Strategies in the treatment of distal cerebellar aneurysms: report of a series of 11 patients.

BACKGROUND: Distal cerebellar artery aneurysms are rare entities and treatment modalities technically challenging. In recent years, new therapeutic options have emerged through microsurgical and endovascular means. OBJECTIVE: Based on a series of 11 cases, we describe combined interdisciplinary treatment strategies and report the outcome in a midterm follow-up interval of 12 months. METHODS: Collection of clinical case data during acute phase and follow-up including standardized angiographic control intervals during follow-up and assessment of the outcome. RESULTS: 7 of 11 reported cases had flow-related aneurysms based on an underlying arteriovenous malformation (AVM) or dural arteriovenous fistula (DAVF); we found multiple aneurysms in four cases. All patients with flow-related aneurysms presented with subarachnoid hemorrhage (SAH). Only one of four patients in this series without an underlying AVM or DAVF presented with SAH that was attributable to a distal cerebellar aneurysm. In one case, we observed a de novo formation of two flow-associated distal aneurysms (10 years interval). Two patients were treated conservatively, five patients were treated endovascularly, one patient was treated surgically and three patients were treated with combined methods. 9 of 11 patients with initial SAH had a good outcome. CONCLUSIONS: Distal cerebellar aneurysms associated with AVM or DAVF are rare but characterized by a high risk of hemorrhage. The present series indicates that an experienced interdisciplinary team and the combination of available techniques may lead to a reduction of complications and to a better outcome.

Primary hypophysitis: clinical-pathological correlations.

OBJECTIVE: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized. METHODS: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases). RESULTS: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis. CONCLUSION: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed.

Long-term relapse-free survival with supratentorial primitive neuroectodermal tumor in an adult: a case report.

OBJECTIVE: In adults, supratentorial primitive neuroectodermal tumor (sPNET) is a very rare undifferentiated embryoblastic neoplasm. Prognosis is worse in comparison to infratentorial medulloblastoma. Older age appears to be prognostically favorable. At present, 5-year survival rates remain below 50% in all age groups. Survival longer than 15 years in an adult has only been reported once so far. CASE REPORT: In 1987, a 33-year-old-male patient presented with seizures following a six-month's history of dizziness. CT- and MRI-scans revealed a right occipital tumor with moderate contrast enhancement. The tumor was completely removed. The original histological diagnosis was that of an undifferentiated sarcoma, malignant hemangioendothelioma, grade III. The patient was treated by CyVADIC chemotherapy and conventional radiation therapy (60 Gy). Admission for another reason in 2003 led to a re-evaluation of the original diagnosis. Microscopy revealed a malignant, highly cellular, poorly differentiated tumor with a desmoplastic component. Up to 20% of tumor nuclei were labeled for Ki-67. Almost all cells were stained for neuron specific enolase and NGF-Rp75, with neuronal and glial markers being present to a variable extent. According to these findings, the diagnosis was changed to a sPNET (WHO IVdegrees ). Other tumor entities were excluded by immunohistochemistry. CONCLUSIONS: Although the prognosis of sPNET is reported to be poor, a small fraction with a rather benign biological and clinical behavior exists. Parameters determining long-term-survival in sPNET are not yet known. Whenever possible, complete surgical resection should be attempted followed by postoperative radiotherapy. The value of chemotherapy is an issue of continuous investigation.

CD44 expression and tumour cell density correlate with response to tamoxifen/carboplatin chemotherapy in glioblastomas.

In order to identify response predictors for a post-operative glioblastoma therapy consisting of tamoxifen, carboplatin and radiotherapy, expression of 12 antigens was evaluated in 36 newly diagnosed tumours and 13 recurrences. Results were correlated with the clinical course of the disease. Antigen expression was assessed immunohistochemically for CD44s, TGF-beta2, TGF-alpha, progesterone receptor, estrogen receptor, EGFR, urokinase, urokinase inhibitor 1, CD87, p53 protein and Ki-67. Vessel density was determined by labelling of endothelia with von Willebrand factor. Response to chemotherapy correlated positively with cell density (p < 0.05) and negatively with CD44 over-expression (p < 0.02). Further, a positive correlation between age and CD44 expression (p < 0.05) and a negative correlation between age and p53 accumulation (p < 0.01) was found. In tumour recurrences expression of CD44 was significantly higher in local recurrences than in distant multifocal recurrences (p < 0.02), suggesting that CD44 may predominantly be associated with cell adhesion in glioblastomas.

High-dose tamoxifen treatment increases the incidence of multifocal tumor recurrences in glioblastoma patients.

BACKGROUND: Multifocal tumor recurrences in glioblastoma patients are described in 4% - 14% of cases. Two recent studies, treating newly diagnosed glioblastoma patients with continuous high-dose tamoxifen (TAM), reported an increased incidence of multifocal tumor recurrences in 45.5% and 33% of study patients. PATIENTS AND METHODS: Fifty newly diagnosed patients with glioblastoma were treated with 3 cycles of carboplatin, continuous high-dose TAM and radiotherapy. Tumor progression was determined on follow-up MRI studies at 3-month intervals and categorized as either local or multifocal. RESULTS: Multifocal tumor recurrence was found in 16 (33%) out of 49 study patients. Compared to tumors which remained local, multifocal tumor recurrences were characterized by a significantly longer median time to tumor progression (41 vs. 23 weeks, Breslow test: p = 0.0123). Multifocal tumor recurrences were mainly observed after an initial response to the study treatment (81%), whereas local regrowth was more often associated with initial treatment failure, i.e. progressive disease (64%). CONCLUSION: The association of the pattern of tumor recurrence with the type of response to TAM treatment suggests that acquired resistance to TAM might be an important contributing mechanism in the development of multifocal glioblastoma disease.

The influence of tamoxifen on the secretion of transforming growth factor-beta2 (TGF-beta2) in glioblastomas: in vitro and in vivo findings.

BACKGROUND: Only a minority of patients with malignant gliomas respond to continuous high-dose tamoxifen (TAM) treatment. Therefore a method to predict the efficiency of TAM-treatment would be desirable. Analogous to previous studies in breast cancer patients, we investigated whether the dynamics of TGF-beta2 plasma levels allow the prediction of response to TAM-treatment in glioblastoma patients as well. MATERIALS AND METHODS: TGF-beta2 plasma levels of glioblastoma patients treated with 200 mg TAM/day on a continuous basis and of control patients not treated with TAM were measured by using an ELISA. In addition, the effect of TAM and 4-OH-TAM on the secretion of TGF-beta2 by established glioma cell lines as well as the effect of TGF-beta2 itself on cell proliferation were investigated in vitro. RESULTS: The effect of TAM on TGF-beta2 plasma levels did not correlate with the clinical response to TAM-therapy in glioblastoma patients. The in vitro experiments showed that TAM and 4-OH-TAM stimulate established glioma cell lines to increase their secretion of TGF-beta2. Externally added TGF-beta2 (nM) had no effect on cell proliferation of the same cell lines. CONCLUSION: In contrast to breast cancer patients, the clinical response to TAM in glioblastoma patients is not reflected by changes of TGF-beta2 plasma levels. It has to be assumed that, despite an increase of TGF-beta2 production by glioblastoma cells in response to TAM in vitro, such elevated production in vivo does not reach the plasma due to either the lower tumor burden in glioblastoma disease compared to breast cancer patients or due to some local sequestration process.

In vivo labeling with1251-CRH of human ACTH-producing pituitary adenomas heterotransplanted to nude mice.

Tissue from 23 pituitary adenomas causing Cushing's disease was implanted subcutaneously into 159 NuNu/NMRi mice, resected after 21 or 35 days, and evaluated histologically and immunohistochemically. After 21 days, 74.3% of the grafts survived, 59% having less than 30% necrotic adenoma cells. After 35 days, 45% of the adenoma fragments survived, 37% having less than 30% necrotic adenoma cells. The preservation of the grafts was essentially dependent on the grade of vascularization accomplished by migration of the host's capillaries. As assessed by adrenal weight and histologically, biological activity of the transplants could not be detected. Histologically, the grafts maintained the features of their primary tumors, and adrenocorticotropic hormone (ACTH) could be visualized immunohistologically.Seventeen mice with subsequently proved preserved adenoma tissue received an intravenous injection of 12.5 µCi125l-corticotropin-releasing hormone (CRH) and light microscopy-autoradiography was performed. Specific labeling, as verified by positive and negative controls, was exhibited by 1 1 of 15 transplants originating from 3 highly differentiated ACTH cell adenomas. Four did not label clearly positive. Two grafts of an undifferentiated mucoid cell pituitary adenoma did not show any labeling.The nude mouse model is a useful tool for the study of ACTH-producing pituitary adenomas in vivo. Highly differentiated ACTH cell adenomas can be labeled with radioactive CRH in vivo.