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Background: Cavernous hemangioma are the most common benign lesions of the orbit. Their surgical resection is still challenging and several surgical approaches have been proposed. Case Description: We present the case of a 59-year-old woman with a cavernous hemangioma of the orbital apex, which was diagnosed incidentally. The hemangioma was extraconal and involved mainly the medial orbital apex; it also extended to the pterygoid fossa, to the middle fossa, to the maxillary and sphenoid sinuses. The surgical resection was performed by a pure endoscopic transphenoidal, transmaxillary, transethmoidal approach, achieving a total removal. The patient had a transient and incomplete paresis of the VI cranial nerve on the left side and did not experience other postoperative complications. Conclusion: The endoscopic endonasal approach proved successful in the management of this case and it should be considered in the surgical management of extraconal orbital apex lesions with medial or inferior extension. [ABSTRACT FROM AUTHOR]

Background: The current standard-of-care for glioblastoma (GBM) is represented by concomitant radiotherapy (RT) and temozolomide (TMZ), according to Stupp's protocol. Second-line treatments for GBM have not been yet defined. Tamoxifen is an anti-estrogen molecule with anti-neoplastic effects whose role is under investigation. tamoxifen is generally well tolerated but thromboembolic complications have been reported. In this study, we report our experience on the administration of tamoxifen plus dose-dense TMZ in patients with recurrent GBM., Patients and Methods: All patients underwent surgical resection of GBM and completed concomitant RT and TMZ. Eligibility criteria also included evidence of GBM recurrence and good general conditions [Karnofsky Performance Score (KPS) >70] at recurrence. Patients with rapidly progressive disease, clearly unfavorable prognosis, or history of deep-venous thrombosis were excluded. The second-line treatment consisted of dose-dense TMZ (75-150 mg/m(2) one week on/ one week off) plus daily tamoxifen (80 mg/m(2)). Follow-up was performed with contrast-enhanced brain Magnetic Resonance Imaging (MRI) every three months., Results: Thirty-two patients (18 males, 14 females; median age 57 years) with GBM relapse were included. Median overall survival time (OS) and time to tumor progression after recurrence (TTP-2) were 17.5 and 7 months, respectively. Interestingly, no differences in OS and TTP-2 were noted in GBM between those with methylated and unmethylated MGMT. None of the patients had complications related to TMZ plus tamoxifen administration., Conclusion: The combinatorial administration of tamoxifen and TMZ appeared to be well-tolerated, and potentially effective in increasing the efficacy of dose-dense TMZ schedule as a second-line therapeutic strategy.

Objective: Subcortical stimulation can be used to identify functional language tracts during resection of gliomas located close to or within language areas or pathways. The objective of the present study was to investigate the feasibility of the routine use of subcortical stimulation for identification of language tracts in a large series of patients with gliomas and to determine the influence that subcortical language tract identification exerted on the extent of surgery and on the appearance of immediate and definitive postoperative deficits., Methods: Subcortical stimulation for language tract identification was systematically used during surgical removal of 88 gliomas (44 high-grade and 44 low-grade gliomas) involving language pathways. Procedures were performed during asleep/awake craniotomy. Subcortical stimulation was continuously alternated with surgical resection in a back-and-forth fashion. Language performances were tested by neuropsychological language evaluation preoperatively and at 3, 30, and 90 days after surgery., Results: Language tracts were identified in 59% of patients, with differences according to tumor location but not according to histological grade. Language tract identification influenced the ability to reach a complete tumor removal in low-grade gliomas, in which tracts were documented inside the peripheral mass of the tumor. Identification of language tracts was associated with a higher occurrence of transient postoperative deficits (67.3% of cases), but a low occurrence of definitive morbidity (2.3% of cases). A pattern of typical language disturbances related to the phonological and semantic system can be identified according to tumor location, with preservation being important for the maintenance of language integrity., Conclusion: Our study supports the routine use of subcortical stimulation for language tract identification as a reliable tool for guiding surgical removal of gliomas in or in close proximity to language areas or pathways.

The systemic administration of endogenous inhibitors significantly reduced the growth of human glioma in vivo, but required the production of a large amount of biologically active protein. In this study we reduced the amount of protein needed and optimized the therapeutical response by delivering the endogenous inhibitors locally into the brain by osmotic minipumps. Human hemopexin fragment of MMP-2 or COOH-terminal fragment of platelet factor-4 were delivered locally and continuously into the brain of mice implanted intracranially with glioma cells, by osmotic minipumps connected to an intracranial catheter. Local delivery of human hemopexin fragment of MMP-2 and COOH-terminal fragment of platelet factor-4 significantly inhibited the growth of well-established malignant glioma in nude and BALB/C mice. When the inhibitors were given at the same concentration, the efficacy of the local delivery was much higher than that reached with the systemic administration, both when the inhibitor was administered daily or continuously by s.c. minipumps. Moreover, the local delivery reduced the amount of protein needed to reach a significant therapeutic response. Intracerebral delivery maintained a long-term control of glioma growth and inhibited glioma recurrence in a surgical resection model. Treatment showed no side effects. Histochemical analysis of tumors showed that the tumor growth inhibition was the result of a decrease in tumor vasculature and a change in tumor vessel morphology. Our data demonstrate that local intracerebral delivery of endogenous inhibitors effectively inhibits malignant glioma growth and reduces the amount of protein needed to reach a therapeutical response.

Objective: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS20I on human malignant gliomas., Methods: The in vitro effects of IS20I were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS20I was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models., Results: IS20I reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS20I strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS20I induced endothelial and tumor cell apoptosis. In vivo, when IS20I was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation., Conclusion: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS20I inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo.

A few peptide residues in structurally important locations often determine biological functions of proteins implicated in the regulation of angiogenesis. We have shown recently that the short COOH-terminal segment PF-4(47-70) derived from platelet factor 4 (PF-4) is the smallest sequence that conserves potent antiangiogenic activity in vitro and in vivo. Here we show that modified COOH-terminal PF-4 peptides containing the sequence ELR (or related DLR), a critical domain present in proangiogenic chemokines, surprisingly elicit several times greater antiangiogenic potential than the original peptide. The modified peptides inhibit binding of iodinated vascular endothelial growth factor and fibroblast growth factor 2 to endothelial cell receptors, endothelial cell proliferation, migration, and microvessel assembly in the rat aortic ring model at lower doses than PF-4(47-70). On the differentiated chick chorioallantoic membrane, topical application of 40 micro g of modified peptides potently reduces capillary angiogenesis induced by vascular endothelial growth factor(165), a dose where peptide PF-4(47-70) was inactive. Established intracranial glioma in nude mice decreased significantly in size when treated locally with a total dose of 250 micro g of peptide PF-4(47-70)DLR (n = 10) compared with the same dose of the original PF-4(47-70) peptide (n = 10) or controls (n = 30). Tailored PF-4 peptides represent a new class of antiangiogenic agents with a defined mode of action and a strong in vivo activity.

Glioma recurrences develop at the borders of the surgical cavity and are the main cause of their poor prognosis. There are no therapeutic advances to reduce the incidence of recurrence or animal models that closely mimic the clinical scenario to evaluate novel therapeutics. This work investigates the efficacy of endogenous inhibitors, in preventing the recurrence of human malignant gliomas, in a newly developed animal model of glioma surgical resection. We developed a nude mice model in which human glioma xenografts were microsurgically removed. After surgery, small islets of tumor cells persisted in the normal brain parenchyma, grew, and formed a recurrence. As inhibitors we used PEX and a fragment of platelet factor 4 (PF-4/CTF), which were administered systemically on a daily basis or in metronomic combination with chemotherapy for 120 days. Treatment was started 1 or 15 days after tumor removal. PEX or PF-4/CTF produced a significant improvement in survival, and delayed the appearance of glioma recurrence. Survival of animals that received daily PEX or PF-4/CTF was similar to that of animals that received metronomic PEX or PF-4/CTF and chemotherapy, respectively. The effect of treatment was dependent on the time at which the treatment was initiated. The highest level of inhibition was observed when the treatment was administered 1 day after surgical resection and when PEX was used as the inhibitor (120 days versus 35 days of the control). Tumors treated with PEX or PF-4/CTF were small and well delineated, with few vessels. Postsurgical administration of PEX or PF-4/CTF significantly reduces the incidence human malignant glioma recurrences for a long period of time.