Prognostic Factors and Histopathological Features of Pediatric Intracranial Ependymomas: Nationwide Brain Tumor Registry-based Study of Japan.

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.

[Association of Cigarette Smoking with Muscle Mass Reduction and Low Muscle Strength in Community-Dwelling Elderly Men].

OBJECTIVES: Recently, attention has been paid to the impact of cigarette smoking on skeletal muscles, as its underlying pathophysiological mechanism has been gradually elucidated. In this study, we aimed to examine whether cigarette smoking is associated with muscle mass reduction and low muscle strength in elderly men. METHODS: The study participants comprised 417 community-dwelling elderly men (aged 73±6 years) without severe glucose intolerance, chronic kidney disease, or liver disease. Bioelectrical impedance analysis was performed to estimate appendicular skeletal muscle mass (ASM), which was normalized for height (ASM index, kg/m2). Handgrip strength (HGS) was measured using a Smedley grip dynamometer. Cumulative smoking exposure level during a lifetime was expressed in pack-years, which is a product of the average number of packs of cigarettes smoked per day and smoking duration in years. RESULTS: When the participants were stratified on the basis of cumulative smoking exposure (<10 pack-years, 10-39 pack-years, ≥40 pack-years), the ASM index and HGS progressively decreased with increasing exposure level (P for trend <0.01). In multiple regression analysis, heavy smoking (defined as ≥40 pack-years) was found to be a significant determinant of the ASM index and HGS, independent of potential confounding factors. Among former smokers, the subgroup that quit smoking for ≥20 years had a significantly higher ASM index and HGS than the subgroup that quit smoking for <10 years. The duration of smoking cessation was significantly associated with the ASM index and HGS, even after adjusting for cumulative smoking exposure. CONCLUSIONS: These findings suggest that cigarette smoking contributes to the loss of muscle mass and function in elderly men and that smoking cessation could reverse the impact of cigarette smoking on skeletal muscles.

Associations between deterioration of self-rated health and occupational form among community-dwelling Japanese individuals.

Objectives: In occupational therapy, occupations refer to everyday activities that people perform as individuals, in families, and with communities to live a meaningful life. Thus far, there has been no large-scale survey conducted using quantitative data to study deterioration of self-rated health from an occupational perspective. This large-scale study therefore aimed to clarify the associations between deterioration of self-rated health and occupational form, performance, and satisfaction using quantitative data. Study design: One-year prospective cohort study. Methods: Subjects included 438 community-dwelling individuals (175 males and 263 females; mean age, 66.3 ± 10.5 years) who participated in the study during 2017-2018. We administered to patients a questionnaire on self-rated health and occupational form (number, frequency, and duration), occupational performance, and occupational satisfaction. A multi-level Poisson regression analysis was performed, wherein deterioration of self-rated health was the dependent variable and occupational form, performance, and satisfaction were the independent variables. In Model 1, the independent variables were adjusted for each other; in Model 2, sex, living alone, and alcohol consumption were added to Model 1; and in Model 3, disease was added to Model 2. Results: The frequency of occupation monthly/yearly was associated with deterioration of self-rated health compared to that daily/weekly among those aged <65 years. Adjusted prevalence ratios (95% confidence interval) for models 1, 2, and 3 were 2.95 (1.07-8.18), 3.19 (1.13-8.99), and 3.81 (1.29-11.20), respectively. Conclusions: This study revealed factors for the deterioration of self-rated health from an occupational perspective that was directly related to daily life. Increasing the occupation frequency may be more important than increasing the number and duration of occupation to prevent deterioration of self-rated health.

Muscle mass reduction, low muscle strength, and their combination are associated with arterial stiffness in community-dwelling elderly population: the Wakayama Study.

Age-related loss of skeletal muscle mass and function is associated with some predisposing factors that increase the risk of vascular damage. This study aimed to examine whether muscle mass reduction, low muscle strength, and their combination were related to arterial stiffness in community-dwelling elderly population. Study participants consisted of 1046 elderly individuals (aged 72 ± 5 years) without cardiovascular disease, chronic kidney disease, or liver disease. Bioelectrical impedance analysis was performed to estimate appendicular skeletal muscle mass (ASM). A value for ASM was normalized for height (ASM index, kg/m2). Handgrip strength (HGS) was measured using a Smedley grip dynamometer. Brachial-ankle pulse wave velocity (baPWV) was evaluated as an index of arterial stiffness using a simple automatic oscillometric technique. When participants were stratified based on baPWV cut-off values (< 1800 cm/s, 1800 to 1999 cm/s, ≥ 2000 cm/s), ASM index and HGS progressively decreased with an increase in baPWV levels (P for trend < 0.001). In multiple regression analysis, baPWV was significantly associated with ASM index (ß = -0.270, P < 0.001) and HGS (ß = -0.102, P < 0.001) independent of potential confounding factors. The baPWV of the subgroup with low ASM index and low HGS was significantly higher than that of those with only low ASM index or low HGS (P < 0.001). These results suggest that loss of skeletal muscle mass and function is associated with increased arterial stiffness in the elderly population, and the combination of muscle mass reduction and low muscle strength may lead to greater arterial stiffness than each of the individual conditions.

Relationship between Fall History and Self-Perceived Motor Fitness in Community-Dwelling People: A Cross-Sectional Study.

History of falling is an important fall risk factor. If a relationship between fall history and self-perceived motor fitness could be established, then treating it as a correctable risk of re-fall due to falls may be possible. We conducted a cross-sectional study of the relationship between fall history and self-perceived motor fitness in daily life among 670 community-dwelling people (mean age 62.0 ± 9.6 years, 277 men and 393 women) who had participated in health examinations. They completed a self-administered questionnaire that asked about their history of single or multiple falls and included a 14-item motor fitness scale. The responses were analyzed using multivariate logistic regression analysis. The results showed that in both younger and older (<65 years) subjects, a history of single or multiple falls was associated with a negative response to "being able to put on socks, pants or a skirt while standing without support". For subjects ≥65 years, an association was also observed with "shortness of breath when climbing stairs". Self-perceived motor fitness related to fall history can easily be noticed by an individual and may help them become aware of fall-related factors earlier in everyday life.

Molecular characteristics and clinical outcomes of elderly patients with IDH-wildtype glioblastomas: comparative study of older and younger cases in Kansai Network cohort.

Aging is a known negative prognostic factor in glioblastomas (GBM). Whether particular genetic backgrounds are a factor in poor outcomes of elderly patients with GBM warrants investigation. We aim to elucidate any differences between older and younger adult patients with IDH-wildtype GBM regarding both molecular characteristics and clinical outcomes. We collected adult cases diagnosed with IDH-wildtype GBM from the Kansai Network. Clinical and pathological characteristics were analyzed retrospectively and compared between older (≥ 70 years) and younger (≤ 50 years) cases. Included were 92 older vs. 33 younger cases. The older group included more patients with preoperative Karnofsky performance status score < 70 and had a shorter survival time than the younger group. MGMT promoter was methylated more frequently in the older group. TERT promoter mutation was more common in the older group. There were significant differences in DNA copy-number alteration profiles between age groups in PTEN deletion and CDK4 amplification/gain. In the older group, no molecular markers were identified, but surgical resection was an independent prognostic factor. Age-specific survival difference was significant in the MGMT methylated and TERT wildtype subgroup. Elderly patients have several potential factors in poor prognosis of glioblastomas. Varying molecular profiles may explain differing rates of survival between generations.

The Relationship Between Meaningful Occupation and Self-Rated Health in Japanese Individuals: The Wakayama Study.

In this study, we conducted a quantitative cross-sectional evaluation of the relationships between self-related health and occupational form, occupational performance, and occupational satisfaction. The participants were 675 community-dwelling subjects (283 men, 392 women) who completed a self-administered questionnaire. From this data, we performed a multiple logistic regression analysis using the high and low values of self-rated health as the dependent variables and the characteristics of occupational form, occupational performance, and occupational satisfaction as the independent variables. There were three analysis models: Model 1, which mutually adjusted for all the independent variables; Model 2, with adjustment of the basic attributes, in addition to the first model; and Model 3, which was based on Model 2, but also adjusted for diseases. In all three models, high self-rated health was significantly correlated with high occupational performance scores. These findings confirmed that supporting occupational performance improvement is useful for improving self-rated health.

Radiomics and MGMT promoter methylation for prognostication of newly diagnosed glioblastoma.

We attempted to establish a magnetic resonance imaging (MRI)-based radiomic model for stratifying prognostic subgroups of newly diagnosed glioblastoma (GBM) patients and predicting O (6)-methylguanine-DNA methyltransferase promotor methylation (pMGMT-met) status of the tumor. Preoperative MRI scans from 201 newly diagnosed GBM patients were included in this study. A total of 489 texture features including the first-order feature, second-order features from 162 datasets, and location data from 182 datasets were collected. Supervised principal component analysis was used for prognostication and predictive modeling for pMGMT-met status was performed based on least absolute shrinkage and selection operator regression. 22 radiomic features that were correlated with prognosis were used to successfully stratify patients into high-risk and low-risk groups (p = 0.004, Log-rank test). The radiomic high- and low-risk stratification and pMGMT status were independent prognostic factors. As a matter of fact, predictive accuracy of the pMGMT methylation status was 67% when modeled by two significant radiomic features. A significant survival difference was observed among the combined high-risk group, combined intermediate-risk group (this group consists of radiomic low risk and pMGMT-unmet or radiomic high risk and pMGMT-met), and combined low-risk group (p = 0.0003, Log-rank test). Radiomics can be used to build a prognostic score for stratifying high- and low-risk GBM, which was an independent prognostic factor from pMGMT methylation status. On the other hand, predictive accuracy of the pMGMT methylation status by radiomic analysis was insufficient for practical use.

Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors.

INTRODUCTION: This study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas. METHODS: We collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival. RESULTS: Included in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis. CONCLUSIONS: This community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.

Rapid regression of glioblastoma following carmustine wafer implantation: A case report.

Carmustine wafers, which are locally delivered chemotherapy in the form of biodegradable implants, confer a survival benefit to patients with glioblastoma (GB) following surgical resection. While the adverse events of this method, including gas retention and perifocal edema, have been extensively investigated, the immediate efficacy of the implant has rarely been reported. To the best of our knowledge, this is the first reported case of GB in which the tumor rapidly regressed after partial surgical removal followed by implantation of carmustine wafers. A 77-year-old woman presented with motor aphasia and right hemiparesis. Neuroimaging revealed a tumor located in the left frontal lobe of the brain. The tumor was partially removed under 5-aminolevulinic acid fluorescence guidance and 8 carmustine wafers were implanted in the resection cavity. The histopathological findings suggested the diagnosis of GB. Genetic and immunohistochemical analyses revealed O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and low MGMT protein expression, respectively, in the tumor cells. One month after the operation, when adjuvant temozolomide chemotherapy was planned, computed tomography and magnetic resonance imaging revealed a marked regression of the residual tumor and perifocal edema. The patient's symptoms and signs had improved. As adjuvant temozolomide without radiation was therapeutically beneficial, the tumor gradually regressed and the patient has remained progression-free for >12 months after the operation. Therefore, adjuvant local chemotherapy with carmustine wafer implants was able to induce rapid regression of GB.

Relationships of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genotypes with alcohol sensitivity, drinking behavior and problem drinking in Japanese older men.

OBJECTIVES: Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan. METHODS: The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ(2) test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors. RESULTS: The frequency of 'always' facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group. CONCLUSIONS: We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

Effect of metabolic syndrome components and their clustering on carotid atherosclerosis in a sample of the general Japanese population.

The objective of this study was to investigate the impact of metabolic syndrome (MS) on carotid atherosclerosis in a Japanese population. A total of 1727 subjects (805 males and 922 females) were included. Intima-media thickness (IMT) was measured using ultrasonography. To evaluate the independent determinants of IMT, a stepwise multiple regression analysis was employed that included age, current smoking habit, LDL-C, HbA1c and the MS components (SBP, DBP, TG, HDL-C, FBG, and WC) as independent variables. Multivariate regression analyses were performed to determine the independent associations of the MS components with IMT. In males, age (ß=0.383, P<0.001), SBP (ß=0.237, P<0.001), LDL-C (ß=0.188, P<0.001), current smoking habit (ß=0.124, P=0.007) and HbA1c (ß=0.110, P=0.014) were significantly associated with IMT. In females, age (ß=0.474, P<0.001), SBP (ß=0.130, P=0.003) and FBG (ß=0.110, P=0.038) were significantly associated with IMT. The present study demonstrated that an elevated number of MS components, with or without central obesity, is associated with higher IMT. Among the analyzed components, hypertension has the strongest association with higher IMT.

Orthostatic Blood Pressure Changes and Subclinical Markers of Atherosclerosis.

BACKGROUND: Using a simple standing-up test in normotensive subjects, we evaluated orthostatic upright postural blood pressure (BP) changes and autonomic nervous function, as well as the relationship between orthostatic BP changes and subclinical markers of atherosclerosis. METHODS: A total of 515 normotensive subjects aged 35-75 years (58.4±10.0 years) were enrolled. We measured body mass index (BMI), systolic BP (SBP) and diastolic BP (DBP), serum lipids, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and urinary albumin-to-creatinine ratio. Brachial to ankle pulse wave velocity (baPWV) and carotid mean intima-media thickness (IMT) were measured. Participants underwent a simple standing-up test involving sitting then standing for 2 minutes each, followed again by sitting. To evaluate autonomic fluctuations, we calculated the coefficient of variation of the R-R interval, the ratio of low to high frequency heart rate variability (LF/HF), and the coefficient of component variance of high frequency. RESULTS: SBP and DBP decreased when standing, with a reduction of SBP when changing position of -8.0±10.2mm Hg. Orthostatic hypotension (OH) produced a significantly higher SBP than without OH. The baPWV was significantly higher in OH than in without OH. Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, HbA1c, hs-CRP, IMT, late systolic peak of the pressure wave form (SBP2), and baPWV confirmed that baPWV, SBP2, and triglycerides were independently related to orthostatic BP changes. Multiple regression analyses showed that a decrease in SBP as well as baseline SBP, age, BMI, and fasting glucose were independent determinants of PWV. CONCLUSIONS: We have shown that increased arterial stiffness was associated with OH during a standing-up test. Arterial stiffness may contribute to greater BP responses to postural changes from standing.

Relationship between blood pressure response during step exercise test and atherosclerotic markers.

Abstract The relationship between blood pressure (BP) response to exercise and atherosclerotic markers were evaluated in a population based sample of 426 normotensive subjects. The subjects with greater increase of SBP during exercise and delayed recovery of SBP after exercise showed higher hs-CRP and SBP2. Multiple regression analysis revealed that the greater BP response and delayed BP recovery were independently associated with SBP2 after adjusting for resting SBP, age, and gender. These results suggest that early atherosclerosis may contribute to greater BP responses to exercise, supporting the concept that exercise BP adds incremental information of cardiovascular risks to resting BP.

Intracranial extension of adenoid cystic carcinoma: potential involvement of EphA2 expression and epithelial-mesenchymal transition in tumor metastasis: a case report.

BACKGROUND: Adenoid cystic carcinoma is a malignant epithelial tumor derived from salivary glands and tends to invade the surrounding structures including nervous system. We present a case of adenoid cystic carcinoma with intracranial extension and propose a novel molecular mechanism of adenoid cystic carcinoma metastasis. CASE PRESENTATION: A 29-year-old Japanese male presented with left trigeminal nerve disturbance. Neuroimaging revealed a tumor located at the right middle cranial and infratemporal fossa. The tumor was removed via a subtemporal extradural and infratemporal fossa approach and histologically diagnosed as adenoid cystic carcinoma. Radiological and operative findings confirmed a perineural spread of the tumor along the mandibular nerve. Immunohistochemical analyses of molecular consequences in this case were performed for better understanding of the biological processes associated with adenoid cystic carcinoma metastasis. First, the neoplastic cells were not immunoreactive for E-cadherin, an epithelial marker, but for vimentin, a mesenchymal marker, suggesting changes in cell phenotype from epithelial to mesenchymal states. Correspondingly, immunoreactivity of transcriptional factors, such as Slug, Twist, matrix metalloproteinase-2 and -9, which are involved in epithelial-mesenchymal transition, were observed. Second, elevated expression of EphA2 receptor, not ephrin-A1, was notable in the neoplastic cells, suggesting morphological changes reminiscent of epithelial-mesenchymal transition and ligand-independent promotion of tumor cell migration and invasion. CONCLUSIONS: We report a case of adenoid cystic carcinoma with perineural spread and provide the first published evidence that EphA2 expression without ephrin-A1 and epithelial-mesenchymal transition might play important roles in adenoid cystic carcinoma progression.

A case of in-stent neoatherosclerosis 10 years after carotid artery stent implantation: observation with optical coherence tomography and plaque histological findings.

We report a patient's case of slow progressive in-stent restenosis 10 years after bare-metal stent implantation to his carotid artery. We treated the patient with an additional stent placement under a distal filter protection device. Optical coherence tomographic assessment and plaque histology during the carotid artery stenting (CAS) revealed atheromatous change at in-stent neointima, which contained lipid-rich plaque and calcification deposits. These findings suggest that in-stent neoatherosclerosis may play an important role in the pathogenesis of very late stent restenosis after CAS.

Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base Ewing Sarcoma/PNET: Case Report.

Background Aneurysm formation after stereotactic irradiation of skull base tumors is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor (PNET), who underwent surgery followed by multiple courses of intensity-modulated radiation therapy (IMRT) and chemotherapy, is described. Case Description A 25-year-old man presented with a sinonasal tumor with intraorbital and intracranial growth. At that time cerebral angiography did not reveal any vascular abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and three courses of IMRT at 3, 28, and 42 months after initial surgery. The total biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months after the third IMRT, the patient experienced profound nasal bleeding that resulted in hypovolemic shock. Angiography revealed a ruptured right C4-C5 aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular trapping of the right ICA was done. The patient recovered well after surgery but died due to tumor recurrence 6 months later. Conclusion Excessive irradiation of the ICA may occasionally result in aneurysm formation, which should be borne in mind during stereotactic irradiation of malignant skull base tumors.