Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells.

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Validation of real-time inside-out tracking and depth realization technologies for augmented reality-based neuronavigation.

PURPOSE: Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. METHODS: We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. RESULTS: Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. CONCLUSIONS: The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.

A 3-month survival model after Gamma Knife surgery in patients with brain metastasis from lung cancer with Karnofsky performance status ≤ 70.

Gamma Knife surgery (GKS) for brain metastasis (BM) has been generally advocated for patients with a Karnofsky performance status (KPS) scale of ≥ 70. However, some patients with a poor KPS scale of < 70 are recoverable after GKS and show durable survival. A purpose of this study is to devise a 3-month survival prediction model to screen patients with BM with a KPS of ≤ 70 in whom GKS is needed. A retrospective analysis of 67 patients with a KPS scale of 60-70 undergoing GKS for BM of non-small cell lung cancer (NSCLC) from 2016 to 2020 in our institute was performed. Univariate and multivariate logistic regression analyses were performed to investigate factors related to survival for more than 3 months after GKS. The probability (P) prediction model was designed by giving a weight corresponding to the odds ratio of the variables. The overall survival was 9.9 ± 12.7 months (range 0.2-53.2), with a 3-month survival rate of 59.7% (n = 40). In multivariate logistic regression analysis, extracranial disease (ECD) control (p = .033), focal neurological deficit (FND) (p = .014), and cumulative tumor volume (∑ TV) (p = .005) were associated with 3-month survival. The prediction model of 3-month survival (Harrell's C index = 0.767) was devised based on associated factors. In conclusion, GKS for BMs is recommended in selected patients, even if the KPS scale is ≤ 70.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Language Mapping in Brain Tumor Surgery: Validation With Direct Cortical Stimulation and Cortico-Cortical Evoked Potential.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. MATERIALS AND METHODS: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. RESULTS: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). CONCLUSION: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.

Changes of Resection Goal After Using 3-Dimensional Printing Brain Tumor Model for Presurgical Planning.

BACKGROUND: Conventional 2-Dimensional magnetic resonance imaging-based neuronavigation systems can improve the maximal safe resection in brain tumor surgery but can be unintuitive. A 3-Dimensional (3D)-printed brain tumor model allows for a more intuitive and stereoscopic understanding of brain tumors and adjacent neurovascular structures. This study aimed to identify the clinical efficacy of a 3D-printed brain tumor model in presurgical planning by focusing on differences in the extent of resection (EOR). METHODS: Thirty two neurosurgeons (14 faculty members, 11 fellows, 7 residents) randomly selected the two 3D-printed brain tumor models from the 10 manufactured models and performed presurgical planning following a standardized questionnaire. To compare the 2-Dimensional magnetic resonance imaging-based planning results with the 3D-printed model-based planning results, we analyzed the changing patterns and characteristics of the EOR. RESULTS: Of 64 randomly generated cases, the resection goal changed in 12 cases (18.8%). When the tumor was located intra-axially, the surgical posture required a prone position, and when the neurosurgeon was dexterous in surgery, there was a higher rate of EOR changes. 3D-printed models 2, 4, and 10, which all represented tumors in the posterior of the brain, had high rates of changing EOR. CONCLUSIONS: A 3D-printed brain tumor model could be utilized in presurgical planning to effectively determine the EOR.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Optimal mask fixation method for frameless radiosurgery with Leksell Gamma Knife IconTM.

The Leksell Gamma Knife (LGK) IconTM is used for mask-based and frame-based fixation. The mask fixation provides a noninvasive method. However, an optimal mask fixation method is yet to be established. We evaluated the characteristics of three mask fixation methods (Plain, Folded, and Wide) for the LGK IconTM . Force-sensitive resistor sensors were attached to the forehead, supraorbital, zygoma, mandible, and occipital bone of the phantom, and digital humidity and temperature sensors were attached to both temporal lobes. Cone-beam computed tomography (CBCT) and high-definition motion management (HDMM) for each mask fixation method were used to evaluate the phantom motion during the initial application. Subsequently, the mask was removed and reapplied on the second (1st reapplication) and third days (2nd reapplication). In the initial application, forces acting on most portions of the phantom were stabilized within 1.5 h. The largest force acted on the occipital bone for the Plain and Wide methods and on the mandible for the Folded method. The temperature rapidly approaches the initial temperature, whereas the humidity gradually approached the initial humidity in all fixation methods. The Folded method exhibited a significantly lower translation along the Y-axis of the Leksell coordinate system, and rotations along all axes were under 0.5°. The HDMM values remained at 0.1 mm for all fixation methods. In the reapplications, the force acting on the occipital bone was significantly greater than that during the initial application for all mask fixation methods; the temperature and humidity remained unchanged. All mask fixation methods in the 1st reapplication were not significantly different from those in the 2nd reapplication. The Folded method is recommended as an optimal mask fixation for patients who require tight fixation; the Wide method can be considered if patient comfort is a priority.

Avoiding a Collision in Gamma Knife Radiosurgery : A Modified Mask Fixation Method.

OBJECTIVE: The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method. METHODS: This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations. RESULTS: When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation. CONCLUSION: Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.

Development of 3-dimensional printed simulation surgical training models for endoscopic endonasal and transorbital surgery.

Background: Endoscopic skull base surgery (ESBS) is complex, requiring methodical and unremitting surgical training. Herein, we describe the development and evaluation of a novel three-dimensional (3D) printed simulation model for ESBS. We further validate the efficacy of this model as educational support in neurosurgical training. Methods: A patient-specific 3D printed simulation model using living human imaging data was established and evaluated in a task-based hands-on dissection program. Endoscopic endonasal and transorbital procedures were simulated on the model by neurosurgeons and otorhinolaryngology surgeons of varying experience. All procedures were recorded using a high-definition camera coupled with digital video recorder system. The participants were asked to complete a post-procedure questionnaire to validate the efficacy of the model. Results: Fourteen experts and 22 trainees participated in simulations, and the 32 participants completed the post-procedure survey. The anatomical realism was scored as 4.0/5.0. The participants rated the model as helpful in hand-eye coordination training (4.7/5.0) and improving surgical skills (4.6/5.0) for ESBS. All participants believed that the model was useful as educational support for trainees (4.7 [ ± 0.5]). However, the color (3.6/5.0) and soft tissue feedback parameters (2.8/5) scored low. Conclusion: This study shows that high-resolution 3D printed skull base models for ESBS can be generated with high anatomical accuracy and acceptable haptic feedback. The simulation program of ESBS using this model may be supplemental or provide an alternative training platform to cadaveric dissection.

Preservation of language function by mapping the arcuate fasciculus using intraoperative corticocortical evoked potential under general anesthesia in glioma surgery.

OBJECTIVE: Intraoperative language mapping under general anesthesia is imperative for brain tumor surgery because awake surgery is not always feasible. Monitoring corticocortical evoked potential (CCEP) is known to be a useful method for tracking neuronal connectivity and localizing functional areas. The authors evaluated the clinical benefit of intraoperative CCEP monitoring for language function preservation in patients undergoing glioma surgery. METHODS: Between January 2019 and June 2021, the authors performed a total of 29 consecutive glioma surgeries using CCEP monitoring under general anesthesia because of a risk of speech impairment; these were analyzed. Language area mapping was implemented by the anterior language area to posterior language area CCEP method for arcuate fasciculus mapping, and tumor resection was performed while avoiding the localized language areas. Language function before and after surgery was evaluated by the Controlled Oral Word Association Test (COWAT). RESULTS: Intraoperative CCEP was successfully monitored in 25 patients (86.2%), and a valid signal was undetectable in the other 4 patients. Language function evaluation was possible before and after surgery in a total of 20 patients. Overall, the preservation rate of language function was 65.0%, and the deterioration rate was 35.0% after tumor resection with CCEP monitoring. Among those 8 patients with preoperative COWAT scores ≥ 18, 5 patients (62.5%) successfully preserved their language function, with COWAT scores > 18 after tumor resection. Among the 12 patients with preoperative deteriorated language function (COWAT score < 18), 8 patients (66.7%) showed improvement or preserved language function after surgery. CONCLUSIONS: Intraoperative CCEP monitoring of the arcuate fasciculus is an acceptable technology for the preservation of language function under general anesthesia in glioma surgery in patients in whom awake surgery is not feasible.

Navigation of frameless fixation for gamma knife radiosurgery using fixed augmented reality.

Augmented reality (AR) offers a new medical treatment approach. We aimed to evaluate frameless (mask) fixation navigation using a 3D-printed patient model with fixed-AR technology for gamma knife radiosurgery (GKRS). Fixed-AR navigation was developed using the inside-out method with visual inertial odometry algorithms, and the flexible Quick Response marker was created for object-feature recognition. Virtual 3D-patient models for AR-rendering were created via 3D-scanning utilizing TrueDepth and cone-beam computed tomography (CBCT) to generate a new GammaKnife Icon™ model. A 3D-printed patient model included fiducial markers, and virtual 3D-patient models were used to validate registration accuracy. Registration accuracy between initial frameless fixation and re-fixation navigated fixed-AR was validated through visualization and quantitative method. The quantitative method was validated through set-up errors, fiducial marker coordinates, and high-definition motion management (HDMM) values. A 3D-printed model and virtual models were correctly overlapped under frameless fixation. Virtual models from both 3D-scanning and CBCT were enough to tolerate the navigated frameless re-fixation. Although the CBCT virtual model consistently delivered more accurate results, 3D-scanning was sufficient. Frameless re-fixation accuracy navigated in virtual models had mean set-up errors within 1 mm and 1.5° in all axes. Mean fiducial marker differences from coordinates in virtual models were within 2.5 mm in all axes, and mean 3D errors were within 3 mm. Mean HDMM difference values in virtual models were within 1.5 mm of initial HDMM values. The variability from navigation fixed-AR is enough to consider repositioning frameless fixation without CBCT scanning for treating patients fractionated with large multiple metastases lesions (> 3 cm) who have difficulty enduring long beam-on time. This system could be applied to novel GKRS navigation for frameless fixation with reduced preparation time.

Histopathological predictors of progression-free survival in atypical meningioma: a single-center retrospective cohort and meta-analysis.

To determine the prognostic significance of histopathological features included in the diagnostic criteria of atypical meningioma for progression-free survival (PFS). We performed a retrospective cohort study and meta-analysis. Brain invasion, mitotic index, spontaneous necrosis, sheeting, prominent nucleoli, high cellularity, and small cells were the histopathological features of interest. The data from 25 studies involving 3590 patients including our cohort (n = 262) were included. The pooled HR of mitotic index at a cutoff value of 4 showed no statical significance in the gross analysis (pooled HR, 1.09; 95% CI 0.61-1.96; p = 0.7699). Furthermore, it failed to prognosticate PFS in other pooled analyses. For brain invasion, no consistent association with the progression was found in each pooled analysis according to the included studies. Among the remaining five atypical features, spontaneous necrosis, sheeting, and prominent nucleoli showed a significant correlation with PFS in the gross analysis. In the analysis that pooled the HRs from the multivariate analyses, only spontaneous necrosis had significant association with PFS. The available evidence supports that the current cutoff value of mitotic index for diagnosing atypical meningioma might be improper to have prognostic value. The prognostic significance of brain invasion also needs further evaluation.

Development of an inside-out augmented reality technique for neurosurgical navigation.

OBJECTIVE: With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)-based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system. METHODS: The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature-detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed. RESULTS: ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos. CONCLUSIONS: The authors developed a novel inside-out tracking-based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.

Outcomes of the endoscopic endonasal approach for tumors in the third ventricle or invading the third ventricle.

We aimed to retrospectively analyze the surgical and clinical outcomes of the endoscopic endonasal approach (EEA) for tumors in the third ventricle or invading the third ventricle. In total, 82 patients who had undergone surgical treatment using the EEA for tumors involving the third ventricle were enrolled in this study. This cohort study comprised 46 male and 36 female patients. The median age was 37 years (range, 5-76), and the median follow-up duration was 56.5 months (range, 6-117). Seventy-six patients had craniopharyngiomas, and 6 had gangliocytomas, gangliogliomas, astrocytomas, diffuse midline gliomas and lymphomas. Gross total removal was performed in 71 (86.5%) of the 82 patients, subtotal tumor removal in 7 patients and partial removal or biopsy in 4 patients. The pituitary stalk was preserved in 20 cases. Visual function improved in 40 (81.6%) of 49 patients. Endocrine function worsened in 41 (50%) of 82 patients. Hypothalamic function improved in 16 (72.7%) of 22 cases. Postoperative obesity occurred in 3 (20.0%) of 15 children and 11 (23.9%) of 46 adult patients. The postoperative cerebrospinal fluid leakage rate was 3.6%. Postoperative meningitis occurred in 18 (21.9%) cases. Permanent diabetes insipidus was identified in 73 (89.0%) of 82 patients. Tumor recurrence was observed in 10 patients (12%). The EEA appears to be a safe and effective treatment modality for tumors in the third ventricle or involving the third ventricle. However, more cases and long-term follow-up outcomes are required to confirm the clinical efficacy of the EEA.

Multi-Layer Onlay Graft Using Hydroxyapatite Cement Placement without Cerebrospinal Fluid Diversion for Endoscopic Skull Base Reconstruction.

OBJECTIVE: The skull base reconstruction step, which prevents cerebrospinal fluid (CSF) leakage, is one of the most challenging steps in endoscopic skull base surgery (ESS). The purpose of this study was to assess the outcomes and complications of a reconstruction technique for immediate CSF leakage repair using multiple onlay grafts following ESS. METHODS: A total of 230 consecutive patients who underwent skull base reconstruction using multiple onlay grafts with fibrin sealant patch (FSP), hydroxyapatite cement (HAC), and pedicled nasoseptal flap (PNF) for high-flow CSF leakage following ESS at three institutions were enrolled. We retrospectively reviewed the medical and radiological records to analyze the preoperative features and postoperative results. RESULTS: The diagnoses included craniopharyngioma (46.8%), meningioma (34.0%), pituitary adenoma (5.3%), chordoma (1.6%), Rathke's cleft cyst (1.1%) and others (n=21, 11.2%). The trans-planum/tuberculum approach (94.3%) was the most commonly adapted surgical method, followed by the trans-sellar and transclival approaches. The third ventricle was opened in 78 patients (41.5%). Lumbar CSF drainage was not performed postoperatively in any of the patients. Postoperative CSF leakage occurred in four patients (1.7%) due to technical mistakes and were repaired with the same technique. However, postoperative meningitis occurred in 13.5% (n=31) of the patients, but no microorganisms were identified. The median latency to the diagnosis of meningitis was 8 days (range, 2-38). CSF leakage was the unique risk factor for postoperative meningitis (p<0.001). CONCLUSION: The use of multiple onlay grafts with FSP, HAC, and PNF is a reliable reconstruction technique that provides immediate and complete CSF leakage repair and mucosal grafting on the skull base without the need to harvest autologous tissue or perform postoperative CSF diversion. However, postoperative meningitis should be monitored carefully.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1.

BACKGROUND: There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As 'diffuse midline glioma' was recently defined, and there was no international guideline, trials and guidelines of 'diffuse intrinsic pontine glioma' or 'brain stem glioma' were thoroughly reviewed first. RESULTS: The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma's protocol is recommended. CONCLUSION: The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1.

BACKGROUND: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. RESULTS: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. CONCLUSION: The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

Clinical application of patient-specific 3D printing brain tumor model production system for neurosurgery.

The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.