Management of Noncatastrophic Internal Carotid Artery Injury in Endoscopic Skull Base Surgery.

Arterial injuries are the most feared complication of endoscopic skull base surgery. During resection of the middle fossa component of a large ventral skull base chondrosarcoma, arterial bleeding was encountered near the right internal carotid artery (ICA). Durable hemostasis could not be achieved with packing and the patient was taken for an emergent angiogram that revealed a pseudoaneurysm of the proximal intradural ICA. Given the presence of good collateral flow through the anterior and posterior communicating arteries, the right ICA was sacrificed by coil embolization. The patient was taken back to the operating room for closure then transferred to the intensive care unit and maintained on vasopressors for five days to ensure adequate perfusion. The right ICA was coil embolized and the patient was taken back to the operating room for closure. The patient recovered without complication. Arterial injuries, although serious, are not always catastrophic. Critical steps are immediate recognition of bleeding, vascular imaging, and vessel sacrifice if necessary

Impact of Human Immunodeficiency Virus in the Pathogenesis and Outcome of Patients with Glioblastoma Multiforme.

BackgroundImprovement in antiviral therapies have been accompanied by an increased frequency of non-Acquired Immune Deficiency Syndrome (AIDS) defining malignancies, such as glioblastoma multiforme. Here, we investigated all reported cases of human immunodeficiency virus (HIV)-positive patients with glioblastoma and evaluated their clinical outcomes. A comprehensive review of the molecular pathogenetic mechanisms underlying glioblastoma development in the setting of HIV/AIDS is provided.MethodsWe performed a PubMed search using keywords "HIV glioma" AND "glioblastoma," and "AIDS glioma" AND "glioblastoma." Case reports and series describing HIV-positive patients with glioblastoma (histologically-proven World Health Organization grade IV astrocytoma) and reporting on HAART treatment status, clinical follow-up, and overall survival (OS), were included for the purposes of quantitative synthesis. Patients without clinical follow-up data or OS were excluded. Remaining articles were assessed for data extraction eligibility.ResultsA total of 17 patients met our inclusion criteria. Of these patients, 14 (82.4%) were male and 3 (17.6%) were female, with a mean age of 39.5±9.2 years (range 19-60 years). Average CD4 count at diagnosis of glioblastoma was 358.9±193.4 cells/mm3. Tumor progression rather than AIDS-associated complications dictated patient survival. There was a trend towards increased median survival with HAART treatment (12.0 vs 7.5 months, p=0.10).ConclusionOur data suggests that HAART is associated with improved survival in patients with HIV-associated glioblastoma, although the precise mechanisms underlying this improvement remain unclear

The role of epidermal growth factor-like module containing mucin-like hormone receptor 2 in human cancers.

G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous proteins in all of biology. The epidermal growth factor-seven span transmembrane (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly expressed on the surface of leukocytes. The EGF domains on the N-terminus add significant size to these receptors and they are considered to be among the largest members of the TM7 family. Although not all of their ligands or downstream targets have been identified, there is evidence implicating the EGF-TM7 family diverse processes such as cell adhesion, migration, inflammation, and autoimmune disease. Recent studies have identified expression of EGF-TM7 family members on human neoplasms including those of the thyroid, stomach, colon, and brain. Their presence on these tissues is not surprising given the ubiquity of GPCRs, but because their functional significance and pathways are not completely understood, they are of tremendous clinical and scientific interest. Current evidence suggests that expression of certain EGF-TM7 receptors is correlated with tumor grade, confers a more invasive phenotype, and increases the likelihood of metastatic disease. In this review, we will discuss the structure, function, and regulation of these receptors. We also describe the expression of these receptors in human cancers and explore their potential mechanistic significance

Immunocompetent murine models for the study of glioblastoma immunotherapy.

Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (NEJM 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing immunosuppression will play a critical role in improving treatment outcomes for glioblastoma patients. In vivo murine models of glioma provide an invaluable resource to achieving that end, and their use is an essential part of the preclinical workup for novel therapeutics that need to be tested in animal models prior to testing experimental therapies in patients. In this article, we review five contemporary immunocompetent mouse models, GL261 (C57BL/6), GL26 (C57BL/6) CT-2A (C57BL/6), SMA-560 (VM/Dk), and 4C8 (B6D2F1), each of which offer a suitable platform for testing novel immunotherapeutic approaches

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity