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Eric Marmor, Laurence D. Rhines, Jeffrey S. Weinberg and Ziya L. Gokaslan

✓ The authors describe a technique for total en bloc spondylectomy that can be used for lesions involving the lumbar spine. The technique involves a combined anterior—posterior approach and takes into account the unique anatomy of the lumbar spine. This technique allows for the en bloc resection of lumbar vertebral tumors, thus optimizing outcome while minimizing the risk of neurological injury. The technique is described in detail with the aid of neuroimaging studies, photographs of gross pathological specimens, and illustrations, and a discussion of other authors' experiences is provided for comparison.

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Xiang Y. Han, Jeffrey S. Weinberg, Sujit S. Prabhu, Samuel J. Hassenbusch, Gregory N. Fuller, Jeffrey J. Tarrand and Dimitrios P. Kontoyiannis

Object. The cases of five patients with fusobacterial brain abscess are presented. The authors discuss their attempt to determine the pathogenesis.

Methods. The clinical and microbiological features of five cases of fusobacterial brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other anaerobes collected (1989–2002) at our institution were analyzed and compared for incidences and isolation sources. The findings were correlated with extensive literature on the subject.

The five patients were men between 45 and 74 years of age. All experienced an insidious onset of the disease and probable hematogenous seeding of the organism(s). One patient had a monomicrobic Fusobacterium necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses. Despite surgery and a regimen of antibiotic medications and dexamethasone, three patients experienced a paradoxical deterioration 3 days postoperatively that necessitated reevacuation of the lesion. The evacuants observed at that time contained numerous leukocytes but no microorganisms, suggesting intensified inflammation as the likely cause of deterioration. This explanation is supported by literature that fusobacteria strongly activate neutrophils. An analysis of the 2031 anaerobes from blood, wounds, and abscesses showed the considerable virulence of Fusobacterium spp., which were able to enter and/or sustain themselves in the blood circulation. This pattern was similar to that of Clostridium spp., but different from those of Peptostreptococcus spp., Bacteroides spp., and Prevotella spp., which were less invasive but more abundant.

Conclusions. Some fusobacterial brain abscesses may be associated with a paradoxical postoperative deterioration, which is probably due to intensified inflammation following treatment. The blood-borne dissemination and invasive behavior of fusobacteria likely initiate such a brain abscess, and further seeding of other synergic bacteria leads to a polymicrobic abscess.

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Anita Mahajan, Ian E. McCutcheon, Dima Suki, Eric L. Chang, Samuel J. Hassenbusch, Jeffrey S. Weinberg, Almon Shiu, Moshe H. Maor and Shiao Y. Woo

Object. The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma multiforme (GBM) was evaluated in a case—control study.

Methods. All patients who underwent SRS for recurrent GBM before March 2003 formed the case group. A control group of patients who did not undergo SRS was created from an institutional database, and each case was matched for known prognostic factors in GBM. The medical and neuroimaging records of all the patients were reviewed, and survival and treatment outcomes were recorded.

The case and control groups were well matched with regard to demographics and pre-SRS interventions. In the control group, the date on which magnetic resonance imaging identified a recurrent lesion that would have been eligible for SRS was deemed the “SRS” date. The number of surgeries performed in the control group was statistically higher than that in the case group. The median duration of overall survival from diagnosis was 26 months in the case group and 23 months in the control group. From the date of SRS or “SRS”, the median duration of survival was 11 months in the case group and 10 months in the control group, a difference that was not statistically significant.

Conclusions. It appears that a subgroup of patients with GBMs has a higher than expected median survival duration despite the initial prognostic factors. In patients with localized recurrences, survival may be prolonged by applying aggressive local disease management by using either SRS or resection to equal advantage.

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Eric L. Chang, Almon S. Shiu, Ehud Mendel, Leni A. Mathews, Anita Mahajan, Pamela K. Allen, Jeffrey S. Weinberg, Barry W. Brown, Xin Shelly Wang, Shiao Y. Woo, Charles Cleeland, Moshe H. Maor and Laurence D. Rhines

Object.

The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors.

Methods.

Sixty-three cancer patients underwent near-simultaneous computed tomography–guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit. The National Cancer Institute Common Toxicity Criteria 2.0 assessments were used to evaluate toxicity.

Results.

The median tumor volume of 74 spinal metastatic lesions was 37.4 cm3 (range 1.6–358 cm3). No neuropathy or myelopathy was observed during a median follow-up period of 21.3 months (range 0.9–49.6 months). The actuarial 1-year tumor progression–free incidence was 84% for all tumors. Pattern-of-failure analysis showed two primary mechanisms of failure: 1) recurrence in the bone adjacent to the site of previous treatment, and 2) recurrence in the epidural space adjacent to the spinal cord. Grade 3 or 4 toxicities were limited to acute Grade 3 nausea, vomiting, and diarrhea (one case); Grade 3 dysphagia and trismus (one case); and Grade 3 noncardiac chest pain (one case). There was no subacute or late Grade 3 or 4 toxicity.

Conclusions.

Analysis of the data obtained in the present study supports the safety and effectiveness of SBRT in cases of spinal metastatic cancer. The authors consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures. For patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in this study could be applied to help reduce failures in the epidural space.

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Dima Suki, Hiba Abouassi, Akash J. Patel, Raymond Sawaya, Jeffrey S. Weinberg and Morris D. Groves

Object

The authors tested the hypothesis that patients with metastatic posterior fossa lesions (MPFLs) treated with resection have a higher risk of leptomeningeal disease (LMD) than those with MPFLs treated with stereotactic radiosurgery (SRS).

Methods

Between 1993 and 2004, 379 patients with MPFLs were treated with resection or SRS at The University of Texas M. D. Anderson Cancer Center. The authors' primary study outcome was the incidence of LMD, as diagnosed with cerebrospinal fluid cytological analysis and/or neuroimaging.

Results

Resection was performed in 260 patients, whereas 119 patients underwent SRS. The median patient age was 56 years, 51% of patients were male, and 93% had a Karnofsky Performance Scale score $ 70. The most common primary cancers were those of the lung, breast, and kidney, as well as melanoma. Leptomeningeal dissemination of cancer occurred in 33 patients: 26 in the resection group and 7 in the SRS group (resection group: rate ratio [RR] 2.06, 95% confidence interval [CI] 0.89–4.75, p = 0.09). Piecemeal tumor resection (137 cases) was associated with a significantly higher risk of LMD than en bloc resection (123 cases; RR 3.4, 95% CI 1.43–8.12, p = 0.006) or SRS (RR 3.37, 95% CI 1.41–8.04, p = 0.006), and there was no significant difference in the risk for LMD between en bloc resection and SRS (en bloc resection: RR 0.98, 95% CI 0.34–2.81, p = 0.98). The multivariate RR and significance associated with piecemeal resection, however, were consistent, with a strong effect (RR 2.45, 95% CI 1.19–5.02, p = 0.02) and no indication of biases associated with tumor size, location, or cystic/necrotic appearance.

Conclusions

There is an increased risk of LMD after piecemeal resection of an MPFL. This increase, although clinically and statistically significant, is not as alarming as previously reported and is absent when en bloc removal is achieved. Further assessment of the role of resection in a controlled prospective setting is warranted.

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Vikram V. Nayar, Rod Foroozan, Jeffrey S. Weinberg and Daniel Yoshor

Various transcortical approaches have been described for the resection of tumors that lie in the atrium of the lateral ventricle. An approach through the middle temporal gyrus has a short trajectory to the atrium and can grant early access to the tumor's blood supply, but it typically results in damage to the optic radiations that course lateral to the atrium. Anatomical studies have suggested that an approach inferior to the inferior temporal sulcus would avoid traversing through the optic radiations. The authors describe 2 cases of meningioma in the atrium that were exposed and resected through an incision in the inferior temporal gyrus. They provide data from neuroophthalmological testing that shows full preservation of the visual fields with this approach.

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Terri S. Armstrong, Ibrahima Gning, Tito R. Mendoza, Elizabeth Vera-Bolanos, Mark R. Gilbert, Laurence D. Rhines, Jeffrey S. Weinberg, Gisela Sanchez-Williams, Victor Levin, Allen W. Burton and Charles Cleeland

Object

Tumors involving the spine have unique associated neurological symptoms. The occurrence of spine-related symptoms has been shown to predict treatment course and survival in several studies conducted in patients with solid tumors and consequent spinal cord dysfunction. Currently, no instrument that measures both neurological and cancer-related symptoms exists for patients with spine tumors. The objective of this study was to develop a reliable and valid self-reporting instrument for patients with spine tumors.

Methods

Patients with diagnosed tumors involving the spine (both primary and metastatic) participated in this study. Data collection tools included a patient-completed demographic data sheet, an investigator-completed clinician checklist, and the core M. D. Anderson Symptom Inventory to which were added 16 neurological symptoms (M. D. Anderson Symptom Inventory–Spine Tumor Module [MDASI-SP]). The authors evaluated the reliability and validity of the MDASI-SP in patients with spine tumors.

Results

One hundred twenty-six patients participated in the study. Participants were primarily white (73%) males (53%) with metastatic spine tumors (76%). They ranged in age from 18–81 years (median 56 years). Cognitive debriefing of the MDASI-SP was conducted showing the instrument was clear, concise, and easily understood by patients. The most severe core symptoms were pain, fatigue, numbness, disturbed sleep, and distress. The most severe spine module symptoms were spine pain, numbness, weakness in the legs, neck stiffness, and changes in bowel or sexual function. The mean symptom severity of items as well as a cluster analysis was used to reduce the number of total items to 18 (5 spine module items). Regression analysis showed that 57.4% of the variability in symptom interference with daily function was explained by the final instrument. Factor analysis was performed to determine the underlying constructs being evaluated by the symptom items. The 18-item MDASI-SP measures 4 underlying constructs including a disease, an autonomic, a constitutional/treatment, and an emotional factor. The internal consistency (reliability) of the MDASI-SP was 0.946, and the instrument was sensitive to disease severity based on the Karnofsky Performance Scale (KPS). The mean symptom severity was 1.52 for those with good KPS scores (80–100) versus 2.46 for those with poor scores (p < 0.01). The instrument was also sensitive to neurological status according to the Frankel grade (p < 0.001) and inpatient status (p < 0.01).

Conclusions

The 18-item MDASI-SP demonstrated validity and reliability in patients with spine tumors as a composite measure of disease-related symptoms. This instrument can be used to describe symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management.

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Wael Hassaneen, Nicholas B. Levine, Dima Suki, Abhijit L. Salaskar, Alessandra de Moura Lima, Ian E. McCutcheon, Sujit S. Prabhu, Frederick F. Lang, Franco DeMonte, Ganesh Rao, Jeffrey S. Weinberg, David M. Wildrick, Kenneth D. Aldape and Raymond Sawaya

Object

Multiple craniotomies have been performed for resection of multiple brain metastases in the same surgical session with satisfactory outcomes, but the role of this procedure in the management of multifocal and multicentric glioblastomas is undetermined, although it is not the standard approach at most centers.

Methods

The authors performed a retrospective analysis of data prospectively collected between 1993 and 2008 in 20 patients with multifocal or multicentric glioblastomas (Group A) who underwent resection of all lesions via multiple craniotomies during a single surgical session. Twenty patients who underwent resection of solitary glioblastoma (Group B) were selected to match Group A with respect to the preoperative Karnofsky Performance Scale (KPS) score, tumor functional grade, extent of resection, age at time of surgery, and year of surgery. Clinical and neurosurgical outcomes were evaluated.

Results

In Group A, the median age was 52 years (range 32–78 years); 70% of patients were male; the median preoperative KPS score was 80 (range 50–100); and 9 patients had multicentric glioblastomas and 11 had multifocal glioblastomas. Aggressive resection of all lesions in Group A was achieved via multiple craniotomies in the same session, with a median extent of resection of 100%. Groups A and B were comparable with respect to all the matching variables as well as the amount of tumor necrosis, number of cysts, and the use of intraoperative navigation. The overall median survival duration was 9.7 months in Group A and 10.5 months in Group B (p = 0.34). Group A and Group B (single craniotomy) had complication rates of 30% and 35% and 30-day mortality rates of 5% (1 patient) and 0%, respectively.

Conclusions

Aggressive resection of all lesions in selected patients with multifocal or multicentric glioblastomas resulted in a survival duration comparable with that of patients undergoing surgery for a single lesion, without an associated increase in postoperative morbidity. This finding may indicate that conventional wisdom of a minimal role for surgical treatment in glioblastoma should at least be questioned.

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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.