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PDF file, 65K, mAb-mediated depletion of T-cells.

PDF file, 66K, Murine glioma-derived CD11b+ cells inhibit CD8+ T-cells in vitro.

PDF file, 129K, Critical role of IL-4Ralpha in T-cell-suppressing function of BM-derived myeloid cells.

PDF file, 65K, Confirmation of chimerism using enhanced green fluorescence protein (EGFP+) donor BM cells.

PDF file, 89K.

Malignant gliomas are lethal cancers in the brain and heavily infiltrated by myeloid cells. Interleukin-4 receptor-α (IL-4Rα) mediates the immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Rα gene are associated with altered glioma risk and prognosis. In this study, we sought to evaluate a hypothesized causal role for IL-4Rα and myeloid suppressor cells in glioma development. In both mouse de novo gliomas and human glioblastoma cases, IL-4Rα was upregulated on glioma-infiltrating myeloid cells but not in the periphery or in normal brain. Mice genetically deficient for IL-4Rα exhibited a slower growth of glioma associated with reduced production in the glioma microenvironment of arginase, a marker of myeloid suppressor cells, which is critical for their T-cell inhibitory function. Supporting this result, investigations using bone marrow-derived myeloid cells showed that IL-4Rα mediates IL-13–induced production of arginase. Furthermore, glioma-derived myeloid cells suppressed T-cell proliferation in an IL-4Rα–dependent manner, consistent with their identification as myeloid-derived suppressor cells (MDSC). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a central role for the induction of IL-4Rα expression on myeloid cells, and we found that GM-CSF is upregulated in both human and mouse glioma microenvironments compared with normal brain or peripheral blood samples. Together, our findings establish a GM-CSF–induced mechanism of immunosuppression in the glioma microenvironment via upregulation of IL-4Rα on MDSCs. Cancer Res; 73(21); 6413–23. ©2013 AACR.

PDF file, 129K, IL-4Ralpha on CD11b+Gr1+ BILs and SPCs.

Background: Muir-Torre syndrome (MTS) is an autosomal dominant syndrome characterized by neoplasms of the sebaceous gland or keratoacanthomas, in addition to visceral malignancies. Cerebral neoplasms in patients with hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis suffer from Turcot's syndrome. Genetic mutations in MutS homolog (MSH)-2, MutL homolog (MLH)-1, and MutS homolog (MSH)-6 DNA mismatch repair genes are the most common in MTS with MSH-2 being the most predominant. In HNPCC MLH-1 and MSH-2 mutations are approximately equal in prevalence. Case Description: We present the case of a 58-year-old male with a prior history of being treated for colonic adenocarcinoma and skin lesions leading to a diagnosis of MTS. The patient later developed a World Health Organization (WHO) grade 4 glioma requiring surgical resection. Pathology revealed mutations in MSH-2 and MSH-6 mismatch repair genes. Conclusions: This case represents the first report of Turcot's and MTS with extensive molecular testing on the cerebral neoplasm demonstrating a molecular relationship between Turcot's and MTS and only the second published report of simultaneous Turcot's and MTS.

The authors report the safety and efficacy of using a percutaneous minimal-access insertion technique for distal shunt catheter placement in 100 cases. From June 2007 to March 2008, they attempted 100 minimal-access insertions of distal shunt catheters in 91 patients who required ventriculoperitoneal shunting. Using the minimal-access approach, they avoided utilizing laparoscopic assistance or a mini-laparotomy in 91% of the cases. There were no bowel injuries or misplaced distal catheters. Additional outcomes in terms of operative times, cases that required conversion to open or laparoscopically assisted implantation, and infection rates are presented. They conclude that intraperitoneal shunt catheter placement can be safely and effectively accomplished using a simplified percutaneous minimal-access insertion method that does not require direct laparoscopic visualization.

The authors introduce a novel technique of intraparenchymal brain tumor resection using a rod lens endoscope and parallel instrumentation via a transparent conduit.Over a 4-year period, 21 patients underwent completely endoscopic removal of a subcortical brain lesion by means of a transparent conduit. Image guidance was used to direct the cannulation and resection of all lesions. Postoperative MR imaging or CT was performed to assess for residual tumor in all patients, and all patients were followed up postoperatively to assess for new neurological deficits or other surgical complications.The histopathological findings were as follows: 12 metastases, 5 glioblastomas, 3 cavernous malformations, and 1 hemangioblastoma. Total radiographically confirmed resection was achieved in 8 cases, near-total in 6 cases, and subtotal in 7 cases. There were no perioperative deaths. Complications included 1 infection and 1 pulmonary embolus. There were no postoperative hematomas, no postoperative seizures, and no worsened neurological deficits in the immediate postoperative period.Fully endoscopic resection may be a technically feasible method of resection for selected subcortical masses. Further experience with this technique will help to determine its applicability and safety.

Craniopharyngiomas have always been an extremely challenging type of tumor to treat. The transsphenoidal route has been used for resection of these lesions since its introduction. The authors present a historical review of the literature from the introduction of the endonasal route for resection of craniopharyngiomas until the present. Abandoned early due to technological limitations, this approach has been expanded both in its application and in its anatomical boundaries with subsequent progressive improvements in outcomes. This expansion has coincided with advances in visualization devices, imaging guidance techniques, and anatomical understanding. The progression from the use of headlights, to microscopy, to endoscopy and fluoroscopy, and finally to modern intraoperative magnetic resonance-guided techniques, combined with collaboration between otolaryngologists and neurosurgeons, has provided the framework for the development of current techniques for the resection of sellar and suprasellar craniopharyngiomas.

The purpose of this study was to describe the technique used to safely identify the petrous carotid artery during expanded endonasal approaches to the skull base. A series of 20 cadaveric studies was undertaken to isolate the vidian artery and nerve and to use them as landmarks to the petrous internal carotid artery (ICA). Twenty-five consecutive paraclival endoscopic cases were also reviewed to determine the consistency of the vidian artery in vivo as an intraoperative landmark to the ICA. These data were then correlated with results from a separate study in which computed tomography scans from 44 patients were evaluated to delineate the course of the vidian canal and its relationship to the petrous ICA. In all 20 cadaveric dissections and all 25 surgical cases, the vidian artery was consistently identified and could be reliably used as a landmark to the ICA. The correlation between anatomical and clinical data in this paper supports the consistent use of the vidian artery as an important landmark to the petrous ICA.

BACKGROUND Cerebral metastasis is a common oncologic problem that occurs in 15–30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis. METHODS A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions. RESULTS Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3–11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9–7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was; ce70% did not differ between the 2 groups. CONCLUSIONS This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis. Cancer 1996;78:1470-6.