver operating characteristic analysis). The significant difference in the prognosis between two groups classified by using this cutoff value of minimum ADC was noted (P = .002, log-rank test).
The minimum ADC of malignant astrocytomas can provide additional information about their clinical malignancy related to posttreatment prognosis.
Abstract
Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the ...cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.
Abstract
Background
We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality.
Methods
...We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks.
Results
Our trial met neither the primary (overall survival OS) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio HR: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0–2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA− activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively.
Conclusion
This phase III trial met neither the primary nor secondary endpoints.
The aim of this study was to determine if molecular alterations are associated with tumor location and radiological characteristics in anaplastic gliomas. We performed a retrospective analysis of 122 ...anaplastic gliomas for molecular alterations (
IDH1/2
mutations,
TP53
mutations, and 1p19q co-deletion) to compare MRI features (location and image characteristics). We observed that
IDH
mutation is strongly associated with frontal location (
P
= 0.001). However, 13 tumors not located in the cerebral cortex were
IDH
intact tumors (
P
< 0.0001). While
IDH
mutation and
TP53
mutation are significantly associated with AA (
p
< 0.0001),
IDH
mutation and 1p19q co-deletion were significantly associated with AO/AOA (
p
< 0.0001). No tumors with
IDH
mutation and 1p19q co-deletion infiltrated the temporal lobe (
P
= 0.003). The tumors with 1p19q co-deletion and histologically diagnosed as AO/AOA were associated with contrast enhancement on MR images (
p
= 0.007,
p
= 0.002, respectively) and those with
TP53
mutation had a weak association with sharp tumor borders (
p
= 0.043). MRI features might be useful to predict molecular profiles in anaplastic gliomas.
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