To test the gliomagenic potential of adult glial progenitors, we infected adult rat white matter with a retrovirus that expresses high levels of PDGF and green fluorescent protein (GFP). Tumors that closely resembled human glioblastomas formed in 100% of the animals by 14 d postinfection. Surprisingly, the tumors were composed of a heterogeneous population of cells, Ͻ20% of which expressed the retroviral reporter gene (GFP). The vast majority of both GFPϩ and GFP-tumor cells expressed markers of glial progenitors. Thus, the tumors arose from the massive expansion of both infected and uninfected glial progenitors, suggesting that PDGF was driving tumor formation via autocrine and paracrine stimulation of glial progenitor cells. To explore this possibility further, we coinjected a retrovirus expressing PDGF-IRES-DsRed with a control retrovirus expressing only GFP. The resulting tumors contained a mixture of red cells (PDGFexpressing/tumor-initiating cells) and green cells (recruited progenitors). Both populations were highly proliferative and infiltrative. In contrast, when the control GFP retrovirus was injected alone, the animals never formed tumors and the majority of infected cells differentiated along the oligodendrocyte lineage. Together, these results reveal that adult white matter progenitors not only have the capacity to give rise to gliomas, but resident progenitors are recruited to proliferate within the mitogenic environment of the tumor and in this way contribute significantly to the heterogeneous mass of cells that compose a malignant glioma.

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.

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.

Hemangioblastomas occur in 2% to 15% of reported series of intramedullary spinal cord tumors. They are benign, highly vascular tumors that can be cured with surgical resection. Complete removal of these tumors with low morbidity is possible with current microneurosurgical techniques and a thorough understanding of the typical relationship of the tumor to adjacent neural structures. We describe our experience with 16 intramedullary and 2 lumbosacral nerve root hemangioblastomas and review the relevant published literature. A detailed discussion of the operative technique is provided along with an operative video. Three illustrative cases are used to demonstrate clinical considerations that can arise with these tumors, including surgery during pregnancy, symptoms related to syrinx or syringomyelia, and postoperative consequences of neurological deficits.

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.

The vertebrate lens is a relatively simple cellular structure that has evolved to refract light. The ability of the lens to focus light on the retina derives from a number of properties including the expression at high levels of a selection of soluble proteins referred to as the crystallins. In the present study, we have used differential cDNA display techniques to identify a novel, highly abundant and soluble lens protein. Though related to the family of soluble lectins called galectins, it does not bind ␤-galactoside sugars and has atypical sequences at normally conserved regions of the carbohydrate-binding domain. Like some galectin family members, it can form a stable dimer. It is expressed only in the lens and is located at the interface between lens fiber cells despite the apparent lack of any membrane-targeting motifs. This protein is designated GRIFIN (galectin-related inter-fiber protein) to reflect its exclusion from the galectin family given the lack of affinity for ␤-galactosides. Although the abundance, solubility, and lens-specific expression of GRIFIN would argue that it represents a new crystallin, its location at the fiber cell interface might suggest that its primary function is executed at the membrane.

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.

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.