Purpose: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4 + T cell numbers and function. We have previously shown that increased regulatory T cell (T reg ) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model. Experimental Design: A monoclonal antibody (9H10) to CTLA-4 was employed against wellestablished glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4 + T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4 + CD25À responderTcells were evaluated. Results: CTLA-4 blockade confers long-term survival in 80 % of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4 À T cells from treated mice show improved proliferative responses and resistance to T reg -mediated suppression, whereas T regs from the same mice remain anergic and exhibit no restriction of their suppressive capacity. Conclusions: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance toT reg -mediated suppression, and not through direct effects onT regs .

Purpose: Elevated proportions of regulatory T cells (T reg ) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examinedT regs in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. + T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25 + cells but fails to completely eliminate T regs , reducing their number only moderately, yet eliminating their suppressive function. This elimination of T reg function permits enhanced lymphocyte proliferative and IFN-g responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis. Conclusions: Systemic anti-CD25 administration does not entirely eliminateT regs but does prevent T reg function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T reg compartments seen in patients with malignant glioma.

Background Superior-level facet joint violation by pedicle screws may result in increased stress to the level above the instrumentation and may contribute to adjacent segment disease (ASD). Previous studies have evaluated facet joint violations in open or percutaneous screw cases, but there are no reports describing a direct institutional comparison. Objective To compare the incidence of superior-level facet violation for open versus percutaneous pedicle screws, and evaluate patient and surgical factors that impact this outcome. Methods We reviewed 279 consecutive patients who underwent an index instrumented lumbar fusion from 2007 to 2011 for degenerative spine disease with stenosis with or without spondylolisthesis. We used a CT grading system which represents progressively increasing grades of facet joint violation. Patient and surgical factors were evaluated to determine their impact on facet violation. Results Our cohort consisted of 126 open and 153 percutaneous cases. Percutaneous procedures had a higher overall violation grade (p=0.018) and greater incidence of high-grade violations (p=0.0059) compared to open procedures. Bivariate analysis showed significantly greater violations in percutaneous cases for age<65, obesity, pedicle screws at L4, and 1- and 2-level surgeries. Multivariate analysis showed the percutaneous approach and depth of the spine to be independent risk factors for high-grade violations. Conclusion This study demonstrates greater facet violations for percutaneously placed pedicle screws compared to open.

abbreviatioNs EOR = extent of resection; GBM = glioblastoma; GTR = gross-total resection; HR = hazard ratio; KPS = Karnofsky Performance Scale; RT = radiotherapy; SRS = stereotactic radiosurgery; STR = subtotal resection; TMZ = temozolomide. obJective The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. methods A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. results A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio coNclusioN This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevaciz...

This study demonstrates that MVD is a safe, effective, and durable surgical procedure for producing prolonged pain relief in patients with medically intractable glossopharyngeal neuralgia.