Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo.

Plasminogen activators regulate a variety of processes involved in tissue morphogenesis, as well as cell differentiation, migration, and invasion. We examined the relative amounts of mRNA and protein and localization of urokinase-type plasminogen activator (uPA) in human astrocytomas in vivo. Using fibrin zymography and densitometric quantitation, we found that uPA activity was significantly higher in malignant astrocytomas, especially in glioblastomas, than it was in normal brain tissues or low-grade gliomas. The amounts of uPA mRNA, as determined by Northern blot analysis, were higher in anaplastic astrocytomas and glioblastomas than in normal brain tissues and low-grade gliomas, consistent with the amount of uPA activity. To investigate the cellular source of uPA in various tissues, we performed immunocytochemical localization of uPA protein and in situ hybridization of uPA mRNA with astrocytomas and normal brain tissues. Immunocytochemical staining for uPA showed strong immunoreactivity in the tumor cells and vasculature of glioblastomas and anaplastic astrocytomas but undetectable or very low immunoreactivity for uPA in low-grade gliomas and normal brain tissues. uPA mRNA was located in astrocytoma and endothelial cells and was heterogeneously distributed within glioblastoma, with preferential localization near vascular proliferation and at the leading edge of the tumor. uPA expression was dramatically higher in highly malignant astrocytomas, especially glioblastomas, and was correlated with malignant progression of astrocytomas.

Occipital meningoceles in patients with the Dandy-Walker syndrome.

Occipital cephaloceles in the Dandy-Walker syndrome are not rare. To date, 28 cases have been reported. We report on 8 cases of associated occipital meningocele, totalling 16% of all patients with the Dandy-Walker syndrome in our series. In all patients, communication existed between the posterior fossa cyst and the occipital meningocele. In 2 patients, the occipital meningocele disappeared after cerebrospinal fluid shunting and never required surgical repair. It appears that the cranial defect had ossified and resulted in self-closure. Poor intellectual development in persons with the Dandy-Walker syndrome is associated with the presence of other central nervous system and systemic abnormalities and not with occipital meningoceles alone.

Chiari I malformation: classification and management.

Considerable debate exists about which surgical options are best for the management of the Chiari I malformation. We present a classification system for the Chiari I malformation that improves the prediction of outcome and guides the selection of surgical treatment. Twenty-seven adult patients with Chiari I malformations were grouped on the basis of the presence of signs and symptoms of brain stem compression, syringomyelia, or both. To objectively assess changes in clinical status postoperatively, a scale was developed to quantify the signs and symptoms, which were statistically analyzed by the paired t test. Five patients were asymptomatic and underwent no treatment. Ten patients had symptoms of brain stem compression without associated syringomyelia and underwent brain stem decompression, including anterior decompression in one patient with basilar invagination; all 10 patients had significant improvement at 4-year mean follow-up visits (P < 0.0001). In 12 patients with syringomyelia, 5 were symptomatic from syringomyelia only, 6 were symptomatic from both brain stem compression and syringomyelia, and 1 was symptomatic from brain stem compression only. The median length of symptoms before presentation was longer for patients with syringomyelia than for patients without (2 yr versus 9 mo; P < 0.025); the mean follow-up was 4 years. Surgical procedures included posterior brain stem decompression in 12 patients, plugging of the obex in 7, and placement of syringosubarachnoid shunts in 7, a syringopleural shunt in 1, and fourth ventricular stents in 2. In the 12 patients with syringomyelia, symptoms from brain stem compression dramatically improved with surgical decompression (P < 0.025), whereas symptoms from syringomyelia less dramatically improved or stabilized. The slight improvement or stabilization of syrinx symptoms represents a successful result, given the documented progressive nature of syringomyelia in this group. We conclude that surgical treatment for the Chiari I malformation can stabilize or slightly improve the symptoms attributed to syringomyelia and dramatically relieve the symptoms of brain stem compression. Furthermore, early diagnosis and treatment are critical in obtaining the best outcome for the patient.

Management of intracranial plasmacytoma.

The authors report on a study of eight cases of intracranial plasmacytoma to identify the risk of progression to multiple myeloma and suggest the treatment required for cure of solitary lesions. The diagnosis of multiple myeloma or myelomatous changes was made in the immediate postoperative period in four patients (50%), two of whom had skull base lesions. Of the four remaining patients, three were treated with complete surgical resection and radiation therapy and had no recurrence of plasmacytoma or progression to multiple myeloma during mean follow up of 12 years (range 2-25 years); one patient underwent subtotal surgical resection and had recurrence of the tumor despite radiation therapy. It is concluded that multiple myeloma is unlikely to develop during the long term in patients with intracranial plasmacytoma who do not develop multiple myeloma or myelomatous changes in the early postoperative period. However, lesions that infiltrate the skull base are not likely to be solitary, and patients who harbor these neoplasms should undergo complete evaluation and close follow-up review to exclude multiple myeloma. A recurrence of solitary intracranial plasmacytoma is possible with subtotal surgical resection despite radiation therapy. Definitive treatment should consist of complete surgical resection with adjuvant radiation therapy.

Surgery versus radiosurgery in the treatment of brain metastasis.

Surgery and radiosurgery are effective treatment modalities for brain metastasis. To compare the results of these treatment modalities, the authors followed 13 patients treated by radiosurgery and 62 patients treated by surgery who were retrospectively matched. Patients were matched according to the following criteria: histological characteristics of the primary tumor, extent of systemic disease, preoperative Karnofsky Performance Scale score, time to brain metastasis, number of brain metastases, and patient age and sex. For patients treated by radiosurgery, the median size of the treated lesion was 1.96 cm3 (range 0.41-8.25 cm3) and the median dose was 20 Gy (range 12-22 Gy). The median survival was 7.5 months for patients treated by radiosurgery and 16.4 months for those treated by surgery; this difference was found to be statistically significant using both univariate (p = 0.0018) and multivariate (p = 0.0009) analyses. The difference in survival was due to a higher rate of mortality from brain metastasis in the radiosurgery group than in the surgery group (p < 0.0001) and not due to a difference in the rate of death from systemic disease (p = 0.28). Log-rank analysis showed that the higher mortality rate found in the radiosurgery group was due to a greater progression rate of the radiosurgically treated lesions (p = 0.0001) and not due to the development of new brain metastasis (p = 0.75). On the basis of their data, the authors conclude that surgery is superior to radiosurgery in the treatment of brain metastasis. Patients who undergo surgical treatment survive longer and have a better local control. The data lead the authors to suggest that the indications for radiosurgery should be limited to surgically inaccessible metastatic tumors or patients in poor medical condition. Surgery should remain the treatment of choice whenever possible.

Management of the Dandy-Walker syndrome.

The charts of 50 patients with the Dandy-Walker Syndrome were reviewed. Initial therapy was cystoperitoneal (CP) shunt in 21 (42%), ventriculoperitoneal (VP) shunt in 13 (26%), and both (CPVP) in 7 (14%), with the remaining 9 (18%) requiring no shunting procedure. Conversion from single to double shunt secondary to expansion of the unshunted compartment occurred in 9 (42%) of CP only and 4 (30%) of VP only patients. Final therapy was CP in 12 (24%), VP in 9 (18%), CPVP in 20 (40%) and none in 9 (18%). Patients who were unshunted remained shunt-free. When CPVP shunts were present, there was a statistically significant probability that shunt malfunction was due to the CP component only or both components, but not the VP component only. However, there was no statistical difference in malfunction or complication rates between patients with CP only or VP only shunts. Associated anomalies, intellectual outcome, and mortality were also analyzed. Seizures, hearing or visual problems, various CNS abnormalities, and systemic abnormalities were associated with poor intellectual development and could be used to predict intellectual outcome.

Utilization of ascorbic acid during post-embryonic development of chick skeletal muscle.

Ascorbic acid is utilized during the post-embryonic differentiation of skeletal muscle fibres in chick. While the fibres lose their heterogeneity with regard to ascorbic acid, they continue to exhibit differences in their metabolic rates in terms of the succinate dehydrogenase activity throughout life.

Lipoma of the cerebral cortex: case report.

The first clinically diagnosed and successfully operated case of a symptomatic lipoma involving the cerebral cortex is reported. The patient presented with severe headaches and recurring focal seizures with secondary generalization. Computer tomography scan and magnetic resonance imaging suggested a left frontoparietal lipoma. After undergoing a craniotomy and tumor excision, the patient has shown resolution of headaches and seizures at 1-year follow-up. Lipomas of the cerebral cortex should be excised if symptomatic and accessible.

Primary T-cell lymphoma of the brain in acquired immunodeficiency syndrome: case report.

In patients with acquired immunodeficiency syndrome (AIDS), primary central nervous system lymphoma (PCNSL) is now the most common noninfectious intracranial mass lesion and the fourth leading cause of death. Most cases of PCNSL are B-cell in origin and are only rarely of T-cell origin. We report the first complete clinical description of T-cell PCNSL in a patient with AIDS. This patient underwent stereotactic biopsy of a cerebellar lesion that demonstrated T-cell lymphoma by immunohistochemical staining. The patient died from opportunistic infection after partial radiation therapy. Complete autopsy revealed no evidence of residual T-cell lymphoma. The authors compare T-cell PCNSL in patients with and without AIDS, and discuss differences between T-cell and B-cell PCNSL. In conclusion, T-cell PCNSL can occur in patients with AIDS. The tumor is often located infratentorially and appears to be radiosensitive. However, the patient's survival is short because death is usually caused by opportunistic infection rather than mass effect from lymphoma.

Surgical treatment of metastatic brain tumors.

The most common structural neurologic complication of systemic cancer is brain metastasis. For the most part, treatment is palliative because the majority of patients (> or = 50%) have uncontrollable systemic cancer. However, for patients in whom the only metastasis is to the brain, death is more likely to result from the metastasis than from the systemic disease; hence, treatment of the metastasis is vitally important. Although radiotherapy is generally considered the preferred treatment, surgical removal of the mass, whether single or multiple, may be the most effective palliation, especially for tumors from radio-resistant diseases such as melanoma, kidney and colon cancer. We review the information regarding therapeutic decision-making; advances in surgical procedures, namely computer-assisted stereotactic and/or intraoperative ultrasound and mapping techniques; the efficacy of postoperative WBRT; complications and benefits of surgery; our experience with reoperation for recurrent metastatic brain tumors, the results of which indicate that reoperation for recurrent brain metastasis can prolong survival and improve quality of life for most individuals; our results comparing surgery versus radiosurgery, which show that patients who undergo surgical treatment live longer and have better tumor control than those treated with radiosurgery; and the patient's prognosis. The conclusion is that surgery should remain the treatment of choice whenever possible.

Prognostic significance of proteolytic enzymes in human brain tumors.

Proteases and their inhibitors have been shown to play roles in tumor invasion and metastasis in a number of experimental models. Recently, relative increases in the amounts of urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in tumor samples have been correlated with poorer, pathological grade, shorter disease-free interval, and shorter survival. To date, all studies investigating the prognostic significance of proteases and their inhibitors have been limited to extracranial cancer. In this article, we review the literature and present our data on the prognostic significance of proteases in human brain tumors. High levels of uPA were seen in malignant glioma and metastatic tumors (n = 82), whereas normal levels of uPA were found in low-grade gliomas. Analysis with magnetic resonance imaging (MRI) demonstrated a significant correlation between high levels of uPA and necrosis and edema (n = 50; P < 0.05). Similarly, patients with high levels of uPA had shorter survival than did patients with low levels of uPA. Tissue-type plasminogen activator (tPA), which was virtually absent in glioblastoma multiforme (GBM), colon lung, and breast metastasis, was found in normal quantities in anaplastic astrocytoma (AA), low-grade glioma (LGG), and meningioma. Melanoma had significantly more tPA activity than normal brain did. A reverse correlation was found between tPA and MRI findings of necrosis, enhancement, and edema. Similarly, patients with no detectable tPA activity had shorter survival than did patients with detectable tPA activity. We conclude that high levels of uPA and absent tPA activity correlate with histologically malignant brain tumors, aggressive characteristics, and shorter survival.