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Leonardo Rangel-Castilla, Fangxiang Chen, Lawrence Choi, Justin C. Clark and Peter Nakaji

Object

An optimal entry point and trajectory for endoscopic colloid cyst (ECC) resection helps to protect important neurovascular structures. There is a large discrepancy in the entry point and trajectory in the neuroendoscopic literature.

Methods

Trajectory views from MRI or CT scans used for cranial image guidance in 39 patients who had undergone ECC resection between July 2004 and July 2010 were retrospectively evaluated. A target point of the colloid cyst was extended out to the scalp through a trajectory carefully observed in a 3D model to ensure that important anatomical structures were not violated. The relation of the entry point to the midline and coronal sutures was established. Entry point and trajectory were correlated with the ventricular size.

Results

The optimal entry point was situated 42.3 ± 11.7 mm away from the sagittal suture, ranging from 19.1 to 66.9 mm (median 41.4 mm) and 46.9 ± 5.7 mm anterior to the coronal suture, ranging from 36.4 to 60.5 mm (median 45.9 mm). The distance from the entry point to the target on the colloid cyst varied from 56.5 to 78.0 mm, with a mean value of 67.9 ± 4.8 mm (median 68.5 mm). Approximately 90% of the optimal entry points are located 40–60 mm in front of the coronal suture, whereas their perpendicular distance from the midline ranges from 19.1 to 66.9 mm. The location of the “ideal” entry points changes laterally from the midline as the ventricles change in size.

Conclusions

The results suggest that the optimal entry for ECC excision be located at 42.3 ± 11.7 mm perpendicular to the midline, and 46.9 ± 5.7 mm anterior to the coronal suture, but also that this point differs with the size of the ventricles. Intraoperative stereotactic navigation should be considered for all ECC procedures whenever it is available. The entry point should be estimated from the patient's own preoperative imaging studies if intraoperative neuronavigation is not available. An estimated entry point of 4 cm perpendicular to the midline and 4.5 cm anterior to the coronal suture is an acceptable alternative that can be used in patients with ventriculomegaly.

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Robert C. Rennert, Reid R. Hoshide, Jason W. Signorelli, Deirdre Amaro, Jayson A. Sack, Cameron W. Brennan and Clark C. Chen

The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimens analyzed. Analysis of the 1000+ gliomas profiled by The Cancer Genome Atlas (TCGA) data set revealed one case of chromosome 6 chromothripsis resembling the case described here. This TCGA patient died within 6 months of undergoing tumor resection. Implications of these findings are reviewed in the context of the current literature.

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Brandon A. McCutcheon, Brian R. Hirshman, Brandon C. Gabel, Michael W. Heffner, Logan P. Marcus, Tyler S. Cole, Clark C. Chen, David C. Chang and Bob S. Carter

OBJECTIVE

The subspecialization of neurosurgical practice is an ongoing trend in modern neurosurgery. However, it remains unclear whether the degree of surgeon specialization is associated with improved patient outcomes. The authors hypothesized that a trend toward increased neurosurgeon specialization was associated with improved patient morbidity and mortality rates.

METHODS

The Nationwide Inpatient Sample (NIS) was used (1998–2009). Patients were included in a spinal analysis cohort for instrumented spine surgery involving the cervical spine (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 81.31–81.33, 81.01–81.03, 84.61–84.62, and 84.66) or lumbar spine (codes 81.04–81.08, 81.34–81.38, 84.64–84.65, and 84.68). A cranial analysis cohort consisted of patients receiving a parenchymal excision or lobectomy operation (codes 01.53 and 01.59). Surgeon specialization was measured using unique surgeon identifiers in the NIS and defined as the proportion of a surgeon’s total practice dedicated to cranial or spinal cases.

RESULTS

A total of 46,029 and 231,875 patients were identified in the cranial and spinal analysis cohorts, respectively. On multivariate analysis in the cranial analysis cohort (after controlling for overall surgeon volume, patient demographic data/comorbidities, hospital characteristics, and admitting source), each percentage-point increase in a surgeon’s cranial specialization (that is, the proportion of cranial cases) was associated with a 0.0060 reduction in the log odds of patient mortality (95% CI 0.0034–0.0086) and a 0.0042 reduction in the log odds of morbidity (95% CI 0.0032–0.0052). This resulted in a 15% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of cranial specialization. In the spinal analysis cohort, each percentage-point increase in a surgeon’s spinal specialization was associated with a 0.0122 reduction in the log odds of mortality (95% CI 0.0074–0.0170) and a 0.0058 reduction in the log odds of morbidity (95% CI 0.0049–0.0067). This resulted in a 26.8% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of spinal specialization.

CONCLUSIONS

For both spinal and cranial surgery patient cohorts derived from the NIS database, increased surgeon specialization was significantly and independently associated with improved mortality and morbidity rates, even after controlling for overall case volume.

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Brandon A. McCutcheon, David C. Chang, Logan Marcus, David D. Gonda, Abraham Noorbakhsh, Clark C. Chen, Mark A. Talamini and Bob S. Carter

OBJECT

This study was designed to assess the relationship between insurance status and likelihood of receiving a neurosurgical procedure following admission for either extraaxial intracranial hemorrhage or spinal vertebral fracture.

METHODS

A retrospective analysis of the Nationwide Inpatient Sample (NIS; 1998–2009) was performed. Cases of traumatic extraaxial intracranial hematoma and spinal vertebral fracture were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Within this cohort, those patients receiving a craniotomy or spinal fusion and/or decompression in the context of an admission for traumatic brain or spine injury, respectively, were identified using the appropriate ICD-9 procedure codes.

RESULTS

A total of 190,412 patients with extraaxial intracranial hematoma were identified between 1998 and 2009. Within this cohort, 37,434 patients (19.7%) received a craniotomy. A total of 477,110 patients with spinal vertebral fracture were identified. Of these, 37,302 (7.8%) received a spinal decompression and/or fusion. On multivariate analysis controlling for patient demographics, severity of injuries, comorbidities, hospital volume, and hospital characteristics, uninsured patients had a reduced likelihood of receiving a craniotomy (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.71–0.82) and spinal fusion (OR 0.67, 95% CI 0.64–0.71) relative to insured patients. This statistically significant trend persisted when uninsured and insured patients were matched on the basis of mortality propensity score. Uninsured patients demonstrated an elevated risk-adjusted mortality rate relative to insured patients in cases of extraaxial intracranial hematoma. Among patients with spinal injury, mortality rates were similar between patients with and without insurance.

CONCLUSIONS

In this study, uninsured patients were consistently less likely to receive a craniotomy or spinal fusion for traumatic intracranial extraaxial hemorrhage and spinal vertebral fracture, respectively. This difference persisted after accounting for overall injury severity and patient access to high- or low-volume treatment centers, and potentially reflects a resource allocation bias against uninsured patients within the hospital setting. This information adds to the growing literature detailing the benefits of health reform initiatives seeking to expand access for the uninsured.

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David D. Gonda, Alexander A. Khalessi, Brandon A. McCutcheon, Logan P. Marcus, Abraham Noorbakhsh, Clark C. Chen, David C. Chang and Bob S. Carter

Object

Using a database that enabled longitudinal follow-up, the authors assessed the long-term outcomes of unruptured cerebral aneurysms repaired by clipping or coiling.

Methods

An observational analysis of the California Office of Statewide Health Planning and Development (OSHPD) database, which follows patients longitudinally in time and through multiple hospitalizations, was performed for all patients initially treated for an unruptured cerebral aneurysm in the period from 1998 to 2005 and with follow-up data through 2009.

Results

Nine hundred forty-four cases (36.5%) were treated with endovascular coiling, 1565 cases (60.5%) were surgically clipped, and 76 cases were treated with both coiling and clipping. There was no significant difference in any demographic variable between the two treatment groups except for age (median: 55 years for the clipped group, 58 years for the coiled group, p < 0.001). Perioperative (30-day) mortality was 1.1% in patients with coiled aneurysms compared with 2.3% in those with clipped aneurysms (p = 0.048). The median follow-up was 7 years (range 4–12 years). At the last follow-up, 153 patients (16.2%) in the coiled group had died compared with 244 (15.6%) in the clipped group (p = 0.693). The adjusted hazard ratio for death at the long-term follow-up was 1.14 (95% CI 0.9–1.4, p = 0.282) for patients with endovascularly treated aneurysms. The incidence of intracranial hemorrhage was similar in the two treatment groups (5.9% clipped vs 4.8% coiled, p = 0.276). One hundred ninety-three patients (20.4%) with coiled aneurysms underwent additional hospitalizations for aneurysm repair procedures compared with only 136 patients (8.7%) with clipped aneurysms (p < 0.001). Cumulative hospital costs per patient for admissions involving aneurysm repair procedures were greater in the clipped group (median cost $98,260 vs $81,620, p < 0.001) through the follow-up.

Conclusions

For unruptured cerebral aneurysms, an observed perioperative survival advantage for endovascular coiling relative to that for surgical clipping was lost on long-term follow-up, according to data from an administrative database of patients who were not randomly allocated to treatment type. A cost advantage of endovascular treatment was maintained even though endovascularly treated patients were more likely to undergo subsequent hospitalizations for additional aneurysm repair procedures. Rates of aneurysm rupture following treatment were similar in the two groups.

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Ali A. Alattar, Michael G. Brandel, Brian R. Hirshman, Xuezhi Dong, Kate T. Carroll, Mir Amaan Ali, Bob S. Carter and Clark C. Chen

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.

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Aaron J. Clark, Joy L. Ware, Mike Y. Chen, Martin R. Graf, Timothy E. Van Meter, Wagner G. Dos Santos, Helen L. Fillmore and William C. Broaddus

Object

Wilms tumor 1 (WT1) is overexpressed in many human cancers, including glioblastoma multiforme (GBM). In another study, the authors showed that transient WT1 silencing increases the radiosensitivity of glioma cells. Studies of nonglioma cell lines have demonstrated that WT1 promotes cell proliferation and survival; however, this ability has not been rigorously analyzed in human GBM.

Methods

The authors tested the efficacy of 2 sequences of short hairpin RNA (shRNA) directed against WT1 in U251MG human GBM cells and found that 1 sequence was capable of stably silencing WT1 expression. They then evaluated the effect of WT1 silencing on cellular proliferation, invasion, and in vivo tumor formation.

Results

Stable WT1-shRNA expression significantly decreased the proliferation of U251MG cells in vitro as demonstrated by both an adenosine 5′-triphosphate–based viability assay and tritiated thymidine uptake. Furthermore, stable WT1 silencing caused significantly slower growth after the subcutaneous inoculation of tumor cells in the flanks of athymic nude mice and was associated with an increased latency period.

Conclusions

Data in this study provide proof of the principle that downregulation of WT1 causes decreased tumorigenicity of a GBM cell line in vitro and in vivo and suggest that WT1 is a promising target for novel molecular GBM therapies, perhaps in combination with standard treatment modalities.

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Aaron J. Clark, Wagner G. Dos Santos, Jessica Mccready, Mike Y. Chen, Timothy E. Van Meter, Joy L. Ware, Sharon B. Wolber, Helen Fillmore and William C. Broaddus

Object

The WT1 gene is overexpressed in many types of human cancer. It has been demonstrated that Wilms tumor 1 (WT1) promotes tumor cell proliferation and survival in some cell lines by inhibiting p53-mediated apoptosis; however, this relationship has not been investigated in gliomas. The goal in this study was to characterize the expression pattern of WT1 in human gliomas and to determine if a correlation exists between WT1 expression and p53 status.

Methods

The authors screened nine malignant glioma cell lines, 50 glioblastoma multiforme (GBM) samples, and 16 lower-grade glial tumors for WT1 expression.

Results

Five of nine cell lines, 44 of 50 GBM samples, and 13 of 16 lower-grade gliomas expressed WT1 mRNA on reverse transcriptase polymerase chain reaction (PCR) analysis. Expression of WT1 was not detected in normal astrocytes. Two WT1 isoforms, +/+ and −/+, were expressed in the majority of these samples. Real-time PCR analysis of the GBM cell lines revealed that the level of WT1 mRNA ranged from 6.33 to 214.70 ng per ng 18S ribosomal RNA. The authors screened the GBM samples for p53 mutation by using PCR and single-stranded conformational polymorphism analysis, and they demonstrated an association between WT1 expression and p53 status. Tumors that contained wild-type p53 were significantly more likely to express WT1 than tumors that contained mutant p53.

Conclusions

The presence of WT1 in glioma cell lines and the majority of primary tumor samples and its absence in normal astrocytes support the suggestion that WT1 expression is important in glioma biology.

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Logan P. Marcus, Brandon A. McCutcheon, Abraham Noorbakhsh, Ralitza P. Parina, David D. Gonda, Clark Chen, David C. Chang and Bob S. Carter

Object

Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection.

Methods

The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions.

Results

A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20–1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06–2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20–2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84–8.18).

Conclusions

Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.

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Abraham Noorbakhsh, Jessica A. Tang, Logan P. Marcus, Brandon McCutcheon, David D. Gonda, Craig S. Schallhorn, Mark A. Talamini, David C. Chang, Bob S. Carter and Clark C. Chen

Object

There is limited information on the relationship between patient age and the clinical benefit of resection in patients with glioblastoma. The purpose of this study was to use a population-based database to determine whether patient age influences the frequency that gross-total resection (GTR) is performed, and also whether GTR is associated with survival difference in different age groups.

Methods

The authors identified 20,705 adult patients with glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) registry (1998–2009). Surgical practice patterns were defined by the categories of no surgery, subtotal resection (STR), and GTR. Kaplan-Meier and multivariate Cox regression analyses were used to assess the pattern of surgical practice and overall survival.

Results

The frequency that GTR was achieved in patients with glioblastoma decreased in a stepwise manner as a function of patient age (from 36% [age 18–44 years] to 24% [age ≥ 75]; p < 0.001). For all age groups, glioblastoma patients who were selected for and underwent GTR showed a 2- to 3-month improvement in overall survival (p < 0.001) relative to those who underwent STR. These trends remained true after a multivariate analysis that incorporated variables including ethnicity, sex, year of diagnosis, tumor size, tumor location, and radiotherapy status.

Conclusions

Gross-total resection is associated with improved overall survival, even in elderly patients with glioblastoma. As such, surgical decisions should be individually tailored to the patient rather than an adherence to age as the sole clinical determinant.