Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2.

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

Leukocyte transcriptome of Cushing's disease are associated with nerve impairment and psychiatric disorders.

INTRODUCTION: The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol is a major response mechanism to stress and plays a critical role in many psychiatric disorders. Cushing's disease (CD) serves as a valuable in vivo "hyperexpression" model to elucidate the effect of cortisol on brain function and mental disorders. Changes in brain macroscale properties measured by magnetic resonance imaging (MRI) have been detailed demonstrated, but the biological and molecular mechanisms underlying these changes remain poorly understood. MATERIAL AND METHODS: Here we included 25 CD patients and matched 18 healthy controls for assessment, and performed transcriptome sequencing of peripheral blood leukocytes. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network of the relationships between genes and we identified a significant module and hub gene types associated with neuropsychological phenotype and psychiatric disorder identified in enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis preliminarily explored the biological functions of these modules. RESULTS: The WGCNA and enrichment analysis indicated that module 3 of blood leukocytes was enriched in broadly expressed genes and was associated with neuropsychological phenotypes and mental diseases enrichment. GO and KEGG enrichment analysis of module 3 identified enrichment in many biological pathways associated with psychiatric disorders. CONCLUSION: Leukocyte transcriptome of Cushing's disease is enriched in broadly expressed genes and is associated with nerve impairment and psychiatric disorders, which may reflect some changes in the affected brain.

Mobile internet-based mixed-reality interactive telecollaboration system for neurosurgical procedures: technical feasibility and clinical implementation.

OBJECTIVE: To increase access to health interventions and healthcare services for patients in resource-constrained settings, strategies such as telemedicine must be implemented for the allocation of medical resources across geographic boundaries. Telecollaboration is the dominant form of surgical telemedicine. In this study, the authors report and evaluate a novel mobile internet-based mixed-reality interactive telecollaboration (MIMIT) system as a new paradigm for telemedicine and validate its clinical feasibility. METHODS: The application of this system was demonstrated for long-distance, real-time collaboration of neuroendoscopic procedures. The system consists of a local video processing workstation, a head-mounted mixed-reality display device, and a mobile remote device, connected over mobile internet (4G or 5G), allowing global point-to-point communication. Using this system, 20 cases of neuroendoscopic surgery were performed and evaluated. The system setup, composite video latency, technical feasibility, clinical implementation, and future potential business model were analyzed and evaluated. RESULTS: The MIMIT system allows two surgeons to perform complex visual and verbal communication during the operation. The average video delay time is 184.25 msec (range 160-230 msec) with 4G mobile internet, and 23.25 msec (range 20-26 msec) with 5G mobile internet. Excellent image resolution enabled remote neurosurgeons to visualize all critical anatomical structures intraoperatively. Remote instructors could easily make marks on the surgical view; then the composite image, as well as the audio conversation, was transferred to the local surgeon. In this way, a real-time, long-distance collaboration can occur. This system was used for 20 neuroendoscopic surgeries in various cities in China and even across countries (Boston, Massachusetts, to Jingzhou, China). Its simplicity and practicality have been recognized by both parties, and there were no technically related complications recorded. CONCLUSIONS: The MIMIT system allows for real-time, long-distance telecollaborative neuroendoscopic procedures and surgical training through a commercially available and inexpensive system. It enables remote experts to implement real-time, long-distance intraoperative interaction to guide inexperienced local surgeons, thus integrating the best medical resources and possibly promoting both diagnosis and treatment. Moreover, it can popularize and improve neurosurgical endoscopy technology in more hospitals to benefit more patients, as well as more neurosurgeons.

Smartphone navigated endoscopic port surgery of hypertensive basal ganglia hemorrhage.

OBJECTIVE: Endoscopic port surgery is a promising alternative for the surgical treatment of intracerebral hypertensive basal ganglia hemorrhage (HBGH). The precise location of hematoma is a crucial step for surgery. The authors developed a simple, low-cost navigation method using an Android smartphone for the localization of HBGH. METHODS: All patients' CT DICOM data were processed with an open-source software (3D Slicer). The volume of hematoma, angle, and length of trajectory were calculated automatically. A smartphone running the Android system and the Compass APP was used to help insert the inner introducer. An endoscopic port system was applied to create a working channel for neuro-endoscopic hematoma evacuation. RESULTS: There were 27 patients enrolled in this study (mean age 56). All patients underwent successful surgical evacuation of HBGH with neuroendoscopic evacuation. The mean time taken for the surgical plan was 4 min. The total operation time from skin incision to final suture was 82.6 min. Compared with standard neuronavigation, mean error of trajectory was 5.1 mm. The mean preoperative hematoma volume was 44.8 ml. The optimal trajectory angle averaged 39.5°and the length was 71 mm. Intraoperative blood loss was about 45 ml. Post-operative hematoma volume was 2.9 ml, and the average evacuation rate was 93.6%. One week after surgery, the mean GCS score was improved from 8.2 to 13.8 (p < 0.01). CONCLUSIONS: This simple, low-cost navigation method using 3D Slicer, an Android smartphone with the Compass APP, helps precisely insert the endoscopic working channel to the desired point, which is crucial for satisfactory evacuation of HBGH.

Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma.

Glioblastoma (GBM) is the deadliest primary brain tumor and is generally resistant to immunotherapy because of severe dysfunction of T cells. Novel treatment options are critically needed to overcome the immunotherapy resistance of GBM. Here we demonstrate that Zika virus (ZIKV) treatment improves the efficacy of anti-PD ligand 1 (PD-L1) immunotherapy in GBM. We found that ZIKV induces a strong pro-inflammatory response and increases CD4+ and CD8+ T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.

A novel 3D-vision-based collaborative robot as a scope holding system for port surgery: a technical feasibility study.

OBJECTIVE: A clear, stable, suitably located vision field is essential for port surgery. A scope is usually held by hand or a fixing device. The former yields fatigue and requires lengthy training, while the latter increases inconvenience because of needing to adjust the scope. Thus, the authors innovated a novel robotic system that can recognize the port and automatically place the scope in an optimized position. In this study, the authors executed a preliminary experiment to test this system's technical feasibility and accuracy in vitro. METHODS: A collaborative robotic (CoBot) system consisting of a mechatronic arm and a 3D camera was developed. With the 3D camera and programmed machine vision, CoBot can search a marker attached to the opening of the surgical port, followed by automatic alignment of the scope's axis with the port's longitudinal axis so that optimal illumination and visual observation can be achieved. Three tests were conducted. In test 1, the robot positioned a laser range finder attached to the robot's arm to align the sheath's center axis. The laser successfully passing through two holes in the port sheath's central axis defined successful positioning. Researchers recorded the finder's readings, demonstrating the actual distance between the finder and the sheath. In test 2, the robot held a high-definition exoscope and relocated it to the setting position. Test 3 was similar to test 2, but a metal holder substituted the robot. Trained neurosurgeons manually adjusted the holder. The manipulation time was recorded. Additionally, a grading system was designed to score each image captured by the exoscope at the setting position, and the scores in the two tests were compared using the rank-sum test. RESULTS: The CoBot system positioned the finder successfully in all rounds in test 1; the mean height errors ± SD were 1.14 mm ± 0.38 mm (downward) and 1.60 mm ± 0.89 mm (upward). The grading scores of images in tests 2 and 3 were significantly different. Regarding the total score and four subgroups, test 2 showed a more precise, better-positioned, and more stable vision field. The total manipulation time in test 2 was 20 minutes, and for test 3 it was 52 minutes. CONCLUSIONS: The CoBot system successfully acted as a robust scope holding system to provide a stable and optimized surgical view during simulated port surgery, providing further evidence for the substitution of human hands, and leading to a more efficient, user-friendly, and precise operation.

Vestibular Schwannomas in Young Patients: A 12-Year Experience in a Single Center.

OBJECTIVE: This study evaluated the characteristics of vestibular schwannomas (VS) in young patients, including clinical features, treatment, prognosis, and histopathologic characteristics. METHODS: We retrospectively reviewed medical records and follow-up data for 36 pediatric patients <21 years of age who were surgically treated for VS in the Chinese PLA General Hospital between 2008 and 2019. RESULTS: Mean patient age was 17.4 years. Mean tumor size was 2.8 cm. Hearing loss (n = 32, 88.9%) and tinnitus (n = 20, 55.6%) were the most common symptoms. Ten patients (27.8%) had impaired facial nerve function after surgery. Gross total resection (GTR) was achieved in 26 cases (72.2%). The median tumor Ki-67 level was 5%. Tumor size was related to incomplete tumor resection (odds ratio, 0.2; 95% confidence interval, 0.1-0.9) and postoperative facial nerve dysfunction (odds ratio, 24.9; 95% confidence interval, 1.2-539.1). Tumor size was nonlinearly associated with prognosis and 2.2 cm corresponded to the inflection point at which the probability of tumor remnant and postoperative facial nerve dysfunction significantly increased. The GTR and low Ki-67 groups achieved better 3-year tumor control rate. Histopathologic findings confirmed the presence of cellular schwannoma subtype in young patients. CONCLUSIONS: Tumor size is an important factor affecting the prognosis of VS in young patients. For large VS, surgical treatment should be the first choice, rather than wait-and-scan. VS in young patients shows high tumor proliferation and a tendency to relapse. The cellular schwannoma subtype requires special attention; an accurate histopathologic diagnosis is necessary for young patients with VS, and a closer follow-up strategy should be adopted for cellular VS.

Three-Dimensional Semantic Segmentation of Pituitary Adenomas Based on the Deep Learning Framework-nnU-Net: A Clinical Perspective.

This study developed and evaluated nnU-Net models for three-dimensional semantic segmentation of pituitary adenomas (PAs) from contrast-enhanced T1 (T1ce) images, with aims to train a deep learning-based model cost-effectively and apply it to clinical practice. METHODS: This study was conducted in two phases. In phase one, two models were trained with nnUNet using distinct PA datasets. Model 1 was trained with 208 PAs in total, and model 2 was trained with 109 primary nonfunctional pituitary adenomas (NFPA). In phase two, the performances of the two models were investigated according to the Dice similarity coefficient (DSC) in the leave-out test dataset. RESULTS: Both models performed well (DSC > 0.8) for PAs with volumes > 1000 mm3, but unsatisfactorily (DSC < 0.5) for PAs < 1000 mm3. CONCLUSIONS: Both nnU-Net models showed good segmentation performance for PAs > 1000 mm3 (75% of the dataset) and limited performance for PAs < 1000 mm3 (25% of the dataset). Model 2 trained with fewer samples was more cost-effective. We propose to combine the use of model-based segmentation for PA > 1000 mm3 and manual segmentation for PA < 1000 mm3 in clinical practice at the current stage.

Virtual endoscopy assisted pure ventriculoscopic resection of cavernomas occluding foramen of Monroe: Technical note and literature review.

OBJECTIVE: Cavernomas at Foramen of Monroe (FoM) are rare cases among the intracranial cavernomas. Pure ventriculoscopic removal of cavernoma at FoM through a single burr hole is challenging and rarely reported. METHODS: We herein introduced the virtual endoscopy (VE) assisted ventriculoscopic resection to treat the cavernomas at FoM. Two cases diagnosed with cavernomas at FoM, a 31-year-old male patient (case 1) and a 26-year-old male patient (case 2), were included. Both of them suffered from headache, nausea and vomiting. The pre-operative MRI revealed masses at the FoM. We reconstructed the VE on a free and open-source platform (3D Slicer) for the pre-surgical evaluation. And then ventriculoscopic operation through a single burr hole was made to remove the cavernomas at FoM. RESULTS: The VE displayed a 14×19×16 mm lesion in case 1 and an 18×20×29 mm lesion in case 2 and both cases revealed some attachment between the lesions and the periventricular tissue. The ventriculoscopic operations indicated by VE were performed to achieve total resection of the cavernomas without neurological deficit. CONCLUSIONS: Although the neuroendoscopic treatment to cavernoma at FoM through a single burr hole was rarely reported among the previous literatures, it was a quite effective and useful method in our cases. And the application of VE before ventriculoscopic operation could help to provide a three-dimensional and panorama view of the intraventricular lesions.

Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth.

Glioma stem-like cells (GSCs) are a subset of tumor cells that initiate malignant growth and promote the therapeutic resistance of glioblastoma, the most lethal primary brain tumor. Ribosome biogenesis is an essential cellular process to maintain cell growth, but its regulatory mechanism in GSCs remains largely unknown. Here, we show that WD repeat domain 12 (WDR12), a component of the Pes1-Bop1 complex (PeBoW), is required for ribosome biogenesis in GSCs. WDR12 is preferentially expressed in GSCs compared to non-stem tumor cells and normal brain cells. High levels of WDR12 are associated with glioblastoma progression and poor prognosis. Silencing WDR12 results in the degradation of PeBoW complex components and prevents the maturation of 28S rRNA, thereby inhibiting ribosome biogenesis in GSCs. Subsequently, WDR12 depletion compromises GSC proliferation, inhibits GSC-derived orthotopic tumor growth, and extends animal survival. Together, our results suggest that WDR12 is crucial for ribosome biogenesis in GSCs, and is thus a potential target for GSC-directed therapy of glioblastoma.

Holographic mixed-reality neuronavigation with a head-mounted device: technical feasibility and clinical application.

OBJECTIVE: The authors aimed to evaluate the technical feasibility of a mixed-reality neuronavigation (MRN) system with a wearable head-mounted device (HMD) and to determine its clinical application and accuracy. METHODS: A semiautomatic registration MRN system on HoloLens smart glasses was developed and tested for accuracy and feasibility. Thirty-seven patients with intracranial lesions were prospectively identified. For each patient, multimodal imaging-based holograms of lesions, markers, and surrounding eloquent structures were created and then imported to the MRN HMD. After a point-based registration, the holograms were projected onto the patient's head and observed through the HMD. The contour of the holograms was compared with standard neuronavigation (SN). The projection of the lesion boundaries perceived by the neurosurgeon on the patient's scalp was then marked with MRN and SN. The distance between the two contours generated by MRN and SN was measured so that the accuracy of MRN could be assessed. RESULTS: MRN localization was achieved in all patients. The mean additional time required for MRN was 36.3 ± 6.3 minutes, in which the mean registration time was 2.6 ± 0.9 minutes. A trend toward a shorter time required for preparation was observed with the increase of neurosurgeon experience with the MRN system. The overall median deviation was 4.1 mm (IQR 3.0 mm-4.7 mm), and 81.1% of the lesions localized by MRN were found to be highly consistent with SN (deviation < 5.0 mm). There was a significant difference between the supine position and the prone position (3.7 ± 1.1 mm vs 5.4 ± 0.9 mm, p = 0.001). The magnitudes of deviation vectors did not correlate with lesion volume (p = 0.126) or depth (p = 0.128). There was no significant difference in additional operating time between different operators (37.4 ± 4.8 minutes vs 34.6 ± 4.8 minutes, p = 0.237) or in localization deviation (3.7 ± 1.0 mm vs 4.6 ± 1.5 mm, p = 0.070). CONCLUSIONS: This study provided a complete set of a clinically applicable workflow on an easy-to-use MRN system using a wearable HMD, and has shown its technical feasibility and accuracy. Further development is required to improve the accuracy and clinical efficacy of this system.

Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance.

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.

The utility of magnetic resonance spectroscopy in frame-less stereotactic needle biopsy of glioma.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) can benefit the differentiation of gliomas preoperative grading and facilitate guiding biopsy. This study was to investigate the optimal metabolite or metabolic ratios of MRS for the biopsy target delineating by using the technique of MRS imaging guided frame-less stereotactic biopsy. METHODS: During a 4 year period between the Sep 2012 and Oct 2016, 57 patients (25 women, 32 men; mean age, 46.4) with histologic diagnosis of glioma, who underwent the 1H-MRS imaging guided frameless stereotactic biopsy, were retrospectively reviewed. The metabolite or metabolic ratios values of MRS was measured. And the sensitivity, specificity, accuracy as well as the area under the curve (AUC) of those parameters for glioma grading are calculated based on the receiver operating characteristic curve (ROC) analysis. RESULTS: 65 stereotactic biopsy samples from 57 patients were histopathologically clarified to HGGs (25) or LGGs (40) for quantitative analysis. The Cho, Cho/NAA and Cho/Cr values of LGGs group were significantly lower than that of HGGs (P = 0.09, 0.001, 0.003), and the NAA value of LGGs group was significantly higher than that of HGGs (P = 0.001). The cutoff value of 3.65 for the Cho/NAA ratio provided the best combination of sensitivity (92.0%), specificity (95.0%), and diagnostic accuracy (93.8%) for identifying glioma grade, which was superior to other parameters. CONCLUSION: The results of our study provided evidence that Cho/NAA ratio had the superior diagnostic performance in distinguishing glioma grade, indicating that the spot of highest Cho/NAA ratio was optimal metabolic targets for spectroscopic guided tissue sampling in homogenous glioma.

The utility of combined neuroendoscopic- and laparoscopic-assisted ventriculo- peritoneal shunt as a treatment for patients with communicating hydrocephalus.

BACKGROUND: Ventriculo-peritoneal shunt (VPS) is one of the routine methods used to treat communicating hydrocephalus. OBJECTIVE: To sum up the clinical effectiveness of ventriculo-peritoneal shunt (VPS), assisted with neuroendoscopy and laparoscopy, for the treatment of patients with communicating hydrocephalus. METHODS: From January 2010 to 2014, we performed VPS surgery on 209 patients with communicating hydrocephalus, using neuroendoscopy and laparoscopy, which helped to implant the shunt catheter in a suitable position in the ventricles and abdominal cavity, respectively. The subsequent survival following the surgery was analyzed using Kaplan-Meier analysis. RESULTS: A total of 209 patients received 255 VPSs or revisions and all the operations were successfully completed. Open operation or oraniotomy was not needed for any technical complications, while 46 revisions were performed. After the operations, 203 patients with communicating hydrocephalus exhibited improvement of symptoms following surgery. The follow-up period ranged from one month to four years; the shunt surgery efficiencies were 91.0%, 86.7%, 83.9%, and 82.0% in the first, second, third, and fourth years, respectively. CONCLUSION: For ventriculo-peritoneal shunt, laparoscopy and neuroendoscopy can help to implant shunt catheter in a suitable position, in the ventricles or abdominal cavity, respectively. Hence, the combination of the two techniques can reduce the failure rate of VPS, and has an obvious impact on survival following the surgery.

Identification of risk factors for poor language outcome in surgical resection of glioma involving the arcuate fasciculus: an observational study.

The arcuate fasciculus is a critical component of the neural substrate of human language function. Surgical resection of glioma adjacent to the arcuate fasciculus likely damages this region. In this study, we evaluated the outcome of surgical resection of glioma adjacent to the arcuate fasciculus under the guidance of magnetic resonance imaging and diffusion tensor imaging, and we aimed to identify the risk factors for postoperative linguistic deficit. In total, 54 patients with primary glioma adjacent to the arcuate fasciculus were included in this observational study. These patients comprised 38 men and 16 women (aged 43 ± 11 years). All patients underwent surgical resenction of glioma under the guidance of magnetic resonance imaging and diffusion tensor imaging. Intraoperative images were updated when necessary for further resection. The gross total resection rate of the 54 patients increased from 38.9% to 70.4% by intraoperative magnetic resonance imaging. Preoperative language function and glioma-to-arcuate fasciculus distance were associated with poor language outcome. Multivariable logistic regression analyses showed that glioma-to-arcuate fasciculus distance was the major independent risk factor for poor outcome. The cutoff point of glioma-to-arcuate fasciculus distance for poor outcome was 3.2 mm. These findings suggest that intraoperative magnetic resonance imaging combined with diffusion tensor imaging of the arcuate fasciculus can help optimize tumor resection and result in the least damage to the arcuate fasciculus. Notably, glioma-to-arcuate fasciculus distance is a key independent risk factor for poor postoperative language outcome. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. S2014-096-01) on October 11, 2014.

Robot-assisted neurosurgery versus conventional treatment for intracerebral hemorrhage: A systematic review and meta-analysis.

The aim of this review is to determine the efficacy and safety of robotic surgery for intracranial hemorrhage (ICH). PICO question was formulated as: whether robot-assisted neurosurgery is more effective and safer than conventional treatment for ICH with respect to drainage time, complications, operation time, extent of evacuation and neurological function improvement. We searched PubMed, Web of Science, Wiley Online, OVID, Embase, Cochrane Library, Clinical Trails, Current Controlled Trials, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), OpenGrey and references of related papers. Key words included robot, robotic, hematoma, hemorrhage and neurosurgery. Then we used Microsoft Excel to collect data. Except from qualitative analysis, we did meta-analysis using Review Manager 5.3. 9 papers were included in qualitative synthesis, 6 in meta-analysis for rebleeding rate and 4 in analysis for operative and drainage time. Qualitative synthesis showed shorter operative time and drainage time, a larger extent of evacuation, better neurological function improvement and less complications in robotic group, while meta-analysis suggested that robot-assisted surgery reduced rebleeding rate compared to other surgical procedures, but whether it is superior to conservative treatment in preventing rebleeding still needs more proof. Meta-analysis for operative and drainage time should be explained cautiously because a significant heterogeneity existed and we supposed that differences in baseline characteristics might influence the results. Finally, we drew a conclusion that robotic neurosurgery is a safe and effective approach which is better than conventional surgery or conservative treatment with respect to rebleeding rate, intracranial infection rate and neurological function improvement.

Applications of cerebrospinal fluid circulating tumor DNA in the diagnosis of gliomas.

OBJECTIVE: The 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was revised to include molecular biomarkers as diagnostic criteria. However, conventional biopsies of gliomas were spatially and temporally limited. This study aimed to determine whether circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) could provide more comprehensive diagnostic information to gliomas. METHODS: Combined with clinical data, we analyzed gene alterations from CSF and tumor tissues of newly diagnosed patients, and detected mutations of ctDNA in recurrent patients. We simultaneously analyzed mutations of ctDNA in different glioma subtypes, and in lower-grade gliomas (LrGG) versus glioblastoma multiforme (GBM). RESULTS: CSF ctDNA mutations had high concordance rates with tumor DNA (tDNA). CSF ctDNA mutations of PTEN and TP53 were commonly detected in recurrent gliomas patients. IDH mutation was detected in most of CSF ctDNA derived from IDH-mutant diffuse astrocytomas, while CSF ctDNA mutations of RB1 and EGFR were found in IDH-wild-type GBM. IDH mutation was detected in LrGG, whereas Rb1 mutation was more commonly detected in GBM. CONCLUSIONS: CSF ctDNA detection can be an alternative method as liquid biopsy in gliomas.

Diagnostic performance of clinical properties and conventional magnetic resonance imaging for determining the IDH1 mutation status in glioblastoma: a retrospective study.

BACKGROUND: Glioblastoma (GBM), the most malignant form of gliomas, is a relatively common primary brain tumor in adults. Preoperative identification of isocitrate dehydrogenase 1 (IDH1) mutations in GBM is of critical prognostic importance. The aim of the present study was to explore the feasibility and diagnostic performance of basic patient information combined with conventional magnetic resonance imaging (MRI) findings for determination of the IDH1 status (mutant vs wild type) in patients with GBM. METHODS: From January 1, 2016 to December 31, 2017, a consecutive series of 50 patients with GBM was retrospectively collected. The patients were divided into two group according to their IDH1 mutation status. Basic information and MRI features were analyzed for the establishment of a diagnostic prediction model using logistic regression. A receiver operating characteristic curve was used to evaluate the diagnostic performance. RESULTS: Patients with IDH1-mutant tumors were younger than those with IDH1-wild type tumors, and exhibited a larger tumor volume. The diagnostic predictive model established by combining age and the tumor size exhibited a sensitivity and specificity of 70% and 93%, respectively. The area under the curve was 0.88, which indicated high diagnostic performance. CONCLUSION: Patient age and tumor volume can be used as indicators of IDH1 mutation status in patients with GBM, with high diagnostic performance for simple evaluations in clinical practice. The combined use of these two indicators can further enhance the diagnostic specificity.