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Ankush Chandra, Jonathan W. Rick, Cecilia Dalle Ore, Darryl Lau, Alan T. Nguyen, Diego Carrera, Alexander Bonte, Annette M. Molinaro, Philip V. Theodosopoulos, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM.

METHODS

This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors’ institution (2007–2015).

RESULTS

Of the 354 patients (median age 61 years, and 37.6% were females), 32 (9.0%) had no insurance, whereas 322 (91.0%) had insurance, of whom 131 (40.7%) had Medicare, 45 (14%) had Medicaid, and 146 (45.3%) had private insurance. On average, insured patients survived almost 2-fold longer (p < 0.0001) than those who were uninsured, whereas differences between specific insurance types did not influence survival. The adjusted hazard ratio (HR) for death was higher in uninsured patients (HR 2.27 [95% CI 1.49–3.33], p = 0.0003). Age, mean household income, tumor size at diagnosis, and extent of resection did not differ between insured and uninsured patients, but there was a disparity in primary care physician (PCP) status—none of the uninsured patients had PCPs, whereas 72% of insured patients had PCPs. Postoperative adjuvant treatment rates with temozolomide (TMZ) and radiation therapy (XRT) were significantly less in uninsured (TMZ in 56.3%, XRT in 56.3%) than in insured (TMZ in 75.2%, XRT in 79.2%; p = 0.02 and p = 0.003) patients. Insured patients receiving both agents had better prognosis than uninsured patients receiving the same treatment (9.1 vs 16.34 months; p = 0.025), suggesting that the survival effect in insured patients could only partly be explained by higher treatment rates. Moreover, having a PCP increased survival among the insured cohort (10.7 vs 16.1 months, HR 1.65 [95% CI 1.27–2.15]; p = 0.0001), which could be explained by significant differences in tumor diameter at initial diagnosis between patients with and without PCPs (4.3 vs 4.8 cm, p = 0.003), and a higher rate of clinical trial enrollment, suggesting a critical role of PCPs for a timelier diagnosis of GBM and proactive cancer care management.

CONCLUSIONS

Access to health care is a strong determinant of prognosis in newly diagnosed patients with GBM. Any type of insurance coverage and having a PCP improved prognosis in this patient cohort. Higher rates of treatment with TMZ plus XRT, clinical trial enrollment, fewer comorbidities, and early diagnosis may explain survival disparities. Lack of health insurance or a PCP are major challenges within the health care system, which, if improved upon, could favorably impact the prognosis of patients with GBM.

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Darryl Lau, Andrew K. Chan, Vedat Deverin and Christopher P. Ames

OBJECTIVE

Adult spinal deformity (ASD) develops in the setting of asymmetrical arthritic degeneration, and can also be due to iatrogenic causes, such as prior surgery. Many patients who present with ASD have undergone prior spine surgery with instrumentation. Unfortunately, contemporary studies that evaluate the effect of prior surgery or instrumentation on perioperative outcomes, readmission rates, and need for reoperation are lacking.

METHODS

All ASD patients who underwent a 3-column osteotomy performed by the senior author at the authors’ institution for correction of thoracolumbar spinal deformity between 2006 and 2016 were identified. The authors compared surgical outcomes between primary (first-time) and revision cases. Further subgroup analysis was conducted to investigate the effect of the number of prior surgeries (0, 1, 2, 3, 4, and 5 or more) and the presence of spinal instrumentation on outcomes. Multivariate analysis was used to adjust for relevant and significant confounders.

RESULTS

A total of 300 patients were included; 38.3% of patients were male. The overall perioperative complication rate was 24.7%, and the mean length of hospitalization was 8.2 days. The 90-day readmission rate was 9.0%, and the overall follow-up reoperation rate was 26.7%. There were no significant differences in complication rates (26.6% vs 24.0%, p = 0.645), length of hospitalization (8.7 vs 7.9 days, p = 0.229), readmission rates (11.4% vs 8.1%, p = 0.387), or reoperation rates (26.6% vs 26.7%, p = 0.984) between primary and revision cases. There was no significant difference in wound complications (infections/dehiscence) requiring reoperation (5.1% vs 6.3%, p = 0.683). Subgroup analysis conducted to evaluate the effect of the number of prior spinal surgeries or the presence of spinal instrumentation did not reveal significant differences for the aforementioned surgical outcomes. In adjusted multivariate analysis, there were no significant associations between history of prior surgery (number of prior surgeries and prior instrumentation) and all of the surgical outcomes of interest.

CONCLUSIONS

The findings from this study suggest that patients who have undergone prior spine surgery with or without instrumentation are not at increased risk for perioperative complications, need for readmission, or reoperation following 3-column osteotomy of the thoracolumbar spine.

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Darryl Lau, Ethan A. Winkler, Khoi D. Than, Dean Chou and Praveen V. Mummaneni

OBJECTIVE

Cervical curvature is an important factor when deciding between laminoplasty and laminectomy with posterior spinal fusion (LPSF) for cervical spondylotic myelopathy (CSM). This study compares outcomes following laminoplasty and LPSF in patients with matched postoperative cervical lordosis.

METHODS

Adults undergoing laminoplasty or LPSF for cervical CSM from 2011 to 2014 were identified. Matched cohorts were obtained by excluding LPSF patients with postoperative cervical Cobb angles outside the range of laminoplasty patients. Clinical outcomes and radiographic results were compared. A subgroup analysis of patients with and without preoperative pain was performed, and the effects of cervical curvature on pain outcomes were examined.

RESULTS

A total of 145 patients were included: 101 who underwent laminoplasty and 44 who underwent LPSF. Preoperative Nurick scale score, pain incidence, and visual analog scale (VAS) neck pain scores were similar between the two groups. Patients who underwent LPSF had significantly less preoperative cervical lordosis (5.8° vs 10.9°, p = 0.018). Preoperative and postoperative C2–7 sagittal vertical axis (SVA) and T-1 slope were similar between the two groups. Laminoplasty cases were associated with less blood loss (196.6 vs 325.0 ml, p < 0.001) and trended toward shorter hospital stays (3.5 vs 4.3 days, p = 0.054). The perioperative complication rate was 8.3%; there was no significant difference between the groups. LPSF was associated with a higher long-term complication rate (11.6% vs 2.2%, p = 0.036), with pseudarthrosis accounting for 3 of 5 complications in the LPSF group. Follow-up cervical Cobb angle was similar between the groups (8.8° vs 7.1°, p = 0.454). At final follow-up, LPSF had a significantly lower mean Nurick score (0.9 vs 1.4, p = 0.014). Among patients with preoperative neck pain, pain incidence (36.4% vs 31.3%, p = 0.629) and VAS neck pain (2.1 vs 1.8, p = 0.731) were similar between the groups. Similarly, in patients without preoperative pain, there was no significant difference in pain incidence (19.4% vs 18.2%, p = 0.926) and VAS neck pain (1.0 vs 1.1, p = 0.908). For laminoplasty, there was a significant trend for lower pain incidence (p = 0.010) and VAS neck pain (p = 0.004) with greater cervical lordosis, especially when greater than 20° (p = 0.011 and p = 0.018). Mean follow-up was 17.3 months.

CONCLUSIONS

For patients with CSM, LPSF was associated with slightly greater blood loss and a higher long-term complication rate, but offered greater neurological improvement than laminoplasty. In cohorts of matched follow-up cervical sagittal alignment, pain outcomes were similar between laminoplasty and LPSF patients. However, among laminoplasty patients, greater cervical lordosis was associated with better pain outcomes, especially for lordosis greater than 20°. Cervical curvature (lordosis) should be considered as an important factor in pain outcomes following posterior decompression for multilevel CSM.

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Ramin A. Morshed, Darryl Lau, Peter P. Sun and Lauren R. Ostling

Choroid plexus papillomas (CPPs) are typically benign tumors that can occur in any age group but are more commonly found in pediatric patients. Although these tumors are benign, there are several reports in adult patients of distant metastases present either at the time of diagnosis or occurring months to years after initial resection. Here, the authors report the case of a 14-year-old boy who presented with symptoms of elevated intracranial pressure due to obstructive hydrocephalus that was caused by a large fourth ventricular mass. Preoperative imaging included a full MRI of the spine, which revealed an intradural lesion that encased the distal sacral nerve roots at the tip of the thecal sac and was concerning for a drop metastasis. The patient underwent gross-total resection of both the fourth ventricular and sacral tumors with histology of both lesions consistent with benign CPP (WHO Grade I). In addition, the authors review prior reports of both pediatric and adult patients in whom benign CPPs have metastasized with either benign or atypical pathology found at a distant site. Taking into account this unusual case and reports in the literature, patients with even benign CPPs may warrant initial and routine follow-up imaging of the total neural axis in search of the rare, but possible, occurrence of drop metastasis.

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Darryl Lau and Dean Chou

OBJECTIVE

During the mini-open posterior corpectomy, percutaneous instrumentation without fusion is performed above and below the corpectomy level. In this study, the authors' goal was to compare the perioperative and long-term implant failure rates of patients who underwent nonfused percutaneous instrumentation with those of patients who underwent traditional open instrumented fusion.

METHODS

Adult patients who underwent posterior thoracic corpectomies with cage reconstruction between 2009 and 2014 were identified. Patients who underwent mini-open corpectomy had percutaneous instrumentation without fusion, and patients who underwent open corpectomy had instrumented fusion above and below the corpectomy site. The authors compared perioperative outcomes and rates of implant failure requiring reoperation between the open (fused) and mini-open (unfused) groups.

RESULTS

A total of 75 patients were identified, and 53 patients (32 open and 21 mini-open) were available for followup. The mean patient age was 52.8 years, and 56.6% of patients were male. There were no significant differences in baseline variables between the 2 groups. The overall perioperative complication rate was 15.1%, and there was no significant difference between the open and mini-open groups (18.8% vs 9.5%; p = 0.359). The mean hospital stay was 10.5 days. The open group required a significantly longer stay than the mini-open group (12.8 vs 7.1 days; p < 0.001). Overall implant failure rates requiring reoperation were 1.9% at 6 months, 9.1% at 1 year, and 14.7% at 2 years. There were no significant differences in reoperation rates between the open and mini-open groups at 6 months (3.1% vs 0.0%, p = 0.413), 1 year (10.7% vs 6.2%, p = 0.620), and 2 years (18.2% vs 8.3%, p = 0.438). The overall mean follow-up was 29.2 months.

CONCLUSIONS

These findings suggest that percutaneous instrumentation without fusion in mini-open transpedicular corpectomies offers similar implant failure and reoperation rates as open instrumented fusion as far out as 2 years of follow-up.

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Edward F. Chang, Jonathan D. Breshears, Kunal P. Raygor, Darryl Lau, Annette M. Molinaro and Mitchel S. Berger

OBJECTIVE

Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site.

METHODS

Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a “classic” or an “atypical” location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis.

RESULTS

Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67–31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22–71.42, p < 0.01), than were patients with classic speech localization.

CONCLUSIONS

This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.

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Darryl Lau, Andrew K. Chan, Alexander A. Theologis, Dean Chou, Praveen V. Mummaneni, Shane Burch, Sigurd Berven, Vedat Deviren and Christopher Ames

OBJECTIVE

Because the surgical strategies for primary and metastatic spinal tumors are different, the respective associated costs and morbidities associated with those treatments likely vary. This study compares the direct costs and 90-day readmission rates between the resection of extradural metastatic and primary spinal tumors. The factors associated with cost and readmission are identified.

METHODS

Adults (age 18 years or older) who underwent the resection of spinal tumors between 2008 and 2013 were included in the study. Patients with intradural tumors were excluded. The direct costs of index hospitalization and 90-day readmission hospitalization were evaluated. The direct costs were compared between patients who were treated surgically for primary and metastatic spinal tumors. The independent factors associated with costs and readmissions were identified using multivariate analysis.

RESULTS

A total of 181 patients with spinal tumors were included (63 primary and 118 metastatic tumors). Overall, the mean index hospital admission cost for the surgical management of spinal tumors was $52,083. There was no significant difference in the cost of hospitalization between primary ($55,801) and metastatic ($50,098) tumors (p = 0.426). The independent factors associated with higher cost were male sex (p = 0.032), preoperative inability to ambulate (p = 0.002), having more than 3 comorbidities (p = 0.037), undergoing corpectomy (p = 0.021), instrumentation greater than 7 levels (p < 0.001), combined anterior-posterior approach (p < 0.001), presence of a perioperative complication (p < 0.001), and longer hospital stay (p < 0.001). The perioperative complication rate was 21.0%. Of this cohort, 11.6% of patients were readmitted within 90 days, and the mean hospitalization cost of that readmission was $20,078. Readmission rates after surgical treatment for primary and metastatic tumors were similar (11.1% vs 11.9%, respectively) (p = 0.880). Prior hospital stay greater than 15 days (OR 6.62, p = 0.016) and diagnosis of lung metastasis (OR 52.99, p = 0.007) were independent predictors of readmission.

CONCLUSIONS

Primary and metastatic spinal tumors are comparable with regard to the direct costs of the index surgical hospitalization and readmission rate within 90 days. The factors independently associated with costs are related to preoperative health status, type and complexity of surgery, and postoperative course.

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Darryl Lau, Shawn L. Hervey-Jumper, Susan Chang, Annette M. Molinaro, Michael W. McDermott, Joanna J. Phillips and Mitchel S. Berger

OBJECT

There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.

METHODS

A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.

RESULTS

A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.

CONCLUSIONS

The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

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Shawn L. Hervey-Jumper, Jing Li, Joseph A. Osorio, Darryl Lau, Annette M. Molinaro, Arnau Benet and Mitchel S. Berger

OBJECT

Though challenging, maximal safe resection of insular gliomas enhances overall and progression-free survival and deters malignant transformation. Previously published reports have shown that surgery can be performed with low morbidity. The authors previously described a Berger-Sanai zone classification system for insular gliomas. Using a subsequent dataset, they undertook this study to validate this zone classification system for predictability of extent of resection (EOR) in patients with insular gliomas.

METHODS

The study population included adults who had undergone resection of WHO Grade II, III, or IV insular gliomas. In accordance with our prior published report, tumor location was classified according to the Berger-Sanai quadrant-style classification system into Zones I through IV. Interobserver variability was analyzed using a cohort of newly diagnosed insular gliomas and independent classification scores given by 3 neurosurgeons at various career stages. Glioma volumes were analyzed using FLAIR and T1-weighted contrast-enhanced MR images.

RESULTS

One hundred twenty-nine procedures involving 114 consecutive patients were identified. The study population from the authors’ previously published experience included 115 procedures involving 104 patients. Thus, the total experience included 244 procedures involving 218 patients with insular gliomas treated at the authors’ institution. The most common presenting symptoms were seizure (68.2%) and asymptomatic recurrence (17.8%). WHO Grade II glioma histology was the most common (54.3%), followed by Grades III (34.1%) and IV (11.6%). The median tumor volume was 48.5 cm3. The majority of insular gliomas were located in the anterior portion of the insula with 31.0% in Zone I, 10.9% in Zone IV, and 16.3% in Zones I+IV. The Berger-Sanai zone classification system was highly reliable, with a kappa coefficient of 0.857. The median EOR for all zones was 85%. Comparison of EOR between the current and prior series showed no change and Zone I gliomas continue to have the highest median EOR. Short- and long-term neurological complications remain low, and zone classification correlated with short-term complications, which were highest in Zone I and in Giant insular gliomas.

CONCLUSIONS

The previously proposed Berger-Sanai classification system is highly reliable and predictive of insular glioma EOR and morbidity.