Michael G. Brandel

Oligodendroglioma resection: a Surveillance, Epidemiology, and End Results (SEER) analysis

OBJECTIVE The available evidence suggests that the clinical benefits of extended resection are limited for chemosensitive tumors, such as primary CNS lymphoma. Oligodendroglioma is generally believed to be more sensitive to chemotherapy than astrocytoma of comparable grades. In this study the authors compare the survival benefit of gross-total resection (GTR) in patients with oligodendroglioma relative to patients with astrocytoma. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) Program (1999-2010) database, the authors identified 2378 patients with WHO Grade II oligodendroglioma (O2 group) and 1028 patients with WHO Grade III oligodendroglioma (O3 group). Resection was defined as GTR, subtotal resection, biopsy only, or no resection. Kaplan-Meier and multivariate Cox regression survival analyses were used to assess survival with respect to extent of resection. RESULTS Cox multivariate analysis revealed that the hazard of dying from O2 and O3 was comparable between patients who underwent biopsy only and GTR (O2: hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.73-1.53; O3: HR 1.18, 95% CI 0.80-1.72). A comprehensive search of the published literature identified 8 articles without compelling evidence that GTR is associated with improved overall survival in patients with oligodendroglioma. CONCLUSIONS This SEER-based analysis and review of the literature suggest that GTR is not associated with improved survival in patients with oligodendroglioma. This finding contrasts with the documented association between GTR and overall survival in anaplastic astrocytoma and glioblastoma. The authors suggest that this difference may reflect the sensitivity of oligodendroglioma to chemotherapy as compared with astrocytomas.

The Association between Psychiatric Comorbidities and Outcomes for Inpatients with Traumatic Brain Injury

It is well established that traumatic brain injury (TBI) is associated with the development of psychiatric disorders. However, the impact of psychiatric disorders on TBI outcome is less well understood. We examined the outcomes of patients who experienced a traumatic subdural hemorrhage and whether a comorbid psychiatric disorder was associated with a change in outcome. A retrospective observational study was performed in the California Office of Statewide Health Planning and Development (OSHPD) and the Nationwide Inpatient Sample (NIS). Patients hospitalized for acute subdural hemorrhage were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Patients with coexisting psychiatric diagnoses were identified. Outcomes studied included mortality and adverse discharge disposition. In OSPHD, diagnoses of depression (OR = 0.64, p < 0.001), bipolar disorder (OR = 0.45, p < 0.05), and anxiety (OR = 0.37, p < 0.001) were associated with reduced mortality during hospitalization for TBI, with a trend toward psychosis (OR = 0.56, p = 0.08). Schizophrenia had no effect. Diagnoses of psychosis (OR = 2.12, p < 0.001) and schizophrenia (OR = 2.60, p < 0.001) were associated with increased adverse discharge. Depression and bipolar disorder had no effect, and anxiety was associated with reduced adverse discharge (OR = 0.73, p = 0.01). Results were confirmed using the NIS. Analysis revealed novel associations between coexisting psychiatric diagnoses and TBI outcomes, with some subgroups having decreased mortality and increased adverse discharge. Potential mechanisms include pharmacological effects of frequently prescribed psychiatric medications, the pathophysiology of individual psychiatric disorders, or under-coding of psychiatric illness in the most severely injured patients. Because pharmacological mechanisms, if validated, might lead to improved outcome in TBI patients, further studies may provide significant public health benefit.

Analysis of a Resident Aesthetic Clinic: Process for Rhinoplasty, Resident Experience, and Patient Satisfaction

Goals/Purpose Plastic surgery residents often desire additional training in rhinoplasty than what is provided by their residency program. The goal of this study was to define and evaluate a specific process used to structure preoperative, intraoperative, and postoperative protocols for rhinoplasty patients in the resident aesthetic clinic (RAC) to enhance qualitative and quantitative experience. Complication rates and patient/resident satisfaction scores were also examined. Methods Resident clinic rhinoplasty patients underwent a well-defined and established process that included patient education and informed consent, preoperative planning in a conference-based session, specific adherence to established surgical techniques, and structured postoperative management and follow-up. This process also included supervision criteria for residents in the operating room and clinical setting. Patient and resident satisfaction at the RAC was evaluated by a Web-based survey. A database of procedural complications and methods was compiled and evaluated. Results Between June 2012 and June 2015, 146 aesthetic resident cases were completed through the University of California, San Diego Residency Aesthetic Surgery Program. Of these cases, 34 (17%) were rhinoplasty procedures. Residents at our institution assisted on an average of 55 rhinoplasty procedures with the faculty and performed an average of 12 rhinoplasty procedures as primary surgeons. The residents surveyed felt that they had a good autonomous experience (P < 0.001), and 90% reported confidence with rhinoplasty. Postoperative complications were recorded and included asymmetry (n = 4, 10.5%), septal perforation (n = 1, 2.6%), and difficulty in breathing (n = 6, 15.8%). There were no patients who experienced infections, and the complication rate requiring revision in the operating room was 0%. Conclusions Optimizing protocols in rhinoplasty in an RAC has allowed for the RAC to flourish in the breadth and complexity of rhinoplasty operations. This has enabled residents to gain a structured and autonomous exposure to rhinoplasty cases. Cases were done with an acceptable complication rate and with good patient and resident satisfaction. This is a unique report in that it provides a structured process for preoperative, intraoperative, and postoperative care in rhinoplasty operations.

Quantification of glioblastoma mass effect by lateral ventricle displacement

Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were determined. Associations with patient survival and tumor genomics were investigated using data from The Cancer Genome Atlas (TCGA). Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not explained by tumor volume, as defined by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which accounted for both age and Karnofsky’s Performance Scale (KPS) (p = 0.006). Glioblastomas with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes associated with tumor invasion. Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.

Markov modeling for the neurosurgeon: a review of the literature and an introduction to cost-effectiveness research

OBJECTIVE Markov modeling is a clinical research technique that allows competing medical strategies to be mathematically assessed in order to identify the optimal allocation of health care resources. The authors present a review of the recently published neurosurgical literature that employs Markov modeling and provide a conceptual framework with which to evaluate, critique, and apply the findings generated from health economics research. METHODS The PubMed online database was searched to identify neurosurgical literature published from January 2010 to December 2017 that had utilized Markov modeling for neurosurgical cost-effectiveness studies. Included articles were then assessed with regard to year of publication, subspecialty of neurosurgery, decision analytical techniques utilized, and source information for model inputs. RESULTS A total of 55 articles utilizing Markov models were identified across a broad range of neurosurgical subspecialties. Sixty-five percent of the papers were published within the past 3 years alone. The majority of models derived health transition probabilities, health utilities, and cost information from previously published studies or publicly available information. Only 62% of the studies incorporated indirect costs. Ninety-three percent of the studies performed a 1-way or 2-way sensitivity analysis, and 67% performed a probabilistic sensitivity analysis. A review of the conceptual framework of Markov modeling and an explanation of the different terminology and methodology are provided. CONCLUSIONS As neurosurgeons continue to innovate and identify novel treatment strategies for patients, Markov modeling will allow for better characterization of the impact of these interventions on a patient and societal level. The aim of this work is to equip the neurosurgical readership with the tools to better understand, critique, and apply findings produced from cost-effectiveness research.

Abstract: A Comparison of Intracranial Volumes in Normal Children and Patients with Metopic Craniosynostosis

PURPOSE: Non-syndromic craniosynostosis is associated with a multitude of language deficits. Early detection and prevention is essential for language remediation in these cohorts. The current standard assessment, the Bayley Scales of Infant Development (BSID), provides little predictive value for long-term development. Auditory event-related potentials (ERPs), in particular the mismatch negativity (MMN), measure passive neurological responses to speech sounds and suggest a promising avenue for analyzing infant speech development, particularly in craniosynostosis. We now provide long-term follow up neurocognitive assessment of patients with midline synostosis (sagittal and metopic) in comparison to BSID and ERP testing in infancy.

Impact of preoperative endovascular embolization on immediate meningioma resection outcomes

OBJECTIVE Preoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection. METHODS Meningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002-2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated. RESULTS Overall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality. CONCLUSIONS Relative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.

Endoscopic surgery for nonsyndromic craniosynostosis: a 16-year single-center experience.

OBJECTIVE In this paper the authors review their 16-year single-institution consecutive patient experience in the endoscopic treatment of nonsyndromic craniosynostosis with an emphasis on careful review of any associated treatment-related complications and methods of complication avoidance, including preoperative planning, intraoperative management, and postoperative care and follow-up. METHODS A retrospective chart review was conducted on all patients undergoing endoscopic, minimally invasive surgery for nonsyndromic craniosynostosis at Rady Childrens Hospital from 2000 to 2015. All patients were operated on by a single neurosurgeon in collaboration with two plastic and reconstructive surgeons as part of the institutions craniofacial team. RESULTS Two hundred thirty-five patients underwent minimally invasive endoscopic surgery for nonsyndromic craniosynostosis from 2000 to 2015. The median age at surgery was 3.8 months. The median operative and anesthesia times were 55 and 105 minutes, respectively. The median estimated blood loss (EBL) was 25 ml (median percentage EBL 4.2%). There were no identified episodes of air embolism or operative deaths. One patient suffered an intraoperative sagittal sinus injury, 2 patients underwent intraoperative conversion of planned endoscopic to open procedures, 1 patient experienced a dural tear, and 1 patient had an immediate reexploration for a developing subgaleal hematoma. Two hundred twenty-five patients (96%) were admitted directly to the standard surgical ward where the median length of stay was 1 day. Eight patients were admitted to the intensive care unit (ICU) postoperatively, 7 of whom had preexisting medical conditions that the team had identified preoperatively as necessitating a planned ICU admission. The 30-day readmission rate was 1.7% (4 patients), only 1 of whom had a diagnosis (surgical site infection) related to their initial admission. Average length of follow-up was 2.8 years (range < 1 year to 13.4 years). Six children (< 3%) had subsequent open procedures for perceived suboptimal aesthetic results, 4 of whom (> 66%) had either coronal or metopic craniosynostosis. No patient in this series either presented with or subsequently developed signs or symptoms of intracranial hypertension. CONCLUSIONS In this large single-center consecutive patient series in the endoscopic treatment of nonsyndromic craniosynostosis, significant complications were avoided, allowing for postoperative care for the vast majority of infants on a standard surgical ward. No deaths, catastrophic postoperative morbidity, or evidence of the development of symptomatic intracranial hypertension was observed.

Management of glioblastoma at safety-net hospitals

BackgroundSafety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival.MethodsThe National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized.ResultsOverall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p < 0.001), GTR (OR = 0.84, p < 0.001), radiation (OR = 0.73, p < 0.001), and chemotherapy (OR = 0.78, p < 0.001) than those treated at LBHs. Patients treated at HBHs had significantly increased 30-day (OR = 1.25, p = 0.031) and 90-day mortality (OR = 1.24, p = 0.001), and reduced overall survival (HR = 1.05, p = 0.039).ConclusionsGBM patients treated at SNHs are less likely to receive standard-of-care therapies and have increased short- and long-term mortality. Additional research is needed to evaluate barriers to providing equitable care for GBM patients at SNHs.

Molecular physiology of contrast enhancement in glioblastomas: An analysis of The Cancer Imaging Archive (TCIA)

The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CEi), the intensity heterogeneity in CE (CEh), and volumetric ratio of CE to necrosis (CEr). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CEi was associated with expression of genes that mediate inflammatory responses. High CEh was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CEr was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.