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.

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

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.

Thoracic spine fusion may be indicated in the surgical treatment of a wide range of pathologies, including trauma, deformity, tumor, and infection. Conventional open procedures for surgical treatment of thoracic spine disease can be associated with significant approach-related morbidity, which has motivated the development of minimally invasive approaches. Thoracoscopy and, later, video-assisted thoracoscopic surgery were developed to address diseases of the thoracic cavity and subsequently adapted for thoracic spine surgery. Although video-assisted thoracoscopic surgery has been used to treat a variety of thoracic spine diseases, its relatively steep learning curve and high rate of pulmonary complications have limited its widespread use. These limitations have motivated the development of minimally invasive posterior approaches to address thoracic spine pathology without the added risk of morbidity involved in surgically entering the chest. Many of these advances are ongoing and represent the forefront of minimally invasive spine surgery. As these techniques are developed and applied, it will be important to assess their equivalence or superiority in comparison with standard open techniques using prospective trials. In this paper the authors focus on minimally invasive posterior thoracic procedures that include fusion, and provide a review of the current literature, a discussion of future pathways for development, and case examples. The topic is divided by pathology into sections including trauma, deformity, spinal column tumors, and osteomyelitis.

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.

Surgical intervention is indicated for pyogenic vertebral discitis and osteomyelitis in patients in whom medical therapy has failed, and in those with neurological compromise, mechanical instability, epidural abscess, or intractable pain. Surgical management has evolved to include single-stage operations for debridement and stabilization as well as more aggressive reconstruction strategies with respect to instrumentation. A review of the literature demonstrates excellent outcomes with single-stage operations and placement of hardware wherever it is required. Using this method, the authors have treated 16 patients without a single incidence of recurrent infection or hardware failure after almost 2 years of follow up.