In Vitro and In Vivo Drug-Response Profiling Using Patient-Derived High-Grade Glioma.

BACKGROUND: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their in vivo microenvironment and their susceptibility to therapies. The aim of the study was to establish a functional drug prediction model utilizing patient-derived GBM tumor samples for in vitro testing of drug efficacy followed by in vivo validation to overcome the disadvantages of a strict pharmacogenomics approach. METHODS: High-throughput in vitro pharmacologic testing of patient-derived GBM tumors cultured as 3D organoids offered a cost-effective, clinically and phenotypically relevant model, inclusive of tumor plasticity and stroma. RNAseq analysis supplemented this 128-compound screening to predict more efficacious and patient-specific drug combinations with additional tumor stemness evaluated using flow cytometry. In vivo PDX mouse models rapidly validated (50 days) and determined mutational influence alongside of drug efficacy. We present a representative GBM case of three tumors resected at initial presentation, at first recurrence without any treatment, and at a second recurrence following radiation and chemotherapy, all from the same patient. RESULTS: Molecular and in vitro screening helped identify effective drug targets against several pathways as well as synergistic drug combinations of cobimetinib and vemurafenib for this patient, supported in part by in vivo tumor growth assessment. Each tumor iteration showed significantly varying stemness and drug resistance. CONCLUSIONS: Our integrative model utilizing molecular, in vitro, and in vivo approaches provides direct evidence of a patient's tumor response drifting with treatment and time, as demonstrated by dynamic changes in their tumor profile, which may affect how one would address that drift pharmacologically.

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability.

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the Oct3/4 network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including Gata6, FoxA2, Sall4, Zic2, H2afJ, Stc1 and Bmi1 were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of Sall4, c-Myc, Mmp1, Mmp9 and Dkk1 genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus, Oct3/4 transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.

Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome.

BACKGROUND: Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. MATERIALS AND METHODS: In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. RESULTS: Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. CONCLUSION: We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS: MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10µL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 µg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.

Factors influencing cage subsidence in anterior cervical corpectomy and discectomy: a systematic review.

PURPOSE: Various factors have been examined in relation to cage subsidence risk, including cage material, cage geometry, bone mineral density, device type, surgical level, bone graft, and patient age. The present study aims to compare and synthesize the literature of both clinical and biomechanical studies to evaluate and present the factors associated with cage subsidence. METHODS: A comprehensive search of the literature from January 2003 to December 2021 was conducted using the PubMed and ScienceDirect databases by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following the screening for inclusion and exclusion criteria, a total of 49 clinical studies were included. Correlations between clinical and biomechanical studies are also discussed. RESULTS: Patients treated with the cage and plate combination had a lower subsidence rate than patients with the stand-alone cage. Overall, Polyetheretherketone material was shown to have a lower subsidence rate than titanium and other materials. The subsidence rate was also higher when the surgery was performed at levels C5-C7 than at levels C2-C5. No significant correlation was found between age and cage subsidence clinically. CONCLUSIONS: Cage subsidence increases the stress on the anterior fixation system and may cause biomechanical instability. Severe cage subsidence decreases the Cobb angle and intervertebral height, which may cause destabilization of the implant system, such as screw/plate loosening or breakage of the screw/plate. Various factors have been shown to influence the risk of cage subsidence. Examining clinical research alongside biomechanical studies offers a more comprehensive understanding of the subject.

Gliomagenesis is orchestrated by the Oct3/4 regulatory network.

Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by developmental hierarchical phenotypic heterogeneity, therapy resistance and recurrent growth. Neural stem cells (NSCs) from human central nervous system (CNS), and glioblastoma stem cells from patient-derived GBM (pdGSC) samples and cultured in both 2D well-plate and 3D monoclonal neurosphere culture system (pdMNCS). The pdMNCS model shows promise to establish a relevant 3D-tumor environment that maintains GBM cells in the stem cell phase within suspended neurospheres. Utilizing the pdMNCS, we examined GBM cell-lines for a wide spectrum of developmental cancer stem cell markers, including the early blastocyst inner-cell mass (ICM)-specific Nanog, Oct3/4,B, and CD133. We observed that MNCS epigenotype is recapitulated using gliomasphere-derived cells. CD133, the marker of GSC is robustly expressed in 3D-gliomaspheres and localized within the plasma membrane compartment. Conversely, gliomasphere cultures grown in conventional 2D culture quickly lost CD133 expression, indicating its variable expression is dependent on cell-culture conditions. Critically, this experiment demonstrates incomplete differentiation of cytoskeleton microtubules and intermediate filaments (IFs) of patient derived cells, similar to commercially available GBM cell lines. Subsequently, in order to determine whether Oct3/4 it was necessary for CD133 expression and cancer stemness, we transfected 2D and 3D culture with siRNA against Oct3/4 and found a significant reduction in gliomasphere formation. These results suggest that expression of Oct3/4,Aand CD133 suppress differentiation of GSCs.

Radiolucent Carbon Fiber-Reinforced Implants for Treatment of Spinal Tumors-Clinical, Radiographic, and Dosimetric Considerations.

The management of spine tumors is multimodal and personalized to each individual patient. Patients often require radiation therapy after surgical fixation. Although titanium implants are used most commonly, they produce significant artifact, leading to decreased confidence in target-volume coverage and normal tissue sparing. Carbon-based materials have been found to have minimal effects on dose perturbation in postoperative radiation therapy and have shown biostability and biocompatibility that are comparable to titanium implants. Using the PubMed and Web of Sciences databases, we conducted a systematic review of carbon-based screw and rod fixation systems in the treatment of spinal tumors. We reviewed clinical studies regarding safety of spine fixation with carbon fiber-reinforced (CFR) implants and biomechanical studies, as well as radiation and dosimetric studies. The radiolucency of CFR-polyether ether ketone implants has the potential to benefit patients with spine tumor. Clinical studies have shown no increase in complications with implementation of CFR-polyether ether ketone implants, and these devices seem to have sufficient stiffness and pullout strength. However, further trials are necessary to determine if there is a clinically significant impact on local tumor control.

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). PATIENTS AND METHODS: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. RESULTS: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007). CONCLUSIONS: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.

Robotic Replica of a Human Spine Uses Soft Magnetic Sensor Array to Forecast Intervertebral Loads and Posture after Surgery.

Cervical disc implants are conventional surgical treatments for patients with degenerative disc disease, such as cervical myelopathy and radiculopathy. However, the surgeon still must determine the candidacy of cervical disc implants mainly from the findings of diagnostic imaging studies, which can sometimes lead to complications and implant failure. To help address these problems, a new approach was developed to enable surgeons to preview the post-operative effects of an artificial disc implant in a patient-specific fashion prior to surgery. To that end, a robotic replica of a person's spine was 3D printed, modified to include an artificial disc implant, and outfitted with a soft magnetic sensor array. The aims of this study are threefold: first, to evaluate the potential of a soft magnetic sensor array to detect the location and amplitude of applied loads; second, to use the soft magnetic sensor array in a 3D printed human spine replica to distinguish between five different robotically actuated postures; and third, to compare the efficacy of four different machine learning algorithms to classify the loads, amplitudes, and postures obtained from the first and second aims. Benchtop experiments showed that the soft magnetic sensor array was capable of precisely detecting the location and amplitude of forces, which were successfully classified by four different machine learning algorithms that were compared for their capabilities: Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Random Forest (RF), and Artificial Neural Network (ANN). In particular, the RF and ANN algorithms were able to classify locations of loads applied 3.25 mm apart with 98.39% ± 1.50% and 98.05% ± 1.56% accuracies, respectively. Furthermore, the ANN had an accuracy of 94.46% ± 2.84% to classify the location that a 10 g load was applied. The artificial disc-implanted spine replica was subjected to flexion and extension by a robotic arm. Five different postures of the spine were successfully classified with 100% ± 0.0% accuracy with the ANN using the soft magnetic sensor array. All results indicated that the magnetic sensor array has promising potential to generate data prior to invasive surgeries that could be utilized to preoperatively assess the suitability of a particular intervention for specific patients and to potentially assist the postoperative care of people with cervical disc implants.

Cervical osteochondroma: surgical planning.

INTRODUCTION: Osteochondromas are benign bone tumors which occur as solitary lesions or as part of the syndrome multiple hereditary exostoses. While most osteochondromas occur in the appendicular skeleton, they can also occur in the spine. Most lesions are asymptomatic however some may encroach on the spinal cord or the nerve roots causing neurological symptoms. While most patients with osteochondromas undergo laminectomy without fusion, laminectomy with fusion is indicated in appropriately selected cases of spinal decompression. CASE PRESENTATION: We present a case of a 32-year-old male with history of multiple hereditary exostoses who presented with symptoms of bilateral upper extremity numbness and complaints of gait imbalance and multiple falls. He reported rapid progression of his symptoms during the 10 days before presentation. Computed tomography of the cervical spine revealed a lobulated bony tumor along the inner margin of the cervical 4 lamina. He underwent cervical 3 and 4 laminectomies, partial cervical 2 and 5 laminectomies and cervical 3-5 mass screw placement. Pathology was consistent with osteochondroma. The patient's symptoms had markedly improved at follow-up. CONCLUSION: According to our literature review, osteochondromas most commonly occur at cervical 2 and cervical 5. We present a case of an osteochondroma at a less common level, cervical 4. While most osteochondromas are addressed with laminectomy without arthrodesis, the decision of whether arthrodesis is necessary should be considered in all patients with osteochondroma as with any cervical decompression.

Clinical Efficacy of Frameless Stereotactic Radiosurgery in the Management of Spinal Metastases From Thyroid Carcinoma.

STUDY DESIGN: A retrospective data review. OBJECTIVE: To evaluate the efficacy of CyberKnife (CK) stereotactic radiosurgery (SRS) for thyroid spinal metastasis (SMs). SUMMARY OF BACKGROUND DATA: Thyroid carcinoma is an infrequent cause of SM. The absolute efficacy of SRS generally and CK in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CK SRS for thyroid SMs. METHODS: A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose and the equivalent total dose in 2 Gy fractions were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan-Meier method. Risk factors for local failure were assessed using multivariate logistic regression. RESULTS: A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (ß-coefficient -27.72, P = 0.01). No complications occurred in the immediate or late follow-up period. CONCLUSION: This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control. LEVEL OF EVIDENCE: 4.

The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG).

Multiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing, efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs.

Report of an Isolated L5 Radiculopathy Caused by an L2-3 Disc Herniation and Review of the Literature.

Intervertebral disc herniation is a common cause of radiculopathy. Disc herniations occurring in the lumbar spine typically affect the nerve root exiting under the pedicle of the vertebral body, one level caudal. However, in rare cases, a disc herniation can cause remote isolated radicular symptoms. The authors present the case of a 70-year-old male who presented with an acute, new-onset, left-sided foot drop, low back pain, and a classic L5 monoradiculopathy. Imaging revealed a large, left-sided paracentral extruded L2-3 disc and the absence of any pathology at the L4/5 level. Although the patient's clinical presentation and imaging did not classically correlate, it was felt that the L2-L3 disc was the etiology of the patient's L5 radiculopathy and a left L2-3 microsurgical discectomy was performed. At the six-week follow-up, his foot drop was near normal, sensation was intact with minimal paresthesias, and he remained pain-free. At the one-year follow-up, he experienced full resolution of his foot drop and remained symptom-free. Although rare, disc herniations may cause isolated, remote, painful mononeuropathies not related to the direct level of nerve root compression and should be considered along with other etiologies of peripheral neuropathies.

Induction chemoradiotherapy versus chemotherapy alone for superior sulcus lung cancer.

OBJECTIVES: Although treatment of superior sulcus tumors with induction chemoradiotherapy (CRT) followed by surgery employed in the Intergroup INT-0160 trial is widely adopted as a standard of care, there may be significant associated morbidity and mortality. We describe our experience using standard and alternative induction regimens to assess survival rates and treatment toxicity in these patients. MATERIALS AND METHODS: Electronic medical records of all patients who underwent multimodality treatment including resection of lung cancer invading the superior pulmonary sulcus between 1994 and 2016 were retrospectively reviewed. Multivariable Cox Proportional Hazards model was constructed. RESULTS: Of 102 consecutive patients, 53 (52%) underwent induction CRT, 34 (33%) underwent induction chemotherapy only (Ch) followed by adjuvant radiotherapy, and 15 (15%) underwent no induction therapy followed by adjuvant therapy. There were 2 postoperative deaths (1.9%). To date, 42 patients are alive with a median follow-up 72.5 months. Overall 5-year survival rate was 45.4%. Survival was significantly influenced by age, FEV1, positive resection margins, surgical complications, but not the induction regimen. CRT resulted in higher complete pathological response rate than Ch: 38% vs. 3% (p < 0.001). CRT was associated with higher post-operative re-intubation rate: 13% vs. 0% (p = 0.03). CONCLUSIONS: Our single-institutional experience indicated that while induction CRT produced greater complete pathological response than Ch, it also increased the risk of post-operative complications. With careful patient selection, induction Ch followed by adjuvant radiotherapy may provide comparable survival outcomes to induction CRT. Since induction Ch is associated with lower risk of complications, it may be a particularly desirable choice for patients with impaired performance status.

Myelopathy from Intradural Extramedullary Metastasis as an Initial Presentation of Metastatic Melanoma.

The incidence of metastatic melanoma (MM) has been steadily rising, and it is the third most common metastatic lesion to the central nervous system (CNS). Spinal intradural extramedullary (IDEM) MM is rare, and it is associated with coexisting or antecedent brain metastasis. Metastatic disease to the CNS is a complication of advanced disease, and it generally occurs months to years after initial diagnosis and treatment. We describe the first case of an initial presentation of MM, presenting as cervical myelopathy secondary to spinal cord compression from IDEM spinal metastasis. Further work-up revealed additional lesions in the temporal lobe and cauda equina region as well as a scalp lesion that was presumed to be the primary site. MM should be considered in the differential of myelopathy secondary to a spinal intradural mass, particularly in those with a history of or risk factors for melanoma.

Unusual Metastasis of Papillary Thyroid Cancer to the Thoracic Spine: A Case Report, New Surgical Management Proposal, and Review of the Literature.

Papillary thyroid carcinoma (PTC) is significantly more common than follicular thyroid carcinoma (FTC), yet FTC has a much higher tendency to metastasize to the spinal column. We present a rare case of a metastatic thoracic spinal column lesion originating from the PTC. Thyroid carcinoma is known to be highly vascular with a significant tendency to hemorrhage during surgical resection. This increased tendency to hemorrhage leads to unanticipated intraoperative risks when the type of cancer is not diagnosed before surgical resection. Complications related to intraoperative bleeding can be prevented by visualization using angiography and preoperative embolization. The type of cancer is ideally diagnosed before tumor resection either by the standard metastatic workup or histologically after the biopsy. However, limitations exist in these methods, therefore, hypervascular tumors such as metastatic thyroid cancer can go undiagnosed until after surgical resection. In addition to our case report, we present a review of the literature regarding diagnostic and treatment strategies for hypervascular thyroid tumors and propose a new algorithm for the surgical management of spinal tumors with an unknown origin for optimization of preoperative and perioperative care.

Minimally Invasive Surgical Techniques for Management of Painful Metastatic and Primary Spinal Tumors.

Patients with metastatic spinal disease are affected by disabling pain. The treatment of spinal metastases is focused on pain reduction and improvement in quality of life. Until recently, many patients with metastatic spinal disease did not qualify as surgical candidates due to the risks of surgery and length of recovery period. However, recent advances in minimally invasive surgery such as kyphoplasty and vertebroplasty allow patients to safely undergo surgery for pain relief with a short recovery period. The studies reviewed here suggest that vertebral augmentation is successful in reducing pain and disability scores in patients with painful metastases and multiple myeloma and are a safe modality to provide lasting pain relief. As the use of kyphoplasty and vertebroplasty for treatment of vertebral metastases is becoming more common, new combinations of cement augmentation with other techniques such as percutaneous pedicle screws and radiofrequency ablation are being explored. The implementation of kyphoplasty and vertebroplasty, in conjunction with other minimally invasive surgical techniques as well as nonsurgical modalities, may lead to the best palliative management of cancer patients with spinal metastases and help them ultimately achieve a better quality of life.

Clinical outcomes from maximum-safe resection of primary and metastatic brain tumors using awake craniotomy.

OBJECTIVE: To retrospectively analyze outcomes in patients undergoing awake craniotomies for tumor resection at our institution in terms of extent of resection, functional preservation and length of hospital stay. PATIENTS AND METHODS: All cases of adults undergoing awake-craniotomy from September 2012-February 2015 were retrospectively reviewed based on an IRB approved protocol. Information regarding patient age, sex, cancer type, procedure type, location, hospital stay, extent of resection, and postoperative complications was extracted. RESULTS: 76 patient charts were analyzed. Resected cancer types included metastasis to the brain (41%), glioblastoma (34%), WHO grade III anaplastic astrocytoma (18%), WHO grade II glioma (4%), WHO grade I glioma (1%), and meningioma (1%). Over a half of procedures were performed in the frontal lobes, followed by temporal, and occipital locations. The most common indication was for motor cortex and primary somatosensory area lesions followed by speech. Extent of resection was gross total for 59% patients, near-gross total for 34%, and subtotal for 7%. Average hospital stay for the cohort was 1.7days with 75% of patients staying at the hospital for only 24h or less post surgery. In the postoperative period, 67% of patients experienced improvement in neurological status, 21% of patients experienced no change, 7% experienced transient neurological deficits, which resolved within two months post op, 1% experienced transient speech deficit, and 3% experienced permanent weakness. CONCLUSIONS: In a consecutive series of 76 patients undergoing maximum-safe resection for primary and metastatic brain tumors, awake-craniotomy was associated with a short hospital stay and low postoperative complications rate.

Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment.

BACKGROUND: Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue. METHODS: Key points on the physiology of CSF as well as the diagnostic and treatment options for hydrocephalus are discussed. RESULTS: Understanding the fundamentals of the production, absorption, dynamics, and pathophysiology of CSF is crucial for addressing hydrocephalus. Shunts and endoscopic third ventriculostomy have changed the therapeutic landscape of hydrocephalus. CONCLUSIONS: The treatment of hydrocephalus in adults and children represents a large part of everyday practice for the neurologist, both in benign cases and cancer-related diagnoses.