Intratumor injection of CCL21-coupled vault nanoparticles is associated with reduction in tumor volume in an in vivo model of glioma.

PURPOSE: Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM. METHODS: GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS. RESULTS: The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume. CONCLUSIONS: This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.

Outcomes of middle fossa craniotomy for the repair of superior semicircular canal dehiscence.

Superior semicircular canal dehiscence (SSCD) is a rare defect of the arcuate eminence that causes an abnormal connection between the superior semicircular canal and middle cranial fossa. Patients often present with a variety of auditory and vestibular symptoms. Trigger avoidance is the initial strategy, but surgery may be necessary in debilitating cases. We retrospectively reviewed SSCD patients undergoing repair via a middle fossa craniotomy between March 2011 and September 2015. Forty-nine patients undergoing 58 surgeries were identified. Autophony was the most common symptom at presentation (n=44; 90%). Mean follow-up was 10.9months, with 100% of patients reporting resolution of at least one symptom. Aural fullness was the most commonly resolved symptom following surgical repair (n=19/22; 86%). Hearing loss (n=11/25; 44%) and tinnitus (n=11/38; 29%) were the most common symptoms to persist following surgery. The most common symptom to develop after surgery was disequilibrium (n=4/18; 22%). Upon comparing the overall pre-operative and post-operative groups, the number of patients with autophony (p<0.0001), aural fullness (p=0.0006), hearing loss (p=0.0119), disequilibrium (p=0.0002), sound- and pressure-induced vertigo (p<0.0001), and tinnitus (p<0.0001) were significantly different. Improved clinical outcomes were demonstrated in patients undergoing SSCD repair through a middle cranial fossa approach. The most common presenting symptom (autophony) was also most likely to resolve after surgery. Hearing loss is less amenable to surgical correction. Disequilibrium developed in a small number of patients after repair.

Blood transfusion indications in neurosurgical patients: A systematic review.

Neurosurgical procedures can be complicated by significant blood losses that have the potential to decrease tissue perfusion to critical brain tissue. Red blood cell transfusion is used in a variety of capacities both inside, and outside, of the operating room to prevent untoward neurologic damage. However, evidence-based guidelines concerning thresholds and indications for transfusion in neurosurgery remain limited. Consequently, transfusion practices in neurosurgical patients are highly variable and based on institutional experiences. Recently, a paradigm shift has occurred in neurocritical intensive care units, whereby restrictive transfusion is increasingly favored over liberal transfusion but the ideal strategy remains in clinical equipoise. The authors of this study perform a systematic review of the literature with the objective of capturing the changing landscape of blood transfusion indications in neurosurgical patients.

Analyzing the efficacy of frequent sodium checks during hypertonic saline infusion after elective brain tumor surgery.

OBJECTIVE: To assess the utility of frequent sodium checks (every 6h) in patients receiving hypertonic saline (HS) after elective brain tumor surgeries. PATIENTS AND METHODS: A single-institution retrospective review of patients having undergone elective craniotomies for brain tumors and treated with postoperative continuous intravenous infusions of 3% HS was performed. Changes in serum sodium values were analyzed at different time points. The rates of <12.5, 25, and 50cc/h infusions were also examined. Healthcare cost analysis was performed by extrapolating our cohort to the total number of craniotomies performed in the United States. RESULTS: No significant differences among sodium values checked between 0 to 4, 4-6, 6-8, 8-10, and >10h were observed (P=.64). In addition, no differences in serum sodium values among the rates of <12.5, 25, and 50cc/h were found (P=.30). No patients developed symptoms of acute hypernatremia. CONCLUSIONS: Serum sodium values did not significantly change more than 10h after infusion of HS. Further studies are needed to determine the optimal frequency of routine sodium checks to increase the quality of care and decrease healthcare costs.

Utilizing virtual and augmented reality for educational and clinical enhancements in neurosurgery.

Neurosurgery has undergone a technological revolution over the past several decades, from trephination to image-guided navigation. Advancements in virtual reality (VR) and augmented reality (AR) represent some of the newest modalities being integrated into neurosurgical practice and resident education. In this review, we present a historical perspective of the development of VR and AR technologies, analyze its current uses, and discuss its emerging applications in the field of neurosurgery.

Evaluating the utility of a scoring system for lipomas of the cerebellopontine angle.

BACKGROUND: Cerebellopontine angle (CPA) lipomas are rare, benign, slow-growing masses. Resections are considered in symptomatic patients who are refractory to targeted medical therapies, but at those stages the lipomas have often reached considerable sizes and encompass critical neurovascular structures. The objective of this study is to develop and to evaluate the utility of a scoring system for CPA lipomas. The hypothesis is that CPA lipomas with lower scores are probably best managed with early surgery. METHODS: The PubMed database was searched using relevant terms. Data on patient and lipoma characteristics were extracted and used to design a scoring system. CPA lipomas were stratified by scores with corresponding managements and outcomes analyzed. RESULTS: One hundred and seventeen patients with CPA lipomas were identified and 40 CPA lipomas were scored. The remaining CPA lipomas were deficient in data and not scored. No lipomas were scored as 1. Score 2 lipomas (n = 12; 30%) most often underwent serial surveillances (n = 5; 41.6%), with the majority of symptoms remaining unimproved (n = 2; 40%). Patients with score 2 CPA lipomas treated with medical therapies (n = 3; 25%) often experienced symptom resolution (n = 2; 66.6%) (p = 0.0499). Patients with score 2 CPA lipomas undergoing surgical resections (n = 3; 25%) all experienced symptom resolution (n = 3; 100%) (p = 0.0499). Score 3 was most common (n = 16; 40%) and these lipomas were often surgically resected (n = 10; 62.5%). The majority of patients with score 3 CPA lipomas having undergone surgical resections (n = 10; 62.5%) experienced symptom improvement (n = 1; 10%) or resolution (n = 4; 40%). CONCLUSIONS: Score 2 CPA lipomas are smaller and would be deemed non-surgical in general practice. However, our data suggest that these lipomas may benefit from either medical therapies or early surgical resections. The advantages of early surgery are maximal resection, decreased surgical morbidity, and improved symptom relief.

Adjuvant Radiosurgery Versus Serial Surveillance Following Subtotal Resection of Atypical Meningioma: A Systematic Analysis.

BACKGROUND: Atypical meningioma (AM) is an aggressive subtype of meningioma associated with a high recurrence rates (RR) following surgical resection. Recent studies have compared outcomes of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, we systematically analyzed the current literature on AM and compared outcomes of ARS versus SS after STR. METHODS: Embase, PubMed, and Cochrane databases were queried using relevant search terms. Retrospective case series that described patients with AM treated with ARS and SS after STR were included. Tests of proportions were performed to detect significant variations in RR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) between the treatment strategies (ARS vs. SS) and among individual studies. RESULTS: A total of 619 patients (263 in the ARS group and 356 in the SS group) were identified. Mean RR, 5-year PFS, and 5-year OS were 53.5%, 50.3%, and 74.9%, respectively, for ARS versus 89.8%, 19.1%, and 89.8% for SS. RR differed between treatment strategies and ARS studies (P < 0.001), and 5-year PFS differed among treatment strategies, ARS, and SS studies (P < 0.001, P = 0.007, and P < 0.001, respectively). CONCLUSIONS: The data presented here show significant differences in RR and 5-year PFS between ARS and SS, suggesting a potential benefit of ARS. As our understanding of the clinical outcomes of various treatment strategies for AM increases, we also move closer to integrating modalities, such as radiosurgery, into management guidelines.