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Frank J. Attenello, Ian A. Buchanan, Timothy Wen, Daniel A. Donoho, Shirley McCartney, Steven Y. Cen, Alexander A. Khalessi, Aaron A. Cohen-Gadol, Joseph S. Cheng, William J. Mack, Clemens M. Schirmer, Karin R. Swartz, J. Adair Prall, Ann R. Stroink, Steven L. Giannotta and Paul Klimo Jr.

OBJECTIVE

Excessive dissatisfaction and stress among physicians can precipitate burnout, which results in diminished productivity, quality of care, and patient satisfaction and treatment adherence. Given the multiplicity of its harms and detriments to workforce retention and in light of the growing physician shortage, burnout has garnered much attention in recent years. Using a national survey, the authors formally evaluated burnout among neurosurgery trainees.

METHODS

An 86-item questionnaire was disseminated to residents in the American Association of Neurological Surgeons database between June and November 2015. Questions evaluated personal and workplace stressors, mentorship, career satisfaction, and burnout. Burnout was assessed using the previously validated Maslach Burnout Inventory. Factors associated with burnout were determined using univariate and multivariate logistic regression.

RESULTS

The response rate with completed surveys was 21% (346/1643). The majority of residents were male (78%), 26–35 years old (92%), in a stable relationship (70%), and without children (73%). Respondents were equally distributed across all residency years. Eighty-one percent of residents were satisfied with their career choice, although 41% had at some point given serious thought to quitting. The overall burnout rate was 67%. In the multivariate analysis, notable factors associated with burnout included inadequate operating room exposure (OR 7.57, p = 0.011), hostile faculty (OR 4.07, p = 0.008), and social stressors outside of work (OR 4.52, p = 0.008). Meaningful mentorship was protective against burnout in the multivariate regression models (OR 0.338, p = 0.031).

CONCLUSIONS

Rates of burnout and career satisfaction are paradoxically high among neurosurgery trainees. While several factors were predictive of burnout, including inadequate operative exposure and social stressors, meaningful mentorship proved to be protective against burnout. The documented negative effects of burnout on patient care and health care economics necessitate further studies for potential solutions to curb its rise.

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Ian A. Buchanan, Brian Lee, Arun P. Amar and Steven L. Giannotta

Abciximab is a glycoprotein IIb/IIIa receptor antagonist that functions to prevent platelet aggregation, thus reducing thrombus initiation and propagation. It has been widely used during percutaneous endovascular interventions, such as aneurysm coil embolization, angioplasty, atherectomy, and stent placement, as both a preventative and a salvage therapy. The use of abciximab in cardiac and neurosurgical procedures has been associated with a reduced incidence of ischemic complications and a decreased need for repeated intervention. In these settings, abciximab has been delivered transarterially via a microcatheter or infused intravenously for systemic administration. The authors describe novel in situ delivery of abciximab as an agent to dissolve “white clots,” which are composed primarily of platelets, during an intracranial superficial temporal artery to middle cerebral artery bypass in a 28-year-old woman with severe intracranial occlusive disease. Abciximab was able to resolve multiple platelet-based clots after unsuccessful attempts with conventional clot dispersal techniques, such as heparinized saline, tissue plasminogen activator, mechanical passage of a wire through the vessel lumen, and multiple takedowns and re-anastomosis. After abciximab was administered, patency was demonstrated intraoperatively using indocyanine green dye and confirmed postoperatively at 1 and 10 months via CT angiography. The in situ use of abciximab as an agent to disperse a thrombus during intracranial bypass surgery is novel and has not previously been described in the literature, and serves as an additional tool during intracranial vessel bypass surgery.

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Brian Lee, Yvette D. Marquez and Steven L. Giannotta

Lesions of the brainstem pose a technical challenge due to their close proximity to critical vascular structures, neural pathways, and nuclei. Hemangioblastomas are rare lesions of the central nervous system and can cause significant neurological dysfunction, primarily due to enlargement of the cystic component. This is especially relevant when hemangioblastomas occur in eloquent brainstem regions. However, the outcomes after hemangioblastoma resection are good if complete surgical resection of the tumor of the mural nodule, can be achieved. This video demonstrates the excision of a brainstem hemangioblastoma via a left retrosigmoid craniotomy under Stealth guidance.

The video can be found here: http://youtu.be/bCkuaPwMV20.

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Xiao Chang, Lingling Shi, Fan Gao, Jonathan Russin, Liyun Zeng, Shuhan He, Thomas C. Chen, Steven L. Giannotta, Daniel J. Weisenberger, Gabriel Zada, Kai Wang and William J. Mack

Object

Meningiomas are among the most common primary adult brain tumors. Although typically benign, roughly 2%–5% display malignant pathological features. The key molecular pathways involved in malignant transformation remain to be determined.

Methods

Illumina expression microarrays were used to assess gene expression levels, and Illumina single-nucleotide polymorphism arrays were used to identify copy number variants in benign, atypical, and malignant meningiomas (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression data sets generated on Affymetrix microarrays (n = 68, including 6 malignant ones; n = 56, including 3 malignant ones). A weighted gene coexpression network approach was used to identify coexpression modules associated with malignancy.

Results

At the genomic level, malignant meningiomas had more chromosomal losses than atypical and benign meningiomas, with average length of 528, 203, and 34 megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one of the primary chromosomal level abnormalities in all subtypes of meningiomas. At the transcriptome level, the authors identified 23 coexpression modules from the weighted gene coexpression network. Gene functional enrichment analysis highlighted a module with 356 genes that was highly related to tumorigenesis. Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were oncogenic in other cancers such as leukemia. A putative meningioma tumor suppressor MN1 was also identified in this module with differential expression between malignant and benign meningiomas.

Conclusions

The authors' genomic and transcriptome analysis of meningiomas provides novel insights into the molecular pathways involved in malignant transformation of meningiomas, with implications for molecular heterogeneity of the disease.

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Steven L. Giannotta, Lawrence S. Chin and Warren R. Selman

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Gabriel Zada, Parham Yashar, Aaron Robison, Jesse Winer, Alexander Khalessi, William J. Mack and Steven L. Giannotta

Object

Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as “hard” or “soft,” no objective criteria exist for grading, studying, and conveying the consistency of meningiomas.

Methods

The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability.

Results

Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency grade was 0.87 (SE 0.06, 95% CI 0.76–0.99), with 90% user agreement. Kappa analysis scores for minimum and maximum grades of tumor regions were 0.69 (agreement 72%) and 0.75 (agreement 78%), respectively. The kappa analysis score for tumor vascularity grading was 0.56 (agreement 76%). Overall consistency did not correlate with patient age, tumor location, or tumor size. A higher tumor vascularity grade was associated with a larger tumor diameter (p = 0.045) and with skull base location (p = 0.02).

Conclusions

The proposed grading system provides a reliable, practical, and objective assessment of meningioma consistency and facilitates communication among providers. This system also accounts for heterogeneity in tumor consistency. With the proposed scale, meningioma consistency can be standardized as groundwork for future studies relating to surgical outcomes, predictability of consistency and vascularity using neuroimaging techniques, and effectiveness of various surgical instruments.

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Shuhan He, Martin H. Pham, Matthew Pease, Gabriel Zada, Steven L. Giannotta, Kai Wang and William J. Mack

Object

A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas.

Methods

The authors performed a review of the current literature to identify the epigenetic modifications associated with the formation and/or progression of meningiomas.

Results

Several epigenomic alterations, mainly pertaining to DNA methylation, have been associated with meningiomas. Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2 (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2, and TGF-β epigenetic modifications allow either upregulation or downregulation of critical pathways for meningioma development, progression, and recurrence.

Conclusions

Genome-wide methylation profiling demonstrated that global hypomethylation correlates with tumor grades and severity. Identification of additional epigenetic changes, such as histone modification and higher-order chromosomal structure, may allow for a more thorough understanding of tumorigenesis and enable future individualized treatment strategies for meningiomas.

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Parham Yashar, Gabriel Zada, Brianna Harris and Steven L. Giannotta

Object

Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve sheath, representing approximately 6%–8% of all newly diagnosed brain tumors, with an annual incidence of 2000–2500 cases in the US. Although most of these lesions are solid, cystic vestibular schwannomas (CVSs) compose 4%–20% of all VSs and are commonly larger at the time of presentation. The authors present their experience with the operative management of CVSs, including surgical approach, extent of resection, and postoperative facial nerve outcomes. The literature pertaining to clinical and histopathological differences between CVSs and their solid counterparts is reviewed.

Methods

The University of Southern California Department of Neurosurgery database was retrospectively reviewed to identify patients who had undergone resection of a VS between 2000 and 2010. One hundred seventy-nine patients with VS were identified. Patients with CVSs were the subject of the present analysis. Diagnosis of a CVS was made based on MRI findings. Clinical and neuroimaging data, including pre- and postoperative assessments and operative notes, were collected and reviewed.

Results

Twenty-three patients, 14 men (61%) and 9 women (39%), underwent 24 operations for CVSs. These patients composed 12.8% of all cases of VS. Patient ages ranged from 28 to 78 years (mean 55 years), and the mean maximal tumor diameter was 3.6 cm (range 2.0–4.0 cm). Patients most frequently presented with headache, hearing loss, vertigo, and dizziness. Preoperative facial numbness was reported in 44% of patients. Among the 24 cases, 13 were treated with retrosigmoid craniotomy and 11 via a translabyrinthine approach. Complete resection was achieved in 11 patients (48%), subtotal resection (STR) in 8 patients (35%), and near-total resection (NTR) in 4 patients (17%). Facial nerve outcomes were available in all except one case. Good facial nerve outcomes (House-Brackmann [HB] Grades I–III) were achieved in 82% of the patients who had undergone either NTR or STR, as compared with 73% of patients who had undergone gross-total resection (GTR; p > 0.05, Fisher exact test). In comparison, 83% of patients with solid VSs had a good HB grade (p = 0.38, Fisher exact test), although this finding did not reach statistical significance. Complications included wound infection (2 patients), delayed CSF leakage (1 patient), and a delayed temporal encephalocele following a translabyrinthine approach and requiring surgical repair (1 patient).

Conclusions

Cystic vestibular schwannoma represents a clinical and surgical entity separate from its solid counterpart, as demonstrated by its more rapid clinical course and early surgical outcomes. Facial nerve grades may correlate with the degree of tumor resection, trending toward poorer grades with more significant resections. Although GTR is recommended whenever possible, performing an STR when facial nerve preservation is in jeopardy to improve facial nerve outcomes is the preferred strategy at the authors' institution.

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Martin H. Pham, Gabriel Zada, Gina M. Mosich, Thomas C. Chen, Steven L. Giannotta, Kai Wang and William J. Mack

Although a majority of meningiomas are benign neoplasms, those occurring at the cranial base may be challenging tumors to treat because of extensive tissue invasion, an inability to achieve gross-total microscopic resection, and local tumor recurrence and/or progression. A more comprehensive understanding of the genetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide novel targets for grading assessments and individualizing molecular therapies for skull base meningiomas. The authors performed a review of the current literature to identify genes that have been associated with the formation and/or progression of meningiomas. Mutations in the NF2 gene have been most commonly implicated in the formation of the majority of meningiomas. Inactivation of other tumor suppressor genes, including DAL-1 and various tissue inhibitors of matrix metalloproteinases, upregulation of several oncogenes including c-sis and STAT3, and signaling dysregulation of pathways such as the Wnt pathway, have each been found to play important, and perhaps, complementary roles in meningioma development, progression, and recurrence. Identification of these genetic factors using genome-wide association studies and high-throughput genomics may provide data for future individualized treatment strategies.

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Steven L. Giannotta and DanieL L. Barrow