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Ziya L. Gokaslan, Julie E. York, Garrett L. Walsh, Ian E. McCutcheon, Frederick F. Lang, Joe B. Putnam Jr., David M. Wildrick, Stephen G. Swisher, Dima Abi-Said and Raymond Sawaya

Object. Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Methods. Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

Conclusions. These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

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Akash J. Patel, Dima Suki, Mustafa Aziz Hatiboglu, Hiba Abouassi, Weiming Shi, David M. Wildrick, Frederick F. Lang and Raymond Sawaya

Object

Local recurrence (LR) of a resected brain metastasis occurs in up to 46% of patients. Postoperative whole-brain radiation therapy (WBRT) reduces that incidence. To isolate factors associated with the risk of LR after resection, the authors only studied patients who did not receive adjuvant radiotherapy.

Methods

The authors reviewed data from 570 cases involving patients who had undergone resection of a previously untreated single brain metastasis at The University of Texas M. D. Anderson Cancer Center between 1993 and 2006 without receiving postoperative WBRT. All tumors were measured preoperatively on MR images. The resection method (en bloc resection [EBR] or piecemeal resection [PMR]) was noted at the time of surgery. Predictors of LR were assessed using the Cox proportional hazards model.

Results

The median patient age was 58 years, 55% were male, and 88% had a Karnofsky Performance Scale Score ≥ 80. The most common primary cancers were those of the lung (28%), skin (melanoma, 21%), kidney (19%), and breast (11%). Piecemeal resection was performed in 201 patients (35%) and EBR in 369 (65%). Local recurrence developed in 84 patients (15%). The histological type of the primary cancer did not significantly predict LR; however, 7 of 22 patients with sarcoma developed LR (p = 0.16). The authors identified 2 variables that increased the risk of LR. Undergoing PMR carried a significantly higher LR risk than EBR (crude hazard ratio [HR] 1.7, 95% CI 1.1–2.6, p = 0.03). Tumors exceeding the median volume (9.7 cm3) had a significantly higher LR risk than those that were < 9.7 cm3 (crude HR 1.7; 95% CI 1.1–2.6; p = 0.02). In the multivariate analysis, small tumors removed by EBR had a significantly lower LR risk.

Conclusions

The LR risk of a single brain metastasis is influenced by biological factors (such as tumor volume) and treatments (such as the resection method). Early administration of postoperative WBRT may be particularly warranted when such negative tumor-related prognostic factors are noted or when treatment-related ones such as PMR are unavoidable.

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Adam S. Wu, Victoria T. Trinh, Dima Suki, Susan Graham, Arthur Forman, Jeffrey S. Weinberg, Ian E. McCutcheon, Sujit S. Prabhu, Amy B. Heimberger, Raymond Sawaya, Xuemei Wang, Wei Qiao, Kenneth R. Hess and Frederick F. Lang

Object

Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas.

Methods

Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned.

Results

The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients.

Conclusions

The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%–18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.

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Benjamin D. Fox, Hassan H. Amhaz, Akash J. Patel, Daniel H. Fulkerson, Dima Suki, Andrew Jea and Raymond E. Sawaya

Object

Medical student exposure to neurosurgery is limited. To improve the educational interactions between neurosurgeons and medical students as well as neurosurgical medical student rotations or clerkships (NSCs) we must first understand the current status.

Methods

Two questionnaires were sent, one to every neurosurgery course coordinator or director at each US neurosurgery residency program (99 questionnaires) and one to the associated parent medical school dean's office (91 questionnaires), to assess the current status of NSCs and the involvement of neurosurgeons at their respective institutions.

Results

We received responses from 86 (87%) of 99 neurosurgery course coordinators or directors and 64 (70%) of 91 medical school deans' offices. Most NSCs do not have didactic lectures (53 [62%] of 86 NSCs), provide their medical students with a syllabus or educational handouts (53 [62%] of 86), or have a recommended/required textbook (77 [90%] of 86). The most common method of evaluating students in NSCs is a subjective performance evaluation. Of 64 medical school deans, 38 (59%) felt that neurosurgery should not be a required rotation. Neurosurgical rotations or clerkships are primarily offered to students in their 4th year of medical school, which may be too late for appropriate timing of residency applications. Only 21 (33%) of 64 NSCs offer neurosurgery rotations to 3rd-year students.

Conclusions

There is significant room for improvement in the neurosurgeon-to–medical student interactions in both the NSCs and during the didactic years of medical school.

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Brian J. Williams, Dima Suki, Benjamin D. Fox, Christopher E. Pelloski, Marcos V. C. Maldaun, Raymond E. Sawaya, Frederick F. Lang and Ganesh Rao

Object

Stereotactic radiosurgery (SRS) is commonly used to treat brain metastases. Complications associated with this treatment are underreported. The authors reviewed a large series of patients who underwent SRS for brain metastases to identify complications and factors predicting their occurrence.

Methods

Prospectively collected clinical data from 273 patients undergoing SRS for 1 or 2 brain metastases at The University of Texas M. D. Anderson Cancer Center between June 1993 and December 2004 were reviewed. Patients who had received prior treatment for their tumor, including whole-brain radiation, SRS, or surgery, were excluded from the study. Data on adverse neurological and nonneurological outcomes following treatment were collected.

Results

Three hundred sixteen lesions were treated. Complications were associated with 127 (40%) of 316 treated lesions. New neurological complications were associated with 101 (32%) of 316 lesions. The onset of seizure was the most common complication, occurring in 41 (13%) of 316 SRS cases. On multivariate analysis, progressing primary cancer (hazard ratio [HR] = 2.4, 95% CI 1.6–3.6, p < 0.001), tumor location in eloquent cortex (HR = 2.3, 95% CI 1.6–3.4, p < 0.001), and lower (< 15 Gy) SRS dose (HR = 2.1, 95% CI 1.1–4.2, p = 0.04) were significantly associated with new complications. On multivariate analysis, a tumor location in the eloquent cortex (HR = 2.5, 95% CI 1.6–3.8, p < 0.001) and progressing primary cancer (HR = 1.6, 95% CI 1.1–2.5, p = 0.03) were significantly associated with new neurological complications.

Conclusions

The authors showed that new neurological and nonneurological complications were associated with 40% of SRS treatments for brain metastases. Patients with lesions in functional brain regions have a significantly increased risk of treatment-related complications.

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Michel Lacroix, Dima Abi-Said, Daryl R. Fourney, Ziya L. Gokaslan, Weiming Shi, Franco DeMonte, Frederick F. Lang, Ian E. McCutcheon, Samuel J. Hassenbusch, Eric Holland, Kenneth Hess, Christopher Michael, Daniel Miller and Raymond Sawaya

Object. The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time.

Methods. The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively.

Conclusions. Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4–14.6 months), compared with 8.8 months (95% CI 7.4–10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1–3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4–5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.

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Marcos V. C. Maldaun, Shumaila N. Khawja, Nicholas B. Levine, Ganesh Rao, Frederick F. Lang, Jeffrey S. Weinberg, Sudhakar Tummala, Charles E. Cowles, David Ferson, Anh-Thuy Nguyen, Raymond Sawaya, Dima Suki and Sujit S. Prabhu

Object

The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex.

Methods

From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome.

Results

Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0–13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR ≥ 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%).

Conclusions

There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010