Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-024-64972-y

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To re-evaluate images recovered from JCOG0911, a randomized phase 2 trial for newly diagnosed glioblastoma (nGBM) conducted by the Japan Clinical Oncology Group (JCOG) Brain Tumor Study Group. METHODS: The correlation between tumor volumes and survival was evaluated, followed by progression-free survival (PFS) analysis by independent central review based on Response Assessment in Neuro-Oncology (RANO) criteria using MRI recovered from 118 nGBM patients enrolled in the JCOG0911 trial. A radiomic analysis was also performed to identify radiomic features predictive of nGBM prognosis. RESULTS: The distribution of the Gd-enhancing and T2-weighted image/fluid attenuated inversion recovery-high intensity lesions mainly occupied white matter. JCOG0911 consisted of more subjects with right-sided lesions. The median extent of resection of the Gd-enhancing lesions was 99%. The overall survival showed a nonsignificant negative trend with postoperative Gd-enhancing lesion volume (P = 0.22), with the hazard ratio increasing in parallel with its volume. The median PFS after registration was 302 and 308 days for local Response Evaluation Criteria in Solid Tumors (RECIST)-based and central RANO-based diagnoses. However, an apparent discrepancy was observed between the two in the early phase, presumably due to the misdiagnosis of pseudoprogression by local RECIST-based diagnosis. Radiomic analysis identified 28 radiomic features predictive of nGBM prognosis, 5 of which were those previously identified in a separate cohort. The constructed radiomics-based prognostic model stratified the cohort into high- and low-risk groups (P = 0.028). CONCLUSION: Novel analytical methods that could be incorporated into future clinical trials were successfully tested. RANO and RECIST may not differ in progression calls if pseudoprogression is appropriately handled.

DOI： 10.2463/mrms.mp.2024-0103

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications. METHODS: Total 228 patients were classified into three groups for treatment: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years. RESULTS: The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cell, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively. CONCLUSIONS: Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.

DOI： 10.1093/neuonc/noae229

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本癌治療学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-024-00489-6

Scopus

PubMed

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(一社)日本言語聴覚士協会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Gliomas vary in prognosis with World Health Organization (WHO) grade. Low-grade gliomas can undergo malignant progression (MP), becoming aggressive high-grade tumors, worsening prognosis. This is prevalent in isocitrate dehydrogenase-mutant (IDH-mt) gliomas like astrocytoma and oligodendroglioma, but the mechanism of MP is still not fully understood. High-grade IDH-mt gliomas have been reported to exhibit TET-mediated DNA hydroxymethylation, which is suggested to potentially influence gene expression. We hypothesized that hydroxymethylation in specific regions could be implicated in triggering MP. METHODS: We collected glioma tumor samples over a decade, using WHO 2021 classification to study IDH-mt astrocytoma grade 2 progression to grades 3 or 4, indicating MP. Samples from five patients, demonstrating MP, were analyzed for DNA hydroxymethylation status across more than 850,000 genomic locations using the oxidative bisulfite process and Infinium EPIC methylation array. This was complemented by RNA sequencing for gene expression analysis and its correlation with hydroxymethylation, and motif-enrichment analysis to infer transcription factor involvement in hydroxymethylation-based gene regulation. Additionally, to delve into the fundamental causes of hydroxymethylation, we exposed an IDH-mt glioma cell line to hypoxic conditions and systematically explored the genomic locations where hydroxymethylation occurred. RESULTS: Our comprehensive analysis identified a significant overlap of hydroxymethylated genomic regions across samples during MP, with a notable enrichment in open sea and intergenic regions (P<0.001). These regions were significantly associated with cancer-related signalling pathways. Integration with RNA sequencing data revealed 91 genes with significant correlations between hydroxymethylation and gene expression, implying roles in cell cycle regulation and antineoplastic functions. Furthermore, motif-enrichment analysis suggested the potential regulatory role of KLF4 in these processes. The cell culture results revealed that a certain similarity exists between the hydroxymethylation patterns observed during MP and those in glioma cells cultured under hypoxic conditions. CONCLUSIONS: This study elucidates the importance of region-specific DNA hydroxymethylation in the MP of IDH-mt astrocytomas, suggesting its potential impact on gene expression relevant to cancer malignancy. Our findings propose a complex interplay between hydroxymethylation and gene regulation, which may offer new insights into the mechanisms driving glioma progression and highlight potential targets for therapeutic intervention.

DOI： 10.21037/cco-24-ab019

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Preoperative embolization(POE)of intracranial meningioma is performed worldwide. Although clear evidence of the effectiveness of POE has not been reported in the literature, the technique plays an important role in open surgery, especially for large or skull base meningiomas. The purposes of embolization include: 1)induction of tumor necrosis, resulting in a safer operation, 2)reduction in intraoperative bleeding, and 3)decrease in operative time. Knowledge of the functional vascular anatomy, embolic materials, and endovascular techniques is paramount to ensure safe embolization. Our standard procedure is as follows: 1)embolization is performed several days before open surgery; 2)in cases with strong peritumoral edema, steroid administration or embolization may be performed immediately prior to surgery; 3)patients undergo the procedure under local anesthesia; 4)the microcatheter is inserted as close as possible to the tumor; 5)particulate emboli are the first-line material; 6)embolization is occasionally performed with N-butyl cyanoacrylate(NBCA)glue; and 7)if possible, additional proximal feeder occlusion with coils is performed. The JR-NET study previous showed the situation regarding intracranial tumor embolization in Japan. Endovascular neurosurgeons should fully discuss the indications and strategies for POE with tumor neurosurgeons to ensure safe and effective procedures.

DOI： 10.11477/mf.1436204978

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.12951

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The ventriculoperitoneal (VP) shunt is one of the most common surgical procedures in neurosurgery, frequently resulting in malfunctions. Shunt malfunctions, which can include mechanical failure, obstruction, infection, or disconnection, occur in a significant percentage of patients, often necessitating multiple revisions. These revisions can lead to increased healthcare costs due to additional surgeries or treatments. Therefore, addressing the economic impacts of these revisions is crucial. Our report presents a cost-effective approach to shunt revisions, demonstrated through a case study of an 82-year-old woman with hydrocephalus. Although initially treated with a VP shunt, she required a revision after six years due to shunt malfunction. Through comprehensive preoperative and intraoperative evaluations, including a shuntogram with iodine contrast and meticulous examination, we identified the cause of malfunction as a connective tissue sac blocking the peritoneal catheter. The surgery involved flushing the catheter lumen with saline to confirm the obstruction and careful removal of the obstructive tissue. This accurate diagnosis facilitated a minimally invasive revision, enabling the reuse of existing shunt components and avoiding the need for new devices, thus reducing costs and surgical invasiveness. Our study serves as a call to action for healthcare providers and surgeons to consider more cost-effective and patient-friendly approaches in managing VP shunt malfunctions, ultimately benefiting both the healthcare system and the patients it serves.

DOI： 10.7759/cureus.62334

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.16127

Scopus

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

The superior petrosal sinus and petrosal vein are important drainage routes for the posterior cranial fossa, with some variations and collateral vessels. An anterolateral-type tentorial dural arteriovenous fistula, which occurs around the petrosal vein, often develops aggressive symptoms due to venous reflux to the brainstem and cerebellum. Neuroendovascular treatment of this fistula is usually challenging because transarterial embolization has a high risk and indications for transvenous embolization are limited. In the cavernous sinus and transverse sinus/sigmoid sinus dural arteriovenous fistulas, venous reflux to the petrosal vein is dangerous, and a treatment strategy with the occlusion of the petrosal vein is indispensable. Furthermore, attention should be paid to venous approaches through the superior petrosal sinus.

DOI： 10.11477/mf.1436204953

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbcan.2024.189102

Scopus

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経外科学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経外科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eclinm.2024.102447

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00401-023-02668-9

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The medulla oblongata is one of the rarest sites of occurrence for germ cell tumors (GCTs) of the central nervous system. As there is scant data regarding epidemiology, clinical presentations, optimal intervention, and long-term prognosis, we aimed to delineate the features of this rare entity by presenting our representative case and performing a quantitative review of the literature. A 24-year-old woman presented to our department with vertigo and swallowing difficulties. Magnetic resonance imaging revealed a homogenously enhanced exophytic lesion arising from the medulla oblongata and extending to the fourth ventricle. Surgical resection was performed and a histological diagnosis of pure germinoma was made. The patient underwent chemotherapy and whole-ventricular irradiation. No recurrence has been experienced for 4 months after the surgery. According to the literature, the prognosis of GCTs at the medulla oblongata seems no worse than those at typical sites. Striking features including occurrence at an older age, female preponderance, and a predominance of germinoma were noteworthy. The pattern of local recurrence suggests extensive radiation coverage is not a prerequisite. Special attention is needed for cardiac and respiratory functions as the main factors eliciting mortality.

DOI： 10.7759/cureus.51861

PubMed

researchmap

Publishing type：Part of collection (book)  

DOI： 10.1002/9781119196235.ch66

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fimmu.2024.1328375

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.18926/AMO/67877

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.13008

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-024-00494-9

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Vertebral artery dissection (VAD) is a rare cause of non-traumatic subarachnoid hemorrhage (SAH) with significant clinical implications. This study compared the clinical characteristics and outcomes of SAH from intracranial VAD rupture to those from other etiologies, primarily aneurysmal rupture. METHODS: This single-center retrospective cohort study at Okayama University Hospital included patients with non-traumatic SAH diagnosed between 2019 and 2023. Patients were categorized into "VAD rupture" and "other etiologies" groups. The main outcome was clinical presentation and symptoms. Additional outcomes included ICU mortality, in-hospital mortality, and unfavorable outcomes at discharge and 6 months, defined as a modified Rankin Scale score of 3-6. RESULTS: A total of 66 patients were included, with 14 in the VAD rupture group and 52 in the other etiologies group. The VAD rupture group was younger (median age 49 vs. 64 years, p = 0.003) and had a higher incidence of out-of-hospital cardiac arrest (42.9% vs. 9.6%, p = 0.011). Preceding headache was more common in the VAD rupture group (78.6% vs. 11.5%, p < 0.001), with a median duration of 36 h before presentation. ICU and in-hospital mortality was higher in the VAD rupture group (both 50.0% vs. 19.3%, p = 0.019). No significant differences were found in unfavorable neurological outcomes at hospital discharge and 6 months. CONCLUSIONS: VAD-related SAH often presents with prodromal headaches, severe symptoms like out-of-hospital cardiac arrest, and higher ICU and in-hospital mortality than other SAH causes, though long-term outcomes are similar. Larger, prospective studies are needed to refine interventions.

DOI： 10.1002/ams2.70031

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41598-023-42842-3

Scopus

PubMed

researchmap

Other Link： https://www.nature.com/articles/s41598-023-42842-3

Publishing type：Research paper (scientific journal)  

DOI： 10.3171/CASE23296

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-023-00469-2

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-023-04411-6

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Preoperative imaging diagnosis is critical to planning treatment strategies; however, it is occasionally challenging and sometimes misleading. The effects of molecularly targeted therapies on imaging appearances remain uncharted. We investigated the imaging characteristics of brain metastasis during tyrosine kinase inhibitor (TKI) administration. METHODS: We analyzed the 12 cases of brain metastasis from lung cancer in our institute, including a case of a 49-year-old woman under gefitinib. Additionally, we reviewed the cases of brain metastasis from lung cancer with gefitinib treatment in the literature. RESULTS: A woman during five-year gefitinib treatment for postoperative recurrence of lung adenocarcinoma was found to have a cerebellar tumoral lesion incidentally on magnetic resonance imaging (MRI). This lesion did not harbor any peritumoral edema, along with appearing hypometabolic on fluorodeoxyglucose (FDG) positron emission tomography (PET). This appearance was inconsistent with a typical metastatic appearance, and high-grade glioma was instead highly suspected, leading to a decision to proceed to gross total tumor resection. The pathological diagnosis, however, was brain metastasis from lung cancer. The other 11 cases without TKI treatment showed peritumoral edema on MRI and higher accumulation of FDG on PET. The two cases of brain metastasis with gefitinib in the literature showed no peritumoral edema on MRI. CONCLUSION: TKIs like gefitinib can affect tumor biology, leading to a loss of typical imaging findings such as peritumoral brain edema and hyper-metabolism. As preoperative imaging diagnosis guides us in surgical planning, including biopsy or resection, ongoing treatment information should be fully integrated into imaging interpretation.

DOI： 10.7759/cureus.43591

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-023-04381-9

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12883-023-03274-8

Scopus

PubMed

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-023-00449-6

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12185-023-03545-7

Scopus

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1111/his.14823

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jjco/hyad001

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.15717

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-022-00448-z

Scopus

PubMed

researchmap

Language：English  

DOI： 10.1080/02688697.2021.1927982

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fneur.2023.1270046

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fonc.2023.1101552

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, n = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated MGMT. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab.

DOI： 10.3390/cancers14225522

PubMed

researchmap

Language：English   Publisher：(一社)日本癌治療学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(株)中外医学社  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Pre-surgical diagnosis of skull base chondrosarcoma (SBC) is often challenging due to the resemblance to chordoma. The goal of this study was to develop an optimal method for predicting SBC diagnosis. METHODS: This retrospective study included patients with histologically diagnosed SBC and skull base chordoma. Their clinical and radiologic features were compared, and the predictive factors of SBC were examined. RESULTS: Forty-one patients with SBC and 41 with chordoma were included. Most SBCs exhibited hypointensity (25, 64.1%) or isointensity (12, 30.8%) on T1-weighted images, and hyperintensity (34, 87.1%) or mixed intensity (5, 12.8%) on T2-weighted images. MRI contrast enhancement was usually avid or fair (89.7%) with "arabesque"-like pattern (41.0%). The lateral/paramidline location was more common in SBC than in chordoma (85.4% vs. 9.8%; P < 0.01), while midline SBCs (14.6%) were also possible. Multivariate analysis demonstrated that higher apparent diffusion coefficient (ADC) value (unit odds ratio 1.01; 95% confidence interval 1.00-1.02; P < 0.01) was associated with an SBC diagnosis. An ADC value of ≥ 1750 × 10-6 mm2/s demonstrated a strong association with an SBC diagnosis (odds ratio 5.89 × 102; 95% confidence interval 51.0-6.80 × 103; P < 0.01) and yielded a sensitivity of 93.9%, specificity of 97.4%, positive predictive value of 96.9%, and negative predictive value of 95.0%. CONCLUSION: The ADC-based method is helpful in distinguishing SBC from chordoma and readily applicable in clinical practice. The prediction accuracy increases when other characteristics of SBC, such as non-midline location and arabesque-like enhancement, are considered together.

DOI： 10.1007/s11060-022-04097-2

PubMed

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Glioblastoma (GBM) inevitably recurs due to a resistance to current standard therapy. We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor formation through AMPK-FOXO3 activation. In this study, we design a phase I/II study to examine the clinical effect of MF. We aim to determine a recommended phase II MF dose with maintenance temozolomide (TMZ) in patients with newly diagnosed GBM who completed standard concomitant radiotherapy and TMZ. MF dose-escalation was planned using a 3 + 3 design. Dose-limiting toxicities (DLTs) were assessed during the first six weeks after MF initiation. Three patients were treated with 1500 mg/day MF and four patients were treated with 2250 mg/day MF between February 2021 and January 2022. No DLTs were observed. The most common adverse effects were appetite loss, nausea, and diarrhea, all of which were manageable. Two patients experienced tumor progression at 6.0 and 6.1 months, and one died 12.2 months after initial surgery. The other five patients remained stable at the last follow-up session. The MF dose of up to 2250 mg/day combined with maintenance TMZ appeared to be well tolerated, and we proceeded to a phase II study with 2250 mg/day MF.

DOI： 10.3390/cancers14174222

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Syringomyelia often accompanies spinal hemangioblastoma (SHB). It often shows progression to the medulla oblongata, dubbed as "syringobulbia", which presents critical symptoms such as dysphagia and respiratory compromise. Appropriate management of chronological syringomyelia progression toward syringobulbia is not set in stone. This study aims to unravel the clinical and chronological behavior of syringobulbia and its management. METHODS: A single-institution case series study of 5 patients operated for SHB with syringobulbia was conducted. Serial preoperative magnetic resonance imaging scans were analyzed in further details, especially focusing on the chronological progression of syringomyelia. A literature review was performed to describe clinical/imaging characteristics. RESULTS: Chronological imaging analyses revealed that despite the relatively steady progression of syringomyelia over years, it accelerated when developing syringobulbia. Intramedullary signal change ("presyringomyelia") was observed in the area where syringomyelia subsequently occurred. Literature review yielded another 15 cases of SHB with syringobulbia, totaling 20 cases. Bulbar dysfunction was seen in 4 cases (20%). Gross total resection was performed in all cases except 1, which underwent just syringotomy. Rapid postoperative symptom improvement was observed in all cases, as well as immediate imaging resolution of syringomyelia. CONCLUSIONS: The symptoms associated with syringobulbia often become life-threatening. Notably, its resolution may be near-synchronous to surgical resection of the spinal lesion. The speed of progression of syringomyelia is usually steady, but it may accelerate when extending to syringobulbia. Regular imaging follow-up is thus highly recommended to determine the best timing of intervention when presyringomyelia and syringomyelia are ascending toward the medulla oblongata.

DOI： 10.1016/j.wneu.2022.07.118

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Tractography is one way to predict the distribution of cortical functional domains preoperatively. Diffusion tensor tractography (DTT) is commonly used in clinical practice, but is known to have limitations in delineating crossed fibers, which can be overcome by Q-ball imaging tractography (QBT). We aimed to compare the reliability of these 2 methods based on the spatial correlation between the arcuate fasciculus depicted by tractography and direct cortical stimulation during awake surgery. METHODS: In this study, 15 patients with glioma underwent awake surgery with direct cortical stimulation. Tractography was depicted in a three-dimensional computer graphic model preoperatively, which was integrated with a photograph of the actual brain cortex using our novel mixed-reality technology. The termination of the arcuate fasciculus depicted by either DTT or QBT and the results of direct cortical stimulation were compared, and sensitivity and specificity were calculated in speech-associated brain gyri: pars triangularis, pars opercularis, ventral precentral gyrus, and middle frontal gyrus. RESULTS: QBT had significantly better sensitivity and lower false-positive rate than DTT in the pars opercularis. The same trend was noted for the other gyri. CONCLUSIONS: QBT is more reliable than DTT in identification of the motor speech area and may be clinically useful in brain tumor surgery.

DOI： 10.1016/j.wneu.2022.05.041

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

To assess the clinicopathological features and prognostic factors of pediatric intracranial ependymomas and to explore the current diagnostic practice, we analyzed clinical data from the Brain Tumor Registry of Japan (BTRJ). Data of fifty children under 18 years of age diagnosed with intracranial ependymoma were extracted from the BTRJ database. Cases were reviewed for overall survival (OS) and progression-free survival (PFS), with attention to gender, preoperative Karnofsky performance status score, location of the tumor, the extent of resection, World Health Organization (WHO) histopathological grading, and adjuvant therapy. The median age at diagnosis was 6.1 years, ranging from 7 months to 17.6 years. Based on the WHO histopathological grading, 27 patients were classified under grade 2 (54%) and 23 patients were classified under grade 3 (46%). Gross total resection (GTR) was achieved in 30 patients (60%). The median follow-up time was 65 months. Five-year PFS and OS were 47.2 ± 7.3% and 73.3 ± 6.7%, respectively. GTR was associated with longer OS (P = 0.02). The histopathological grading was not an independent prognostic factor for the OS. Mitosis and microvascular proliferation were higher among patients with grade 3 than in those with grade 2, which aided in deciding the WHO grade. This nationwide study revealed the characteristics and outcomes of patients with childhood ependymomas. GTR was the factor most consistently associated with improved survival. In contrast, the histopathological grading in this cohort was not a significant prognostic factor. More reproducible and practical criteria for the diagnosis of intracranial ependymomas should be further pursued in future studies.

DOI： 10.2176/jns-nmc.2022-0027

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Chordoma and chondrosarcoma share common radiographic characteristics yet are distinct clinically. A radiomic machine learning model differentiating these tumors preoperatively would help plan surgery. MR images were acquired from 57 consecutive patients with chordoma (N = 32) or chondrosarcoma (N = 25) treated at the University of Tokyo Hospital between September 2012 and February 2020. Preoperative T1-weighted images with gadolinium enhancement (GdT1) and T2-weighted images were analyzed. Datasets from the first 47 cases were used for model creation, and those from the subsequent 10 cases were used for validation. Feature extraction was performed semi-automatically, and 2438 features were obtained per image sequence. Machine learning models with logistic regression and a support vector machine were created. The model with the highest accuracy incorporated seven features extracted from GdT1 in the logistic regression. The average area under the curve was 0.93 ± 0.06, and accuracy was 0.90 (9/10) in the validation dataset. The same validation dataset was assessed by 20 board-certified neurosurgeons. Diagnostic accuracy ranged from 0.50 to 0.80 (median 0.60, 95% confidence interval 0.60 ± 0.06%), which was inferior to that of the machine learning model (p = 0.03), although there are some limitations, such as the risk of overfitting and the lack of an extramural cohort for truly independent final validation. In summary, we created a novel MRI-based machine learning model to differentiate skull base chordoma and chondrosarcoma from multiparametric signatures.

DOI： 10.3390/cancers14133264

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002-2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

DOI： 10.3390/curroncol29070360

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：American Society of Clinical Oncology (ASCO)  

2036

Background: Glioblastoma (GBM) is one of the worst prognostic cancers and there is no effective treatment after failure of bevacizumab. Eribulin is a microtubule inhibitor used for the treatment of patients with metastatic breast cancer and liposarcoma. We previously reported that eribulin strongly inhibits the RNA-dependent RNA polymerase (RdRP) activity of TERT protein in cancer cells, and has a strong anti-tumor effect against GBM cells with TERT promoter mutation. In this study we aim to investigate the efficacy and safety of eribulin in patients with bevacizumab-resistant recurrent GBM. Methods: This is an open-label, multicenter, single-arm phase II trial. Eligible patients aged 20-75 years with bevacizumab-resistant recurrent GBM were enrolled from 2018-2020. Patients received eribulin 1.4 mg/m² on days 1 and 8 of 21-day cycle until disease progression or intolerable toxicity was observed. The primary endpoint was one-year overall survival rate (1yOS%). The 35 patients are needed to achieve an 80% power at a one-sided alpha of 10%, under threshold 1yOS% of 10% and expected 1yOS% of 25%. Results: Thirty-seven patients aged 26-73 (median: 54) years were treated. Twenty-six of 37 (70.3%) patients were diagnosed as IDH-wildtype GBM, 4 (10.8%) were with IDH-mutant GBM and 7 (18.9%) were GBM, NOS. Thirty-four (91.9%) patients had a Karnofsky performance status of 70 or 80 at the registration. Thirty-one (83.8%) patients received additional treatments, including 28 (75.7%) bevacizumab, 11 (29.7%) re-irradiation and 3 (8.1%) resection after failure of eribulin. Among 37 subjects, 32 surgical specimens were analyzed for TERT promoter mutation and 15 for RdRP activity. 1yOS% was 29.7% [80% CI: 20.5 to 39.5 (p &lt; 0.0001), 95% CI: 16.1 to 44.6]. Median OS was 9.0 months [95% CI: 6.2 to 11.0] and median progression-free survival was 1.5 months [95% CI: 1.4 to 1.7]. Neither TERT nor RdRP statuses was associated with prolonged OS. Among all the target lesions evaluated, two lesions decreased more than 50% in size and the patients survived more than one year, however no obvious PR was confirmed at the final evaluation. The disease control rate was 25.7% [95% CI: 12.5 to 43.3]. Common ≥ grade 2 AEs were neutropenia (70.3%), leukopenia (56.8%), lymphopenia (27.0%), elevation of γ-GTP (13.5%), elevation of ALT (10.8%), elevation of AST (8.1%), alopecia (8.1%). Treatment-related grade 3 or 4 AEs occurred in 59.5% of subjects. There were no AEs leading to death. Conclusions: Eribulin was safely applied for the patients with recurrent GBM. This phase II study met its primary endpoint of 1yOS%, although no obvious response was observed. Further investigation to reveal the biomarkers related to longer survival is underway. Clinical trial information: UMIN000030359.

DOI： 10.1200/jco.2022.40.16_suppl.2036

researchmap

Publishing type：Research paper (scientific journal)   Publisher：American Society of Clinical Oncology (ASCO)  

1551

Background: Cancer genomic profiling (CGP) tests have been approved in Japan since June 2019, with the requisite that all test results be discussed by molecular tumor boards (MTBs). More than 20,000 patients in over 200 designated hospitals have taken CGP tests by December 2021. As CGP tests have entered clinical practice, streamlining decision making by MTBs and standardizing interpretation of test results and treatment recommendations have become urgent issues. Here, we evaluated the utility of Chrovis, an annotation algorithm for reporting CGP tests to support MTBs make their recommendations. Methods: We retrospectively reviewed the reporting process of all approved CGP tests done at The University of Tokyo Hospital between December 2019 and November 2021. Chrovis provided annotation for each genetic variant by incorporating biologic, clinical, and therapeutic information by referencing several public knowledge databases and using natural language processing, and generated reports using the automated program. The MTB reviewed and made any necessary changes before finalizing the report. Changes in disclosure of germline findings were made according to the recommendations of a national guideline with consideration of past and family history. Results: Of the 243 tests, 91 changes in 81 Chrovis reports (33% of all reports) were made by the MTB. The most common type of change was germline disclosure with 26 changes (29%), followed by clinical trial information in Japan (18 changes, 20%) and recommendation of the patient-proposed national basket trial with multiple targeted agents (17 changes, 19%). Changes in germline disclosure increased from June 2021, when an update to a national guideline was released, while the proportion of changes in the latter two types remained unchanged. Gene alterations that led to the highest number of changes was TP53, with 13 changes. Changes in therapeutic recommendations were frequently observed in the RAS/MAPK pathway ( BRAF, KRAS, NF1, NRAS) with 12 changes. More changes were required with a tumor-only tissue CGP panel (57 of 149) compared with a matched tumor/normal tissue CGP panel (24 of 94, p = 0.04), mostly due to germline disclosure (24 vs. 2 changes). Conclusions: We observed that automated algorithm-based reporting was sufficient in 67% of reports. Recommendation for germline disclosure still requires manual supervision, particularly with tumor-only tissue CGP panels if algorithms do not incorporate medical history. The process of recommending clinical trials needs improvement, e.g., standardizing database formats for inclusion and exclusion criteria.

DOI： 10.1200/jco.2022.40.16_suppl.1551

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs.

Methods

Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH).

Results

A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs.

Conclusions

12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

DOI： 10.1093/neuonc/noab246

researchmap

Other Link： https://academic.oup.com/neuro-oncology/article-pdf/24/5/834/43548783/noab246.pdf

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：医歯薬出版(株)  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00060&link_issn=&doc_id=20220412010008&doc_link_id=issn%3D0039-2359%26volume%3D281%26issue%3D2%26spage%3D193&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D281%26issue%3D2%26spage%3D193&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while non-germinomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and non-germinoma/non-seminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

DOI： 10.1093/neuonc/noac021

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Craniopharyngioma is a pathologically benign but clinically malignant brain tumor typically located in the parasellar region. It is treated by surgical resection, but in most cases, total removal is not amenable due to its adhesion to the adjacent vital structures, such as the optic nerve, hypothalamus, and pituitary stalk. Often, tumor regrowth or recurrence occursand it is usually treated with either re-resection or radiotherapy, including stereotactic radiosurgery. Either treatment carries some important risks, including blindness, hypopituitarism, and cognitive impairment. A recent comprehensive genomic analysis revealed that the majority of papillary craniopharyngioma cases harbor a hotspot BRAF-V600E mutation. Several case reports have illustrated dramatic response of the residual or recurrent papillary craniopharyngioma to molecularly targeted therapy with a BRAF inhibitor(vemurafenib or dabrafenib)and a MEK inhibitor(trametinib), which are currently approved for melanoma and non-small cell lung carcinoma. This medical treatment can potentially be a wonderful treatment option for papillary craniopharyngioma, given its freedom from the aforementioned serious risks associated with surgery and radiotherapy.

DOI： 10.11477/mf.1436204542

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Genomic and epigenomic analyses have progressed the exploration of the pathogenesis of CNS germ cell tumors(GCTs)in the past decade. GCTs are characterized by mutations in MAPK or PI3K pathways(55%)and unstable chromosomes, especially 12p gain(45%), as well as global hypomethylation in germinoma. Highly specific microRNA, miR-371a-3p, can be a diagnostic marker in serum and cerebrospinal fluid. Tumor cell content examined in H-E specimens has a prognostic value in germinoma: cases with higher tumor cell content show a worse prognosis. 12p gain in non-germinomatous GCTs(NGGCTs)has an unfavorable prognostic significance. PD-L1 and PD-1 are highly expressed in germinomas and the tumor cell microenvironment, respectively, highlighting the potential effectiveness of immune checkpoint inhibitors. Clinical trials from the Children's Oncology Group(COG)in the US and the Society for Paediatric Oncology(SIOP)in Europe and Japan have shown that whole ventricular irradiation is the most appropriate for germinomas, and that radiation fields can be reduced to the whole ventricle or a local area for localized NGGCTs. Toward personalized medicine, investigations into the structural abnormalities and variants in non-coding regions are needed to develop targeted therapy. A stratified treatment regimen is expected by incorporating newly-found biomarkers to reduce the treatment burden for generally young patients and circumvent late toxicity and sequelae. Establishing effective treatments is crucial for relapsed GCT that has a dismal prognosis.

DOI： 10.11477/mf.1436204530

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Hemangioblastoma(HB)is a tumor that frequently occurs in von Hippel-Lindau(VHL)disease, a hereditary tumor disease. It is a benign tumor and excision is the first choice of treatment, but in VHL disease, where HB occurs frequently, the emergence of more promising molecularly-targeted therapeutic agents has been desired. In this paper, we first explain HB and VHL disease and then outline the function of the VHL gene and the mechanism of onset of VHL disease. After that, we explain the analysis technology and frequency of VHL gene abnormalities and finally describe HIF2α inhibitors, which are promising as molecularly-targeted therapeutic agents for VHL disease. As the medical system for personalized medicine/precision medicine is being developed in Japan, it is expected that HB and VHL diseases will attract attention as target diseases in the future.

DOI： 10.11477/mf.1436204535

PubMed

researchmap

Language：English  

Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel ("Todai-OncoPanel") analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features.

DOI： 10.1177/11795476221131189

PubMed

researchmap

Language：English  

Background: Solitary plasmacytoma is a localized lesion comprising monoclonal neoplastic proliferation of plasma cells. This disease is rarely encountered and few reports have described primary intracranial solitary plasmacytoma (PISP). Case Description: We report a case of PISP that presented initially as status epilepticus and exhibited massive intratumoral hemorrhage at the subcortical area. To the best of our knowledge, this is the first recorded presentation of this pathology in this manner. Following evacuation of the hematoma and decompressive craniectomy, the patient underwent radiation therapy and showed no sign of tumor recurrence at 3 years after diagnosis. Conclusion: This case reveals that PISP can present as subcortical intraparenchymal hemorrhage. It should be emphasized that the precise diagnosis of this disease is of utmost importance, because solitary plasmacytoma without a background of multiple myeloma responds well to radiation therapy.

DOI： 10.25259/SNI_66_2022

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/ons/opab353

Scopus

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本脳神経外科コングレス  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02632&link_issn=&doc_id=20211202230007&doc_link_id=1390572012410134912&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390572012410134912&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.

DOI： 10.1007/s10147-021-02028-1

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

DOI： 10.1093/ons/opab353

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. METHODS: We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. RESULTS: By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. CONCLUSIONS: These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

DOI： 10.1007/s11060-021-03816-5

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Primary anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) is a subtype of primary CNS lymphoma (PCNSL). There are very few comprehensive reports on this extremely rare tumor. Therefore, it is necessary to investigate the clinical features and prognostic factors for primary ALCL of the CNS. We performed a systematic review of the published literature. Past cases were comprehensively searched using PubMed, Cochrane Library, and Web of Science. Clinical information, such as age, sex, anaplastic lymphoma kinase (ALK) status, lesion sites, treatment methods, and survivorship were extracted. Thirty-nine cases with information on ALK status and treatment course were identified. The average observation period was 13 months, and the overall 2-year survival rate was 58%. Univariate analyses showed a statistically significantly better prognosis among patients < 40 years of age (p = 0.039, HR 0.32 (0.11-0.95)) and in relation to ALK positivity (p = 0.010, HR 0.24 (0.08-0.71) and methotrexate treatment (p = 0.003, HR 0.17 (0.05-0.56)). Because of the sparsity of cases, it is necessary to accumulate cases in order to perform more detailed analyses.

DOI： 10.3390/cancers13174358

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

DOI： 10.1007/s00401-021-02337-9

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本医学放射線学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. EXPERIMENTAL DESIGN: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. RESULTS: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. CONCLUSIONS: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

DOI： 10.1158/1078-0432.CCR-20-4518

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. Methods: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. Results: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. Conclusions: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

DOI： 10.1016/j.wnsx.2021.100102

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its treatment requires a multidisciplinary approach, which consists of maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Bevacizumab is approved for newly diagnosed as well as recurrent malignant glioma in Japan. NovoTTF is a novel medical device that emits alternating electric fields; it inhibits the proliferation and growth of the tumor by interfering with tumor cell mitosis at anaphase. A photodynamic therapy with talaporfin sodium has been approved for primary malignant brain tumor including glioblastoma in Japan. For epilepsy secondary to glioblastoma, a novel class of antiepileptics such as levetiracetam and lacosamide is preferred given the lack of drug-drug interactions. Perampanel is a selective antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors; it may be a preferred antiepileptics for glioblastoma, given the in vitro and in vivo analyses suggesting that it decreases the proliferation and invasion of tumor cells. In this chapter, I describe the overview of the multidisciplinary treatments of glioblastoma. I also describe the future perspectives.

DOI： 10.11477/mf.1436204436

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Although the incidence of central nervous system (CNS) cancers is not high, it significantly reduces a patient's quality of life and results in high mortality rates. A low incidence also means a low number of cases, which in turn means a low amount of information. To compensate, researchers have tried to increase the amount of information available from a single test using high-throughput technologies. This approach, referred to as single-omics analysis, has only been partially successful as one type of data may not be able to appropriately describe all the characteristics of a tumor. It is presently unclear what type of data can describe a particular clinical situation. One way to solve this problem is to use multi-omics data. When using many types of data, a selected data type or a combination of them may effectively resolve a clinical question. Hence, we conducted a comprehensive survey of papers in the field of neuro-oncology that used multi-omics data for analysis and found that most of the papers utilized machine learning techniques. This fact shows that it is useful to utilize machine learning techniques in multi-omics analysis. In this review, we discuss the current status of multi-omics analysis in the field of neuro-oncology and the importance of using machine learning techniques.

DOI： 10.3390/biom11040565

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 ± 0.137, whereas that of the BraTS model was lower (0.717 ± 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (p < 0.0001) and the BraTS and fine-tuning models (p = 0.002); however, no significant difference between the JC and fine-tuning models (p = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.

DOI： 10.3390/cancers13061415

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

DOI： 10.1093/neuonc/noaa199

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion?


</sec>
<sec>
<title>Methods</title>
Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI).


</sec>
<sec>
<title>Results</title>
A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI.


</sec>
<sec>
<title>Conclusion</title>
CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.


</sec>

DOI： 10.1093/noajnl/vdab086

researchmap

Other Link： http://academic.oup.com/noa/article-pdf/3/1/vdab086/39555495/vdab086.pdf

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response.


</sec>
<sec>
<title>Methods</title>
A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS).


</sec>
<sec>
<title>Results</title>
The tumor cell content was widely distributed from &amp;lt;5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (P = .002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (P = .03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (&amp;lt;50%) (P = .03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (P = .04). Among the 7 cases treated with local radiation and chemotherapy, all 3 cases that recurred (2 outside of the radiation field, 1 unknown) had tumor cell content of ≥50% in the original specimen, whereas all 4 cases without recurrence had tumor cell contents of &amp;lt;50%.


</sec>
<sec>
<title>Conclusions</title>
We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.


</sec>

DOI： 10.1093/noajnl/vdab110

researchmap

Other Link： http://academic.oup.com/noa/article-pdf/3/1/vdab110/40404167/vdab110.pdf

Language：Japanese   Publisher：(株)中外医学社  

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.7887/JCNS.30.871

Scopus

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Down-regulated genes in the 19q-loss astrocytomas were heavily clustered to 19q and 4p, and up-regulated genes to 4q. It was noted that fibroblast growth factor 1 associated with stem cell maintenance was down-regulated in 19q-loss astrocytomas and genes associated with glioma progression were differentially expressed, these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, 19q-loss astrocytomas did not shift to oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas is more likely to be an acquired event rather than early event in oncogenesis like 1p/19q codeletion in oligodendrogliomas, and the biological and morphological features of 19q-loss astrocytomas were possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

DOI： 10.1093/noajnl/vdaa143.053

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

DOI： 10.1186/s40478-020-01078-2

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. Comparing expression level of each genes between 19q-loss and 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Gene expression patterns of 19q-loss astrocytomas were partially different from that of 19q-intact astrocytomas. More down-regulated genes distributed on 19q and 4p, and more up-regulated genes distributed on 4q. Multiple genes associated with stem cell maintenance were down-regulated in 19q-loss astrocytomas, and genes associated with glioma progression were differentially expressed. Comparing expression patterns among 19q-loss astrocytomas and other IDH-mutant glioma subgroups using TCGA datasets by t-SNE analysis revealed that expression pattern of 19q-loss astrocytomas did not shift to that of oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas was an acquired event different from 1p/19q codeletion in oligodendrogliomas, and better prognosis morphological features in 19q-loss astrocytomas were derived from differentially expressed genes associated with stem cell maintenance and glioma progression.

DOI： 10.1093/neuonc/noaa215.692

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(一社)日本小児神経外科学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The factors associated with health-related quality of life in patients with glioma remain unclear; particularly, the impact of symptoms on quality of life has not been studied comprehensively. This study aims to document the quality of life of patients with glioma and clarify the impact of symptoms. METHODS: In this cross-sectional study, participants were recruited from patients at The University of Tokyo Hospital and from patients who were registered at the Japan Brain Tumor Alliance. We included adult patients with World Health Organization grade II-IV glioma and excluded those with disturbances of consciousness or aphasia. We used the European Organization for Research and Treatment of Cancer QLQ-C30 and BN20 to evaluate quality of life and the symptoms. Multiple regression analyses were performed to investigate the impact of symptoms on European Organization for Research and Treatment of Cancer global health status and QLQ-C30 social functioning. In addition, we performed univariate subgroup analyses classified by World Health Organization grade and history of chemotherapy. RESULTS: This study included 76 patients. Seven symptoms occurred in more than 50% of the patients: fatigue, future uncertainty, drowsiness, communication deficit, financial difficulties, motor dysfunction and weakness of legs. Multiple regression analyses showed that insomnia affected their global health status, and appetite loss, financial difficulties and motor dysfunction were significantly related to their social functioning. In subgroup analysis, the number of symptom subscales that were significantly related to global health status and social functioning was larger in World Health Organization grade II patients compared with grade III/IV patients. CONCLUSIONS: In addition to neurological deficits, symptoms were associated with poor quality of life in patients with glioma. This study provided the basis on further investigation of usefulness of symptom evaluation on quality of life improvement.

DOI： 10.1093/jjco/hyaa068

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本言語聴覚士協会  

researchmap

Language：Japanese   Publisher：日本がん免疫学会  

researchmap

Language：Japanese   Publisher：(株)メディカ出版  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J03120&link_issn=&doc_id=20200826180004&doc_link_id=issn%3D0917-1495%26volume%3D30%26issue%3D9%26spage%3D970&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0917-1495%26volume%3D30%26issue%3D9%26spage%3D970&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(NPO)日本レーザー医学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). METHODS: Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. RESULTS: Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5-30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach's coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test-retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. CONCLUSIONS: The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

DOI： 10.1093/jjco/hyaa036

PubMed

researchmap

Language：English  

BACKGROUND: Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)-positive ALCL have been reported so far, with no reported cases of a small cell variant. CASE DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). CONCLUSIONS: In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.

DOI： 10.1016/j.wneu.2020.02.171

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Glioma is characterized by a high heterogeneity in the brain tumor. Abundant tumor-associated macrophages (TAMs) exist as neoplastic tissues, implicating tumor plasticity and thus leading to therapeutic challenges. Vascular adhesion protein (VAP-1) potentially serves as a mediator for TAM immunity in tumor milieu. We previously demonstrated that VAP-1 could contribute to tumor malignancy, but its characteristics in TAM immunity of glioma progression are still unclear. This study explored the association of VAP-1 expression with TAM distribution as well as the resulting clinical significance and prognostic value in human gliomas. An in-depth analysis of AOC3 (VAP-1) gene expression was performed using 695 glioma samples derived from the cancer genome atlas (TCGA)-lower grade glioma and glioblastoma (GBMLGG) cohort. Bioinformatic analysis confirmed that VAP-1 expression is associated with poor prognosis of glioma patients (p = 0.0283). VAP-1 and TAM biomarkers (CD68, iNOS, and CD163) were evaluated by immunohistochemistry in 108 gliomas from Kaohsiung Medical University Hospital. VAP-1+ was expressed in 56 (51.85%) cases and this phenotype revealed a significant association with overall survival in Kaplan-Meier analysis (p < 0.0001). Immunohistochemical double staining showed that VAP-1 immunoreactivity was present around CD163+ M2 infiltration location, including aggressive lesions and neighboring neovasculature. We demonstrated that high VAP-1 expression levels positively correlated with CD163+ M2 activation and coexpression of these two proteins was associated with worse survival in gliomas (p < 0.0001). Multivariate analysis indicated that VAP-1 alone and co-expressed with CD163 were the significantly independent indicators (both p < 0.0001). Furthermore, VAP-1/CD163 coexpression exhibited excellent diagnostic accuracy in gliomas (AUC = 0.8008). In conclusion, VAP-1 and TAM CD163 M2 coexpression was found in glioma tissues belonging to a highly malignant subgroup that was associated with poor prognosis. These results implied VAP-1 abundance is closely linked to alternative M2 activation during glioma progression. From the aforementioned data, a reasonable inference is that VAP-1 combined with targeting M2 immunity might be an effective therapeutic target for human gliomas.

DOI： 10.3390/diagnostics10050256

PubMed

researchmap

Language：English  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41598-020-60086-3

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Medical care-related decision-making among patients with malignant brain tumors has not been sufficiently discussed. This study aimed to develop a framework for understanding patients’ experiences in the decision-making process. Semi-structured interviews with 14 patients were analyzed using a grounded theory approach, focusing on their 48 decision-making points. Additionally, interviews with two family members and seven healthcare providers, and participant observations were used to gain contextual insight into patients’ experiences. Patients faced decisions while they struggled in vulnerability under shock, fear, and anxiety while hoping. Under this context, they showed four decision-making patterns: (1) led by the situation, (2) controlled by others, (3) entrusted someone with the decision, and (4) myself as a decision-making agent. Across these patterns, the patients were generally satisfied with their decisions even when they did not actively participate in the process. Healthcare providers need to understand patients’ contexts and their attitudes toward yielding decision-making to others.

DOI： 10.1177/2333393620960059

PubMed

researchmap

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/2333393620960059

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Despite the high frequency of EGFR genetic alterations in glioblastoma (GBM), EGFR-targeted therapies have not had success in this disease. To improve the likelihood of efficacy, we targeted adult patients with recurrent GBM enriched for EGFR gene amplification, which occurs in approximately half of GBM, with dacomitinib, a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that penetrates the blood-brain barrier, in a multicenter phase II trial. PATIENTS AND METHODS: We retrospectively explored whether previously described EGFR extracellular domain (ECD)-sensitizing mutations in the context of EGFR gene amplification could predict response to dacomitinib, and in a predefined subset of patients, we measured post-treatment intratumoral dacomitinib levels to verify tumor penetration. RESULTS: We found that dacomitinib effectively penetrates contrast-enhancing GBM tumors. Among all 56 treated patients, 8 (14.3%) had a clinical benefit as defined by a duration of treatment of at least 6 months, of whom 5 (8.9%) remained progression free for at least 1 year. Presence of EGFRvIII or EGFR ECD missense mutation was not associated with clinical benefit. We evaluated the pretreatment transcriptome in circulating extracellular vesicles (EVs) by RNA sequencing in a subset of patients and identified a signature that distinguished patients who had durable benefit versus those with rapid progression. CONCLUSION: While dacomitinib was not effective in most patients with EGFR-amplified GBM, a subset experienced a durable, clinically meaningful benefit. Moreover, EGFRvIII and EGFR ECD mutation status in archival tumors did not predict clinical benefit. RNA signatures in circulating EVs may warrant investigation as biomarkers of dacomitinib efficacy in GBM.

DOI： 10.1200/PO.19.00295

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon-Mann-Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873-0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705-0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.

DOI： 10.1038/s41598-019-55922-0

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: A noninvasive diagnostic method to predict the degree of malignancy accurately would be of great help in glioma management. This study aimed to create a highly accurate machine learning model to perform glioma grading. METHODS AND MATERIALS: Preoperative magnetic resonance imaging acquired for cases of glioma operated on at our institution from October 2014 through January 2018 were obtained retrospectively. Six types of magnetic resonance imaging sequences (T2-weighted image, diffusion-weighted image, apparent diffusion coefficient [ADC], fractional anisotropy, and mean kurtosis [MK]) were chosen for analysis; 476 features were extracted semiautomatically for each sequence (2856 features in total). Recursive feature elimination was used to select significant features for a machine learning model that distinguishes glioblastoma from lower-grade glioma (grades 2 and 3). RESULTS: Fifty-five data sets from 54 cases were obtained (14 grade 2 gliomas, 12 grade 3 gliomas, and 29 glioblastomas), of which 44 and 11 data sets were used for machine learning and independent testing, respectively. We detected 504 features with significant differences (false discovery rate <0.05) between glioblastoma and lower-grade glioma. The most accurate machine learning model was created using 6 features extracted from the ADC and MK images. In the logistic regression, the area under the curve was 0.90 ± 0.05, and the accuracy of the test data set was 0.91 (10 out of 11); using a support vector machine, they were 0.93 ± 0.03 and 0.91 (10 out of 11), respectively (kernel, radial basis function; c = 1.0). CONCLUSIONS: Our machine learning model accurately predicted glioma tumor grade. The ADC and MK sequences produced particularly useful features.

DOI： 10.1016/j.ijrobp.2019.07.011

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

PURPOSE

Diffusion tensor-based tractography (DTT) is a method to estimate the direction of white matter fibers, but it is difficult to verify the relationship with brain function spatially with high accuracy. We developed a registration method to fuse the real space (brain surface photograph) and preoperative fused 3D image (virtual space) using the landmark method and thin plate spline method. In our previous study, this method was able to achieve highly accurate alignment registration error 0.7±0.1mm (mean±SE) even after brain shift due to craniotomy. In this study, we proposed a method to examine spatial errors of DTT and direct cortical stimulation (DCS) and verify its accuracy.

METHODS

We included 7 gliomas performed awake surgery. We created the fused three – dimensional image before surgery and acquired the brain surface photograph immediately after craniotomy, then we aligned them using the proposed method. Sites that showed speech arrest by DCS were plotted on the fused image. A circle with a radius of 15 mm centered on the same site was taken as the range over which the current spreads. The surface area of each of the circles was calculated to make it true if there was arcuate fasciculus drawn with DTT in the circle, and false if it did not exist. By using this method, the accuracy of the DTT was verified. RESULT: In 7 cases, speech arrest was shown at 21 DCS plots. The probability of the presence of DTT within the current spread of DCS was 64.4%.

CONCLUSION

The proposed method indicates that DTT does not necessarily match the DCS results by verification using real space and virtual space. We present some illustrative cases.

DOI： 10.1093/neuonc/noz175.718

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Rhabdomyosarcoma is the most common soft-tissue sarcoma affecting children and adolescents. It is defined as a malignant neoplasm characterized by morphologic, immunohistochemical, ultrastructural, or molecular genetic evidence of primary skeletal muscle differentiation, usually in the absence of any other pattern of differentiation. Primary intracranial rhabdomyosarcoma (PIRMS) is an extremely rare neoplasm, with only 60 cases reported in the literature, and generally has poor prognosis with an overall survival of only 9.1 months. The DICER1 gene encodes an RNA endoribonuclease that plays a key role in gene expression regulation through the production of small RNAs. Herein, we report two cases of PIRMS with somatic DICER1 mutation showing morphological and immunohistochemical evidence of primary skeletal muscle differentiation; the two cases share common clinical features, including young age, supratentorial tumor, and onset of intratumoral bleeding. Although methylation profiling was not performed, both cases shared clinical and pathological characteristics in common with recently proposed methylation entity "spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant (SCS-RMSlike-DICER1)''. Our cases provide further evidence of the link between primary intracranial sarcoma and DICER1 mutation which may form a distinct entity.

DOI： 10.1007/s10014-019-00352-z

PubMed

researchmap

Language：English   Publisher：日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Immune-based therapies have shown limited efficacy in glioma thus far. This might be at least in part due to insufficient numbers of neoantigens, thought to be targets of immune attack. In addition, we hypothesized that dynamic genetic and epigenetic tumor evolution in gliomas might also affect the mutation/neoantigen landscape and contribute to treatment resistance through immune evasion. Here, we investigated changes in the neoantigen landscape and immunologic features during glioma progression using exome and RNA-seq of paired primary and recurrent tumor samples obtained from 25 WHO grade II-IV glioma patients (glioblastoma, IDH-wild-type, n = 8; grade II-III astrocytoma, IDH-mutant, n = 9; and grade II-III oligodendroglioma, IDH-mutant, 1p/19q-codeleted, n = 8). The number of missense mutations, predicted neoantigens, or expressed neoantigens was not significantly different between primary and recurrent tumors. However, we found that in individual patients the ratio of expressed neoantigens to predicted neoantigens, designated the "neoantigen expression ratio," decreased significantly at recurrence (P = 0.003). This phenomenon was particularly pronounced for "high-affinity," "clonal," and "passenger gene-derived" neoantigens. Gene expression and IHC analyses suggested that the decreased neoantigen expression ratio was associated with intact antigen presentation machinery, increased tumor-infiltrating immune cells, and ongoing immune responses. Our findings imply that decreased expression of highly immunogenic neoantigens, possibly due to persistent immune selection pressure, might be one of the immune evasion mechanisms along with tumor clonal evolution in some gliomas.

DOI： 10.1158/2326-6066.CIR-18-0599

PubMed

researchmap

Language：English  

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

DOI： 10.1038/s41598-019-43790-7

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Phosphatidylinositol 3-kinase signaling promotes cell growth and survival and is frequently activated in infiltrative gliomas. Activating mutations in PIK3CA gene are observed in 6-15% of glioblastomas, although their clinical significance is largely undescribed. The objective of this study was to examine whether PIK3CA mutations are associated with a specific clinical phenotype in glioblastoma. We retrospectively reviewed 157 consecutive newly diagnosed glioblastoma patients from December 2009 to June 2012 who underwent molecular profiling consisting of targeted hotspot genotyping, fluorescence in situ hybridization for gene amplification, and methylation-specific PCR for O6-methylguanine-DNA methyltransferase promoter methylation. Molecular alterations were correlated with clinical features, imaging and outcome. The Cancer Genome Atlas data was analyzed as a validation set. There were 91 males; median age was 58 years (range, 23-85). With a median follow-up of 20.9 months, median progression-free survival (PFS) and estimated overall survival (OS) were 11.9 and 24.0 months, respectively. Thirteen patients (8.3%) harbored PIK3CA mutation, which was associated with younger age (mean 49.4 vs. 58.1 years, p = 0.02). PIK3CA mutation correlated with shorter PFS (median 6.9 vs. 12.4 months, p = 0.01) and OS (median 21.2 vs. 24.2 months, p = 0.049) in multivariate analysis. A significant association between PIK3CA mutation and more disseminated disease at diagnosis, as defined by gliomatosis, multicentric lesions, or distant leptomeningeal lesions, was observed (46.2% vs. 11.1%, p = 0.004). In conclusion, despite the association with younger age, PIK3CA activating mutations are associated with earlier recurrence and shorter survival in adult glioblastoma. The aggressive course of these tumors may be related to their propensity for disseminated presentation.

DOI： 10.1186/s40478-019-0720-8

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE OF THE REPORT: This study aimed to determine the most effective metabolic index of FDG-PET and MET-PET to differentiate high- and low-grade gliomas, and then to characterize tumor metabolism according to the 2016 WHO classification. We also developed a new calculation method of potential infiltrative tumor volume to overcome the current limitations of tumor evaluation according to metabolic index, which focuses solely on tumor core area. MATERIALS AND METHODS: Patients who underwent both FDG-PET and MET-PET, as well as surgical treatment, were retrospectively identified. All tumors were diagnosed histologically and included 44 high-grade and 19 low-grade gliomas. Metabolic indices of tumor-to-normal (T/N) ratio and maximum value within the tumor itself were compared between high- and low-grade tumors. A calculation method for potential infiltrative tumor volume was developed and compared between these 2 grades. RESULTS: T/N, calculated as tumor value divided by normal cortex value, was the most effective (area under the curve, 0.800 for FDG-PET; area under the curve, 0.773 for MET-PET) for differentiating high- and low-grade gliomas. Potential infiltrative volume effectively distinguished between high- and low-grade glioma (43.8 ± 30.2 mL vs 14.0 ± 12.6 mL; P = 0.005 [t test]). A combination of T/N, with a cutoff value of 0.9 or higher on FDG-PET and/or 3.0 or higher on MET-PET, and potential infiltrative volume, with a cutoff value of 20.0 mL or higher, provided a diagnostic accuracy of 89% in distinguishing high- from low-grade gliomas. CONCLUSIONS: Evaluation of potential infiltrative volume surrounding the tumor core area, in addition to the T/N ratio of the tumor core, may help distinguish between high- and low-grade gliomas.

DOI： 10.1097/RLU.0000000000002460

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-019-38510-0

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

In conducting medical research, a system which can objectively predict the future trends of the given research field is awaited. This study aims to establish a novel and versatile algorithm that predicts the latest trends in neuro-oncology. Seventy-nine neuro-oncological research fields were selected with computational sorting methods such as text-mining analyses. Thirty journals that represent the recent trends in neuro-oncology were also selected. As a novel concept, the annual impact (AI) of each year was calculated for each journal and field (number of articles published in the journal × impact factor of the journal). The AI index (AII) for the year was defined as the sum of the AIs of the 30 journals. The AII trends of the 79 fields from 2008 to 2017 were subjected to machine learning predicting analyses. The accuracy of the predictions was validated using actual past data. With this algorithm, the latest trends in neuro-oncology were predicted. As a result, the linear prediction model achieved relatively good accuracy. The predicted hottest fields in recent neuro-oncology included some interesting emerging fields such as microenvironment and anti-mitosis. This algorithm may be an effective and versatile tool for prediction of future trends in a particular medical field.

DOI： 10.3390/cancers11020178

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Intratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy. A patient with recurrent glioblastoma (MGG70R) harboring focal, high-level EGFR amplification received the irreversible EGFR tyrosine kinase inhibitor dacomitinib. The tumour that subsequently recurred (MGG70RR) showed diploid EGFR, suggesting inhibitor-mediated elimination of EGFR-amplified tumour cells and propagation of EGFR non-amplified cell subpopulations. The MGG70R-GSC line established from MGG70R formed xenografts retaining EGFR amplification and EGFR overexpression, while MGG70RR-GSC established from MGG70RR generated tumours that lacked EGFR amplification and EGFR overexpression. MGG70R-GSC-derived intracranial xenografts were more proliferative than MGG70RR-GSC xenografts, which had upregulated mesenchymal markers, mirroring the pathological observation in the corresponding patient tumours. In vitro MGG70R-GSC was more sensitive to EGFR inhibitors than MGG70RR-GSC. Thus, these molecularly distinct GSC lines recapitulated the subpopulation alteration that occurred during glioblastoma evasion of targeted therapy, and offer a valuable model facilitating therapeutic development for recurrent glioblastoma.

DOI： 10.1038/s41598-018-37437-2

PubMed

researchmap

Language：English  

Brain metastasis frequently develops in non-small-cell lung cancer (NSCLC). Here, we report a patient who developed brain metastasis from ALK-positive NSCLC which mimicked brain abscess. He was admitted for suspected obstructive pneumonia nine months after curative lung resection. Head magnetic resonance imaging revealed a cavitary lesion, which was compatible with brain abscess but rare in brain metastasis. However, after treatment with antibiotics, the brain lesion increased in size. Aspiration of the liquid content of the brain lesion revealed cancer cells. When a brain lesion suggestive of abscess develops in a patient with ALK-positive NSCLC, aspiration may be necessary to differentiate metastasis from abscess.

DOI： 10.1155/2019/9141870

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fonc.2019.00727

Scopus

PubMed

researchmap

Language：English  

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

DOI： 10.3171/2018.6.JNS18729

PubMed

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publisher：日本癌学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本がん免疫学会  

researchmap

Language：English  

DOI： 10.3171/2017.9.JNS172108

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

IDH-mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II-IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next-generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH-mutated gliomas, 12 were 1p-intact/19q-intact (anaplastic astrocytomas [AA]), 7 were 1p-intact/19q-loss (AA), and 23 showed 1p/19q-codeletion (anaplastic oligodendrogliomas). Of the 88 IDH-wild type glioblastomas (GBMs), 14 showed 1p-intact/19q-loss status. All of the seven 1p-intact/19q-loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q-loss AAs had regions presenting oligodendroglioma-like morphology, and were associated with significantly longer overall survival compared to 19q-intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q-loss GBM and 19q-intact GBM (P = .4). In a case of 19q-loss AA, both oligodendroglial morphology and 19q-loss disappeared after recurrence, possibly indicating correlation between 19q-loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH-mutated astrocytomas harboring 19q-loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q-intact astrocytomas.

DOI： 10.1111/cas.13635

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE Chordoma is a slow-growing but clinically malignant tumor, and the prognosis remains poor in many cases. There is a strong impetus to develop more effective targeted molecular therapies. On this basis, the authors investigated the potential of Brachyury, a transcription factor involved in notochord development, as a candidate molecular target for the treatment of chordoma. METHODS Brachyury gene copy number and expression levels were evaluated by quantitative polymerase chain reaction in 27 chordoma samples, and the transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low-expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to investigate the signaling pathways that regulate Brachyury expression. RESULTS All chordoma specimens expressed Brachyury, and expression levels varied widely. Patients with higher Brachyury expression had significantly shorter progression-free survival (5 months, n = 11) than those with lower expression (13 months, n = 16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases, and copy number was positively correlated with Brachyury expression (R = 0.61, p < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high-expression tumors, and suppression of PI3K signaling led to reduced Brachyury expression and inhibition of cell growth in the U-CH2 chordoma cell line. CONCLUSIONS Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.

DOI： 10.3171/2016.12.JNS161444

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2017.08.142

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00401-017-1771-1

Web of Science

PubMed

researchmap

Language：English  

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1507/endocrj.EJ17-0177

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/neuonc/nox034

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1158/0008-5472.CAN-16-2263

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：日本がん免疫学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE The management of vestibular schwannoma (VS) remains controversial. One commonly cited advantage of microsurgery over other treatment modalities is that tumor removal provides the greatest chance of long-term cure. However, there are very few publications with long-term follow-up to support this assertion. The purpose of the current study is to report the very long-term risk of recurrence among a large historical cohort of patients who underwent microsurgical resection. METHODS The authors retrospectively reviewed the medical records of patients who had undergone primary microsurgical resection of unilateral VS via a retrosigmoid approach performed by a single neurosurgeon-neurotologist team between January 1980 and December 1999. Complete tumor removal was designated gross-total resection (GTR), and anything less than complete removal was designated subtotal resection (STR). The primary end point was radiological recurrence-free survival. Time-to-event analyses were performed to identify factors associated with recurrence. RESULTS Four hundred fourteen patients met the study inclusion criteria and were analyzed. Overall, 67 patients experienced recurrence at a median of 6.9 years following resection (IQR 3.9-12.1, range 1.2-22.5 years). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following resection were 93% (95% CI 91-96, 248 patients still at risk), 78% (72-85, 88), 68% (60-77, 47), and 51% (41-64, 22), respectively. The strongest predictor of recurrence was extent of resection, with patients who underwent STR having a nearly 11-fold greater risk of recurrence than the patients treated with GTR (HR 10.55, p < 0.001). Among the 18 patients treated with STR, 15 experienced recurrence at a median of 2.7 years following resection (IQR 1.9-8.9, range 1.2-18.7). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following GTR were 96% (95% CI 93-98, 241 patients still at risk), 82% (77-89, 86), 73% (65-81, 46), and 56% (45-70, 22), respectively. Estimated recurrence-free survival rates at 5, 10, and 15 years following STR were 47% (95% CI 28-78, 7 patients still at risk), 17% (5-55, 2), and 8% (1-52, 1), respectively. CONCLUSIONS Long-term surveillance is required following microsurgical resection of VS even after GTR. Subtotal resection alone should not be considered a definitive long-term cure. These data emphasize the importance of long-term follow-up when reporting tumor control outcomes for VS.

DOI： 10.3171/2016.11.JNS16498

PubMed

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s40478-017-0422-z

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2016.8.SPINE16465

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/02699052.2016.1225986

Web of Science

PubMed

researchmap

Web of Science

researchmap

DOI： 10.1093/neuonc/now090

Web of Science

J-GLOBAL

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2015.9.JNS141368

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jocn.2016.02.019

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2016.06.105

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s40478-016-0351-2

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.1186/s40478-016-0351-2

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ccell.2015.11.006

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2015.08.019

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ca.22615

Web of Science

PubMed

researchmap

DOI： 10.1158/1538-7445.AM2015-1072

Web of Science

researchmap

DOI： 10.1093/neuonc/nou254.13

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1078-0432.CCR-13-3052

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：日本家族性腫瘍学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2013.8.JNS13832

Web of Science

PubMed

researchmap

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.nec.2013.05.010

Web of Science

PubMed

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2012.01.057

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Congress of Neurological Surgeons  

DOI： 10.7887/jcns.22.590

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-013-1058-x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

OBJECT: Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population. METHODS: The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008. RESULTS: The patients' median age was 74 years (range 66-87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40-90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13-0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30-0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31-0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11-0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13-0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively. CONCLUSIONS: The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

DOI： 10.3171/2012.10.JNS112268

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/nrclinonc.2012.204

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1227/neu.0b013e31826a88a9

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1227/NEU.0b013e31826a88a9

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-012-0956-7

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/2012.4.JNS11214

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12028-011-9667-8

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-011-0642-1

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/jns.0.0.0.jns10189

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2010.05.007

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1227/01.NEU.0000370978.31405.A9

Web of Science

PubMed

researchmap

Language：English  

DOI： 10.3171/2010.3.JNS10189

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/FOC.2009.26.2.E10

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.surneu.2007.01.034

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.surneu.2006.10.031

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3171/jns.2007.106.3.514

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.surneu.2006.03.035

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.surneu.2005.11.064

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Society on Surgery for Cerebral Stroke  

The effectiveness of CEA in preventing further stroke of the patient with high grade carotid stenosis is well known. However, controversy still exists as for the choice of CEA or low flow bypass in the cases of near occlusion because of the uncertainty of the patency of distal ICA as well as the risk for postoperative hyperperfusion.<br> We experienced 7 consecutive cases of near occlusion between May and November 2004 and performed CEA. In all cases, the flexible shunt (Furui shunt) was employed to reduce the risk of hemodynamic ischemia during clamping. To prevent distal embolism during distal shunt tube insertion, great care was taken to secure the "true distal lumen" high enough above the stenotic site. If necessary, arteriotomy was added on the distal wall and then connected toward the proximal. The use of a shunt tube was helpful in gaining a fine view of the distal end during endarterectomy because it held the collapsed lumen round open. <br> There were no ischemic complications. Good patencies were demonstrated by postoperative DSAs in all cases.<br> In our experiences, CEA could be safely performed as long as the angiography shows patent ICA distal to stenotic site even in delayed fashion. <br>

DOI： 10.2335/scs.34.27

CiNii Article

CiNii Books

researchmap

Other Link： https://jlc.jst.go.jp/DN/JALC/00273987947?from=CiNii

Language：Japanese   Publishing type：Research paper (international conference proceedings)   Publisher：Japanese Congress of Neurological Surgeons  

DOI： 10.7887/jcns.14.401

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1385/NCC:2:1:067

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(株)中外医学社  

researchmap

Language：English   Publisher：(一社)日本癌治療学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：Japanese   Publisher：(株)医学書院  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220216220019&doc_link_id=10.11477%2Fmf.1436204542&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204542&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(株)医学書院  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220216220007&doc_link_id=10.11477%2Fmf.1436204530&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204530&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(NPO)日本脳神経血管内治療学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本小児神経学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese  

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publisher：(一社)日本癌学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本言語聴覚士協会  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04306&link_issn=&doc_id=20171005130223&doc_link_id=10.11477%2Fmf.6001200137&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.6001200137&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publisher：日本脳腫瘍病理学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本高次脳機能障害学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：(株)日本臨床社  

researchmap

Language：Japanese  

PubMed

researchmap

Language：Japanese   Publisher：日本脳腫瘍病理学会  

researchmap

Language：Japanese  

CiNii Article

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2016058733

Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1200/jco.2015.33.15_suppl.e17658

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1093/neuonc/nou253.30

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publisher：日本脳神経外科コングレス  

CiNii Article

CiNii Books

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1227/01.NEU.0000387049.61328.AD

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

researchmap

Language：Japanese   Publisher：The Japanese Society on Surgery for Cerebral Stroke  

Preoperative angiography is basically essential for a patient of intracerebral hematoma, so as to check any underlying vascular anomaly such as a ruptured aneurysm or an arteriovenous malformation (AVM). When the hematoma causes impending herniation, however, we omit preoperative angiography to save time and perform emergency surgery even if a ruptured aneurysm or an AVM is highly suspected. We experienced 8 such cases during 2.5 years: 6 cases of ruptured aneurysm and 2 of AVM. Three of them achieved good recovery and none died.<br> Some special considerations and tactics are required before and during surgery to ensure safety. When a ruptured aneurysm is suspected, a microscope, a self-retractor and clips should be ready prior to surgery. The superficial temporal artery should be preserved just in case. After the craniotomy, the hematoma is evacuated partially for decompression away from the suspected aneurysm. Then, in case of premature rupture, the dissection is performed directly toward the bleeding site; otherwise sylvian fissure is dissected for aneurysm exploration. When an AVM is suspected, care must be taken not to injure the draining veins. It is safer to finish the emergency surgery after evacuating the hematoma and to go on to cerebral angiography. The resection of an AVM should then be performed in the chronic period.<br> In our experiences, we were able to perform emergency surgery safely for a ruptured aneurysm or an AVM, even when we had to omit preoperative angiography because of impending herniation.<br>

DOI： 10.2335/scs.35.204

CiNii Article

J-GLOBAL

researchmap