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A recurrent tumor is defined as a re-emerging subclone originating from an ancestorial clone of the primary neoplasm. Hence, it should be distinguished from de novo tumor emerging from other clones. Herein, we describe an exceptional case in which the locally re-emerging glioma did not share genetic alterations of the primary tumor. While the initial tumor harbored mutations in IDH1 and TERT genes as well as 1p/19q codeletion, the re-emerging tumor did not present any of these genetic abnormalities. Variant calling for tumor samples using whole-genome sequencing revealed that 1696 mutations within the primary tumor faded in the re-emerging tumor, and that 4591 mutations were newly detected in the re-emerging tumor. These results suggested that the initial and re-emerging tumors did not share same clonal origins, although the second tumor appeared adjacent to the old surgical cavity 5 years after the initial surgery. We finally speculated that the re-emerging tumor could be a "de novo glioma" or "radiation-induced glioblastoma following treatment of a diffuse glioma." This case highlights the importance of molecular re-evaluation of clinically diagnosed "recurrent" glioma lesions.

Objective Accumulating evidence from recent molecular diagnostic studies has indicated the prognostic significance of various genetic markers for patients with glioblastoma (GBM). To evaluate the impact of such genetic markers on prognosis, we retrospectively analyzed the outcomes of patients with IDH‐wildtype GBM in our institution. In addition, to assess the impact of bevacizumab (BEV) treatment, we compared overall survival (OS) between the pre‐ and post‐BEV eras. Methods We analyzed the data of 100 adult patients (over 18 years old) with IDH‐wildtype GBM from our database between February 2006 and October 2018. Genetic markers, such as MGMT methylation status, EGFR amplification, CDKN2A homozygous deletion, and clinical factors were analyzed by evaluating the patients’ OS. Results CDKN2A homozygous deletion showed no significant impact on OS in patients with methylated MGMT status (p = 0.5268), whereas among patients with unmethylated MGMT status, there was a significant difference in OS between patients with and without CDKN2A homozygous deletion (median OS: 14.7 and 16.9 months, respectively, p = 0.0129). This difference was more evident in the pre‐BEV era (median OS: 10.1 and 15.6 months, respectively, p = 0.0351) but has become nonsignificant in the post‐BEV era (median OS: 16.0 and 16.9 months, respectively, p = 0.1010) due to OS improvement in patients with CDKN2A homozygous deletion. However, these findings could not be validated in The Cancer Genome Atlas cohort. Conclusions MGMT and CDKN2A status subdivided our cohort into three race‐specific groups with different prognoses. Our findings indicate that BEV approval in Japan led to OS improvement exclusively for patients with concurrent unmethylated MGMT status and CDKN2A homozygous deletion., CDKN2A homozygous deletion showed no significant impact on OS in patients with methylated MGMT status, while, among patients with unmethylated MGMT status, there was a significant difference in OS between patients with and without CDKN2A homozygous deletion. This difference was more evident in the pre‐BEV era, but has become non‐significant in the post‐BEV era due to OS improvement in patients with CDKN2A homozygous deletion.

Purpose The current study aims to test the hypothesis that the ratio of T1-weighted image to T2-weighted image signal intensity (T1w/T2w-Ratio: rT1/T2), an imaging surrogate developed for myelin integrity, is predictive of histologically lower-grade glioma's IDH mutation status. Materials and Methods 25 histologically and molecularly confirmed lower-grade glioma patients with eight IDH-wildtype (IDHwt) and 17 IDH-mutant (IDHmt) tumors at Asahikawa Medical University Hospital (AMUH) were used as a test cohort. Twenty-nine patients (IDHwt: 13, IDHmt: 16) from Osaka International Cancer Institute (OICI) and 101 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (IDHwt: 19, IDHmt: 82) were used as external cohorts. rT1/T2 images were calculated from T1- and T2-weighted images using a recommended signal correction. The relationship between the mean rT1/T2 (mrT1/T2) and the IDH mutation status was investigated. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) investigated the difference in MRI qualities and characteristics between the three cohorts. Results The test cohort at AMUH revealed that mrT1/T2 of IDHwt tumors was significantly higher than that of IDHmt tumors (p < 0.05) and that the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666-0.677, (AUC = 0.75, p < 0.05), which finding was validated by the external domestic cohort at OICI (AUC = 0.75, p = 0.02). However, the external international cohort deriving from TCIA/TCGA could not validate this (AUC = 0.63, p = 0.08). t-SNE analysis revealed that the difference in image characteristics within the cohort was more diverse for the TCIA/TCGA than for the two domestic cohorts. Conclusion The current study revealed that mrT1/T2 was able to discriminate IDHwt and IDHmt tumors in two domestic cohorts significantly. This was not validated by the TCIA/TCGA cohort due to the wide variety in the original imaging characteristics of the TCIA/TCGA cohort.

Background The differences between 3-dimensional (3D) high definition (HD) and 2-dimensional (2D) 4-K ultra-HD (4K) endoscopy and their respective advantages remain unclear. Objective To evaluate the utility of these endoscopy systems in endonasal skull base surgery. Methods Consecutive series of endoscopic endonasal surgeries performed after introduction of 3D/HD and 2D/4K systems (July 2017) were retrospectively evaluated. Sporadic cases treated with either system, or a conventional 2D standard definition (SD) system, during the rental period from March 2016 were also included. Objective comparisons between the systems were made for newly diagnosed Knosp grade 0 to 3 pituitary adenomas. Surgical procedures were divided into nasal, sphenoidal, and intradural phases, and the surgical procedural time was compared for each phase. The time required for and accuracy of suturing the sellar floor dura was also evaluated. Results A total of 74 cases were treated with 3D/HD and/or 2D/4K, and 12 cases with 2D/SD. 3D/HD was advantageous in the nasal phase because of its intuitive depth perception. 2D/4K was advantageous in the intradural phase because of its superior image quality. Surgical time of the nasal phase with 3D/HD, and that of the intradural phase with 2D/4K, were significantly shorter than that with 2D/SD. The time required for and accuracy of sellar floor dural suturing showed a trend toward improving in the order of 2D/SD, 2D/4K, and 3D/HD. Conclusion 3D/HD and 2D/4K endoscopy systems have different advantages, which are useful in distinct surgical phases. Understanding the characteristics of endoscopy systems is important for selecting the most appropriate system for distinct surgical situations.

OBJECTIVEIt is important to correctly and precisely define the target volume for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission tomography (PET) holds promise for detecting areas of glioma cell infiltration: the authors’ previous research showed that the magnitude of disruption of MET and 18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely reflects glioma cell invasion. The purpose of the present study was to analyze volumetric and geometrical properties of RT target delineation based on DS and compare them with those based on MRI.METHODSTwenty-five patients with a diagnosis of malignant glioma were included in this study. Three target volumes were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and 3) lesions showing high DS (DS ≥ 3; hDS). The geometrical differences of these target volumes were assessed by calculating the probabilities of overlap and one encompassing the other. The correlation of geometrical features of RT planning and recurrence patterns was further analyzed.RESULTSThe analysis revealed that T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6 (24%) patients, which indicates that microscopic invasion of glioma cells often extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage of high DS regions with RT target volumes was suggested to be a risk for out-of-field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher values of “[T1Gd + 2 cm]/hDS”) had a trend to positively impact overall and progression-free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside the Gd-enhanced core lesion, indicative of out-of-field reoccurrence.CONCLUSIONSThe findings of this study indicate that MRI is inadequate for target delineation for RT in malignant glioma treatment. Expanding the treated margins substantially beyond the MRI-based target volume may reduce the risk of undertreatment, but it may also result in unnecessary irradiation of uninvolved regions. As MET/FDG PET-DS seems to provide more accurate information for target delineation than MRI in malignant glioma treatment, this method should be further evaluated on a larger scale.

The diagnosis and prognostication of glioblastoma (GBM) remain to be solely dependent on histopathological findings and few molecular markers, despite the clinical heterogeneity in this entity. To address this issue, we investigated the prognostic impact of copy number alterations (CNAs) using two population-based IDH-wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). The molecular disproportions between these cohorts were dissected in light of cohort differences in GBM. The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The somatic landscape around CNAs was analyzed for 212 KNBTG cases and 359 TCGA cases. Next, the clinical impacts of CNA profiles were investigated for 140 KNBTG cases and 152 TCGA cases treated by standard adjuvant therapy using temozolomide-based chemoradiation. The comparative profiling indicated unequal distribution of specific CNAs such as EGFR, CDKN2A, and PTEN among the two cohorts. Especially, the triple overlap CNAs in these loci (triple CNA) were much higher in frequency in TCGA (70.5%) than KNBTG (24.3%), and its prognostic impact was independently validated in both cohorts. The KNBTG cohort significantly showed better prognosis than the TCGA cohort (median overall survival 19.3 vs 15.6 months). This survival difference between the two cohorts completely resolved after subclassifying all cases according to the triple CNA status. The prognostic significance of triple CNA was identified in IDH-wild-type GBM. Distribution difference in prognostic CNA profiles potentially could cause survival differences across cohorts in clinical studies. Electronic supplementary material The online version of this article (10.1186/s40478-019-0749-8) contains supplementary material, which is available to authorized users.

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

Background The endoscopic endonasal trans-lacerum approach (EETLA) is useful in handling skull base tumors around inferior petrous apex (IPA); however, its surgical corridor is exclusively a triangular space (supra-eustachian triangle [SET]), between the internal carotid artery (ICA) and eustachian tube. Methods We investigated correlation between SET size and extent of resection around the IPA (lateral extent of resection [EOR]) through a retrospective analysis of 15 surgeries using EETLA. Results Of 15 cases (9 chordomas, 4 chondrosarcomas, and 2 meningiomas), 20 sides of IPA were affected by the tumor. When being restricted to sides with severe lateral tumor extension beyond the midpoint of petrous ICA (10 sides), the SET size was significantly broader in the group with lateral EOR of ≥90% (p value = 0.019). Conclusions The SET size was a powerful index of tumor resectability in EETLA, especially in cases with severe tumor extension. The individual anatomical variations should be considered when determining EETLA application.

The nasal cavity is the exclusive surgical corridor for endoscopic endonasal surgery; however, it is sometimes too narrow to allow extensive surgical maneuvering. Here we show the technique of submucosal inferior turbinectomy (SIT) to widen this surgical corridor. Its effectiveness is evaluated quantitatively by comparing pre- and intraoperative magnetic resonance images. Between March 2015 and October 2018, we performed endoscopic endonasal resection of 57 skull base tumors with 3T intraoperative magnetic resonance imaging (iMRI). Among these resections, cases with previous endonasal surgery and cases for which the iMRI did not cover the entire nasal cavity were excluded. Finally, six cases with and 19 cases without SIT were included in the subsequent retrospective analysis. We measured the dimensions of the narrowest area in inferior nasal cavity on pre- and intraoperative coronal plane gadolinium (Gd)-enhanced T1-weighted MR images using dedicated software, and compared them. The incidence rates of postoperative nasal complaints at outpatient clinics were also compared. Considerable widening of the inferior nasal cavity could be achieved with the SIT, which was statistically significant compared with those without the SIT (111.1 ± 56.5% vs. 39.4 ± 59.4%, respectively; P = 0.0093). In terms of the incidence rate of postoperative nasal complaints at 6 months, there was no statistical difference between the groups (33.3% vs. 15.8%, respectively; P = 0.35). SIT is effective for widening the surgical corridor while keeping nasal function and is especially helpful for lower clivus and laterally extended skull base lesions.

Background The endoscopic approach, chiefly via the maxillary sinus, has growing applications for the lateral skull base, and can be classified into the use of “endonasal” or “sublabial” entry. Although the endonasal transmaxillary approach has been well accepted, it has a limitation with respect to the lateral exposure. A possible solution is the use of the sublabial transmaxillary approach via the canine fossa, which assures lateral accessibility. In clinical practice, we have taken advantage of the concomitant use of the endonasal and sublabial transmaxillary approach for selected patients harboring lateral skull base lesions. In addition to binostril pathways, canine fossa trephination was constructed to facilitate this combined approach, termed the endoscopic triportal transmaxillary approach (ETTA). Methods The efficacy of the ETTA was evaluated within a case series. A single-institution retrospective analysis was performed in patients with lateral middle skull base tumors treated via ETTA. Results In clinical practice, 4 patients were eligible for the study, including 1 receiving a combined endoscopic and transcranial approach. No major complications occurred in patients included in this series. The ETTA facilitated the dynamic manipulation of instruments, which led to rapid hemostasis and the satisfactory surgical resection of tumors. Furthermore, it reduced intraoperative postural stress experienced by the surgeons who performed the procedures. Conclusions The concomitant use of the trans-canine fossa approach effectively ameliorated significant technical challenges that tend to occur when using a purely endonasal approach. The ETTA can be an attractive option for treating lateral and middle skull base lesions.

BACKGROUND: Geriatric neuro-oncology is an important research field, because the elderly patients is growing at a very rapid rate. This study investigates molecular features and their prognostic effects in the elderly glioblastomas (GBM). METHODS: We collected adult cases diagnosed with IDH-wildtype GBM and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (212 cases). Clinical and molecular features were analyzed retrospectively and independent prognostic factors were identified statistically. Focusing on the elderly (>=70 years) cases, the association between molecular factors and overall survivals (OS) was examined. RESULTS: Included in the study were 92 elderly cases (43.4%) and median OS was 12.8 months. MGMT promoter was methylated in 50 (54.3%). Triple CNA (EGFR amplification/gain & PTEN deletion & CDKN2A deletion) was detected in 23 (25.0%). NFKBIA was deleted in 23 (25.0%). In the elderly cases, adjuvant radiation and temozolomide (RT+TMZ) was performed in 39 (42.4%) (mOS = 17.1 months). Statistical analyses of the elderly plus non-elderly cases treated with RT+TMZ (148 cases), MGMT promoter, triple CNA and NFKBIA were identified as independent molecular prognostic factors. In the elderly group, however, there was no significant difference in OS according to MGMT status (methylated = 18.7 vs. unmethylated = 17.1, p = 0.3885) or triple CNA status (triple = 13.6 vs. non-triple = 19.6, p = 0.1734). On the other hand, statistical difference was observed according to NFKBIA status (del = 12.1 vs. non-del = 18.7, p = 0.0157*) even in the elderly cases. CONCLUSION: Prognostic effects of molecular factors might be attenuated in the elderly patients. Further investigation in a larger population is necessary.

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

Low-grade glioma (LGG) is often encountered in relatively young individuals, including women of childbearing age. Notably, case series describing pregnant women with LGG have been reported in the literature. The present study reported a case of pilocytic astrocytoma (PA) requiring tumor resection during pregnancy. The patient had a history of γ-knife radiotherapy for a brainstem tumor 17 years previously. The histological diagnosis was unclear. The tumor had remained stable following radiosurgery for 17 years, including during her first pregnancy. However, rapid tumor growth around the fourth ventricle occurred at week 25 of her second pregnancy. Therefore, an urgent tumor resection was performed despite the pregnancy. Partial resection was performed since the tumor had infiltrated the brainstem. The histological diagnosis was PA. The residual tumor volume decreased gradually following the delivery. Immunostaining of the tumor for the expression of progesterone receptor revealed focal staining. It is possible that reproductive factors, including specific hormonal changes during pregnancy, affected the tumor growth. The present study described this rare case of PA, which exhibited rapid growth and required urgent surgery during pregnancy.

BACKGROUND Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence reduction of tumor volume. PATIENTS AND METHODS Plural MRI scans were done before the first course of chemotherapy regimen in 27 patients with primary intracranial germinomas. Their age ranged from 8 to 31 years. 35 lesions from them were enrolled and included 13 pineal, 4 neurohypophyseal, 4 basal ganglia, 4 bifocal type, and 2 multiple lesions. All regions were verified as pure germinoma or HCG-producing germinoma by histopathological examination. Tumor volume of 35 lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. RESULTS Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 8.27). Diagnostic radiation dose: 40.5 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 30.8). In 10 regions, shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p CONCLUSION This study shows that the volume of intracranial germ cell tumors is changing dynamically before chemoradiotherapy in many cases. Diagnostic exposure to low-dose radiation influences tumor shrinkage of intracranial germinomas.

Introduction: Clinical application of survival prediction of primary glioblastoma (pGBM) using preoperative images remains challenging due to a lack of robustness and standardization of the method. This research focused on validating a machine learning-based texture analysis model for this purpose using internal and external cohorts. Method: We included all cases of IDH wild-type pGBM available of preoperative MRI (T1WI, T2WI, and Gd-T1WI) from the databases of Kansai Molecular Diagnosis Network for CNS tumors (KN) and The Cancer Genome Atlas (TCGA). Of 242 cases from KN, we assigned 137 cases as a training dataset (D1), and the remaining 105 cases as an internal validation dataset (D2). Furthermore, we extracted 96 cases from TCGA as an external validation dataset (D3). Preoperative MRI scans were semi-quantitatively analyzed, leading to the acquisition of 489 texture features as explanatory variables. Dichotomous overall survival (OS) with a 16.6 months cutoff was regarded as the response variable (short/long OS). We employed Lasso regression for feature selection, and a survival prediction model constructed for D1 via cross-validation (M1) was applied to D2 and D3 to ensure the model robustness. Results: The population of predicted short OS by M1 significantly showed poorer prognosis in D2 (median OS 11.1 vs. 19.4 months; log-rank test, p=0.03), while there was no significant difference in D3 (median OS 14.2 vs. 11.9 months; p=0.61). In the comparative analysis using t-SNE, there was little variation in the feature distribution among three datasets. Conclusion: We were able to validate the prediction model in the internal but not in the external cohort. The presented result supports the use of machine learning-based texture analysis for survival prediction of pGBM in a localized population or country. However, further consideration is required to achieve a universal prediction model for pGBM, irrespective of regional difference.

Precise delineation of target volume for radiotherapy of malignant glioma is one of the crucial processes in glioma treatment. Although MRI is the modality often chosen for this procedure, the authors’ previous research showed that combined use of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) PET was more accurate for glioma visualization (J Nucl Med, 2012). The aim of this study was to analyze volumetric and geometrical properties of RT-target-delineation based on MET/FDG PET and to compared them with those based on MRI. The impact of geometrical properties on progression free survival was further investigated. Twenty-five patients with a diagnosis of malignant glioma were included in our study. Three target volumes were compared, which included contrast-enhancing core lesions identified by contrast-enhanced T1 weighted images (T1Gd), high intensity lesions on T2 weighted images, and lesions showing high DS, a cell density score calculated from MET/FDG PET (> 3; hDS). T1Gd with 2.0 cm margin was able to cover the entire hDS only in 6 (24%) patients, indicating microscopic invasion of glioma cells beyond 2cm from gadolinium-enhanced core. Insufficient coverage of high DS region with RT target volume was suggested to be a risk for out-field recurrence. Higher coverage of hDS (T1Gd + 2/hDS) by T1Gd with 2 cm margin tended to positively impact overall and progression free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with 2 cm margin was predictive of tumor recurrence outside gadolinium-enhanced core, indicative of out-field reoccurrence. Present findings indicate that MRI is inadequate for target delineation for radiation therapy in malignant glioma treatment. Expanding additional margins to MRI based target volume often reduces this uncertainty while unnecessarily irradiated regions increase and MET/FDG PET seemed to provide more accurate information for target delineation than MRI.

BACKGROUND: Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence shrinkage of tumor volume. PATIENTS AND METHODS: Thirty-nine cases with primary intracranial germinomas and HCG-producing germinomas were treated in our hospital from 1994 to 2017. In twenty-one of them, plural MRI scans were done before the first course of chemotherapy regimen. Their age ranged from 8 to 31 years. Three cases were bifocal type, one case had multiple lesions. Biopsies were performed in all regions. Tumor volume of twenty-four lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. RESULTS: Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 9.67). Diagnostic radiation dose: 52.2 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 28.7). In only 7 regions (29.1%), shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p

Background Atraumatic acute subdural hematoma (ASDH) associated with moyamoya disease (MMD) is rare, and only a few studies have reported the bleeding origin. We present a case of atraumatic ASDH attributable to a transdural anastomosis that developed owing to the compensatory mechanisms involved in the pathogenesis of advanced MMD. This is the first case of life-threatening atraumatic ASDH associated with MMD in which the rupture point was clearly visualized using a 3-dimensional rotational reconstructed image. Case Description A 37-year-old woman presented with sudden-onset, serious, atraumatic ASDH requiring emergency decompressive craniectomy. The cerebral angiograms revealed that she had advanced MMD with transdural anastomosis that was classified as Suzuki stage V with a 5-mm saccular aneurysm in the middle meningeal artery on the affected side, which was suggested as the bleeding origin. Follow-up angiograms demonstrated that the aneurysm spontaneously disappeared and was inferred to be a pseudoaneurysm. We performed a left extraintracranial bypass to prevent recurrent hemorrhage. With intensive rehabilitation, the patient accordingly achieved stroke-free survival with a modified Rankin Scale score of 3 for 1 year. Conclusions Atraumatic ASDH associated with MMD is a rare type of hemorrhagic MMD, and a 3-dimensional-rotational reconstructed image was useful to confirm the origin of the bleeding. The transdural anastomosis development most likely correlates with the occurrence of any type of hemorrhagic MMD. We should consider that the transdural anastomosis collapse can cause a life-threatening atraumatic ASDH and should plan a surgical strategy carefully so as not to destroy collateral supply through the transdural anastomosis in such cases.

INTRODUCTION Aging is a negative prognostic factor in glioblastoma (GB) and the genetic background in clinical outcome of elderly GB could exist. This study investigates the difference of elderly patients from younger ones regarding molecular characteristics as well as clinical outcomes in IDH-wildtype GB. METHODS We collected adult cases diagnosed with IDH-wildtype GB and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network) (212 cases) and The Cancer Genome Atlas (TCGA) project (359 cases). Clinical and pathological characteristics were analyzed retrospectively and compared between elderly cases (≥70 years) and younger ones (≤50 years). Molecular analysis included copy number alterations (CNAs) of eight genes (EGFR, PDGFRA, PTEN, CDKN2A, CDK4, MDM2, TP53, NFKBIA). RESULTS Included in the study were 92 (≥70 years)/33 (≤50 years) cases of Kansai Network and 88 (≥70 years)/69 (≤50 years) cases of TCGA. Median overall survival was 12.8 (≥70 years)/ 21.0 (≤50 years) months in Kansai Network cohort and 8.8 (≥70 years)/ 21.09 (≤50 years) months in TCGA cohort. MGMT promoter was methylated in 50 (54.3%) (≥70 years)/14 (42.4%) (≤50 years) tumors in Kansai Network and 34 (48.6%) (≥70 years)/16 (36.4%) (≤50 years) tumors in TCGA. TERT promoter was mutated in 51 (55.4%) (≥70 years)/13 (39.4%) (≤50 years) tumors in Kansai Network and unknown in TCGA. Significant difference of CNA profiles between ≥70 years and ≤50 years was as follows: PTEN del, 43 (46.7%)/8 (24.2%); CDK4 amp, 17 (18.5%)/1 (3.0%) in Kansai Network and CDKN2A del, 69 (78.4%)/ 42 (60.9%) in TCGA. CONCLUSION Elderly patients have several potential factors for poor prognosis and different molecular profiles might explain the survival differences among generations.

Accurate estimation of tree and forest biomass is key to evaluating forest ecosystem functions and the global carbon cycle. Allometric equations that estimate tree biomass from a set of predictors, such as stem diameter and tree height, are commonly used. Most allometric equations are site specific, usually developed from a small number of trees harvested in a small area, and are either species specific or ignore interspecific differences in allometry. Due to lack of site-specific allometries, local equations are often applied to sites for which they were not originally developed (foreign sites), sometimes leading to large errors in biomass estimates. In this study, we developed generic allometric equations for aboveground biomass and component (stem, branch, leaf, and root) biomass using large, compiled data sets of 1203 harvested trees belonging to 102 species (60 deciduous angiosperm, 32 evergreen angiosperm, and 10 evergreen gymnosperm species) from 70 boreal, temperate, and subtropical natural forests in Japan. The best generic equations provided better biomass estimates than did local equations that were applied to foreign sites. The best generic equations included explanatory variables that represent interspecific differences in allometry in addition to stem diameter, reducing error by 4-12% compared to the generic equations that did not include the interspecific difference. Different explanatory variables were selected for different components. For aboveground and stem biomass, the best generic equations had species-specific wood specific gravity as an explanatory variable. For branch, leaf, and root biomass, the best equations had functional types (deciduous angiosperm, evergreen angiosperm, and evergreen gymnosperm) instead of functional traits (wood specific gravity or leaf mass per area), suggesting importance of other traits in addition to these traits, such as canopy and root architecture. Inclusion of tree height in addition to stem diameter improved the performance of the generic equation only for stem biomass and had no apparent effect on aboveground, branch, leaf, and root biomass at the site level. The development of a generic allometric equation taking account of interspecific differences is an effective approach for accurately estimating aboveground and component biomass in boreal, temperate, and subtropical natural forests.

The prognosis of leptomeningeal dissemination of recurrent glioblastoma is poor, and chemotherapy results in minimal palliative efficacy. Temozolomide (TMZ) is an established therapy for patients with malignant glioma and the standard of care in parenchymal gliomas; however, few reports have been published with regard to its use for the treatment of leptomeningeal dissemination. Only one report has indicated the radiographic response of leptomeningeal dissemination to a TMZ rechallenge, suggesting a potential causative effect. While bevacizumab is an effective therapy for recurrent glioblastoma, its effect on leptomeningeal dissemination of recurrent glioblastoma remains unclear. The present study reports a case of leptomeningeal dissemination of recurrent glioblastoma in which transient neurological and radiological improvement was observed following chemotherapy with TMZ and bevacizumab. However, five months after the diagnosis of leptomeningeal dissemination the patient succumbed to the disease.

Choroid plexus metastasis (CPM) is extremely rare and originates most frequently from renal cell carcinoma (RCC). We herein report the case of a 58-year-old man who developed a solitary CPM lesion derived from follicular thyroid carcinoma in addition to intraventricular hemorrhage. Computed tomography revealed acute hydrocephalus as a result of the hemorrhage, and we planned endoscopic hematoma evacuation. Since it was too difficult to reach the hematoma, we considered the possibility of a neoplasm and performed a biopsy of the lesion, the results of which led to an accurate diagnosis of CPM in this case. We also review previous reports of CPM originating from thyroid carcinoma compared with RCC.

BACKGROUND The opportunity to follow up for asymptomatic meningiomas has increased. We have reported the risk of volume increase by individual continuous volume measurement of asymptomatic meningiomas. However, We have not reached fully understanding about natural history of meningiomas. Among cases are followed up over time, there are some cases that the volume increase rates slows down or almost stops are observed. METHODS We enrolled consecutive adult patients of asymptomatic meningiomas who follow-up for 2 years or more and 3 or more MRI scans. We performed sequential volumetric measurements on 95 patients (105 lesions) who met the criteria. We classified these transient volume curve of each lesion into three groups “Growing”, “Slowdown”, and “Growth arrest” for analysis. RESULTS The average age at the first visit was 62.8 years, the average follow-up period was 61.8 months, and the male-female ratio was 20:75 (male: female). There were 67 cases (73 lesions: 70.9%) that were in increasing trend, and 19 cases of those were received resection. Eleven cases (12 lesions: 11.7%) showed a tendency of “slow down” the increase rate, and one patient who became symptomatic led to surgical excision. In 18 cases (18 lesions: 17.4%) in which almost no volume change was observed during the observation period, no cases resulted in surgical treatment. CONCLUSIONS Among the meningiomas cases that have been followed for a long time, there are not a few those increase rate of tumor volume slows or does not change. Furthermore, most of these cases did not result in surgical treatment. The presence of these “Slowdown” and “Growth arrest” cases at a certain rate may have suggested the possibility of a Gompertz curve model as the natural course of meningiomas.

INTRODUCTION Preoperative magnetic resonance imaging (MRI) is a critical modality for the determination of glioblastoma (GBM) treatment strategy, as it is thought to reflect the biology of the tumor to some extent. The authors attempted to predict prognosis of newly diagnosed GBM (nGBM) using machine learning-based texture analysis of preoperative MRI in this study. METHOD A total of 160 nGBMs with determined overall survival were collected from Kansai Molecular Diagnosis Network for CNS tumors. Preoperative MRI scans (T1WI, T2WI, and Gd-T1WI) from all cases were semi-quantitatively analyzed leading to acquisition of 489 texture features as explanatory variables using Matlab-based in-house software. Dichotomous overall survival (OS) with a cutoff of 15 months was regarded as the response variable (short or long OS). Lasso regression was employed for feature selection to ensure robustness of the prediction model. One hundred patients were randomly assigned as training dataset (TR), followed by predictive model construction via 5-fold cross-validation. Subsequently, the constructed model was transferred to the remaining 60 patients, which was assigned as test dataset (TD). The survival distribution between populations with predicted short and long OS was compared using log-rank test. RESULTS Distributions of the analyzed data were as follows; 53 short OS cases in the TR (53.0%) and 27 cases in the TD (45.0%). As for the result of transfer analysis in TD, 38 cases out of 60 (63.3%) were predicted to be short OS (76.3 % of recall, 54.3% of precision, and 63.5% of F-measure). The population of predicted short OS significantly showed poorer prognosis (median OS 14.0 vs 19.1 months) (p=0.02, log-rank test). CONCLUSION Short OS was successfully identified from preoperative MRI with high recall rates with our algorithm. The presented result ensures the potential of machine learning-based texture analysis for prognostic stratification of nGBM.

INTRODUCTION Recent studies have reported that NFKBIA deletion (dNFKBIA) was potentially associated with worse prognosis in glioblastoma (GBM) patients. However, no consensus has been reached to its universal prognostic value. Here, we investigated the survival impact of dNFKBIA using two primary IDH wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). Additionally, prognostic impact of a combination of NFKBIA copy number and MGMT methylation status was evaluated. METHOD The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The survival impact of dNFKBIA and/or unmethylated MGMT (uMGMT) were analyzed for 212 KNBTG cases and 265 TCGA cases. The hazard ratio (HR) and p-value were computed using Cox regression analysis. RESULTS dNFKBIA was less frequently observed in KNBTG (47 cases, 22.2%) than in TCGA (84 cases, 31.7%). dNFKBIA was associated with unfavorable prognosis in KNBTG (HR 1.52, p = 0.031), while this was not validated in TCGA (HR 1.14, p=0.406). uMGMT was a common adverse prognostic factor in KNBGT (HR 1.72, p = 0.001) and TCGA (HR 1.50, p = 0.008) cohort. When stratified by NFKBIA status, uMGMT was also associated with shorter survival in NFKBIA deleted cases both in KNBTG (HR 1.87, p = 0.002) and TCGA (HR 1.59, p = 0.014). On the other hand, MGMT status was not significantly associated with prognosis in NFKBIA intact cases in either KNBTG (HR 1.45, p = 0.279) or TCGA (HR 1.55, p = 0.131). DISCUSSION Although the prognostic value of dNFKBIA in IDH wild-type GBM patients was not validated in TCGA cohort, our results indicated that the prognostication based on MGMT methylation was potentially interacted by NFKBIA status.

INTRODUCTION: Some differences in the frequencies of cancer genetic alterations across the population have been reported, including EGFR mutations in lung cancer. However, little information is provided in glioblastomas. Here, we investigated the mutational landscape of primary glioblastomas of Japanese population and its trends against the Cancer Genome Atlas (TCGA) dataset. METHOD: We retrospectively analyzed somatic genetic alterations of 220 cases diagnosed as primary glioblastoma based on CNS WHO2016, which were resected in Japan between December 2006 and November 2017. Mutational status of IDH1/2, TERT, and TP53 were determined using the Sanger technique. MGMT promoter methylation status was analyzed by quantitative methylation-specific PCR. Copy number alterations of eight major genes including EGFR were evaluated by using multiplex ligation-dependent probe amplification. The frequency of each alteration was compared with that in TCGA cohort. The relationships and survival impact of each molecular marker were also investigated. RESULTS: Our cohort showed lower frequencies of TERT mutation (56.8%), EGFR gain (55.0%), PTEN loss (44.1%), CDK4 gain (14.1%), and MDM2 gain (9.5%) when comparing with the data of TCGA. On the other hand, the frequencies of TP53 mutation (39.1%) and loss (40.4%) were higher. TERT mutation had a significant positive correlation with EGFR gain (p < 0.001) and PTEN loss (p < 0.001). In survival analysis excluding tumors with IDH mutation, unmethylated MGMT promoter and TERT mutation were significant independent prognostic factors, while other genetic aberrations were not. DISCUSSION: The frequencies of several genetic aberrations differed between Japan and TCGA cohort. Although further studies are needed, our results suggest that the racial differences in genetic alterations may affect the interpretation of clinical trials conducted in different countries.

Understanding how plants are constructed—i.e., how key size dimensions and the amount of mass invested in different tissues varies among individuals—is essential for modeling plant growth, carbon stocks, and energy fluxes in the terrestrial biosphere. Allocation patterns can differ through ontogeny, but also among coexisting species and among species adapted to different environments. While a variety of models dealing with biomass allocation exist, we lack a synthetic understanding of the underlying processes. This is partly due to the lack of suitable data sets for validating and parameterizing models. To that end, we present the Biomass And Allometry Database (BAAD) for woody plants. The BAAD contains 259 634 measurements collected in 176 different studies, from 21 084 individuals across 678 species. Most of these data come from existing publications. However, raw data were rarely made public at the time of publication. Thus, the BAAD contains data from different studies, transformed into standard units and variable names. The transformations were achieved using a common workflow for all raw data files. Other features that distinguish the BAAD are: (i) measurements were for individual plants rather than stand averages; (ii) individuals spanning a range of sizes were measured; (iii) plants from 0.01–100 m in height were included; and (iv) biomass was estimated directly, i.e., not indirectly via allometric equations (except in very large trees where biomass was estimated from detailed sub-sampling). We included both wild and artificially grown plants. The data set contains the following size metrics: total leaf area; area of stem cross-section including sapwood, heartwood, and bark; height of plant and crown base, crown area, and surface area; and the dry mass of leaf, stem, branches, sapwood, heartwood, bark, coarse roots, and fine root tissues. We also report other properties of individuals (age, leaf size, leaf mass per area, wood density, nitrogen content of leaves and wood), as well as information about the growing environment (location, light, experimental treatment, vegetation type) where available. It is our hope that making these data available will improve our ability to understand plant growth, ecosystem dynamics, and carbon cycling in the world's vegetation.

A 62-year-old male patient had a metastatic carcinoma of the thyroid gland from lung cancer for which he had received surgical treatment 4 years ago. The tumor lesion involved the right recurrent nerve and the trachea, resulting in a stenosis at the level of 5 cm beneath the glottis. The tumor lesion was resected together with 2nd to 5th tracheal rings, and end-to-end anastomosis was performed following suprahyoid laryngeal release. A tracheal cannula was inserted from the anastomosed portion where an anterior third of the trachea was left open. The patient had a more reliable airway than endo-tracheal intubation. Histologic examination of both the thyroid lesion and the previously-resected lung cancer revealed that both lesions were very similar. Postoperative course was uneventful, and no signs of recurrence have been detected for 27 months after the operation.