A retrospective cohort study assessing geometrical parameters related to visual deterioration in pituitary macroadenoma.

PURPOSE: We aim to identify specific parameters that will allow identification of those patients at greater risk of vision loss, specifically variables such as geometry, volume and size of the pituitary tumour. METHODOLOGY: Volume measurements were made with both manual (using the formula width × height × length × 0.5) and video size, sub-voxel interpolation using Brainlab software. The shape of the tumour was divided into four categories, ovoid, dumbbell, pyramidal and other. Chiasmal compression was divided into central and lateral compression and the chiasm location was classified based on pre/post and normal fixed chiasm in relation to the tuberculum sella. We used a visual impairment score ranging from (0-100), which was then further subdivided in to four grades: Grade I - 0-25 (mild); Grade II - 26-50 (moderate); Grade III - 51-75 (severe); Grade IV - 76-100 (subtotal or complete). RESULTS: Univariate analysis of variables related to vision loss found tumour volume, suprasellar growth and lateral chiasmal compression related to pre-operative vision loss. On multivariate regression analysis tumour volume and lateral chiasmal compression remained significant (p < 0.008). In relation to post-operative vision, univariate analysis indicated that variables such as giant macroadenoma, pre-operative visual impairment score and suprasellar growth were significant. Multivariate analysis showed pre-operative visual impairment and suprasellar growth as the only statistically significant variables. CONCLUSION: Our ROC analysis suggests tumours with suprasellar extension 16 mm (sensitivity 85 %, specificity 67 %) in sagittal plane are more likely to result in moderate to severe grade vision loss (VIS grade ≥ 2).

Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations.

INTRODUCTION: Gamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations. METHODOLOGY: A retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar's test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model. RESULTS: Thirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12-13). The median follow-up duration from GKSRS was 809 days (IQR 536-960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008-0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004-1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074-0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS. CONCLUSION: GKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

Rare Primary Pleomorphic Adenoma in Posterior Fossa.

BACKGROUND: Pleomorphic adenoma is a benign neoplastic tumor of the salivary gland. Salivary gland tumors in the intracranial cavity are generally restricted to the pituitary gland and sellar region. To our knowledge, there has been only 1 previous case report of a primary central nervous system pleomorphic adenoma outside of the sellar region. In that case report of a posterior fossa pleomorphic adenoma, typical myxochondroid stroma was not identified on histology, and its pathogenesis was not explored. CASE DESCRIPTION: A 71-year-old woman presented with a 6-week history of occipital headache and unsteadiness. Contrast-enhanced computed tomography and magnetic resonance imaging studies revealed a solitary large posterior fossa tumor in the left cerebellopontine angle measuring 47 × 43 × 45 mm. The tumor resulted in moderate hydrocephalus and significant mass effect with compression of the pons and medulla. She underwent a stereotactic right ventriculoperitoneal shunt insertion followed by a stereotactic craniotomy and complete excision of the tumor. The operation went uneventfully, and the patient had an uncomplicated recovery. Histopathologic examination revealed a benign pleomorphic adenoma (benign salivary gland tumor) with a classic appearance comprising an admixture of ductal epithelial cells, myoepithelial elements, and nodules of myxochondroid stroma. No extracranial source has been identified despite extensive investigation and 8 years of follow-up. CONCLUSIONS: This case study illustrates a classic primary central nervous system pleomorphic adenoma in an unusual intracranial site. Its pathogenesis is postulated to involve salivary gland heterotopia.

Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors.

Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state. In other patient lines hyperdiploid cells display genetic drift in vitro and in vivo, suggesting that in these patients hyperdiploidy is a transient cell state that generates novel phenotypes, potentially facilitating rapid tumor evolution. We show that the hyperdiploid cells are resistant to conventional therapy, in part due to infrequent cell division due to a delay in the G0/G1 phase of the cell cycle. Hyperdiploid tumor cells are significantly larger and more metabolically active than euploid cancer cells, and this correlates to an increased sensitivity to the effects of glycolysis inhibition. Together these data identify GB hyperdiploid tumor cells as a potentially important subpopulation of cells that are well positioned to contribute to tumor evolution and disease recurrence in adult brain cancer patients, and suggest tumor metabolism as a promising point of therapeutic intervention against this subpopulation.

Relationship between CT anthropometric measurements, adipokines and abdominal aortic calcification.

BACKGROUND: Visceral obesity and aortic calcification are both associated with cardiovascular events. The purpose of this study was to examine if visceral obesity was associated with the severity of abdominal aortic calcification. METHODS: One hundred and forty eight patients with peripheral artery disease were assessed by CT angiography. The severity of infrarenal abdominal aortic calcification was measured using a validated technique. The size of the visceral and subcutaneous compartments was estimated from anthropometric measurements made from the same CT. Calcification and anthropometric measurements were compared with Spearman's correlation and multiple logistic regression (adjusting for age, gender, hypertension, diabetes, smoking and cholesterol). RESULTS: The relative size of the visceral compartment estimated from CT diameter ratios was correlated with abdominal aortic calcification severity, r=0.27, p=0.001 and independently associated with calcification allowing for other cardiovascular risk factors (OR 6.63, 95% CI 1.90-23.14). The relative size of the visceral compartment was associated with serum osteoprotegerin levels, suggesting a possible mechanism underlying the detrimental influence of visceral adiposity. CONCLUSION: The association of visceral adiposity and arterial calcification suggests one mechanism, which may contribute to the detrimental effects of central obesity.