Multislice CT angiography in the selection of patients with ruptured intracranial aneurysms suitable for clipping or coiling

Introduction We sought to establish whether CT angiography (CTA) can be applied to the planning and performance of clipping or coiling in ruptured intracranial aneurysms without recourse to intraarterial digital subtraction angiography (IA-DSA). Methods Over the period April 2003 to January 2006 in all patients presenting with a subarachnoid haemorrhage CTA was performed primarily. If CTA demonstrated an aneurysm, coiling or clipping was undertaken. IA-DSA was limited to patients with negative or inconclusive CTA findings. We compared CTA images with findings at surgery or coiling in patients with positive CTA findings and in patients with negative and inconclusive findings in whom IA-DSA had been performed. Results In this study, 224 consecutive patients (mean age 52.7 years, 135 women) were included. In 133 patients (59%) CTA demonstrated an aneurysm, and CTA was followed directly by neurosurgical (n=55) or endovascular treatment (n=78). In 31 patients (14%) CTA findings were categorized as inconclusive, and in 60 (27%) CTA findings were negative. One patient received surgical treatment on the basis of false-positive CTA findings. In 17 patients in whom CTA findings were inconclusive, IA-DSA provided further diagnostic information required for correct patient selection for any therapy. Five ruptured aneurysms in patients with a nonperimesencephalic SAH were negative on CTA, and four of these were also false-negative on IA-DSA. On a patient basis the positive predictive value, negative predictive value, sensitivity, specificity and accuracy of CTA for symptomatic aneurysms were 99%, 90%, 96%, 98% and 96%, respectively. Conclusion CTA should be used as the first diagnostic modality in the selection of patients for surgical or endovascular treatment of ruptured intracranial aneurysms. If CTA renders inconclusive results, IA-DSA should be performed. With negative CTA results the complementary value of IA-DSA is marginal. IA-DSA is not needed in patients with negative CTA and classic perimesencephalic SAH. Repeat IA-DSA or CTA should still be performed in patients with a nonperimesencephalic SAH

Protein alterations associated with temozolomide resistance in subclones of human glioblastoma cell lines

Temozolomide (TMZ) is the standard chemotherapeutic agent for human malignant glioma, but intrinsic or acquired chemoresistance represents a major obstacle to successful treatment of this highly lethal group of tumours. Obtaining better understanding of the molecular mechanisms underlying TMZ resistance in malignant glioma is important for the development of better treatment strategies. We have successfully established a passage control line (D54-C10) and resistant variants (D54-P5 and D54-P10) from the parental TMZ-sensitive malignant glioma cell line D54-C0. The resistant sub-cell lines showed alterations in cell morphology, enhanced cell adhesion, increased migration capacities, and cell cycle arrests. Proteomic analysis identified a set of proteins that showed gradual changes in expression according to their 50% inhibitory concentration (IC50). Successful validation was provided by transcript profiling in another malignant glioma cell line U87-MG and its resistant counterparts. Moreover, three of the identified proteins (vimentin, cathepsin D and prolyl 4-hydroxylase, beta polypeptide) were confirmed to be upregulated in high-grade glioma. Our data suggest that acquired TMZ resistance in human malignant glioma is associated with promotion of malignant phenotypes, and our reported molecular candidates may serve not only as markers of chemoresistance but also as potential therapeutic targets in the treatment of TMZ-resistant human malignant glioma, providing a platform for future investigations

ICAR: endoscopic skull‐base surgery

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