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Objective: The safety of transsphenoidal surgery (TSS) for pituitary adenoma in elderly populations is becoming a new topic in our aging society. However, previous studies did not focus on the surgical procedures in elderly patients. We attempted to clarify the safety of TSS and the influence of pseudocapsular resection in elderly patients with non-functioning pituitary adenoma (NFPA)., Methods: A total of 284 patients undergoing initial TSS for NFPA were categorized into two groups as follows: 1) Elderly group (n = 69; age ≥ 70 years); and 2) Younger group (n = 215; age < 70 years). Furthermore, all patients were newly divided into the two following categories: 1) Resected group (n = 121, with total pseudocapsule resection); and 2) Non-Resected group (n = 163, without total pseudocapsule resection). The main outcome measure was the incidence of perioperative complications and the rate of severe growth hormone deficiency (sGHD) after TSS., Results: There were no significant differences in the rates of perioperative complication between the Elderly and Younger groups. Furthermore, pseudocapsular resection did not increase the surgical risks in either group. On the other hand, sGHD only showed a significant improvement in the Younger group. The only factor predicting the new development of sGHD following TSS was an older age, not pseudocapsule resection., Conclusions: Aging does not increase the perioperative complications of TSS for NFPA; however, aging has a negative influence on the postoperative function of GH secretion. In contrast, pseudocapsular resection does not have any negative influence on the perioperative complications or postoperative function of GH secretion, even in elderly patients, based on the authors' experience and surgical technique., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Double pituitary adenomas (DPAs), especially metachronous DPAs, are extremely rare and there has been no report about DPAs with altered transcriptional factors. We describe the case of a 25-year-old man who presented with acromegaly 7 years after surgery for a non-functioning pituitary adenoma (NFPA). Before the initial surgery, endocrine evaluation confirmed NFPA or silent somatotroph pituitary adenoma (SPA) because of normal serum levels of insulin-like growth factor-1 (IGF-1) and insufficient suppression of growth hormone (GH) levels in the oral glucose tolerance test (OGTT). Immunohistochemistry of resected tissue obtained from gross total resection (GTR) with transsphenoidal surgery (TSS) was negative for follicle-stimulating hormone, luteinizing hormone, GH, and Pit-1 but positive for GATA3, which confirmed the gonadotroph pituitary adenoma (GPA) diagnosis. Seven years later, follow-up brain MRI revealed a 13.3 × 5.6 × 4.7 mm tumor within the sellar turcica. The endocrine evaluation confirmed acromegaly because of high serum levels of IGF-1 and insufficient suppression of GH levels upon OGTT. GTR with TSS was again performed, and immunohistochemistry was negative for GATA3 but positive for GH and Pit-1. Surprisingly, he showed altered transcription factor expressions between initial and recurrent surgery. Based on the overall clinical course and hormonal secretion findings, we speculated metachronous development of a DPA, i.e., SPA followed by GPA, wherein a few remaining cells of the SPA might have regrown after the initial surgery. We conducted a literature review of cases that documented altered hormone secretion at recurrence and emphasized the necessity of identifying a small adenoma when there is a discrepancy between pathological findings and hormone secretion tests., Competing Interests: Conflicts of Interest Disclosure The authors declare that they have no conflicts of interest. Akira Taguchi, Yasuyuki Kinoshita, Atsushi Tominaga, and Fumiyuki Yamasaki have registered online self-reported COI disclosure statement Forms through the website for the Japan Neurosurgical Society members., (© 2021 The Japan Neurosurgical Society.)

Background: The sympathetic arterial baroreflex is a closed-loop feedback system for stabilizing arterial pressure (AP). Identification of unique functions of the closed system in humans is a challenge. Here we propose an analytic and integrative framework for identifying a static operating point and open-loop gain to characterize sympathetic arterial baroreflex in humans., Methods and Results: An equilibrium diagram with two crossing functions of mechanoneural (MN) and neuromechanical (NM) arcs was analyzed during graded tilt maneuvers in seven healthy subjects. AP and plasma norepinephrine level (PNE), as a surrogate for sympathetic nerve activity, and were recorded after vagal modulation of heart function was blocked by atropine. The MN-arc curve was described as a locus of operating points during -7, 0, 15, and 60° head-up tilting (HUT) on a PNE-AP plane. The NM-arc curve was drawn as a line between operating points before and after ganglionic blockade (trimethaphan, 0.1 mg⋅ml -1 ⋅kg -1 ) during 0° or 15° HUT. Gain values were estimated from the slopes of these functional curves. Finally, an open-loop gain, which is a most important index for performance of arterial baroreflex, was given by a product of the gain values of MN (G MN ) and NM arcs (G NM ). Gain values of MN was 8.92 ± 3.07 pg⋅ml -1 ⋅mmHg -1 ; and G NM at 0° and 15° HUT were 0.61 ± 0.08 and 0.36 ± 0.05 mmHg⋅ml⋅pg -1 , respectively. A postural change from supine to 15° HUT significantly reduced the open-loop gain from 5.62 ± 0.98 to 3.75 ± 0.62. The effects of HUT on the NM arc and open-loop gain seemed to be similar to those of blood loss observed in our previous animal studies., Conclusion: An equilibrium-diagram analysis contributes to a quantitative and integrative understanding of function of human sympathetic arterial baroreflex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yamasaki, Sato, Sato and Diedrich.)

Purpose: Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution., Methods: We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005-2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed., Results: The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively., Conclusions: Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up.

Purpose: The relationship between endometrial polyps (EPs), chronic endometritis (CE), hysteroscopic findings, and antimicrobial in infertility patients was determined., Methods: We retrospectively enrolled 115 infertility patients with suspected EPs who underwent office hysteroscopy. Patients were divided into 3 groups: 38 with increased plasma cells in EPs (group 1); 31 without increased plasma cells in EPs (group 2); and 46 without EPs (group 3). The 3 groups underwent hysteroscopy with or without polypectomies, and immediately thereafter, an endometrial aspiration biopsy (EAB) was performed. CE was diagnosed based on plasma cell infiltration in the non-polypoid endometrium obtained by EAB., Results: The percentage of CE was 68.4%, 32.2%, and 28.3% in groups 1, 2, and 3, respectively. CE was more frequent in group 1 than group 2 or 3 ( P  = .01 and P  = .002, respectively). The number of polyps was higher in group 1 than group 2. After adjustment for age and assisted reproductive technology, antibiotic therapy was not associated with pregnancy (adjusted odds ratio, 0.44; 95% confidence interval, 0.05-3.57) in patients with EPs and CE., Conclusions: Group 1 was associated with CE, and hysteroscopic findings were different from group 2. Antibiotic therapy after polypectomy for EPs with CE may not always be necessary., Competing Interests: Conflict of interest: The authors declare no conflicts of interest. Human rights statements and informed consent: All of the procedures were followed in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the principles of the 1964 Helsinki Declaration and subsequent amendments. This study was approved by the Institutional Review Board of Takagi Hospital. This was a retrospective study involving patients who submitted informed consent for undergoing fertility treatment in our Department. Animal studies: This article did not involve animal experimentation by any of the authors., (© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Objectives: The present study aimed to examine the effectiveness of proton magnetic resonance spectroscopy (1HMRS) in determining the progression of neurological symptoms resulting in acute ischemic stroke in patients with lenticulostriate artery (LSA) infarction., Materials and Methods: 1HMRS was performed within 72 h after neurological symptom onset. Voxel of interest was placed in tissue that included the pyramidal tract and identified diffusion weighted echo planar spin-echo sequence (DWI) coronal images. Infarct volume in DWI was calculated using the ABC/2 method. 1HMRS data (tNAA, tCr, Glx, tCho, and Ins) were analyzed using LCModel. Progressive neurological symptoms were defined as an increase of 1 or more in the NIHSS score. Patients who underwent 1HMRS after progressive neurological symptoms were excluded., Results: In total, 77 patients were enrolled. Of these, 19 patients had progressive neurological symptoms. The patients with progressive neurological symptoms were significantly more likely to be female and had higher tCho/tCr values, higher rates of axial slices ≥ 3 slices on DWI, higher infarct volume on DWI, higher maximum diameter of infarction of axial slice on DWI, and higher SBP on admission compared to those without. Multivariable logistic analysis revealed that higher tCho/tCr values were independently associated with progressive neurological symptoms after adjusting for age, sex, and initial DWI infarct volume (tCho/tCr per 0.01 increase, OR 1.26, 95% CI 1.03-1.52, P = 0.022)., Conclusions: Increased tCho/tCr score were associated with progressive neurological symptoms in patients with LSA ischemic stroke. Quantitative evaluation of 1HMRS parameters may be useful for predicting the progression of neurological symptoms., Competing Interests: Declaration of Competing Interest Dr. Maruyama received research support from Eisai Co., Ltd, Pfizer Inc., Takeda Pharmaceutical Company Limited, Otsuka Pharmaceutical Co., Ltd, Nihon Pharmaceutical Co., Ltd., Shionogi Co., Ltd., Teijin Pharma Limited, Fujifilm Holdings Corporation, Boehringer Ingelheim, Sumitomo Dainippon Pharma Co., Ltd., Nihon Medi-Physics Co., Ltd., Bayer AG, Merck Sharp & Dohme Corp., Daiichi Sankyo Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi S.A., Novartis International AG, Kowa Pharmaceutical Co., Ltd., Astellas Pharma Inc., Tsumura & Co., Japan Blood Products Organization, Mitsubishi Tanabe Pharma Corporation, and Mylan N.V. The other authors declare they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next-generation sequencing., Methods: We investigated α- and β-diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure., Results: The endometrial microbiotas had higher α-diversities than did the vaginal microbiotas ( P  < .001). The microbiota profiles showed that vaginal and endometrial samples in RIF patients had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in controls. Vaginal Lactobacillus rates in RIF patients were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% ( P  = .018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, P  = .79)., Conclusions: Impaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The vaginal Lactobacillus rates, but not the endometrial, may be a biomarker for RIF., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest. Human rights statement and informed consent: The Ethical Committee of the Institutional Review Board of Saint Mother Obstetrics and Gynecology Clinic and Institute for ART, Fukuoka, Japan, approved this study in November 2017 (No. 17‐ST‐03). The study was registered in the University Hospital Medical Information Network‐Clinical Trial Registration, Japan, in March 2018 (UMIN‐CTR000031731). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. All recruited women provided written informed consent. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Animal studies: This article does not contain any study with animal participants that have been performed by any of the authors., (© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Treatment of elderly glioma patients is a challenge in neurosurgery/neuro-oncology. The International Society of Geriatric Oncology(SIOG)recommends that elderly cancer patients undergo comprehensive geriatric assessment(CGA). The CGA score proved to be a significant predictor of mortality in this cohort, and it could be a useful treatment decision tool. Because of the rapid aging of Japan's population, clinical research focusing on elderly patients with cancer is urgently needed. The Japan Clinical Oncology Group(JCOG)has established a formal policy for research in geriatric cancers. Currently, the JCOG recommends that researchers perform CGA, including G8, to assess the tolerability of treatment for clinical trials in elderly cancer patients, including glioma. Under this policy, elderly cancer patients are categorized into three groups: fit, vulnerable, and frail. For "unfit" glioma/glioblastoma patients, physicians will need to conduct appropriately reduced treatment. Hypofractionated radiotherapy(40.05 Gy/15 fractions)has been an established treatment for elderly patients with glioblastoma. The concurrent and adjuvant temozolomide have reported to have a survival benefit for "fit" elderly patients. Subsequently, alternative hypofractionated radiotherapy, including 34 Gy/10 fractions and monotherapy with temozolomide against MGMT methylated glioblastomas, have been reported as non-inferior alternative treatments. Physicians also need to consider the adverse events associated with anticonvulsants.

Objective: Purpose of our study is to assess the relationship between MRI findings and invasive breast cancer (IBC) with cancer-associated fibroblasts (CAFs) that are positive for podoplanin., Methods: We retrospectively analyzed the consecutive 109 IBCs. The IBCs were dichotomized as with (+) or without (-) podoplanin-positive CAFs. In MRI analyses, the dichotomized IBCs were compared the lesion to muscle ratio (L/M ratio) in STIR images, the ADC value, the distribution of kinetic parameters, and morphological findings., Results: Of the 109 IBCs, 28 (26%) IBCs had podoplanin(+) CAFs. Compared to the podoplanin(-) group, the podoplanin(+) group tended to have a more malignant pathological status. In the STIR images, the podoplanin(+) group had significantly higher L/M ratio (7.59 vs. 6.55, p = 0.040). In a dynamic study, the podoplanin(+) group had a significantly higher percentage of the washout pattern (42.21% vs. 29.43%, p = 0.045). There were 23 mass lesions and 5 non-mass enhancement (NME) lesions in the podoplanin(+) group, and 69 mass lesions and 12 NME lesions in the podoplanin(-) group. The mass lesions of the podoplanin(-) group had a significantly higher likelihood of showing an irregular shape (n = 47 vs. 8, p = 0.035). The podoplanin(+) group's lesions had a significantly higher likelihood of showing a circumscribed margin (n = 14 vs. 6, p < 0.001) and a rim enhancement (n = 10 vs. 13, p = 0.047). In multivariate analyses, only high nuclear grade was significant predictive value of podoplanin(+) CAFs., Conclusion: Although not significant in multivariate analyses, MRI findings may be used to determine the podoplanin-positive CAF status of invasive breast cancer.

Purpose: Differentiating between germinoma and non-germinomatous germ cell tumor (NGGCT) is important because sensitivity to chemotherapy and/or radiotherapy is quite different between these two subgroups. In this study, we evaluated whether the arterial spin labeling (ASL) based perfusion-weighted imaging (PWI) could provide additional information for the differential diagnosis between germinoma and NGGCT., Method: Between 2011 and 2018, 20 patients with central nervous system (CNS) germ cell tumor (GCT) who underwent preoperative MR imaging including ASL-PWI were enrolled in this study. Relative tumor blood flow (rTBF) was evaluated on ASL-PWI by manually placing regions of interest at gadolinium enhanced part of the tumors and normal subcortical white matter. Presence of intratumoral T1 hyperintense foci and apparent diffusion coefficient (ADC) were also evaluated. The final diagnosis was made by the combination of tumor markers and the histological diagnosis., Results: Among 20 patients of CNS-GCT, 11 were diagnosed as germinoma and 9 were diagnosed as NGGCT. In the germinoma subgroup, the rTBF ranged from 0.90 to 1.71 (mean 1.21, median 1.09), while it ranged from 1.14 to 5.75 (mean 3.91, median 3.31) in NGGCT subgroup. The receiver operating characteristic (ROC) curve showed that calculating rTBF is useful for differentiating between germinoma and NGGCT (area under the curve (AUC) 0.929, P = 0.0012) compared to intratumoral T1 hyperintense foci (AUC 0.788, P = 0.0304) and ADC (AUC 0.919, P = 0.0016)., Conclusions: High rTBF obtained by ASL-PWI implied the presence of NGGCT component. This information might help in deciding the chemotherapy/radiotherapy intensity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG., Methods: Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex., Results: In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher's exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test)., Conclusion: T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor., (© 2021 S. Karger AG, Basel.)

We report a case of gamma knife surgery (GKS)-induced chronic encapsulated expanding hematoma with extensive literature review. A 17-year-old young man underwent GKS after embolization for arteriovenous malformation (AVM) in the right frontal lobe and the AVM completely disappeared. He developed a generalized convulsion 15 years after GKS. MRI showed a small oedematous change at the AVM site. His epileptic seizure was controlled with anticonvulsant. His epilepsy recurred after three years, and MRI revealed an intracerebral hematoma with extensive surrounding edema at the same lesion. He underwent cerebral angiography and a recurrence of AVM was prevented. The hematoma was surgically removed, and intraoperative finding confirmed an old hematoma with a capsule and capillary hyperplasia, without developing cavernous angioma. The final diagnosis was a secondary chronic encapsulated expanding hematoma after GKS. This is the first report to show the early-stage imaging findings of this late effect after GKS., (Copyright © 2020 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aim: To clarify whether amniotic fluid findings (Gram stain and interleukin [IL]-6 level) can predict early-onset neonatal sepsis (EONS) before delivery., Methods: We compared the sensitivity and specificity and the values of the area under the receiver-operating characteristic (AUROC) curve of maternal inflammatory responses and amniotic fluid findings using IL-6 and Gram stain to predict EONS. Patients who underwent amniocentesis for suspected intra-amniotic infection (IAI) after 22 weeks and 0 days of gestation and delivered on the same day at our hospital between January 2013 and December 2018 were included., Results: Out of 200 patients, EONS developed in 9 patients. The AUROC curves of maternal white blood cells count, C-reactive protein and body temperature were low (range, 0.6-0.7), whereas that of amniotic fluid IL-6 was high (0.90). Sensitivity and specificity for amniotic fluid findings were, respectively, 100% and 67% for IL-6 (cut-off value: 17.4 ng/mL) and 100% and 88% for the Gram stain; these values were superior to those of maternal inflammatory responses. When examining the accuracy of the amniotic fluid Gram stain separately before and after 34 gestation weeks, similar results were obtained. Amniotic fluid IL-6 before 34 gestation weeks showed specificity similar to that of the Gram stain; however, there were large differences in cut-off values based on gestational age., Conclusion: Gram stain results of amniotic fluid can predict EONS with high sensitivity and specificity when IAI is suspected. False-negative amniotic fluid Gram stain results can be prevented by measuring amniotic fluid IL-6 simultaneously., (© 2020 Japan Society of Obstetrics and Gynecology.)

Severe intra-amniotic inflammation, even with a negative bacterial culture, can lead to premature labor. We report a 43-year-old multiparous woman with severe intra-amniotic inflammation and cervical insufficiency at 23 weeks and 5 days of gestation. Continuous transabdominal amnioinfusion was started 2 days after the diagnosis. The amniotic fluid interleukin-6 level normalized after 2 days of treatment. She underwent Shirodkar cervical cerclage on day 7. Despite termination of amnioinfusion and catheter removal on day 16, the pregnancy was maintained without any subsequent treatment. At 33 weeks and 5 days of gestation, an intrauterine Ureaplasma parvum infection and the onset of contractions led to repeat cesarean delivery. The birth weight was 2292 g, and the Apgar scores were 8/8. Both mother and infant had good outcomes. Continuous transabdominal amnioinfusion may have eliminated factors causing intra-amniotic inflammation, thereby prolonging the pregnancy and improving the infant's prognosis., (© 2020 Japan Society of Obstetrics and Gynecology.)

Serum and cerebrospinal fluid (CSF) levels of α-fetoprotein and β-subunit of human chorionic gonadotropin are used as biomarkers for the management of central nervous system (CNS) germ cell tumors (GCTs). However, additional discriminating biomarkers are required. Especially, biomarkers to differentiate non-germinomatous germ cell tumors (NGGCTs) from germinomas are critical, as these have a distinct prognosis. We investigated CSF samples from 12 patients with CNS-GCT patients (8 germinomas and 4 NGGCTs). We analyzed circulating tumor DNA (ctDNA) in CSF to detect mutated genes. We also used liquid chromatography-mass spectrometry to characterize metabolites in CSF. We detected KIT and/or NRAS mutation, known as frequently mutated genes in GCTs, in 3/12 (25%) patients. We also found significant differences in the abundance of 15 metabolites between control and GCT, with unsupervised hierarchical clustering analysis. Metabolites related to the TCA cycle were increased in GCTs. Urea, ornithine, and short-chain acylcarnitines were decreased in GCTs. Moreover, we also detected several metabolites (e.g., betaine, guanidine acetic acid, and 2-aminoheptanoic acid) that displayed significant differences in abundance in patients with germinomas and NGGCTs. Our results suggest that ctDNA and metabolites in CSF can serve as novel biomarkers for CNS-GCTs and can be useful to differentiate germinomas from NGGCTs.

Objective: Posterior fossa ependymoma (PF-EPN) was categorized into PF-EPN-A and PF-EPN-B subgroups based on the DNA methylation profiling. PF-EPN-A was reported to have poorer prognosis compared with PF-EPN-B. In this study, we particularly evaluated preoperative imaging to distinguish PF-EPN-A from PF-EPN-B., Methods: Sixteen cases of PF-EPN were treated in our institution from 1999 to 2018. The patients were divided into PF-EPN-A and PF-EPN-B groups based on H3K27me3 immunostaining positivity. We evaluated progression-free survival, overall survival, as well as preoperative magnetic resonance imaging and computed tomography scan images in both groups. Based on T1WI and Gd-T1WI magnetic resonance images, the tumor contrast rate was determined from dividing the volume of gadolinium enhanced tumor by the overall tumor volume., Results: Nine cases (4 male, 5 female) were grouped as PF-EPN-A, and 7 (4 male, 3 female) as PF-EPN-B. The median age of PF-EPN-A and PF-EPN-B were 4 and 43 years old, respectively. In the PF-EPN-A group, the progression-free survival median value was 32.6 months, and the overall survival median was 96.9 months. In contrast, PFS in PF-EPN-B did not reach a median value (P < 0.05) and all the patients were alive (P < 0.05) at the end of the study. With imaging, tumor contrast rate in PF-EPN-B was more than 50% and significantly different from PF-EPN-A (P = 0.0294). Calcification was mainly observed in PF-EPN-A, whereas cystic formation was only seen in PF-EPN-B., Conclusions: Contrast rate less than 50%, based on the magnetic resonance images, was characteristic in the PF-EPN-A group. Comparatively, cystic component and absence of calcification were more characteristic in the PF-EPN-B group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The pediatric posterior fossa (PF) brain tumors with higher frequencies are embryonal tumors (ET), ependymal tumors (EPN) and pilocytic astrocytomas (PA), however, it is often difficult to make a differential diagnosis among them with conventional MRI. The ADC calculated from DWI could be beneficial for diagnostic work up., Method: We acquired DWI at b = 1000 and 4000(s/mm 2 ). The relationship between ADC and the three types of brain tumors was evaluated with Mann-Whitney U test. We also performed simple linear regression analysis to evaluate the relationship between ADC and cellularity, and implemented receiver operating characteristic curve (ROC curve) to test the diagnostic performance among tumors., Results: The highest ADC (b1000/b4000 × 10 -3  mm 2 /s) was observed in PA (1.02-1.91/0.73-1.28), followed by PF-EPN (0.83-1.28/0.60-0.79) and the lowest was ET (0.41-0.75/0.29-0.47). There was significant difference among the groups in both ADC value (b-1000/b-4000: ET vs. PF-EPN p < 0.0001/0.0001, ET vs. PA p < 0.0001/0.0001, PF-EPN vs. PA p < 0.0001/0.0001). ROC analysis revealed that ADC in both b-values showed complete separation between ET and PF-EPN. And it also revealed that ADC at b-4000 could differentiate PF-EPN and PA (96.0%) better than ADC at b-1000 (90.1%). The stronger negative correlation was observed between the ADC and cellularity at b-4000 than at b-1000 (R 2  = 0.7415 vs.0.7070) CONCLUSIONS: ADC of ET was significantly lower than the other two groups, and ADC of PA was significantly higher than the other two groups in both b-1000 and b-4000. Our results showed that ADC at b-4000 was more useful than ADC at b-1000 especially for differentiation between PF-EPN and PA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: T2-FLAIR mismatch sign was reported as specific imaging marker in non-enhancing diffuse astrocytoma, IDH-mutant & 1p/19q non-codeleted. However, most of the previous studies for T2-FLAIR mismatch sign were confirmed only among lower grade glioma. The aim of this study is to assess the T2-FLAIR mismatch sign in dysembryoplastic neuroepithelial tumor (DNET) and unveil the exception rules of the sign., Method: Eleven patients with histopathologically confirmed DNET were included in this study. The MR images were evaluated by 2 independent reviewers to assess (i) the presence or absence of T2-FLAIR mismatch sign and (ii) the presence or absence of gadolinium enhancement. CT was also performed to evaluate calcification and localized thinning of the skull bone. Inter-reviewer agreement with Cohen's kappa (κ) was calculated., Results: The T2-FLAIR mismatch sign was present in 8 cases (72.7 %) and absent in 3 cases (27.3 %). None of them showed contrast enhancement on initial MR images. The inter-reviewer agreement for T2-FLAIR mismatch and CT characteristics was excellent (κ = 1.00). All of the DNET without T2-FLAIR mismatch presented with calcification on CT. All of the DNET adjacent to skull vault (5 cases) presented with localized bone thinning overlying the tumor., Conclusions: The T2-FLAIR mismatch sign was observed in more than half of the DNET and the sign is not specific for diffuse astrocytoma, IDH-mutant & 1p19q non-codeleted. The localized skull bone thinning overlying the tumor might help for diagnosis of DNET in some cases., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonβ (IFNβ) plus temozolomide (TMZ) with that of TMZ alone., Experimental: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations., Results: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNβ + Radiotherapy (RT) group were found., Conclusion: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNβ addition were identified.

Children with optic pathway gliomas (OPGs) frequently suffer from problems of visual function resulting from tumors. Previous reports showed that bevacizumab improved visual function in patients with OPG via tumor response to treatment. In these two case reports, we show that bevacizumab improved visual field without tumor response as seen in imaging. Both, a 10-year-old girl and a 6-year-old boy, had previous history of treatment with platinum-based chemotherapy. They had visual deterioration without tumor progression on MR imaging. Bevacizumab effectively and immediately improved visual field in both patients without imaging response of OPG. We emphasize that bevacizumab should be considered for patients with OPGs having visual deterioration without tumor progression.

Purpose: Dual-energy computed tomography (DECT) can provide iodine, electron density (ED), and effective atomic number Z (Z eff ) maps, facilitating the identification of tissue types. We investigated whether DECT parameters can predict the vascularity of meningiomas., Method: We acquired DECT and perfusion CT (PCT) images in 24 patients with histologically diagnosed meningioma. Regions of interest (ROIs) were placed at the tumor in iodine, ED, and Z eff maps derived from DECT and in a blood volume (BV) map derived from PCT. To normalize these parameters' values, we divided them by the values of contralateral normal-appearing white matter, i.e., the relative (r)ED, rZ eff , and rBV. The vascular density of the tumor specimens was immunohistochemically analyzed by calculating the von Willebrand factor-positive vessel wall. We calculated Pearson's correlation coefficients to determine the correlation with PCT/DECT parameters and an immunohistopathological index., Results: Contrast rZ eff (r = 0.7020, p = 0.0001) and iodine (r = 0.5814, p = 0.0029) both had positive correlations with rBV derived from PCT. The rED values were negatively correlated with the rBV values (r = -0.4735, p = 0.0194), and the vascular density results confirmed positive correlations with rBV (r = 0.6909, p = 0.0002) and contrast rZ eff (r = 0.4982, p = 0.0132) and a negative correlation with rED (r = -0.4265, p = 0.0377). Regarding the radiation exposure, the mean estimated volume CT dose index (CTDI vol ) of DECT was 33.1 ± 1.72 mGy, much lower than that of PCT (103.3 ± 4.65 mGy)., Conclusions: DECT predicted vascular density with lower radiation exposure compared to PCT. DECT could potentially replace PCT for evaluating the vascularity of meningiomas., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The term "growing teratoma syndrome (GTS)" has been used as follows: patients with germ cell tumor (GCT) who present with enlarging original/metastatic masses during or after appropriate systemic chemotherapy despite normalized serum markers. In other words, the definition of the term GTS is not fully established. We analyzed and reviewed our case series regarding GTS that developed after the treatment of central nervous system (CNS) nongerminoatous germ cell tumors (NGGCTs)., Methods: Our institutional review board approved this retrospective study. Between 2003 and 2018, we treated 16 patients (16 males; age ranging from 5.4 to 51.9 years, median 13.8) with CNS-NGGCT at our institution. We reviewed those patients and also reviewed the literature about GTS of CNS. We defined primary GTS (p-GTS) as the enlargement of cyst size and/or solid tumor occurred during treatment in the absence of marker elevation, and recurrent GTS (r-GTS) as the enlargement of teratoma after complete response of initial tumors., Results: Among 16 patients with CNS-NGGCT, we surgically confirmed mature/immature teratoma components in 15 patients. Two patients underwent surgical removal of tumor before neoadjuvant therapy, and among the rest 14 patients, 6 developed p-GTS, and 2 patients underwent salvage surgery during chemo-/chemoradiotherapy. Those with histologic diagnosis of immature teratoma during salvage surgery had a shorter interval from the initiation of chemoradiotherapy compared with mature teratoma (P < 0.05). One patient developed r-GTS. In the literature review, most of the p-GTS consisted of enlargement with the multicystic component. Histologic diagnosis of immature teratoma during salvage surgery was observed in earlier stages of chemoradiotherapy (P < 0.05, log-rank test). Previous history of p-GTS might be a risk factor of r-GTS., Conclusions: The incidence of p-GTS, enlargement of the cystic component during treatment, is not rare. Physicians need to be aware of this important phenomenon., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although there are a number of Vietnamese native pig (VnP) populations, some are on the verge of extinction, and therefore adequate management and conservation are necessary. In this study, we conducted a field survey of VnP populations and analyzed interrelationships among their characteristics. We also established a relational database for management of field data on these populations. For data collection, we conducted interviews with farmers and visual inspection of 32 VnP populations in 22 provinces of Vietnam, as well as taking photographs of individual animals. Data on the characteristics of VnP populations were subjected to multiple correspondence analysis (MCA). For establishment of the database, normalization and table partitioning were performed to eliminate redundancy and ensure consistency of the collected data items. Passport data, characteristics data, and image data were collected from a total of 1,918 VnPs and entered as a normalized table. Upon MCA, most of the populations were not separated from each other, but the Mong Cai, O Lam, and Chu Prong populations were separated from the other populations. Thus, we have constructed a relational database from comprehensive information on the characteristics of VnP populations., (© 2020 The Authors Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Introduction: H3.3 G34R/V mutation is predominantly identified in the supratentorial nonmidline tumors. However, this tumor is not yet categorized as an entity in 2016 WHO CNS classification. More information is necessary to further determine the characteristics of this tumor., Case Presentation: Three cases of adolescent hemispheric glioma were treated in our institution. All tumors showed the characteristics of huge tumor size with mild peritumoral edema on T2WI/FLAIR, hyperintense on DWI, and slight partial enhancement by gadolinium. The single-voxel proton MR spectroscopy revealed characteristics of high choline peak, marked decrease in N-acetyl aspartate peak, and small lactate peak. The histopathological diagnosis, based on 2007 WHO CNS classification, was high-grade glioma in 2 cases and a PNET. Immuno-staining revealed that the tumor cells were positive against H3.3 G34R, H3K27me3, and p53 antibodies and negative against H3K27M, IDH1-R132H, ATRX, and Olig2 antibodies. Pyrosequencing analysis confirmed H3.3 G34R mutation, IDH-wildtype, and BRAF-wildtype., Conclusion: Radiological and immunostaining findings are characteristic in our 3 cases of H3.3 G34-mutant glioma. It is essential to consider H3.3 G34-mutant glioma as a differential diagnosis particularly in pediatric and adolescents and young adult hemispheric tumors., (© 2020 S. Karger AG, Basel.)

Background: The diaphragm is an important muscle of respiration, and regulates the intrathoracic pressure. Blood pressure is regulated by the baroreceptor reflex system, and is also affected by intrathoracic pressure. We examined the relationship between the diaphragmatic muscle thickness and the degree of drop in blood pressure in the standing position., Methods: We prospectively studied 15 healthy subjects. The diaphragmatic muscle thickness was measured using a B-mode ultrasonic imaging device. The blood pressure before and after standing was measured by a head-up tilt test., Results: The diastolic blood pressure difference during expiration and inspiration showed a significant correlation with the diaphragmatic muscle thickness (r = 0.578, P = 0.024 and r = 0.518, P = 0.048, respectively)., Conclusion: The diaphragmatic muscle thickness was related to the fall in diastolic blood pressure in the standing position. This indicates that adequate diaphragmatic muscle thickness helps to maintain intrathoracic pressure and prevents excessive drop in blood pressure in the standing position.

Background: Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet., Materials and Methods: Between 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change <25%), PD (increase by ≥25%). The effect of BEV on tumor itself was determined according to Response Assessment in Neuro-Oncology criteria., Results: Of the 139 patients, 21 (15.1%) had cystic components. The best responses of cysts to BEV treatment were as follows: CR 6, PR 7, MR 4, SD 4. The group of patients with progressively increasing cysts prior to BEV treatment had significant cyst size reduction compared to stable cyst size groups, at initial imaging after BEV (mean 62.6% vs 22.5%, P = .0055) and at best response timing (mean 76.3% vs 32.8%, P = .0050). Patients with cysts showed significant improvement in symptoms after the treatment with BEV compared to patients without cysts (P = .0033). However, response rate was not different between patients with or without cysts. Overall survival after starting BEV was not different between glioblastoma patients with or without cysts., Conclusion: Bevacizumab is effective against progressively increasing cysts. Although cysts reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cyst enlargement., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Several intracranial pathologies present as a ring-enhancing lesion on conventional magnetic resonance imaging (MRI), creating diagnostic difficulty. We studied the characteristics of the anatomical border of gadolinium enhancement on T1-weighted imaging (WI) and hypointensity on T2WI to employ a simple technique of histogram-profile analysis of MRI for differentiation of various ring-enhancing intracranial lesions., Methods: After approval from the institutional review board, preoperative MRI (T2WI, postcontrast T1WI) scans were analyzed retrospectively in 18 patients with histologically confirmed brain abscess, 66 glioblastomas, 46 brain-metastases, and 16 tumefactive multiple sclerosis (MS). T2WI and postcontrast T1WI were overlapped, and histogram-profile analysis was performed with in-house image-fusion software. The pattern of differential-peaks in histogram-profile was assessed visually. Kaplan-Meier survival analysis incorporating histogram-profile patterns was performed in patients with glioblastoma., Results: The histogram-profile study revealed 4 distinct patterns. Pattern 1 showed no differential T2-hypointensity trough, pattern 2 had T2-hypointensity trough inside, whereas pattern 3 had T2-hypointensity trough overlapping the enhanced margin. Pattern 4 had T2-hypointensity trough immediately external to the enhanced margin. Pattern 1 was specific for tumefactive MS (93.3%), whereas pattern 4 was specific for glioblastoma (40.7%). Pattern 4 glioblastoma was subdivided into rim (T2-hypointensity ≥50% of circumference of contrast-enhanced tumor) and arc (T2-hypointensity <50% of circumference of contrast-enhanced tumor). Pattern 4 glioblastoma was further subdivided into group A (edema: T2-hyperintensity ≥50% of circumference of contrast-enhanced tumor) and group B (less edema: T2-hyperintensity <50% of circumference of contrast-enhanced tumor). Patients with pattern 3 glioblastoma (37.6%) had better survival compared with others (P = 0.0341) and pattern 4B had decreased survival compared with pattern 4A (P = 0.0001) and others (P = 0.0003)., Conclusions: Tumefactive MS and a subset of glioblastomas show specific patterns in histogram-profile analysis. The difference in anatomical border also determines difference in survival in glioblastoma. Histogram-profile analysis is a simple and efficient technique to differentiate these pathologies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is reported that vinblastine monotherapy has promising activity in patients with pediatric optic pathway/hypothalamic glioma(OPHG)who experienced treatment failure after initial treatment with standard chemotherapy. However, there have been no reports on vinblastine monotherapy against OPHG in Japan. Since vinblastine is an unauthorized drug under the Ministry of Health and Welfare, we used it after completing an in-hospital institutional review board application for each case. In the first case, a 6-year-old boy with recurrent OPHG with hydrocephalus was referred to our hospital. Weekly vinblastine was started at a dose of 6mg/m 2 and was then reduced to 5mg/m 2 and 4mg/m 2 sequentially due to hematotoxicity. After 11 cycles of vinblastine, improvement in hydrocephalus was observed. After 22 cycles of vinblastine, the best response was observed, and we continued treatment up to 35 cycles. Progression of the disease was observed after 47 cycles and then we changed treatment to another regimen after 48 cycles of vinblastine. In the second case, a 6-year-old boy with chemotherapy-naïve recurrent OPHG underwent chemotherapy with vincristine and carboplatin. After 9 treatment cycles with carboplatin, hypersensitivity was observed. Subsequently, he was treated using weekly vinblastine as per the same protocol as that in our first case. A moderate response was observed after 18 cycles of vinblastine. After 48 cycles of vinblastine, the best response was observed, and we completed treatment. In both cases, severe adverse events were not observed and the treatment was well-tolerated. Vinblastine administered once per week is well-tolerated and maintains quality of life in children with OPHG.

Background: Asymptomatic carriers of methicillin-resistant Staphylococcus aureus (MRSA) are important sources of nosocomial transmission. MRSA may be transmitted from hospitalized patients to healthcare professionals and vice versa., Methods: The prevalence of MRSA colonization among forty-five healthcare professionals in a Japanese hospital was determined by performing surveillance cultures to identify unrecognized carriers of MRSA. All MRSA isolates were evaluated using multilocus sequence typing (MLST) to identify the transmission routes., Results: The proportion of MRSA colonization was significantly higher in healthcare professionals (11.1%) than in community residents (0.72%; P  < 0.0001) or admission case (2.5%; P  = 0.018). MLST analysis revealed that both the ST8 and ST764 strains were identified in residents, patients, and healthcare professionals. MRSA colonization was more frequently observed among physicians (4/13; 31%) than nurses (1/32; 3%) ( P  = 0.020)., Conclusion: Multilocus sequence typing results suggest that ST8 and ST764 are involved in the occurrence of nosocomial MRSA infections. These findings emphasize the necessity for the effective education of physicians to prevent MRSA transmissions., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Background: Evaluation of plaque protrusion after carotid artery stenting (CAS) is important for predicting periprocedural ischemic complications. In contrast to intravascular ultrasound (IVUS), angioscopy allows direct visualization of the plaque. The aim of this study was to evaluate utility and safety of angioscopy during CAS and compare it with IVUS., Methods: The study included 13 carotid artery stenosis lesions in 11 consecutive patients (mean age 70.5 years; 10 men) at a single center. During CAS procedure, poststenting plaque protrusion was evaluated with angioscopy and IVUS., Results: Mean level of internal carotid artery stenosis was 79.2%. Eight lesions were symptomatic, and 5 lesions were predicted to have vulnerable plaque by preprocedural magnetic resonance imaging. A carotid WALLSTENT was placed in all cases. After stenting, angioscopy provided good visualization in all cases. Plaque protrusions were observed in 1 case by IVUS and in 8 cases by angioscopy. Diffusion-weighted imaging showed positive lesions in 3 cases (23%). For 2 of these lesions, plaque protrusions were observed by angioscopy but not by IVUS. All lesions associated with positive diffusion-weighted imaging findings were observed to have yellow plaque on angioscopy., Conclusions: Angioscopy provided direct visualization of stent lumens after CAS. Angioscopy detected more plaque protrusion than IVUS and allowed clearer observation of plaque characteristics. Angioscopy may be more useful than IVUS for examination of plaque protrusion and plaque evaluation after CAS, especially for plaque identified as potentially vulnerable by preprocedural examination., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To correlate the tumor-stromal ratio (TSR) of invasive breast cancer and MRI findings., Methods: This study was approved by our institutional review board. 126 consecutive patients with surgically proven invasive breast cancer were included. All patients underwent MRI exams including short-tau inversion-recovery (STIR) T 2 weighted imaging, diffusion-weighted imaging (DWI) and post-contrast dynamic imaging. The mean signal intensity (SI) and apparent diffusion coefficient (ADC) value of each lesion were measured. To objectively evaluate the STIR images, the ratio of the SI of the lesion to the muscle (L/M ratio) was also measured. Percentages of MRI kinetic parameters obtained from dynamic images were also measured. The TSR was defined as the percentage of the stromal component, and categorized into high-stroma ( > 50%) and low-stroma (< 50%) groups. Intergroup differences in the SI, L/M ratio, ADC value and percentages of kinetic parameters were examined., Results: The SI and L/M ratio of the high-stroma group were significantly lower than those of the low-stromal group (208.64 vs 331.86 for SI, 5.69 vs 9.31 for L/M ratio) ( p < 0.001). The high-stroma group had significantly lower percentages of a washout pattern (25% vs 34.7 %) ( p = 0.012) and significantly higher percentages of a persistent pattern (36.92% vs 28.26 %) ( p = 0.044). There were no significant correlations between the TSR and ADC value., Conclusion: STIR and dynamic sequence of breast MRI reflects the stromal component of invasive breast cancer., Advances in Knowledge: This is the first study to correlate TSR and MRI findings. STIR and post-contrast dynamic study correlated with the stromal component of breast cancer.

Background: Understanding the history of anthropogenic vegetation is often difficult due to the lack of tangible historical evidence. In this study, we examined chronological changes of farmland demarcation trees planted on alluvial plains along the Hijikawa River in southwestern Japan based on species distribution patterns, folk nomenclature, and multiple usage of the trees., Methods: The species composition of demarcation trees was investigated at 47 sites in 13 villages. We performed hierarchical clustering using Bray-Curtis measures to detect groups of similar tree composition and permutational multivariate analysis of variance to test whether differences in species composition correspond to village units. To better understand the traditional knowledge of demarcation trees, we conducted interviews with 53 farmers, most of whom were over 60 years old., Results: Clustering resulted in six tree composition groups. The group characterized by the most frequently planted species, Chaenomeles speciosa, dominated around lower reach villages. The group characterized by Euonymus japonicus dominated around middle reach villages, and that characterized by Salix pierotii was mainly located around upper reach villages. Chaenomeles speciosa was always identified with the standard Japanese name boke or similar names. Euonymus japonicus and several other species were also called boke by many farmers. Several elderly farmers stated that C. speciosa was pervasive in upper and middle reach villages in their youth, suggesting the prototypical use of C. speciosa in the study area. In addition, some minor species were likely to have been left after commercial crop production or subsistence use between the late nineteenth and mid-twentieth centuries, including Morus sp. and Celtis sinensis for sericulture, Salix koriyanagi for fiber production, and Gardenia jasminoides for food coloration. The name kōshin bana recorded for E. japonicus suggests that the species' use originated from the folk faiths Kōshin-shinkō and/or Shōmen-Kongō., Conclusions: The composition of demarcation trees in the region has not been stable over time, but instead changed to reflect the local livelihood, industry, and faiths. Despite the lack of tangible historical evidence, the spatial distribution patterns, folk nomenclature, and traditional knowledge of plants can provide clues to trace the chronological background of ecotopes in anthropogenic landscapes.

We herein report the case of a 60-year-old man with a "target sign" in the left frontal lobe on magnetic resonance imaging (MRI), which is thought to be a specific sign of cerebral toxoplasmosis. 18 F-fluorodeoxyglucose-positron emission tomography showed no increased uptake, and 201 Tl-single photon emission computed tomography showed the focal uptake in the left frontal lesion. On a brain biopsy, the patient was given a definitive diagnosis of brain metastasis from diffuse large B-cell lymphoma, and cerebral toxoplasmosis was excluded. In the present case, multilayer intensities on MRI may reflect the fast-growing nature of this tumor.

We report for the first time two cases of physiologic pituitary hyperplasia causing visual disturbance during adolescence. Case 1. A 15-year-old boy visited our department with a pituitary mass lesion on magnetic resonance imaging (MRI) associated with headache and transient bitemporal hemianopsia repeating. A visual field defect became apparent on the bitemporal upper side, and the area of the visual field defect enlarged to hemianopsia. The visual defect usually occurred in relation to exercise and continued for approximately 10 min. MRI showed the mass effect of pituitary hyperplasia to the optic chiasm. At six months later after the initial onset of the symptom, the visual field defect disappeared. Case 2. A 14-year-old girl came to our emergency department with a pituitary mass lesion on MRI associated with acute headache and visual disturbance occurring during exercise. MRI revealed the possibility of pituitary hyperplasia compressing the optic chiasm; however, her clinical course showed pituitary apoplexy. We conducted emergency transsphenoidal surgery to decompress her optic chiasm. The operative findings and histological examinations revealed a normal pituitary gland. Her visual disturbance immediately recovered after the surgery. Physiologic pituitary hyperplasia during adolescence can cause visual disturbance. Surgery should be carefully conducted, given the possibility of physiologic pituitary hyperplasia with visual symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality., Methods: We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks., Results: Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively., Conclusion: This phase III trial met neither the primary nor secondary endpoints., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival., Methods: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies., Results: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV., Conclusion: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved., (© 2019 S. Karger AG, Basel.)

Objective: The aim of this study was to identify the etiology of hemifacial spasm (HFS) and trigeminal neuralgia (TN) in patients aged 30 years or younger and to examine the efficacy of microvascular decompression (MVD)., Patients and Methods: Between 1996 and 2012, 228 HFS and 190 TN patients underwent MVD at Atsuchi Neurosurgical Hospital. Of these, 7 patients were 30 years of age or younger at the time of treatment (HFS: n = 6, TN: n = 1). Assessments were based on their medical history and on magnetic resonance imaging, magnetic resonance angiography, surgical, and follow-up findings., Results: The age of the 6 HFS patients ranged from 23 to 30 years (mean 27.8 ± 1.8 [standard deviation] years) at the time of surgery; the earliest symptom onset was in an 11-year-old boy. We noted vascular variations in 5 patients, a duplicate posterior inferior cerebellar artery in 2 patients, a short basilar artery in 1 patient, and an aberrant arterial course in 2 patients. At the latest follow-up, 1-69 months after MVD, 5 of the HFS patients were asymptomatic and the 6 th had mild residual symptoms. A 23-year-old TN female underwent straightening of the trigeminal nerve by separation of a thickened arachnoid membrane from the nerve and dislocation of a small branch of the superior cerebellar artery from the distal end of the root exit zone. While she continued to experience occasional facial pain 48 months after the operation, she required no medication because surgery yielded significant pain amelioration., Conclusion: Although the pathogenesis of early-onset HFS and TN remains unclear, our findings suggest that vascular variations may be related to the etiology of vascular compression symptoms in patients with HFS or TN. MVD was useful for the treatment of neurovascular compression symptoms in young patients., Competing Interests: There are no conflicts of interest.

We present the case of a 68-year-old man with brain metastasis from lung cancer and a history of immune checkpoint inhibitor administration, with overlapping abscess within the metastatic lesion. He initially received antibiotic treatment under a diagnosis of brain abscess because of a hyper-intense area on diffusion-weighted imaging inside the gadolinium-enhanced wall. The size of the enhanced lesion did not change much, but the extent of perifocal edema decreased after antibiotic treatment. After 2-4 months, the lesion gradually enlarged, and imaging characteristics changed from single cyst to multiple cysts. Surgical resection was performed and pathological examination revealed the lesion as metastasis from the lung tumor. Smear preparation of the tumor contents detected Gram-positive bacilli, confirming the dual pathology of metastasis and brain abscess. Discussing the pathogenesis, we speculated that therapy with durvalumab (MEDI4736), an anti-PD-L1 antibody, induced immune status modification including immunosuppressive regulation, which might have promoted abscess formation., Competing Interests: Conflicts of Interest Disclosure Dr. Maruyama reports grants of over ¥2,000,000 from Daiichi Sankyo Company each year for the past three years, outside the submitted work. The other authors have nothing to disclose.

Background: Perfusion computed tomography (PCT) reflects blood flow and capillary condition, which is valuable in assessing brain tumors. We evaluated PCT parameters at the tumor (t) and peritumoral (p) region to differentiate malignant brain tumors., Methods: We performed PCT in 39 patients with supratentorial malignant brain tumors (22 glioblastomas, 6 lymphomas, 11 metastases). Regions of interests were placed manually at tumor, peritumoral region, and contralateral normal-appearing white matter. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability surface (PS) were measured. These parameters were divided by those of contralateral normal-appearing white matter to normalize at tumor (relative [r]CBVt, rCBFt, rMTTt, rPSt) and peritumoral regions (rCBVp, rCBFp, rMTTp, rPSp). The parameters were evaluated with Mann-Whitney U test and receiver operating characteristics analyses. Stepwise analyses also were performed to select useful PCT parameters for differentiating these tumors., Results: The rCBFt and rCBVt of glioblastoma (GBM) were greater than those of primary central nervous system lymphoma (PCNSL) (P = 0.0005, 0.0002) and brain metastasis (METS) (P = 0.0044, 0.0028). The rMTTp of METS was greater than that of GBM and PCNSL (P = 0.0001, 0.0007). The combination of rCBVt and rPSt could differentiate GBM from other tumors with sensitivity and specificity of 81.8% and 94.1%. The combination of rCBFp and rMTTp could differentiate METS from other tumors with sensitivity and specificity of 90.9% and 82.1%., Conclusions: Our study introduces and supports the usefulness of PCT parameters for differentiation among GBM, PCNSL, and METS. rCBVt and rPSt may be the best predictors of GBM. rCBFp and rMTTp may be the best predictors of METS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the value of the cerebral blood volume (CBV) obtained with perfusion computed tomography (CT) and the electron density (ED) measured by dual-energy CT for differentiating high- from low-grade glioma (HGG, LGG).The CBV and ED were obtained in 9 LGG and 7 HGG patients. The CBV and ED of LGGs and HGGs were compared. Receiver operating characteristic (ROC) curves were generated for CBV, ED, and CBV plus ED. The correlation between CBV, ED, and the MIB-1 labeling index of the tumors was examined. All of these analyses were also performed using relative CBV (rCBV) and ED (rED) (the value of tumors/the value of contralateral white matter).The mean CBV, ED, rCBV, and rED values were significantly higher in HGG than LGG (P < .05). By ROC analysis, the combination of rCBV plus rED as well as CBV plus ED were more accurate than CBV, ED, rCBV, rED alone. There was a significant correlation between ED and MIB-1 (P = .04).ED improved diagnostic accuracy of perfusion CT for differentiating HGG from LGG.

Purpose: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design., Experimental Design: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m 2 , daily) followed by TMZ maintenance (100-200 mg/m 2 /day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8)., Results: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%., Conclusions: TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Necrotizing sarcoid granulomatosis (NSG) is a rare disease that is diagnosed based on pathological findings. We herein report the case of a 27-year-old man who had multiple nodular shadows in bilateral lung fields on chest radiography and elevated levels of C-reactive protein (CRP). The pathological evaluation of a lung biopsy specimen showed the infiltration of lymphocytes, granulomas with necrosis and granulomatous angiitis. He was therefore diagnosed with NSG. He has been followed without treatment, as his fever and CRP levels decreased immediately after the surgical lung biopsy. Thereafter, the pulmonary nodular shadows gradually recovered without any treatment within a few months. Our experience suggests the possibility that surgical invasion might trigger an improvement in disease activity.

Purpose: It is often difficult to distinguish between embryonal and ependymal tumors using conventional MR imaging. The apparent diffusion coefficient (ADC) calculated from diffusion-weighted images (DWI) has been widely used for diagnosis, but its usefulness for differential diagnosis between embryonal and ependymal tumors has not been determined yet. Both DWI properties and ADC values of these two types of tumor at regular and high b-values on a 3 T MR scanner were retrospectively reviewed., Materials and Methods: DWI at 3 T was acquired for 16 patients with embryonal tumors (including medulloblastoma, CNS embryonal tumors (NOS), and atypical teratoid/rhabdoid tumor), and 7 patients with ependymal tumors (including ependymoma and anaplastic ependymoma). ADC was measured by manually placing multiple regions of interest (ROIs) on ADC maps corresponding to enhancing lesions on contrast-enhanced T1-weighted images, both on standard (b-1000) and high (b-4000) b-value DWI. The minimum ADC (ADC-MIN) was calculated from several ROIs placed on each tumor. The relationship between tumor cell density and ADC-MIN was also investigated., Results: Both at b-1000 and b-4000, ADC-MIN was significantly lower in embryonal tumors than in ependymal tumors. Embryonal tumors could be completely discriminated from ependymal tumors using both b-values, but ADC-MIN at b-4000 (t-value = -8.312, p < 0.001) was better than ADC-MIN at b-1000. There was a stronger negative correlation between cell density and ADC-MIN at b-4000 (r 2  = 0.50, p < 0.001) than with ADC-MIN at b-1000 (r 2  = 0.41, p < 0.001)., Conclusion: Evaluating ADC-MIN at b-4000 would be a useful tool for distinguishing embryonal from ependymal tumors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The differentiation of germinoma from other tumors by conventional magnetic resonance imaging (MRI) can be very difficult. The purpose of our study was to determine whether diffusion-weighted imaging (DWI) and single-voxel proton magnetic resonance spectroscopy (1H-MRS) could provide additional useful information for a definitive diagnosis of germinomas., Methods: Our hospital's Institutional Review Board approved this retrospective study. We reviewed imaging studies of 26 patients with histologically confirmed germinomas who were treated at our hospital between 2003 and 2016. We also studied 25 patients with pineal tumors, which included 14 nongerminomatous germ cell tumors (NGGCTs), 9 pineal parenchymal tumors (PPTs; including 3 pineocytomas, 4 PPTs of intermediate differentiation [PPTID], and 2 pineoblastomas) and 2 meningiomas. Patients underwent conventional MRI and advanced MRI, including DWI and/or 1H-MRS., Results: The germinoma group comprised 24 males and 2 females, ranging in age from 9.1 to 37.7 years (average, 17.5 years; median, 14.6 years). The NGGCT group was all male, ranging in age from 5.4 to 51.9 years (mean, 20.1 years; median, 14.1 years). In the PPT group, patient age ranged from 4.5 to 64.7 years (mean, 29.9 years; median, 30.7 years). High lipid peaks detected on 1H-MRS were observed in 16 of 16 examined germinomas. In contrast, in the pineocytomas, PPTID, pineoblastomas, and meningiomas, lipid peaks were small or absent in 10 of 10 examined tumors. In the NGGCT group, high lipid peaks on 1H-MRS were observed in 11 of 12 examined tumors; however, no tumors showed high intensity on DWI, with all low to high mixed intensity. ADC was statistically lower in the germinoma group compared with the NGGCT group (P = 0.0002)., Conclusions: Lower ADC values and high lipid peaks detected on 1H-MRS are characteristics of germinomas., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Standard treatment for patients with primary glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Recent reports have demonstrated that TMZ-induced myelosuppression correlates with survival in patients with GBM. However, those results were evaluated before the 2016 revision of the World Health Organization classification. This study examined whether myelosuppression during concomitant TMZ phase correlates with prognosis in GBM, IDH-wildtype patients. We examined circulating blood cell counts in 50 patients with GBM, IDH-wildtype who received the standard treatment protocol between August 2005 and November 2015. We assessed relationships between rates of decrease in blood cells (white blood cells (WBC), neutrophils, lymphocytes, red blood cells, and platelets) during the concomitant TMZ phase and overall survival (OS) using univariate and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Status (KPS), extent of resection, O 6 -methylguanine-DNA methyltransferase (MGMT) status). Log-rank testing revealed that age, KPS, extent of resection, MGMT status, and decrease rates of WBC, neutrophils, and platelets correlated significantly with OS. On multivariate analysis, age, MGMT status, and decrease rate of neutrophils correlated significantly with OS. Patients with a ≥ 40% decrease in neutrophils showed significantly longer OS than those with < 40% (hazard ratio = 2.815; 95% confidence interval = 1.177-7.038; P = 0.0196). A decrease of ≥ 40% in neutrophils represents a predictor of good prognosis for GBM, IDH-wildtype. Blood cell counts during the concomitant TMZ phase can help predict OS in patients with GBM, IDH-wildtype receiving the standard treatment protocol.