Functional Characterization of Brain Tumor-Initiating Cells and Establishment of GBM Preclinical Models that Incorporate Heterogeneity, Therapy, and Sex Differences.

Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4 All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.

NIH funding trends for neurosurgeon-scientists from 1993-2017: Biomedical workforce implications for neurooncology.

INTRODUCTION: Neurosurgeons represent 0.5% of all physicians and currently face a high burden of disease. Physician-scientists are essential to advance the mission of National Academies of Science (NAS) and National Institutes of Health (NIH) through discovery and bench to bedside translation. We investigated trends in NIH neurosurgeon-scientist funding over time as an indicator of physician-scientist workforce training. METHODS: We used NIH Research Portfolio Online Reporting Tools (RePORTER) to extract grants to neurosurgery departments and neurosurgeons from 1993 to 2017. Manual extraction of each individual grant awardee was conducted. RESULTS: After adjusting for U.S. inflation (base year: 1993), NIH funding to neurosurgery departments increased yearly (P < 0.00001). However, neurosurgeon-scientists received significantly less NIH funding compared to scientists (including basic scientists and research only neurosurgeons) (P = 0.09). The ratio of neurosurgeon-scientists to scientists receiving grants was significantly reduced (P = 0.002). Interestingly, the percentage of oncology-related neurosurgery grants significantly increased throughout the study period (P = 0.002). The average number of grants per neurosurgeon-scientists showed an upward trend (P < 0.001); however, the average number of grants for early-career neurosurgeon-scientists, showed a significant downward trend (P = 0.05). CONCLUSION: Over the past 23 years, despite the overall increasing trends in the number of NIH grants awarded to neurosurgery departments overall, the proportion of neurosurgeon-scientists that were awarded NIH grants compared to scientists demonstrates a declining trend. This observed shift is disproportionate in the number of NIH grants awarded to senior level compared to early-career neurosurgeon-scientists, with more funding allocated towards neurosurgical-oncology-related grants.

Cancer Mortality Rates Increasing vs Cardiovascular Disease Mortality Decreasing in the World: Future Implications.

OBJECTIVE: To highlight the current global trends in mortality for cardiovascular disease and cancer. METHODS: The World Health Organization and the World Bank DataBank databases were used to analyze mortality rates for cancer and cardiovascular disease by calculating age-standardized mortality rates (ASRs) from 2000 to 2015 for high-income, upper-middle-income, and lower-middle-income countries. Data for cancer mortality and population for 43 countries representing 5 of the 7 continents (except Australia and Antarctica) were analyzed. RESULTS: From 2000 to 2015, there was an increase in the ASR for cancer for both men and women irrespective of a country's income status, representing an overall 7% increase in cancer ASR (Pearson r, +0.99; P<.00001). We report a higher ASR for cancer in high-income countries than in upper-middle-income and lower-middle-income countries specifically; high-income countries saw a 3% increase in cancer ASR vs +31% for upper-middle-income and +19% for lower-middle-income countries (P<.01). There has been a decrease in the ASR for cardiovascular disease for the 15 years analyzed (P<.00001). In addition, high-income countries had a higher ASR for cardiovascular disease than upper-middle-income countries during the 15-year period (P<.05). CONCLUSION: We suspect that because of early detection and targeted interventions, cardiovascular disease mortality rates have decreased during the past decade. On the basis of our results, cancer mortality rates continue to rise, with the projection of surpassing cardiovascular disease mortality rates in the near future.

The benefits of inferolateral transtubercular route on intradural surgical exposure using the endoscopic endonasal transclival approach.

BACKGROUND: Surgical access to the ventral pontomedullary junction (PMJ) can be achieved through various corridors depending on the location and extension of the lesion. The jugular tubercle (JT), a surgically challenging obstacle to access the PMJ, typically needs to be addressed in transcranial exposures. We describe the endoscopic endonasal transclival approach (EETCA) and its inferolateral transtubercular extension to assess the intradural surgical field gained through JT removal. We also complement the dissections with an illustrative case. METHODS: EETCA was surgically simulated, and the anatomical landmarks were assessed in eight cadaveric heads. Microsurgical dissections were additionally performed along the endoscopic surgical path. Lastly, we present an intraoperative video of the trans-JT approach in a patient with lower clival chordoma. RESULTS: The EETCA allowed adequate extracranial visualization and removal of the JT. The surgical bony window-obtained along the clivus and centered at the JT via the EETCA-measured 11 × 9 × 7 mm. Removal of the JT provided an improved intradural field within the lower third of the cerebellopontine cistern to expose an area bordered by the cranial nerves VII/VIII and flocculus superior and anterior margin of the lateral recess of the fourth ventricle and cranial nerves IX-XI inferiorly, centered on the foramen of Luschka. CONCLUSIONS: Removal of the JT via EETCA improves exposure along the lower third of the cerebellopontine and upper cerebellomedullary cisterns. The inferolateral transtubercular extension of the EETCA provides access to the lateral recess of the fourth ventricle, in combination with the ventral midline pontomedullary region.

Reduced Pain and Opioid Use in the Early Postoperative Period in Patients Undergoing a Frontotemporal Craniotomy under Regional vs General Anesthesia.

INTRODUCTION: This study compares the postsurgical course of frontotemporal craniotomies conducted "awake" under regional anesthesia (RA) versus "asleep" under general anesthesia (GA) to investigate postoperative recovery, pain, opioid use, and anesthesia-related side effects. METHODS: We retrospectively reviewed craniotomies for supratentorial, intra-axial tumors with frontotemporal exposure. Chronic opioid use and emergent cases were excluded. Primary outcomes included pain scores on a 0-10 numerical rating scale, opioid use as oral morphine milligram equivalence, first time to opioid use, nausea, and sedation on the Richmond Agitation and Sedation Scale (RASS). Secondary outcomes included postoperative seizures, Karnofsky Performance Scale (KPS) status, and hospital length of stay (LOS). RESULTS: A total of 91 patients met inclusion criteria: 56 underwent a craniotomy under RA versus 35 under GA. Demographics and operative characteristics were similar between cohorts. A significant reduction in both postoperative pain and opioid use was observed among RA versus GA (first postoperative pain score 2 vs. 5, P < 0.01; postoperative day [POD] 0 median pain score 2.5 vs. 4, P < 0.01; POD 0 mean opioid in mg 14.49 vs. 24.43, P < 0.01). The time until patients requested opioids for pain after surgery was prolonged for RA versus GA [mean 7.23 vs. 3.42 hours, P < 0.01). Somnolence (RASS < 0) on POD 0 was significantly reduced among RA versus GA, with 23% versus 43%. Both cohorts had equivocal postsurgical outcomes such as seizures, KPS, and hospital LOS. CONCLUSIONS: Frontotemporal craniotomy under RA during awake craniotomies provides better pain control, a reduction in opioid use, and less somnolence in the early postoperative period.

A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma.

Clinical scores, molecular markers and cellular phenotypes have been used to predict the clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic assay for the quantification of cell migration and proliferation can categorize patients with glioblastoma according to progression-free survival. We quantified with a composite score the ability of primary glioblastoma cells to proliferate (via the protein biomarker Ki-67) and to squeeze through microfluidic channels, mimicking aspects of the tight perivascular conduits and white-matter tracts in brain parenchyma. The assay retrospectively categorized 28 patients according to progression-free survival (short-term or long-term) with an accuracy of 86%, predicted time to recurrence and correctly categorized five additional patients on the basis of survival prospectively. RNA sequencing of the highly motile cells revealed differentially expressed genes that correlated with poor prognosis. Our findings suggest that cell-migration and proliferation levels can predict patient-specific clinical outcomes.

Inflammatory Mediators in Glioma Microenvironment Play a Dual Role in Gliomagenesis and Mesenchymal Stem Cell Homing: Implication for Cellular Therapy.

Glioblastoma is the most aggressive malignant primary brain tumor, with a dismal prognosis and a devastating overall survival. Despite aggressive surgical resection and adjuvant treatment, average survival remains approximately 14.6 months. The brain tumor microenvironment is heterogeneous, comprising multiple populations of tumor, stromal, and immune cells. Tumor cells evade the immune system by suppressing several immune functions to enable survival. Gliomas release immunosuppressive and tumor-supportive soluble factors into the microenvironment, leading to accelerated cancer proliferation, invasion, and immune escape. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, or umbilical cord are a promising tool for cell-based therapies. One crucial mechanism mediating the therapeutic outcomes often seen in MSC application is their tropism to sites of injury. Furthermore, MSCs interact with host immune cells to regulate the inflammatory response, and data points to the possibility of using MSCs to achieve immunomodulation in solid tumors. Interleukin 1ß, interleukin 6, tumor necrosis factor α, transforming growth factor ß, and stromal cell-derived factor 1 are notably up-regulated in glioblastoma and dually promote immune and MSC trafficking. Mesenchymal stem cells have widely been regarded as hypoimmunogenic, enabling this cell-based administration across major histocompatibility barriers. In this review, we will highlight (1) the bidirectional communication of glioma cells and tumor-associated immune cells, (2) the inflammatory mediators enabling leukocytes and transplantable MSC migration, and (3) review preclinical and human clinical trials using MSCs as delivery vehicles. Mesenchymal stem cells possess innate abilities to migrate great distances, cross the blood-brain barrier, and communicate with surrounding cells, all of which make them desirable "Trojan horses" for brain cancer therapy.

Potential differences between monolingual and bilingual patients in approach and outcome after awake brain surgery.

INTRODUCTION: 20.8% of the United States population and 67% of the European population speak two or more languages. Intraoperative different languages, mapping, and localization are crucial. This investigation aims to address three questions between BL and ML patients: (1) Are there differences in complications (i.e. seizures) and DECS techniques during intra-operative brain mapping? (2) Is EOR different? and (3) Are there differences in the recovery pattern post-surgery? METHODS: Data from 56 patients that underwent left-sided awake craniotomy for tumors infiltrating possible dominant hemisphere language areas from September 2016 to June 2019 were identified and analyzed in this study; 14 BL and 42 ML control patients. Patient demographics, education level, and the age of language acquisition were documented and evaluated. fMRI was performed on all participants. RESULTS: 0 (0%) BL and 3 (7%) ML experienced intraoperative seizures (P = 0.73). BL patients received a higher direct DECS current in comparison to the ML patients (average = 4.7, 3.8, respectively, P = 0.03). The extent of resection was higher in ML patients in comparison to the BL patients (80.9 vs. 64.8, respectively, P = 0.04). The post-operative KPS scores were higher in BL patients in comparison to ML patients (84.3, 77.4, respectively, P = 0.03). BL showed lower drop in post-operative KPS in comparison to ML patients (- 4.3, - 8.7, respectively, P = 0.03). CONCLUSION: We show that BL patients have a lower incidence of intra-operative seizures, lower EOR, higher post-operative KPS and tolerate higher DECS current, in comparison to ML patients.

Detection of after-discharges during intraoperative functional brain mapping in awake brain tumor surgery using a novel high-density circular grid.

OBJECTIVE: To evaluate intraoperative use of a novel high-density circular grid in detecting after-discharges (AD) on electrocorticography (ECoG) during functional brain mapping (FBM). METHODS: FBM during glioma surgery (10/2016 to 5/2019) recorded ADs using a 22-channel circular grid compared to conventional strip electrodes. ADs were analyzed for detection, duration, amplitude, morphology, histology, direction, and clinical signs. RESULTS: Thirty-two patients (mean age 54.2 years; r = 30-75) with glioma (WHO grade II-IV; 20 grade IV) had surgery. ADs during FBM were more likely in patients with wild-type as opposed to IDH-1 mutants (p < 0.0001) using more contacts compared with linear strip electrodes (p = 0.0001). More sensors tended to be involved in ADs detected by the circular grid vs strips (6.61 vs 3.43; p = 0.16) at lower stimulus intensity (3.14 mA vs 4.13 mA; p = 0.09). No difference in the number of cortical stimulations before resection was present (38.9 mA vs 47.9 mA; p = 0.26). ADs longer than 10 seconds were 32.5 seconds (circular grid) vs 58.4 (strips) (p = 0.12). CONCLUSIONS: High-density circular grids detect ADs in 360 degrees during FBM for glioma resection. Provocation of ADs was more likely in patients with wild-type than IDH-1 mutation. SIGNIFICANCE: Circular grids offer high-resolution ECoG during intraoperative FBM for detection of ADs.

Ex vivo virtual and 3D printing methods for evaluating an anatomy-based spinal instrumentation technique for the 12th thoracic vertebra.

INTRODUCTION: Three-dimensional printing and virtual simulation both provide useful methods of patient-specific anatomical modeling for assessing and validating surgical techniques. A combination of these two methods for evaluating the feasibility of spinal instrumentation techniques based on anatomical landmarks has not previously been investigated. MATERIALS AND METHODS: Nineteen anonymized CT scans of the thoracic spine in adult patients were acquired. Maximum pedicle width and height were recorded, and statistical analysis demonstrated normal distributions. The images were converted into standard tessellation language (STL) files, and the T12 vertebrae were anatomically segmented. The intersection of two diagonal lines drawn from the lateral and medial borders of the T12 transverse process (TP) to the lateral border of the pars and inferolateral portion of the TP was identified on both sides of each segmented vertebra. A virtual screw was created and insertion into the pedicle on each side was simulated using the proposed landmarks. The vertebral STL files were then 3D-printed, and 38 pedicles were instrumented according to the individual posterior landmarks used in the virtual investigation. RESULTS: There were no pedicle breaches using the proposed anatomical landmarks for insertion of T12 pedicle screws in the virtual simulation component. The technique was further validated by additive manufacturing of individual T12 vertebrae and demonstrated no breaches or model failures during live instrumentation using the proposed landmarks. CONCLUSIONS: Ex vivo modeling through virtual simulation and 3D printing provides a powerful and cost-effective means of replicating vital anatomical structures for investigation of complex surgical techniques.

Iatrogenic Lumbar Arachnoid Cyst Fenestration for Tethered Cord: 2-Dimensional Operative Video.

Iatrogenic lumbar arachnoid cysts are a rare occurrence after intradural surgery.1,2 To our knowledge, there is only 1 other previous case reported in the literature contributing to a symptomatic tethered cord.3 We present a surgical video (Video 1) demonstrating the history, preoperative workup, and operative technique for exploration and fenestration of a symptomatic iatrogenic lumbar arachnoid cyst with a tethered cord. The patient is a 57-year-old female with a history of a closed neural tube defect with a lipoma that was resected over 20 years before her evaluation. She was lost to follow-up and did not retain any previous medical documentation. She complained of a 2-month history of progressive bilateral lower extremity weakness, leg pain, and worsening of chronic urinary incontinence. Imaging demonstrated a cystic lesion compressing her conus and cauda equina at the L3-4 level. The risks, benefits, and alternatives were discussed, and the patient elected to proceed with surgery. Intraoperative findings demonstrated a complex multiloculated arachnoid cyst with tethering of the conus. The cysts were dissected from the conus and fenestrated, allowing spontaneous flow of cerebrospinal fluid and conus pulsations. Biopsy of the cyst wall confirmed the diagnosis of arachnoid cyst without neoplastic tissue. Due to the presence of multiple loculations, primary pial closure could not be performed. Thus, a circumferential detethering of the conus was performed to ensure complete decompression of the neural elements. Postoperatively, the patient demonstrated improvement in her bilateral lower extremity pain and weakness. Magnetic resonance imaging was scheduled during routine follow-up at 3 months.

Medial Temporal Encephalocele and Medically Intractable Epilepsy: A Tailored Inferior Temporal Lobectomy and Case Report.

BACKGROUND AND IMPORTANCE: Temporal lobe encephaloceles are increasingly recognized as a potential cause of medically refractory epilepsy and surgical treatment has proven effective. Resection of the encephalocele and associated cortex is often sufficient to provide seizure control. However, it is difficult to determine the extent of adjacent temporal lobe that should be resected. We present a case report and our technique of a tailored inferior temporal pole resection. CLINICAL PRESENTATION: A 32-yr-old man with an 11-yr history of medically refractory epilepsy. Prolonged electroencephalography (EEG) revealed frequent left and rare right frontotemporal sharp waves. Numerous seizures were captured with EEG, all of which originated from the left temporal region. Statistical parametric mapping (SPM) subtraction ictal-interictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) demonstrated ictal hyperperfusion in the anterior left temporal lobe. MRI showed 2 encephaloceles in the left anterior temporal lobe with the accompanying bony defects in the floor of the middle cranial fossa apparent on the computed tomography scan. The patient underwent left temporal craniotomy with intraoperative electrocorticography, resection of the encephaloceles, and a tailored inferior temporal lobectomy (IFTL) and repair of the middle fossa defects. At 7 mo follow up he reported seizure-freedom since surgery. CONCLUSION: Resection of temporal encephalocele and adjacent cortex is safe and effective procedure for select patients with medically refractory epilepsy. This video demonstrates our technique which provides a more standardized approach to the resection.

Video-Assisted Bilateral Thoracoscopic Sympathotomy for Palmar Hyperhidrosis.

In this video, we demonstrate a case of a 21-year-old right-handed man who presented with palmar hyperhidrosis. His symptoms started at the age of 4 years and progressively worsened throughout his life. Multiple medical treatments were used without significant benefit. His symptoms worsened to the limit that it affected his work and lifestyle. The patient was taken to the operating room in a supine position with both arms abducted 90°. The right and left chest were prepped and draped in a sterile fashion. The skin incision was done on the left side first, the left lung was isolated, and two 5-mm thoracoports were placed in the sixth and third intercostal spaces, respectively. Carbon dioxide insufflation was used to a pressure of 6 mm Hg for exposure. The chest was visualized, and the sympathetic chain was identified. Ribs were counted and then cautery at a low setting was used. The sympathetic chain was transected at the level of the head of the second rib. Accessory nerves of Kuntz were identified and resected. Carbon dioxide was then evacuated from the left chest using a bronchial tube exchanger and Valsalva maneuver. The lung was completely reinflated and skin was closed in a normal fashion. The same procedure was repeated on the right side. A chest radiograph was obtained intraoperatively, and no pneumothorax was observed. At the end of the procedure, both upper extremity temperature probes showed a significant increase from baseline. Informed patient consent was obtained.

A 360° electronic device for recording high-resolution intraoperative electrocorticography of the brain during awake craniotomy.

OBJECTIVE: Epilepsy is common among patients with supratentorial brain tumors; approximately 40%-70% of patients with glioma develop brain tumor-related epilepsy (BTRE). Intraoperative localization of the epileptogenic zone during surgical tumor resection (real-time data) may improve intervention techniques in patients with lesional epilepsy, including BTRE. Accurate localization of the epileptogenic signals requires electrodes with high-density spatial organization that must be placed on the cortical surface during surgery. The authors investigated a 360° high-density ring-shaped cortical electrode assembly device, called the "circular grid," that allows for simultaneous tumor resection and real-time electrophysiology data recording from the brain surface. METHODS: The authors collected data from 99 patients who underwent awake craniotomy from January 2008 to December 2018 (29 patients with the circular grid and 70 patients with strip electrodes), of whom 50 patients were matched-pair analyzed (25 patients with the circular grid and 25 patients with strip electrodes). Multiple variables were then retrospectively assessed to determine if utilization of this device provides more accurate real-time data and improves patient outcomes. RESULTS: Matched-pair analysis showed higher extent of resection (p = 0.03) and a shorter transient motor recovery period during the hospitalization course (by approximately 6.6 days, p ≤ 0.05) in the circular grid patients. Postoperative versus preoperative Karnofsky Performance Scale (KPS) score difference/drop was greater for the strip electrode patients (p = 0.007). No significant difference in postoperative seizures between the 2 groups was present (p = 0.80). CONCLUSIONS: The circular grid is a safe, feasible tool that grants direct access to the cortical surgical surface for tissue resection while simultaneously monitoring electrical activity. Application of the circular grid to different brain pathologies may improve intraoperative epileptogenic detection accuracy and functional outcomes, while decreasing postoperative complications.

Periodic focal epileptiform discharges.

OBJECTIVE: To report intraoperative periodic focal epileptiform discharges (PFEDs) during awake craniotomy using high-density electrocorticography (HD-ECoG). METHODS: We retrospectively analyzed 81 patients undergoing awake craniotomy between 9/29/2016 and 7/5/2018. Intraoperative HD-ECoG was performed with direct electrocortical stimulation (DECS) for functional brain mapping. Real-time interpretation was performed and compared to scalp EEG when performed. Perioperative seizures, surgical complications, and characteristics of PFEDs were assessed. RESULTS: 69/81 patients (mean age 48.5 years) underwent awake surgery; 55 operated for brain tumor, 11 for epilepsy and 3 for cavernomas. A focal abnormality on brain MRI was present in 63/69 (91.3%) patients. 43/69 (62.3%) patients had seizures preoperatively, 4/69 (5.7%) had seizures during DECS. PFEDs were identified in 11 patients (15.9%); 2 on depth recording and 9 during intraoperative HD-ECoG. 32 patients (46.3%) had preoperative EEG. HD-ECoG detected more epileptiform discharges (EDs) than standard EEG (32/43; 74.4% vs 9/32; 28.1%) (p = <0.001). Of 9/43 patients with PFEDs on HD-ECoG, 7 patients also had scalp EEG but only one case had EDs (p = 0.02), and 0/32 had periodic EDs. CONCLUSIONS: Intraoperative PFEDs are novel, highly focal EDs approximating a single gyrus. In patients with brain tumors, PFEDs did not demonstrate a relationship to pre-operative seizures though has similarities to other common waveforms in patients with epilepsy. SIGNIFICANCE: PFEDs expand our understanding of the interictal-ictal continuum and highlight improved temporo-spatial information obtained from increasing sensor density during intracranial EEG recording.

Potential influence of IDH1 mutation and MGMT gene promoter methylation on glioma-related preoperative seizures and postoperative seizure control.

PURPOSE: To examine the occurrence of glioma-related preoperative seizures (GPS) and post-operative seizure control (PSC) with respect to patients characteristics including five commonly tested tumor molecular markers (TMMs). METHODS: A single-center retrospective cohort study of patients with glioma evaluated at the Mayo Clinic, Florida between 2016 and 2018. RESULTS: 68 adult patients (mean age = 51-years, 45-males) were included. 46 patients had GPS. 57 patients underwent intra-operative electrocorticography during awake craniotomy-assisted glioma resection. All patients underwent glioma resection (53, gross-total resection) with histologies of pilocytic astrocytoma (n = 2), diffuse astrocytoma (n = 4), oligodendroglioma (n = 14), anaplastic astrocytoma (n = 16), anaplastic oligodendroglioma (n = 1), and glioblastoma (n = 31). 31 (67%) patients had PSC (median follow-up = 14.5 months; IQR = 7-16.5 months). IDH1 mutation (IDH1mut) was present in 32, ARTX retention in 53, MGMT gene promotor methylation in 15, 1p/19q co-deletion in 15, and over-expression of p53 in 19 patients. Patients with IDH1mut were more likely to have GPS (p = 0.037) and PSC (p = 0.035) compared to patients with IDH1 wild-type. Patients with MGMT gene promoter methylation were also likely to have PSC (p = 0.032). GPS or PSC did not differ by age, sex, extent of surgery, glioma grade, location, and histopathological subtype, p53 expression, ARTX retention, or 1p/19q co-deletion status. CONCLUSIONS: GPS and PSC may be associated with IDH1 mutation and MGMT gene promoter methylation status but not other glioma characteristics including tumor grade, location, or histopathology. Prospective studies with larger sample size are needed to clarify the exact mechanisms of GPS and PSC by the various TMMs to identify new treatment targets.

The Reliability of YouTube Videos Describing Stereotactic Radiosurgery: A Call for Action.

BACKGROUND: Gamma Knife radiosurgery was introduced in the 1960s and is currently used worldwide. The internet has become a foremost source of information used by patients and their families. In this study, we aim to evaluate the accuracy and reliability of the Gamma Knife radiosurgery-related YouTube videos. METHODS: We searched YouTube and the first 3 pages sorted according to "Relevance-Based Ranking" were included for analysis. Four independent health care workers from different disciplines evaluated the videos using the validated DISCERN tool. RESULTS: Our search resulted in 65,774 videos, and 14 videos met inclusion criteria. Our study found that 50% (7 of 14) of the videos were uploaded by university-affiliated hospitals; 14% of videos scored 3. The search term "Radiosurgery for intraaxial brain lesions" had the highest percentage of moderate videos (DISCERN = 3) (50%). CONCLUSIONS: Patients and caregivers turn to online sources to gather information about the disease. However, the available YouTube published videos are published without proper academic monitoring, as in such a free platform, published videos tend to catch a general audience for different purposes, which leads to diminishing quality control. Academic medical institutions should consider a proper monitoring process for videos to improve the accuracy of the published information for the patients.

Prognostic factors and survival in low grade gliomas of the spinal cord: A population-based analysis from 2006 to 2012.

PURPOSE: Primary spinal cord tumors are rare, and evidence-based management of these patients remains a source of controversy. This study used a large cohort of low-grade spinal cord astrocytomas to determine the effectiveness of prognostic factors and survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify patients with WHO grade I-II primary spinal cord astrocytomas from 1973 to 2012; however, patients before 2006 were excluded due to ambiguity diagnosis. Univariate and multivariate Cox proportional hazard models were created to compare survival across covariates and summarized using the Kaplan-Meier method. RESULTS: A total of 561 patients with low-grade glioma (astrocytoma) were identified. Among these, 15.5% of patients received a gross total resection (GTR), 26.1% subtotal resection (STR), and 46.2% unidentified extent of resection. 59.4% did not receive any radiation therapy at any point of the treatment course, while 40.6% underwent radiation therapy. In our cohort, only patients with GTR demonstrated statistically improved survival (HR: 0.22, P < 0.001). Patients with STR had nearly identical survival compared to patients with no surgery (HR: 0.98), and radiotherapy was associated with increased odds of mortality (HR: 1.47, P < 0.001). Multivariate analysis demonstrated a significant survival benefit among patients with younger age, GTR and absence of radiotherapy. Histologic grade did not statistically impact survival. CONCLUSION: Our study suggests that GTR results in improved survival among patients with low-grade gliomas within the spinal cord. Future, considerable data research efforts will aim to better define the role of radiotherapy and tumor grading in this patient population.

The reliability of YouTube videos in patients education for Glioblastoma Treatment.

BACKGROUND: Glioblastomas (GBMs) are one of the most devastating primary tumors in humans and often results in minimal survival rates. Over the past 2 decades, patients have accessed the internet to obtain information related to their diagnoses. In this study, we aimed to evaluate the accuracy and the reliability of GBM-related YouTube videos. METHODS: In June of 2017, a search was conducted on YouTube using 6 keywords. Videos were sorted using "Relevance-Based Ranking" option, and the first 3 pages for each search were selected for further analysis. Three independent reviewers evaluated the videos using the validated DISCERN Tool. RESULTS: After sorting 23,100 videos, 9 videos were identified and included for analysis. Of the 9 videos analyzed, 88% (8/9) were from hospitals affiliated with prestigious universities across the country. Of the nine videos included in the analysis, two (22%) scored above a 3. There was an average 55% overlap in the videos analyzed by key term and the keyword search of "Malignant Glioma Treatment" had the highest percentage of videos above a score of 3 (66%). CONCLUSION: Many patients with GBM and their families access information on YouTube to familiarize themselves with the epidemiology, survival, and treatment options for this form of tumor. However, the information that is currently available online is not monitored or vetted using an official filtering process prior to its release. Medical institutions must work to produce more peer-reviewed content in order to improve the availability of credible health information on internet platforms.

Comparative Cost Analysis of Endoscopic versus Microscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas.

Objective This study presents a comparative analysis of cost efficacy between the microscopic and endoscopic transsphenoidal approaches, evaluating neurological outcome, extent of resection (EOR), and inpatient hospital costs. Design This study was a retrospective chart review. Setting This study was conducted at a tertiary care center. Participants The study group consisted of 68 patients with transsphenoidal surgeries between January 2007 and January 2014. Main Outcome Measures Two-sample t -tests and Pearson's chi-square test evaluated inpatient costs, quality-adjusted life years (QALYs), volumetric EOR, and neurological outcomes. Results Total inpatient costs per patient was $22,853 in the microscopic group and less ($19,736) in the endoscopic group ( p = 0.049). Operating room costs were $5,974 in the microscopic group and lower in the endoscopic group ($5,045; p = 0.038). Operative time was 203.6 minutes in the microscopic group and 166.3 minutes in the endoscopic group ( p = 0.032). The QALY score, length of hospital stay, and postoperative outcomes were found to be similar between the two cohorts. Multivariate linear regression modeling suggested that length of stay ( p < 0.001) and operative time ( p = 0.008) were important factors that influenced total inpatient costs following transsphenoidal surgery. Conclusion This study shows that transsphenoidal surgery is more cost effective with the endoscopic approach than with the microscopic approach and depends on efficiency in the operating room as well as reduction in the length of hospitalization.