Faculty Bibliography

Although there has been considerable experience with anterior approaches to ventral intradural, extramedullary, and pial-based spinal lesions, there is no information in the literature regarding the safety and feasibility of the resection of an intramedullary tumor via an anterior approach. The authors report on the gross-total resection of an intramedullary cervical pilocytic astrocytoma via a C-7 corpectomy and anterior myelotomy. The surgery proceeded without complication, and postoperatively the patient maintained the preoperative deficit of mild unilateral hand weakness but had no sensory deficits. Follow-up MR imaging at 6 months showed gross-total macroscopic resection. Selected intramedullary tumors can be safely removed via an anterior approach. This approach avoids the typical sensory dysfunction associated with posterior midline myelotomy.

OBJECTIVE:Many patients undergoing lumbar spine fusion are overweight or obese. The relationship between body habitus and outcome after lumbar spine fusion surgery is not well defined. METHODS:We analyzed a prospectively maintained database of self-reported pain and quality of life measures, including Visual Analog Scale pain score, Short Form 36, and Oswestry Disability Index. We selected patients undergoing minimally invasive transforaminal lumbar interbody fusion between September 2002 and June 2006 at a single institution. We used linear regression models and mixed-effects linear models to examine the relationships between body habitus and self-reported outcomes. RESULTS:The analysis identified 110 patients meeting the study criteria, with a median follow-up period of 14.8 months. The mean age was 56 years, mean height was 169 cm, and mean weight was 82.2 kg. The mean body mass index (BMI) was 28.7 kg/m2; 31% of patients were overweight (BMI, 25-29.9), and 32% of patients were obese (BMI, >30). Linear regression analysis did not identify a correlation between weight or BMI and pre- and postsurgery changes in any of the outcome measures. The significant findings observed in the mixed-effects linear models were that the changing patterns of Short Form 36 Body Pain subscale and Short Form 36 Vitality subscale varied significantly by category of BMI (P = 0.01 and P = 0.002, respectively), but not significantly if continuous BMI was used (P = 0.53 and P = 0.46, respectively). BMI correlated marginally with estimated blood loss (P = 0.08), but not operative time, length of hospital stay, or complications. CONCLUSION/CONCLUSIONS:Among this cohort of minimally invasive lumbar fusion patients, body habitus measured by BMI, weight, or height did not have a significant relationship with most self-reported outcome measures, operative time, length of hospital stay, or complications. Obesity should not be considered a contraindication to minimally invasive lumbar spinal fusion surgery.

OBJECTIVE:Several studies have shown that human gliomas contain a small population of cells with stem cell-like features. It has been proposed that these "cancer stem cells" may be uniquely responsible for glioma formation and recurrence. However, human gliomas also contain an abundance of cells that closely resemble more differentiated glial progenitors. Animal model studies have shown that these cells also possess the capacity to form malignant gliomas. METHODS:To investigate the contributions of stem-like and progenitor-like cells in human gliomas, we used flow cytometry to characterize the expression of a cancer stem cell marker (CD133) and a glial progenitor marker (A2B5) in 25 tumors. We found that human gliomas consistently express A2B5 in a large percentage of cells (61.7 +/- 3.8%, standard error of the mean). In contrast, CD133 expression was less abundant and less consistent (14.8 +/- 3.6%, standard error of the mean), with several glioblastomas containing very few or no detectable CD133+ cells. When present, the CD133+ population was almost entirely contained within the A2B5+ population. Thus, most gliomas could be divided into three distinct populations on the basis of these markers (A2B5+CD133+, A2B5+CD133-, and A2B5-CD133-). To test the tumorigenic potential of these populations, we separated cells from six tumors by fluorescence-activated cell sorting and reinjected them into nude rats. RESULTS:We found that the capacity for these different populations to form tumors varied depending on the human tumor specimen from which they were isolated. Of the six human gliomas tested, four contained A2B5+/CD133- cells that formed tumors when transplanted into nude rats, three contained A2B5+/CD133+ cells that formed tumors, and only one glioma contained A2B5-/CD133- cells with the capacity to form tumors. CONCLUSION/CONCLUSIONS:Together, these results demonstrate that human gliomas contain multiple populations of cells with the capacity to form tumors and specifically identify a population of tumorigenic A2B5+ cells that are phenotypically distinct from CD133+ cells.

Recent evidence suggests that suppression of the cellular immune response is often attributable to populations of functionally distinct T cells that act to down-regulate Ag-specific effector T cells. Using flow cytometry, we evaluated tumor-infiltrating lymphocytes (TIL) from patients undergoing neurosurgical resection of glioblastoma multiforme (GBM), metastatic lung carcinoma, and meningioma for markers known to be expressed on immunoregulatory T cells. Ex vivo phenotypic characteristics, cellular proliferation, and cytokine expression patterns were compared between T cell subsets found in the PBMC and within TIL from fresh tumor samples. Interestingly, nearly half of all T cells infiltrating GBM specimens were CD56(+) T cells, while much smaller percentages of similar cells were identified within metastatic lung tumors and meningiomas. CD56(+) T cells identified within GBM were not canonical, or "invariant," NKT cells, as they demonstrated diverse TCR expression, a primarily CD4 single-positive phenotype, and lack of CD1d reactivity. The percentage of CD56(+) T cells exhibiting evidence of proliferation within GBM was 3- to 4-fold higher than the proportion of proliferating CD56(-) T cells from these lesions. In addition, direct ex vivo analysis of cytokine expression by TIL from GBM demonstrated significant numbers of IL-4/IL-13 positive cells, cytokines that are integral in the cell-mediated repression of tumor immunity in experimental models. We propose that GBM has a unique capacity to recruit and activate CD4(+)CD56(+) T cells, a population that has not been previously described within human tumors.

Soft-tissue glomus tumors (or glomangiomas) are unrelated to neuroendocrine paragangliomas (glomus tympanicum, jugulare, and vagale). The authors present the first reported case of an orbital soft-tissue glomus tumor in a child. An 8-year-old girl developed rapidly progressive right-eye blindness, proptosis, and a sixth cranial nerve palsy. Magnetic resonance imaging demonstrated a homogeneously enhancing lesion extending from the right orbit through the superior orbital fissure to the cavernous sinus and middle cranial fossa. A biopsy specimen demonstrated the lesion to be a soft-tissue glomus tumor. Following angiography and embolization, a gross-total resection of the tumor was achieved. The patient was treated with adjuvant proton-beam radiotherapy. At 24 months follow-up her proptosis and sixth cranial nerve palsy had resolved and there was no evidence of tumor recurrence

Intramedullary inclusion cysts are extremely rare within the rostral spinal cord. In this case report the authors outline the clinical features and surgical treatment of one dermoid cyst and one epidermoid cyst of the cervicothoracic junction. The authors also include a relevant literature discussion regarding the treatment and the embryological origin of these lesions.

OBJECTIVE:Better characterization of the changes that occur in the circulating monocytes of patients with glioblastoma has become more important recently as monocyte-derived dendritic cells are used as adjuvants in the development of glioma vaccines. This study seeks to develop understanding of the phenotypic changes that occur in circulating monocytes of patients with intracranial cancer and to assess the ability of these cells to differentiate into mature dendritic cells. METHODS:Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were compared between three cohorts: patients with intracranial glioblastoma (n = 15), patients with intracranial metastases (n = 9), and a group of healthy controls (n = 10). Monocytes were then tested for their ability to differentiate into mature dentritic cells based on morphology, CD83 expression and high levels of co-stimulatory molecules. RESULTS:Comprehensive analysis of monocyte receptor expression demonstrated significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma but not in patients with intracranial metastases compared with a group of healthy controls. GMCSFR expression was significantly reduced in both patients with glioblastoma and intracranial metastases. Additionally, the monocytes of patients with glioblastoma showed a reduced capacity to differentiate into mature dendritic cells as identified by CD83 expression, receptor expression, and morphology. CONCLUSION/CONCLUSIONS:Peripheral monocytes are phenotypically altered in the setting of glioblastoma and display a reduced functional capacity to differentiate into mature dendritic cells.

Medical management of cerebral edema and elevated intracranial pressure (ICP) is a critical component of perioperative care in neurosurgical practice. Traumatic brain injury, arterial infarction, venous hypertension/infarction, intracerebral hemorrhage, subarachnoid hemorrhage, tumor progression, and postoperative edema can all generate clinical situations in which ICP management is a critical determinant of patient outcomes. Although osmotic agents are among the most fundamental tools to control ICP, prospective data to establish clear guidelines on their use are lacking. Hypertonic saline is emerging as an alternative to mannitol. Early data suggest that indications for each agent may ultimately depend on ICP etiology.

Optimal management of pineal region tumors depends on securing an accurate histologic diagnosis to facilitate management customized to the nuances of specific pathologies. As an initial step, surgical intervention by either stereotactic biopsy or open surgery is necessary to obtain tissue for pathologic examination. Stereotactic biopsy has the benefit of relative ease and minimal morbidity but is associated with greater likelihood of diagnostic inaccuracy compared to open surgery where more extensive tissue sampling is possible. The role of surgical debulking in the management of pineal tumors is clearly defined for some tumors but is less evident for others. Among the one third of pineal tumors that are benign or low grade, complete surgical resection is achievable and constitutes optimal management with excellent long-term recurrence-free survival. The benefits of aggressive surgical resection among malignant tumors are less clear but several studies have correlated degree of tumor removal with improved outcome. Advances in technology, surgical technique, and post-operative care have minimized surgical complications, however all surgical procedures in the pineal region, including both stereotactic biopsy and open surgery, are potentially hazardous. Advanced judgment, experience, and expertise are necessary to achieve rates of success sufficient to justify aggressive management. Management strategies using stereotactic biopsy, endoscopy, and radiosurgery can also provide favorable outcomes in some cases. Selective incorporation of these innovations can be expected to improve the already highly favorable outcome for all pineal region tumors.