Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma.

Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patients with recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This trial was conducted to determine the clinical effects of IFN-alpha2a and CRA when given concurrently with radiation therapy to patients with high-grade glioma. Newly diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3 to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4 times a day for 5 days per week during the delivery of partial brain radiation therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy during the 7-week period. Use of the antiepileptic phenytoin was prohibited after observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated with a high rate of dermatologic toxicity not seen in a previous study with concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to 81 years) were enrolled between August 1996 and October 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tumor prior to this therapy; 50% were asymptomatic when treatment was initiated. The planned 7-week course of concurrent therapy was completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a median overall survival of 9.3 months and a 1-year survival rate of 42%. There was no improvement in survival compared with a similar group of 19 patients treated with concurrent IFN-alpha2a and radiation therapy in a previous trial. In the high-risk group of patients in the present study, concurrent treatment with IFN-alpha2a, CRA, and RT was feasible, but was not associated with a better outcome compared with a similar patient population treated with radiation therapy and IFN-alpha2a, or compared with radiation therapy alone in other trials.

Methylprednisolone reduces the bulk flow of water across an in vitro blood-brain barrier.

Cerebral water content is a variable quantity subject to the influence of hemodynamic and biochemical factors. Corticosteroids are frequently used in the therapy of cerebral edema, although their mechanisms of action in promoting the resolution of this state of pathologically increased water content remains unclear. To investigate this, a modified Ussing chamber was designed. The bulk flow of media (mainly composed of water) across a monolayer of cultured mouse cerebral endothelia was measured as a control. The same membranes were then exposed to either micromolar concentrations of hydrocortisone or methylprednisolone. The hydraulic conductivity (Lp) of each membrane before and after exposure to the corticosteroids was calculated as a reflection of membrane tightness. Methyl-prednisolone decreased the Lp of the membrane (i.e. tightened) by 36.1% compared to control. Hydrocortisone actually increased Lp (i.e. loosened the membrane) but not to a significant extent. The decrease in the bulk flow caused by methylprednisolone in vitro suggests that the mechanism of the clinically observed decrease in cerebral edema after corticosteroid administration may be due to the reduction of bulk flow across the blood-brain barrier.

Carcinoma metastatic to a cerebellar vascular malformation: case report.

A 73-year-old woman with a spontaneous intracerebellar hemorrhage was seen and was found to have metastatic adenocarcinoma within a vascular malformation. There was no evidence of other metastatic disease. The association of these two lesions is uncommon and has rarely been reported. The rich vascularity of the malformation may explain the hematogenous deposition of metastatic neoplasm at this site.

Glioma cell influence on cerebral endothelial cell Na(+)-K(+)-ATPase.

Using in vitro techniques, we have shown that astrocytes do not increase the ouabain-sensitive Na(+)-K(+)-ATPase activity in cerebral endothelial cells. However, malignant astrocytoma cells when co-cultured with cerebral endothelial cells significantly enhance ouabain-sensitive Na(+)-K(+)-ATPase activity in cerebral endothelial cells. Also, Na(+)-K(+)-ATPase activity in cerebral endothelial cells co-cultured with malignant astrocytoma cells is inhibited by corticosteroids to the same degree as ouabain. These results suggest that brain edema associated with malignant glioma may in part be due to an increase in ouabain-sensitive Na(+)-K(+)-ATPase activity at the blood-brain barrier and that the antiedema effects of corticosteroids may be due to a reduction in the activity of this enzyme.

Solitary spinal plasmacytomas: management and outcome.

Nine patients with solitary plasmacytoma of the spine were reviewed. Four of these patients progressed to multiple myeloma within 9 +/- 4 months (mean +/- SD) from diagnosis, and died from their disease in 23 +/- 15 months. In contrast to this, the five remaining patients free of systemic disease or local recurrence survived 78 +/- 66 months. No correlation was found between age at diagnosis, lesion location, symptomatology, laboratory studies, surgical treatment, or radiation dosage and progression to systemic disease. Solitary plasmacytoma will progress to systemic multiple myeloma and death in approximately 50% of patients. The remaining patients exhibit long-term survival following local treatment of the solitary lesion.