Intracerebral fibroma: a case report and review of the literature.

Intracerebral fibromas are among the most rare neoplasms found in the central nervous system. Ten previously reported cases have been documented in the literature including only two reported cases since 1985. As a result, little is known about these uncommon intracerebral fibrous tumors. We report a case of an intracerebral fibroma without dural or leptomeningeal attachment, discuss the pertinent diagnostic findings and briefly review all prior reports of this entity.

Brain metastases from cervical cancer--a short review.

AIMS AND BACKGROUND: Brain metastases from cervical cancer are extremely rare yet local recurrence and systemic spread is fairly common. The role of surgical resection and CNS screening for this pathology was interrogated from a review of the literature. CLINICAL EXPERIENCE: We present a case of a single brain metastasis that originated from the cervix and describe chronologically the spread of the disease with pathological confirmations. REVIEW: Following an extensive English literature search, which only yielded 59 reported cases (n = 60 including the present case), we extrapolated basic trends regarding the demographics, pathophysiology, and treatment that portended a longer survival. Despite treatment, the majority of patients do not survive past 1 year from diagnosis of intracranial metastasis. A trend towards prolonged survival was observed among patients who received surgical resection of the brain metastasis. CONCLUSIONS: Cervical carcinoma has been documented to metastasize to the brain, and this may occur via initial seeding of the lungs. Surgical resection and CNS screening may have beneficial roles in the management of metastatic cervical carcinoma.

Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma.

Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ((186)Re)-liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of (186)Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 µL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with (186)Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4-173 days), compared with 49 days (95% CI, 44-53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (χ(2)[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (χ(2)[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by (186)Re-liposomes convection-enhanced delivery in glioma.

Isolated spinal neurenteric cyst presenting as intramedullary calcified cystic mass on imaging studies: case report and review of literature.

Intramedullary neurenteric cysts (NEC) without associated malformations are extremely rare and, to our knowledge, have never been reported in association with calcification. We report a unique imaging presentation as a partially calcified mass of an isolated intramedullary neuroenteric cyst of the lower thoracic spinal cord with pathologic correlation. The literature for isolated forms of intramedullary NEC since the advent of magnetic resonance imaging is also reviewed.

Human bone marrow-derived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Delta24-RGD to human gliomas.

Delta24-RGD is an infectivity-augmented, conditionally replicative oncolytic adenovirus with significant antiglioma effects. Although intratumoral delivery of Delta24-RGD may be effective, intravascular delivery would improve successful application in humans. Due to their tumor tropic properties, we hypothesized that human mesenchymal stem cells (hMSC) could be harnessed as intravascular delivery vehicles of Delta24-RGD to human gliomas. To assess cellular events, green fluorescent protein-labeled hMSCs carrying Delta24-RGD (hMSC-Delta24) were injected into the carotid artery of mice harboring orthotopic U87MG or U251-V121 xenografts and brain sections were analyzed by immunofluorescence for green fluorescent protein and viral proteins (E1A and hexon) at increasing times. hMSC-Delta24 selectively localized to glioma xenografts and released Delta24-RGD, which subsequently infected glioma cells. To determine efficacy, mice were implanted with luciferase- labeled glioma xenografts, treated with hMSC-Delta24 or controls, and imaged weekly by bioluminescence imaging. Analysis of tumor size by bioluminescence imaging showed inhibition of glioma growth and eradication of tumors in hMSC-Delta24-treated animals compared with controls (P < 0.0001). There was an increase in median survival from 42 days in controls to 75.5 days in hMSC-Delta24-treated animals (P < 0.0001) and an increase in survival beyond 80 days from 0% to 37.5%, respectively. We conclude that intra-arterially delivered hMSC-Delta24 selectively localize to human gliomas and are capable of delivering and releasing Delta24-RGD into the tumor, resulting in improved survival and tumor eradication in subsets of mice.

Extended lateral parascapular approach for resection of a giant multi-compartment thoracic schwannoma.

BACKGROUND: Resection of giant thoracic schwannomas is challenging and usually requires a staged approach. The resection of the intraspinal component, usually via laminectomy, is done in one sitting and the intrathoracic component, via thoracotomy, follows at another. We describe the complete resection of a massive multi-compartmental thoracic schwannoma by an extended lateral parascapular approach. METHOD AND FINDINGS: The tumor, which presented with local pain and scapular displacement, had intrathoracic paraspinal (10 x 5 x 4 cm), posterolateral upper thoracic paramuscular (19 x 7 x 4 cm), foraminal, and epidural components. It was removed at a single sitting, via a posterior extended lateral parascapular approach that did not require staged procedures, multiple incisions, or repositioning of the patient. This operation included resection of the thoracic, foraminal, and intraspinal components and posterior stabilization with pedicle screws and rods. There were no postoperative neurological complications. CONCLUSIONS: The extended lateral parascapular approach allows complete resection of giant multi-compartment schwannomas of the thoracic spine that extend from the canal into the thoracic cavity. It also permits posterior stabilization through the same incision used for tumor removal.

Population-based study of medulloblastoma: outcomes in Alberta from 1975 to 1996.

BACKGROUND: The purpose of this study was to determine incidence, survival rate, and prognostic factors as well as the frequency of Collins' Law Violators (CLVs) in an unselected population of medulloblastoma patients. Collins' Law dictates that 'cure' of a child with a tumor occurs after a period that includes the child's age at diagnosis plus 9 months. METHODS: Using the Alberta Cancer Registry a population-based review identified 49 patients with medulloblastoma (19 adults, 30 children) diagnosed from 1975-96. Pathology was reviewed in all cases. All patients had surgical resection, followed by radiotherapy in 47 patients and chemotherapy in 17. RESULTS: The overall 5-year survival was 50%. There was a trend for the extent of resection to be associated with a longer survival (Long rank test, p < 0.06) but this was not significant. Tumor recurrence occurred a median of 22.4 months (range, 6.4-192.3) after diagnosis and median survival after recurrence was 9.3 months (range, 0.4-64.9). The survival curve did not appear to plateau but was affected by tumor-related deaths in 3 (21.4%) of the 21 long-term survivors diagnosed in childhood. These three patients had recurrences a mean of 11.7 years after diagnosis and are designated as CLVs. CONCLUSIONS: The survival rate in an unselected population of patients with medulloblastoma is poor. Aggressive resection of the tumors prolongs survival. The Collins' Law Violators were relatively common and we suggest this concept be abandoned in medulloblastoma.

Interferon-induced hypothyroidism causing reversible pituitary enlargement.

OBJECTIVE: To present the first reported case of interferon-induced hypothyroidism with radiographic confirmation of secondary pituitary hyperplasia. METHODS: We describe the case of a woman with recurrent malignant melanoma, outline the details of her endocrine work-up, and illustrate the serial findings on magnetic resonance imaging of the head. RESULTS: A 26-year-old woman underwent surgical excision of a melanoma of the left thigh and 10 years later had a second melanoma removed from her right knee. Metastatic work-up revealed evidence of tumor involvement in the cervical and mediastinal lymph nodes. After treatment with interferon for 1 year, persistent fatigue and menstrual irregularities led to the laboratory diagnosis of hypothyroidism, and magnetic resonance imaging revealed pituitary enlargement. Both her endocrinopathy and the pituitary hyperplasia resolved with discontinuation of the interferon treatment and with institution of thyroid replacement therapy. CONCLUSION: Clinicians should be aware of the potential adverse effects of interferon therapy to avoid inappropriate diagnosis of a pituitary adenoma or metastatic lesion in patients with cancer who are treated with interferon. In addition, screening for hypothyroidism should be performed in patients receiving interferon.

Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas.

The poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor. Because it has been suggested that circulating bone marrow-derived stem cells can be recruited into solid organs in response to tissue stresses, we hypothesized that human bone marrow-derived mesenchymal stem cells (hMSC) may have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. To test this, we isolated hMSCs from bone marrow of normal volunteers, fluorescently labeled the cells, and injected them into the carotid artery of mice bearing human glioma intracranial xenografts (U87, U251, and LN229). hMSCs were seen exclusively within the brain tumors regardless of whether the cells were injected into the ipsilateral or contralateral carotid artery. In contrast, intracarotid injections of fibroblasts or U87 glioma cells resulted in widespread distribution of delivered cells without tumor specificity. To assess the potential of hMSCs to track human gliomas, we injected hMSCs directly into the cerebral hemisphere opposite an established human glioma and showed that the hMSCs were capable of migrating into the xenograft in vivo. Likewise, in vitro Matrigel invasion assays showed that conditioned medium from gliomas, but not from fibroblasts or astrocytes, supported the migration of hMSCs and that platelet-derived growth factor, epidermal growth factor, or stromal cell-derived factor-1alpha, but not basic fibroblast growth factor or vascular endothelial growth factor, enhanced hMSC migration. To test the potential of hMSCs to deliver a therapeutic agent, hMSCs were engineered to release IFN-beta (hMSC-IFN-beta). In vitro coculture and Transwell experiments showed the efficacy of hMSC-IFN-beta against human gliomas. In vivo experiments showed that treatment of human U87 intracranial glioma xenografts with hMSC-IFN-beta significantly increase animal survival compared with controls (P < 0.05). We conclude that hMSCs can integrate into human gliomas after intravascular or local delivery, that this engraftment may be mediated by growth factors, and that this tropism of hMSCs for human gliomas can be exploited to therapeutic advantage.

Resection of brain metastases previously treated with stereotactic radiosurgery.

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.

Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic adenoviruses.

Adenoviruses have been critical in the development of the molecular approaches to brain tumors. They have been engineered to function as vectors for delivering therapeutic genes in gene therapy strategies, and as direct cytotoxic agents in oncolytic viral therapies. This review outlines the uses of adenoviruses in brain tumor therapy by examining clinical trials of adenovirus-mediated p53 gene therapy and by reviewing the application of two conditionally replicative adenoviruses (CRAds) ONYX-015 and Delta 24 in brain tumors. The potential clinical use of CRAds that deliver trangenes, particularly p53, is also discussed.

Surgical resection of metastatic intraventricular tumors.

The ventricle is a rare site of brain metastases. Renal cell carcinoma has a higher propensity to metastasize to the ventricle compared with more common metastatic tumors (e.g., lung cancer). The trigone is the predominant location for intraventricular metastases, presumably because of the high concentration of choroid plexus in this region. Surgical resection is an important component of the management of these lesions, particularly if there is only a single intraventricular lesion. Despite the deep location of these tumors within the ventricle, survival in patients undergoing surgery for them is comparable to that in patients receiving surgery for intraparenchymal metastases.