Leveraging the neurosurgical operating room for therapeutic development in NeuroOncology.

Glioblastoma (GBM) remains a disease with a dismal prognosis. For all the hope and promise immunotherapies and molecular targeted therapies have shown for systemic malignancies, these treatments have failed to show any promise in GBM. In this context, the paradigm of investigation of therapeutics for this disease itself must be examined and modifications considered. The unique challenge of the presence of blood-brain and blood-tumor barriers (BBB/BTB) raises questions about both the true levels of systemic drug delivery to the affected tissues. Window-of-opportunity (WoO) trials in neuro-oncology allow for proof-of-concept at the start of a classic phase I-II-III clinical trial progression. For therapeutics that do not have the ability to cross the BBB/BTB, direct delivery into tumor and/or tumor-infiltrated brain in the setting of a surgical procedure can provide a novel route of therapeutic access. These approaches permit neurosurgeons to play a greater role in therapeutic development for brain tumors.

Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases.

BACKGROUND: Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma. METHODS: A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM). Patients with fewer than 3 months follow-up or lacking appropriate imaging were excluded. Demographic information, surgical, and anatomic data were collected. RESULTS: Eight hundred and twenty-seven patients were included in the final review. On multivariate analysis for the entire cohort, female gender, dural-based and intraventricular metastasis, and tumor bordering CSF spaces were associated with increased risk of LMD. Surgical resection was not significant for risk of LMD. On multivariate analysis of patients who have undergone surgical resection of a metastatic tumor, dural-based and intraventricular metastasis, ventricular entry during surgery, and metastasis in the infratentorial space were associated with increased risk of LMD. On multivariate analysis of patients who did not undergo surgery, chemotherapy after initial diagnosis and metastasis bordering CSF spaces were associated with increased risk of LMD. CONCLUSION: In a single-institution cohort of MBM, we found that surgical resection alone did not result in an increased risk of LMD. Anatomical factors such as dural-based and intraventricular metastasis were significant for developing LMD, as well as entry into a CSF space during surgical resection. These data suggest a strong correlation between anatomic location and tumor cell seeding in relation to the development of LMD.

Molecular Classification and Therapeutic Targets in Ependymoma.

Ependymoma is a biologically diverse tumor wherein molecular classification has superseded traditional histological grading based on its superior ability to characterize behavior, prognosis, and possible targeted therapies. The current, updated molecular classification of ependymoma consists of ten distinct subgroups spread evenly among the spinal, infratentorial, and supratentorial compartments, each with its own distinct clinical and molecular characteristics. In this review, the history, histopathology, standard of care, prognosis, oncogenic drivers, and hypothesized molecular targets for all subgroups of ependymoma are explored. This review emphasizes that despite the varied behavior of the ependymoma subgroups, it remains clear that research must be performed to further elucidate molecular targets for these tumors. Although not all ependymoma subgroups are oncologically aggressive, development of targeted therapies is essential, particularly for cases where surgical resection is not an option without causing significant morbidity. The development of molecular therapies must rely on building upon our current understanding of ependymoma oncogenesis, as well as cultivating transfer of knowledge based on malignancies with similar genomic alterations.

The cortical organization of language: distilling human connectome insights for supratentorial neurosurgery.

Connectomics is the production and study of detailed "connection" maps within the nervous system. With unprecedented advances in imaging and high-performance computing, the construction of individualized connectomes for routine neurosurgical use is on the horizon. Multiple projects, including the Human Connectome Project (HCP), have unraveled new and exciting data describing the functional and structural connectivity of the brain. However, the abstraction from much of these data to clinical relevance remains elusive. In the context of preserving neurological function after supratentorial surgery, abstracting surgically salient points from the vast computational data in connectomics is of paramount importance. Herein, the authors discuss four interesting observations from the HCP data that have surgical relevance, with an emphasis on the cortical organization of language: 1) the existence of a motor speech area outside of Broca's area, 2) the eloquence of the frontal aslant tract, 3) the explanation of the medial frontal cognitive control networks, and 4) the establishment of the second ventral stream of language processing. From these connectome observations, the authors discuss the anatomical basis of their insights as well as relevant clinical applications. Together, these observations provide a firm platform for neurosurgeons to advance their knowledge of the cortical networks involved in language and to ultimately improve surgical outcomes. It is hoped that this report encourages neurosurgeons to explore new vistas in connectome-based neurosurgery.

Strategies for posterior-only minimally invasive surgery in thoracolumbar metastatic epidural spinal cord compression.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) is a debilitating sequela of cancer. Here, we evaluated various subtypes of posterior-only minimally invasive spinal (MIS) procedures utilized to address different cancers. METHODS: Within this retrospective review, we analyzed the treatment of thoracolumbar MESCC treated with three MIS techniques: decompression and fusion (Subgroup A), partial corpectomy (Subgroup B), and full corpectomy (Subgroup C). RESULTS: There were 51 patients included in the study; they averaged 58.7 years of age, and 51% were females. Most tumors were in the thoracic spine (51%). The average preoperative Frankel grade was D (62.7%); 69% (35) improved postoperatively. The patients were divided as follows: subgroup A (15 patients = 29.4%), B (19 patients = 37.3%), and C (17 patients = 33.3%). The length of hospitalization was similar (~5.4 days) for all groups. The overall complication rate was 31%, while blood loss was lower in Subgroups A and B versus C. CONCLUSION: Different MIS surgical techniques were utilized in patients with thoracic and/or lumbar MESCC. Interestingly, clinical outcomes were similar between MIS subgroups, in this study, with a trend toward higher complications and greater blood loss associated with those undergoing more aggressive MIS procedures (e.g., full corpectomy and fusion).

Laryngeal manifestations of cranial nerve IX/X compression at the brainstem.

OBJECTIVE: We report an association between lower cranial nerve (CN IX/X) vascular compression at the brainstem with laryngeal symptoms utilizing a stepwise algorithm that systematically evaluates and eliminates all other common etiologies. Our experiences with retromastoid craniectomy with lower cranial nerve (LCN) decompression versus non-neurosurgical treatments are detailed. STUDY DESIGN: Retrospective chart review at a tertiary care academic medical center with follow-up telephone survey. METHODS: Baseline demographics, clinical characteristics, quality-of-life surveys, and treatment outcomes were recorded for patients with laryngeal symptoms associated with LCN compression at the brainstem. RESULTS: Forty-nine patients demonstrated LCN compression at the brainstem on imaging and presented with chief complaints of dysphonia (25 of 49, 51%), chronic cough (19 of 49, 39%), dysphoric breathing (3 of 49, 6%), and dysphagia (2 of 49, 4%). Poor initial scores were noted for Voice-Related Quality of Life (V-RQOL), Reflux Symptom Index, and Glottal Closure Index. Twenty-four patients underwent LCN decompression, of which 21 of 24 (88%) reported partial, near-complete, or complete improvement. Major perioperative complications occurred in four of 24 patients (17%). Patients who had undergone decompression were more likely to obtain complete/near-complete symptom resolution (10 of 24 patients, 42%) compared to those undergoing conservative treatments (2 of 25 patients, 8%) (P = 0.02). V-RQOL scores improved more in surgical patients [mean change score, 33.0 (standard deviation [SD], 31.2) than nonsurgical patients (mean change score 9.6, SD 20.9) (P = 0.03) (mean follow-up 3.0 years, SD 2.0). CONCLUSION: Lower cranial nerve compression at the brainstem should be considered when all other etiologies are excluded. Retromastoid craniectomy with LCN decompression demonstrates an acceptable safety profile. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2105-2111, 2019.

A Novel Surgical Technique for Management of Giant Central Calcified Thoracic Disk Herniations: A Dual Corridor Method Involving Tubular Transthoracic/Retropleural Approach Followed by a Posterior Transdural Diskectomy.

BACKGROUND: Thoracic disk herniations (TDHs) represent only 0.15% to 1.8% of surgically managed disk herniations but have posed a particular challenge to spine surgeons. Numerous surgical approaches have been cited in the literature with varying degrees of success, technical complexity, and complication profiles. OBJECTIVE: To report a case of a combined lateral retropleural and dorsal transdural approach for complex thoracic discectomy. METHODS: In this report, we describe a combined lateral/retropleural and posterior transdural approach for a patient with a giant calcified TDH that was not amenable to safe removal using a single approach. RESULTS: In complex situations such as this, a dual corridor approach allows for improved visualization and maximal resection opportunity and opens up yet another option to address recalcitrant TDH. CONCLUSION: The staged dual corridor approach is safe and represents a further surgical option for extremely difficult TDH.

A Comparison of Diffusion-Weighted Imaging Abnormalities Following Balloon Remodeling for Aneurysm Coil Embolization in the Ruptured vs Unruptured Setting.

BACKGROUND: The prothrombotic milieu seen in subarachnoid hemorrhage (SAH) poses a unique challenge to neurovascular surgeons with regard to device use and microcatheter practice. OBJECTIVE: To determine how demographic factors and balloon practices impact diffusion-weighted imaging (DWI) abnormalities and outcomes in patients with SAH compared to those without (non-SAH). METHODS: We retrospectively analyzed 77 patients with SAH treated by balloon-assisted coiling in a single institution compared with 81 consecutive patients with unruptured aneurysms treated by balloon-assisted coiling at the same institution. Data were collected with regard to demographic factors, procedural and anatomic considerations, and DWI abnormalities on postprocedural magnetic resonance imaging. RESULTS: SAH patients were significantly more likely to have DWI abnormality (75% vs 21%, P < .0001) and had a higher number and volume of DWI (4.0 vs 3.0, P = .0421 and 1.3 vs 0.3 cc, P = .0041) despite similar balloon practices. SAH patients were not more likely to have DWI abnormality in vascular territory distal to the treated aneurysm but had a higher likelihood of DWI in a vascular territory unrelated to the aneurysm (81.5% vs 47.1%, P = .0235). Patients without DWI abnormality were significantly more likely to have a good outcome as defined by modified Rankin Score 0 to 2 (95.6% vs 81.6%, P = .0328). Patients with DWI abnormality more often underwent 4-vessel angiography (70.5% vs 48.0%, P = .0174), but this was not found to be significant on multivariate analysis. CONCLUSION: Balloon-assisted coiling does not result in increased incidence of downstream ischemic events in SAH patients compared to non-SAH patients and is safe in this cohort of patients. Other factors, such as 4-vessel angiography of the SAH milieu itself, may predispose patients to a higher rate of ischemic events.

Balloon-augmented Onyx embolization of cerebral arteriovenous malformations using a dual-lumen balloon: a multicenter experience.

INTRODUCTION: Conventional Onyx embolization of cerebral arteriovenous malformations (AVMs) requires lengthy procedure and fluoroscopy times to form an adequate 'proximal plug' which allows forward nidal penetration while preventing reflux and non-targeted embolization. We review our experience with balloon-augmented Onyx embolization of cerebral AVMs using a dual-lumen balloon catheter technique designed to minimize these challenges. METHODS: Retrospectively acquired data for all balloon-augmented cerebral AVM embolizations performed between 2011 and 2014 were obtained from four tertiary care centers. For each procedure, at least one Scepter C balloon catheter was advanced into the AVM arterial pedicle of interest and Onyx embolization was performed through the inner lumen after balloon inflation via the outer lumen. RESULTS: Twenty patients underwent embolization with the balloon-augmented technique over 24 discreet treatment episodes. There were 37 total arterial pedicles embolized with the balloon-augmented technique, a mean of 1.9 per patient (range 1-5). The treated AVMs were heterogeneous in their location and size (mean 3.3±1.6 cm). Mean fluoroscopy time for each procedure was 48±26 min (28 min per embolized pedicle). Two Scepter C balloon catheter-related complications (8.3% of embolization sessions, 5.4% of pedicles embolized) were observed: an intraprocedural rupture of a feeding pedicle and fracture and retention of a catheter fragment. CONCLUSIONS: This multicenter experience represents the largest reported series of balloon-augmented Onyx embolization of cerebral AVMs. The technique appears safe and effective in the treatment of AVMs, allowing more efficient and controlled injection of Onyx with a decreased risk of reflux and decreased fluoroscopy times.

Cost-effectiveness of antiplatelet therapy to prolong primary patency of hemodialysis graft.

INTRODUCTION: The Dialysis Access Consortium (DAC) study group previously reported that treatment with extended-release dipyridamole plus aspirin (DASA) resulted in a significant but clinically modest improvement in primary unassisted arteriovenous graft (AVG) patency. Utilizing DAC published data, the objective of this study is to evaluate the cost effectiveness of antiplatelet interventions aimed at preventing loss of primary AVG patency in hemodialysis (HD) patients. METHODS: We performed a cost-utility analysis, using a decision analysis tree model with a 12-month time horizon and a third party payer perspective. Interventions included DASA with and without concurrent aspirin, aspirin alone, and no prophylaxis. The modeled population was defined as adult (≥ 18 years of age) end-stage renal disease (ESRD) patients who had undergone placement of a new AVG in the United States. The outcomes were costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios, and net monetary benefit. Probabilities were based upon published studies performed by the DAC Study Group while costs of medications and procedures were drawn from public sources. Utilities of health states were derived from published reports and the Short Form 6D (SF-6D) instrument. RESULTS: Aspirin alone is the most cost effective strategy for AVG pharmacologic prophylaxis, as compared to no prophylaxis or DASA with or without concurrent aspirin. The results are robust on multiple scenario analyses using both deterministic and Monte Carlo probabilistic sensitivity analyses. Accounting for both costs and QALY, using aspirin alone to prevent AVG thrombosis can potentially reduce healthcare costs by $24,679,412 per year compared to no aspirin use, at a willingness-to-pay of $50,000/ QALY. CONCLUSIONS: Aspirin monotherapy compared favorably to other strategies based on cost per QALY. Our findings support the use of aspirin prophylaxis in HD patients with a new AVG who do not have a contraindication to aspirin.