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BackgroundGlioblastoma is characterized by neovascularization and diffuse infiltration into the adjacent tissue. T2*-based dynamic susceptibility contrast (DSC) MR perfusion images provide useful measurements of the biomarkers associated with tumor perfusion. This study aimed to distinguish infiltrating tumors from vasogenic edema in glioblastomas using DSC-MR perfusion images.MethodsData were retrospectively collected from 48 patients with primary IDH-wild-type glioblastoma and 24 patients with meningiomas (Edemas-M). First, we attempted histological verification of cell density, Ki-67 index, and microvessel areas to distinguish between non-contrast-enhancing tumors (NETs) and edema (Edemas) which were obtained from stereotactically fused T2-weighted and perfusion images. This was performed for evaluating enhancing tumors (ETs), NETs, and Edemas. Second, we also performed radiological verification to distinguish NETs from Edemas. Two neurosurgeons manually assigned the regions of interests (ROIs) to ETs, NETs, and Edemas. The DSC-MR perfusion imaging-derived parameters calculated for each ROI included the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT).ResultsCell density and microvessel area were significantly higher in NETs than those in Edemas (pConclusionsDSC-MR perfusion images may prove useful in differentiating NETs from Edemas in non-contrast T2 hyperintensity regions of glioblastoma.

Background: Re-resections is one of the treatment options for recurrence brain tumors, including both benign and malignant brain tumors, such as meningioma and glioblastoma. Re-resection for recurrent brain tumor sometimes needs extension of original craniotomy. However, extending original craniotomy is troublesome and can easily damage the adhered brain tissue and reconstruct of bone flap sometimes cause cosmetic problems, thus ideal way to re-resect recurrent brain tumor is to use the same original craniotomy.However, when using an operative microscope, performing re-resections without extending craniotomy requires the surgeon to operate in an awkward position. A recently developed high-definition (4 K-HD) 3-D exoscope system, ORBEYE, can improve this problem. In this study, we analyzed the utility of 4 K-HD 3-D exoscope system, ORBEYE, for re-resecting recurrent brain tumor. Methods: We report 32 cases managed by re-resecting recurrent brain tumor by ORBEYE. Perioperative clinical, surgical, and radiographic data were retrospectively examined. Results: Re-resecting tumors for recurrent brain tumor by ORBEYE were successfully performed for all 32 resections, using ORBEYE, without any severe postoperative neurological deficit. In addition, we could avoid extending original craniotomy as much as possible by adjusting the ORBEYE camera angle. Conclusion: Re-resecting tumors for recurrent brain tumors by ORBEYE are feasible and can avoid extending original craniotomy as much as possible.

Background: Meningiomas are among the most common intracranial tumors. In these tumors, volumetric assessment is not only important for planning therapeutic intervention but also for follow-up examination.However, a highly accurate automated volumetric method for meningiomas using single-modality magnetic resonance imaging (MRI) has not yet been reported. Here, we aimed to develop a deep learning-based automated volumetry method for meningiomas in MRI and investigate its accuracy and potential clinical applications. Methods: For deep learning, we used MRI images of patients with meningioma who were referred to Osaka University Hospital between January 2007 and October 2020. Imaging data of eligible patients were divided into three non-overlapping groups: training, validation, and testing. The model was trained and tested using the leave-oneout cross-validation method. Dice index (DI) and root mean squared percentage error (RMSPE) were measured to evaluate the model accuracy. Result: A total of 178 patients (64.6 ± 12.3 years [standard deviation]; 147 women) were evaluated. Comparison of the deep learning model and manual segmentation revealed a mean DI of 0.923 ± 0.051 for tumor lesions. For total tumor volume, RMSPE was 9.5 ± 1.2%, and Mann–Whitney U test did not show a significant difference between manual and algorithm-based measurement of the tumor volume (p = 0.96). Conclusion: The automatic tumor volumetry algorithm developed in this study provides a potential volume-based imaging biomarker for tumor evaluation in the field of neuroradiological imaging, which will contribute to the optimization and personalization of treatment for central nervous system tumors in the near future

For drugs that are intended to fill unmet medical needs, such as the treatment of rare diseases or a subtype of cancer, it can take a long time to conduct confirmatory clinical trials due to limited patient availability. Delayed access to these drugs increases the risk of mortality of patients with these diseases. To address this issue, the Ministry of Health, Labour, and Welfare of Japan has decided to implement the Conditional Early Approval System with issuing the Ministry Notification in 2017. Drugs eligible for conditional early approval are those that are indicated for the treatment of a serious disease, have proven safety and efficacy, and cannot be examined easily by confirmatory clinical trials. When the benefit of immediate availability outweighs the risk of having less comprehensive data with which to confirm the clinical benefit of a product in the premarketing phase, products can be approved under the Conditional Early Approval System, accompanied by postmarketing regulatory requirements to manage postmarketing risks and, if needed, conduct postmarketing confirmatory clinical studies. Overview of the pre‐approval and post‐approval regulatory considerations will promote to more efficiently develop pharmaceutical products that fill unmet medical needs, leading to the prompt delivery of safe and effective drugs to patients who often have few therapeutic options available. As of March 2020, four drugs had been approved under the Conditional Early Approval System. In this review, we describe the premarketing and postmarketing requirements of these drugs and discuss the regulatory landscape around the Conditional Early Approval System.

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas.Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution.Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex (p = 0.002), age at the time of volumetric analysis (p < 0.001), hyperintense lesions on T2-weighted images (p = 0.029), peritumoral edema (p < 0.001), maximum tumor diameter (p < 0.001), and tumor volume (p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis (p = 0.002), peritumoral edema (p < 0.001), and tumor volume (p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887–0.951]).Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients.

The current research tested the hypothesis that inversion time (TI) shorter than 2,400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL Lower-grade gliomas (LrGGs), 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI < 2,400 ms for 3T or 2,016 ms for 1.5T, and 112 MRI from 112 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the “T2-FLAIR mismatch sign” was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2,400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher’s exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher’s exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31, 90, 79, and 51% to 67, 94, 92, and 74%, respectively and the area under the curve of ROC improved from 0.63 to 0.87 when FLAIR was acquired with shorter TI. We revealed that TI for FLAIR impacts the T2-FLAIR mismatch sign’s diagnostic accuracy and that FLAIR scanned with TI < 2,400 ms in 3T is necessary for LrGG imaging.

Early diagnosis of primary central nervous system lymphoma (PCNSL) in the extra-axial region is difficult due to the corresponding atypical clinical symptoms and radiological findings. This case report documents the rare diagnosis and treatment of PCNSL of the bilateral Bochdalek’s flower baskets (protrusions of the fourth ventricle choroid plexus into the cerebellopontine angles). The patient initially presented with subacute vertigo and left hearing loss. Radiological findings included symmetrical mass lesions in the bilateral cerebellopontine angles. An open biopsy enabled the pathological diagnosis of diffuse large B-cell lymphoma. The primary tumors were successfully removed through chemoradiation. However, the patient died six months after treatment completion due to cerebrospinal dissemination. PCNSL should be considered when diagnosing brain tumors with atypical symptoms and radiological findings.

Background: Although awake surgery is the gold standard for resecting brain tumors in eloquent regions, patients with hearing impairment require special consideration during intraoperative tasks. Case Description: We present a case of awake surgery using sign language in a 45-year-old right-handed native male patient with hearing impairment and a neoplastic lesion in the left frontal lobe, pars triangularis (suspected to be a low-grade glioma). The patient primarily communicated through sign language and writing but was able to speak at a sufficiently audible level through childhood training. Although the patient remained asymptomatic, the tumors gradually grew in size. Awake surgery was performed for tumors resection. After the craniotomy, the patient was awake, and brain function mapping was performed using tasks such as counting, picture naming, and reading. A sign language-proficient nurse facilitated communication using sign language and the patient vocally responded. Intraoperative tasks proceeded smoothly without speech arrest or verbal comprehension difficulties during electrical stimulation of the tumor-adjacent areas. Gross total tumor resection was achieved, and the patient exhibited no apparent complications. Pathological examination revealed a World Health Organization grade II oligodendroglioma with an isocitrate dehydrogenase one mutant and 1p 19q codeletion. Conclusion: Since the patient in this case had no dysphonia due to training from childhood, the task was presented in sign language, and the patient responded vocally, which enabled a safe operation. Regarding awake surgery in patients with hearing impairment, safe tumor resection can be achieved by performing intraoperative tasks depending on the degree of hearing impairment and dysphonia. [ABSTRACT FROM AUTHOR]

Background: Due to the presence of many perforating arteries and the deep location of basal ganglia tumors, dissection of the perforating arteries is critical during tumor resection. However, this is challenging as these arteries are deeply embedded in the cerebrum. Surgeons need to bend their heads for a long time using operative microscope and it is uncomfortable for the operating surgeon. A high-definition (4K-HD) 3D exoscope system can significantly improve the surgeon's posture during resection and widen the operating view field considerably by adjusting the camera angle. Methods: We report two cases of glioblastoma (GBM) involving basal ganglia. We used a 4K-HD 3D exoscope system for resecting the tumor and analyzed the intraoperative visualization of the operative fields. Results: We could approach the deeply located feeding arteries before successfully resecting the tumor using a 4K-HD 3D exoscope system which would have been difficult with the sole use of an operative microscope. The postoperative recoveries were uneventful in both cases. However, postoperative magnetic resonance imaging showed infarction around the caudate head and corona radiata in one of the cases. Conclusion: This study has highlighted using a 4K-HD 3D exoscope system in dissecting GBM involving basal ganglia. Although postoperative infarction is a risk, we could successfully visualize and dissect the tumors with minimal neurological deficits. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) are uncommon neoplasms arising from neuroendocrine cells and are rarely associated with intracranial metastases. Case Description: We discuss the case of a 74-year-old woman with a right CPA tumor. She had a history of retroperitoneal NET, but was diagnosed with vestibular schwannoma due to a right-sided hearing loss and a right CPA tumor along the VII and VIII nerves. After a 3-year follow-up, she presented with repetitive vomiting, a 1-month history of gait instability, and a 3-month history of general fatigue. Brain imaging revealed tumor growth and edematous changes in the right cerebellum. She underwent retrosigmoid craniotomy and partial resection. Histopathological examination revealed metastatic NET. She underwent stereotactic radiosurgery for residual lesion and, at 11 months of follow-up, the lesion was confirmed to have shrunk on magnetic resonance imaging (MRI). Conclusion: This is the first case to report the natural course of cerebellopontine metastasis of a NET. The differential diagnosis of CPA tumors is diverse, and, in our case, we suspected a vestibular schwannoma because of the typical symptoms and imaging features. However, the tumor grew relatively faster than expected and showed intratumoral hemorrhage during the 3-year follow-up. Therefore, in patients with a history of a NET, a careful follow-up is advisable even for lesions highly suspected to be another benign tumor on MRI. Careful follow-up imaging and appropriate treatment strategies were useful to manage the brain metastasis. Although NETs metastasizing to the CPA are extremely rare, this possibility should be considered when patients with NETs have intracranial lesions. [ABSTRACT FROM AUTHOR]

Background: Intraorbital aneurysms are rare, and most of them originate from the ophthalmic arteries. Herein, we report a case of meningolacrimal artery aneurysm associated with a meningioma., Case Description: A 55-year-old woman had a frontal convexity meningioma identified by brain magnetic resonance imaging during a checkup. Cerebral angiography revealed the middle meningeal artery as a feeding artery as well as the presence of an aneurysm associated with the meningolacrimal artery. Embolization of the feeding artery was performed before the removal of the meningioma. The meningioma was resected, and the aneurysm was removed with a bone flap. The patient was discharged without any complications., Conclusion: We report a meningolacrimal artery aneurysm associated with a meningioma. Embolizing the feeding artery of the aneurysm was helpful in safely resecting the meningioma., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)