Search

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.

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.

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 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.

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

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.

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 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.