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1.
Cancer Invest ; : 1-8, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934568

ABSTRACT

This study aimed to investigate the predictive factors of transfer of glioblastoma multiforme (GBM) patients who underwent rehabilitation in acute care hospitals. We retrospectively identified 85 patients with GBM who underwent rehabilitation at our hospital. Multivariable logistic regression analysis showed that age and Barthel index (BI) at rehabilitation initiation significantly influenced the discharge destination. Cut-off values for these factors were 76 years of age and 30 BI points. These findings could help predict the discharge destination and the choice of rehabilitation strategies of newly diagnosed patients with GBM admitted to an acute care hospital.

2.
J Neurooncol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839702

ABSTRACT

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

3.
Surg Neurol Int ; 15: 108, 2024.
Article in English | MEDLINE | ID: mdl-38628517

ABSTRACT

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

4.
Neurol Med Chir (Tokyo) ; 63(3): 111-115, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36682790

ABSTRACT

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.


Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Lymphoma , Humans , Retrospective Studies , Lymphoma/diagnosis , Central Nervous System Neoplasms/pathology , Brain Neoplasms/diagnosis , Receptors, Interleukin-2
5.
Anticancer Res ; 42(10): 4727-4733, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36192008

ABSTRACT

BACKGROUND/AIM: The development of pharmacological inhibitors targeting negative regulators of p53, such as murine double minute (MDM) 2 and, more recently, MDM4, has been actively pursued as a potential strategy to treat cancers with wild-type p53. We previously showed that CEP-1347, a small molecule kinase inhibitor originally developed for the treatment of Parkinson's disease, suppressed MDM4 expression and activated wild-type p53 in retinoblastoma cells. However, it remains unknown whether CEP-1347 acts as an MDM4 inhibitor and as such activates p53 in other types of human cancer cells. MATERIALS AND METHODS: The effects of CEP-1347 and MDM4 knockdown on the mRNA and protein expression of components of the p53 pathway, including MDM4, in human glioma cell lines with and without p53 mutation were examined by RT-PCR and western blot analyses. Trypan blue dye exclusion was used to examine the effect of CEP-1347 on cell growth. RESULTS: CEP-1347 decreased the expression of MDM4, increase that of p53, and activated the p53 pathway in glioma cells with wild-type p53. Knockdown-mediated inhibition of MDM4 expression in a glioma cell line with wild-type p53 that overexpresses MDM4 resulted in increased p53 expression and activation of the p53 pathway. CEP-1347 preferentially inhibited the growth of glioma cells with wild-type p53 without showing toxicity to normal cells at clinically relevant concentrations. CONCLUSION: Our findings suggest CEP-1347 is a novel inhibitor of MDM4 protein expression and as such activates p53 to inhibit the growth of cancer cells with wild-type p53, including retinoblastoma and glioblastoma.


Subject(s)
Glioma , Retinal Neoplasms , Retinoblastoma , Carbazoles , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Gene Expression Regulation, Neoplastic , Glioma/drug therapy , Glioma/genetics , Humans , Nuclear Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , RNA, Messenger/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
6.
Brain Tumor Pathol ; 39(3): 139-150, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35312904

ABSTRACT

Clinicopathological risk factors for a poor prognosis were investigated in elderly patients with malignant lymphoma of the central nervous system. A total of 82 pathologically confirmed, CD20-positive, diffuse large B-cell lymphoma patients aged 71 years or older who underwent therapeutic intervention in the Tohoku and Niigata area in Japan were retrospectively reviewed. A univariate analysis was performed by the log-rank test using the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate analysis of risk factors. Of the 82 patients, 39 were male and 43 were female, and their median age at onset was 75 years. At the end of the study, there were 34 relapse-free patients (41.5%), 48 relapse cases (58.5%), median progression-free survival was 18 months, and median overall survival (OS) was 26 months; there were 41 deaths and 41 survivors. Multivariate analysis of median OS showed that Karnofsky Performance Status less than 60% 3 months after treatment (p = 0.022, hazard ratio (HR) = 2.591) was the clinical risk factor, and double expressor lymphoma (p = 0.004, HR = 3.163), expression of programmed death-ligand 1 in tumor infiltrating lymphocytes or tumor-associated macrophages (p < 0.001, HR = 5.455), and Epstein-Barr virus infection (p = 0.031, HR = 5.304) were the pathological risk factors.


Subject(s)
Brain Neoplasms , Epstein-Barr Virus Infections , Lymphoma, Large B-Cell, Diffuse , Aged , Central Nervous System/pathology , Cohort Studies , Female , Herpesvirus 4, Human , Humans , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Prognosis , Retrospective Studies , Risk Factors
7.
Childs Nerv Syst ; 38(2): 473-477, 2022 02.
Article in English | MEDLINE | ID: mdl-34312708

ABSTRACT

Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered was introduced to the World Health Organization classification of central nervous system tumors in 2016. It is characterized by amplification or fusion of the chromosome 19 microRNA cluster (C19MC) locus at 19q13.42. Medulloepithelioma also an ETMR but lacks C19MC alteration. We report a rare case of spinal medulloepithelioma in a 2-year-old boy and review the literature.


Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , MicroRNAs , Neoplasms, Germ Cell and Embryonal , Neuroectodermal Tumors, Primitive , Brain Neoplasms/pathology , Child, Preschool , Humans , Male , MicroRNAs/genetics , Neuroectodermal Tumors, Primitive/diagnostic imaging , Neuroectodermal Tumors, Primitive/surgery
8.
Neurol Med Chir (Tokyo) ; 62(1): 28-34, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34707068

ABSTRACT

Additional resection beyond contrast enhanced lesion on MRI is recently considered to prolong survival in glioblastoma. Prediction of future recurrent site in the peritumoral lesion on preoperative MRI could be useful for surgical planning. The objective of this study was to determine if the preoperative ADC value was associated with the site of future recurrence in patients with glioblastoma. We retrospectively analyzed 21 patients with primary GBM. The ADC value on MRI were analyzed before and after operation and at recurrence. The region of interests (ROIs) were set to cover almost the FLAIR high-signal lesion surrounding contrast enhanced lesion. We determined whether the value of ADC on MRI was correlated with the spot of future recurrence. Among 1844 ROIs determined in the FLAIR high-signal lesion on preoperative MRI, new enhanced lesions occurred in 186 sites. The other 1258 sites showed no change or decrease in size on follow up MRI, and the other 400 sites were removed in first operation. The pre-operative ADC values of sites corresponding to future recurrence were significantly lower than that of non-recurrent sites (p <0.001). We suggest that a low ADC values in FLAIR high-signal lesion is corresponding to recurrence, and useful for predicting recurrence of the lesion in cases of GBM. These results will be helpful for planning of surgery or radiation therapy and facilitate future prospective studies on GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Diffusion Magnetic Resonance Imaging , Glioblastoma/diagnostic imaging , Glioblastoma/surgery , Humans , Prospective Studies , Retrospective Studies
9.
Int J Clin Oncol ; 27(1): 77-94, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34637053

ABSTRACT

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.


Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Lymphoma, Non-Hodgkin , Aged , Brain Neoplasms/therapy , Central Nervous System , Central Nervous System Neoplasms/therapy , Cohort Studies , Humans , Prognosis , Retrospective Studies , Risk Factors
10.
Neurooncol Adv ; 3(1): vdab086, 2021.
Article in English | MEDLINE | ID: mdl-34355172

ABSTRACT

BACKGROUND: 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? METHODS: 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). RESULTS: 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. CONCLUSION: CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

11.
NMC Case Rep J ; 8(1): 301-307, 2021.
Article in English | MEDLINE | ID: mdl-35079479

ABSTRACT

Brain stem gliomas (BSG) in adults are rare and less aggressive than those in children. However, the molecular profile of adult BSG cases has not been well characterized. We report a case of adult BSG with isocitrate dehydrogenase (IDH) mutation. A 43-year-old male was admitted to our hospital with diplopia and right-sided hypesthesia. An open biopsy led to the tumor being diagnosed as a diffuse astrocytoma. Immunohistochemically, the tumor was positive for IDH1 R132H, but negative for H3K27M. The patient received 54 Gy of local radiotherapy and adjuvant temozolomide, which resulted in the size of the lesion decreasing significantly. At 56 months after the initial diagnosis, the patient was referred to our hospital with a severe headache and ataxia. Magnetic resonance imaging (MRI) revealed a contrast-enhanced lesion in the brain stem, which extended into the left cerebellar hemisphere and brainstem. Partial tumor removal was performed, and a pathological examination revealed the features of glioblastoma. Immunohistochemically, the tumor was positive for IDH1 R132H and p53 and negative for ATRX. To the best of our knowledge, there are few reports about adult case of brain stem astrocytoma to be confirmed via histological and molecular examinations of the primary and recurrent tumor. We exhibit detailed pathological and molecular findings which resembles to IDH mutant supratentorial diffuse astrocytic tumors.

12.
Neuro Oncol ; 23(2): 295-303, 2021 02 25.
Article in English | MEDLINE | ID: mdl-32818237

ABSTRACT

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.


Subject(s)
Brain Neoplasms , Diabetes Insipidus , Diabetes Mellitus , Germinoma , Pineal Gland , Biomarkers, Tumor , Child , Diabetes Insipidus/etiology , Germinoma/complications , Germinoma/diagnosis , Humans , Male , Retrospective Studies
13.
No Shinkei Geka ; 48(12): 1121-1128, 2020 Dec.
Article in Japanese | MEDLINE | ID: mdl-33353874

ABSTRACT

Multiloculated hydrocephalus following severe meningitis with ventriculitis is often therapeutically challenging. Neonatal meningitis is commonly associated with ventricular inflammation, and approximately 30% of patients show septum formation. Although placement of a single ventriculoperitoneal shunt system could serve as optimal treatment for a multiloculated cerebrospinal cavity that is converted into a single chamber, multiple devices are often required for disease stability. We report a case of multiloculated hydrocephalus that occurred after meningitis in a patient who was successfully treated with a single shunt system using staged multimodality treatments.


Subject(s)
Cerebral Ventriculitis , Hydrocephalus , Meningitis , Cerebral Ventriculitis/complications , Cerebral Ventriculitis/diagnostic imaging , Cerebrospinal Fluid Shunts , Humans , Hydrocephalus/diagnostic imaging , Hydrocephalus/etiology , Hydrocephalus/surgery , Meningitis/complications , Meningitis/surgery , Ventriculoperitoneal Shunt
14.
Neurooncol Adv ; 2(1): vdaa114, 2020.
Article in English | MEDLINE | ID: mdl-33134923

ABSTRACT

BACKGROUND: Although mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up. METHODS: We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated. RESULTS: GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, P = .015) and overall survival (16 vs. 24 months, respectively, P = .017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P = .004). According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain, and TP53 deletion. CONCLUSIONS: TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.

15.
Acta Neuropathol Commun ; 8(1): 201, 2020 11 23.
Article in English | MEDLINE | ID: mdl-33228806

ABSTRACT

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.


Subject(s)
Brain Neoplasms/genetics , Chromosome Deletion , Chromosomes, Human, Pair 19 , Chromosomes, Human, Pair 1 , Glioma/genetics , Promoter Regions, Genetic/genetics , Telomerase/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/therapy , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Female , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/therapy , Glioma/pathology , Glioma/therapy , Humans , Isocitrate Dehydrogenase/genetics , Karnofsky Performance Status , Male , Middle Aged , Multivariate Analysis , Mutation , Neoplasm Grading , Neurosurgical Procedures , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Oligodendroglioma/therapy , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Young Adult
16.
Neurol Med Chir (Tokyo) ; 60(11): 543-552, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-33071274

ABSTRACT

Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.


Subject(s)
Astrocytoma/diagnosis , Astrocytoma/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Adolescent , Adult , Age Factors , Aged , Astrocytoma/mortality , Brain Neoplasms/mortality , Child , Female , Humans , Japan , Male , Middle Aged , Mutation/genetics , Nestin/metabolism , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Risk Factors , Survival Rate , Telomerase/genetics , Young Adult
17.
No Shinkei Geka ; 48(9): 801-808, 2020 Sep.
Article in Japanese | MEDLINE | ID: mdl-32938808

ABSTRACT

Diffuse leptomeningeal glioneuronal tumor(DLGNT)is a rare primary neoplasm of the central nervous system, and is a condition that is newly listed in the 2016 World Health Organization(WHO)classification of tumors of the central nervous system. We report an adult case of DLGNT that was characteristically merged with subarachnoid hemorrhage. A 46-year-old woman reported persistent dizziness upon walking. MRI of the brain revealed a diffuse, infiltrating lesion with high intensity on FLAIR around the cerebellopontine angle to the lateral ventricle and in the leptomeninges of the spinal cord. The lesion on the cerebellopontine angle showed high intensity on T1 weighted images with contrast enhancement. Since diffuse glioma and meningeal carcinomatosis were suspected, we performed an endoscopic biopsy for the lesion in the right lateral ventricle. Although the tumor was tentatively diagnosed as WHO grade II diffuse astrocytoma, a definitive diagnosis could not be obtained. One month after surgery, the patient presented with acute headache and dizziness. CT showed subarachnoid hemorrhage in the cerebellopontine angle. To decompress the intracranial pressure and prevent re-bleeding, and to obtain enough tissue samples for definitive diagnosis, we removed the enhanced lesion and hematoma at the cerebellopontine angle. Tumor tissue was composed of oligodendroglial-like cells and was positive for GFAP, Olig2, synaptophysin, and S100 protein, although it was negative for IDH1R132H. Fluorescent in situ hybridization showed KIAA1566-BRAF fusion; however, neither 1p loss nor 1p19q co-deletion was observed. Together with histological and radiological findings, the tumor was ultimately diagnosed as DLGNT. The patient received maintenance chemotherapy with temozolomide, and the tumor was stable at 18 months after surgery.


Subject(s)
Meningeal Neoplasms , Subarachnoid Hemorrhage , Adult , Female , Humans , In Situ Hybridization, Fluorescence , Magnetic Resonance Imaging , Middle Aged , Spinal Cord
18.
No Shinkei Geka ; 48(8): 711-716, 2020 Aug.
Article in Japanese | MEDLINE | ID: mdl-32830136

ABSTRACT

Pituitary metastases(PM)are rare and show a poor prognosis. However, recent advances in diagnostic imaging could increase the chances of PM being diagnosed without a history of cancer. Furthermore, it was unclear whether adjuvant therapy could increase the survival of patients with PM or not. To clarify the clinical course of patients with PM, we report seven cases of PM with a literature review. Most patients showed symptomatic adenohypophyseal dysfunction(AD)and diabetes insipidus(DI)as initial symptoms. All patients underwent radiotherapy for PM and showed good local tumor control. However, except for one patient with improved DI, neither AD nor DI improved with radiotherapy. As for the prognosis, three patients with PM without a history of cancer survived longer than those with a history of cancer(20.3 vs. 11.7 months, respectively). In summary, early diagnosis and appropriate hormone replacement therapies are important in PM. Improvement of the general condition enables adjuvant therapy to prolong patient survival.


Subject(s)
Diabetes Insipidus , Pituitary Neoplasms , Humans , Prognosis
19.
J Neurooncol ; 146(3): 489-499, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32020479

ABSTRACT

INTRODUCTION: We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence. MATERIALS AND METHODS: We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors. RESULTS: The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%). CONCLUSION: An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.


Subject(s)
AC133 Antigen/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Glioblastoma/metabolism , Glioblastoma/pathology , Lateral Ventricles/pathology , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Brain Neoplasms/diagnostic imaging , Female , Glioblastoma/diagnostic imaging , Humans , Lateral Ventricles/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Retrospective Studies , Young Adult
20.
No Shinkei Geka ; 48(1): 25-32, 2020 Jan.
Article in Japanese | MEDLINE | ID: mdl-31983685

ABSTRACT

Intracranial pseudoaneurysms arising after radiotherapy for brain tumors are a relatively rare occurrence and associated with high-volume radiotherapy such as stereotactic radiosurgery. Herein, the authors report a rare case of intracranial pseudoaneurysm after conventional radiotherapy for oligodendroglioma. Case:A 46-year-old female incidentally presented with an intracranial hemorrhage from a middle temporal artery aneurysm. Four years earlier, she underwent surgical resection and conventional radiation therapy for oligodendroglioma. The aneurysm was successfully treated with middle cerebral artery(MCA)aneurysm trapping, in conjunction with a parietal branch superficial temporal artery-MCA bypass, to prevent re-rupture. Formation of intracranial pseudoaneurysm after conventional radiotherapy is extremely rare. However, the occurrence of cerebral aneurysm(s), as well as vascular stenosis during follow-up for brain tumors treated with radiotherapy, should be considered.


Subject(s)
Aneurysm, False , Brain Neoplasms , Intracranial Aneurysm , Oligodendroglioma , Aneurysm, False/diagnosis , Aneurysm, False/etiology , Brain Neoplasms/radiotherapy , Cerebral Angiography , Female , Humans , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/etiology , Middle Aged , Middle Cerebral Artery , Oligodendroglioma/radiotherapy , Temporal Arteries
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