COXIBRAIN: results of the prospective, randomised, phase II/III study for the selective COX-2 inhibition in chronic subdural haematoma patients.

BACKGROUND: Chronic subdural haematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The recurrence rate of cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclo-oxygenase-2 (COX-2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks' time postoperatively in comparison to a control group. METHOD: The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher's exact test (significance level of alpha, 0.05 [two-sided]). RESULTS: After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers. CONCLUSIONS: The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors.

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells.

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.

Computed tomographic angiography: diagnostic procedure of choice in the management of subarachnoid hemorrhage in the elderly patient?

BACKGROUND: The objective of this study was to establish whether 3D computed tomographic angiography (CTA) can be used to determine further management in patients older than 70 years admitted with acute subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: CTA evaluation included analysis of the source images, image-slice-based multiplanar reconstruction, multi-intensity projection (MIP) and finally 3-dimensional rendering. The location and size of the aneurysm, its precise anatomical morphology and the configuration of the circle of Willis were evaluated. Based on these findings, surgery, endovascular coiling or conservative management was selected. RESULTS: Between October 2001 and June 2005, 44 patients over 70 years of age (38 females, 6 males) were admitted to our neurosurgical department with acute SAH. All patients underwent CTA, and additional 2D digital subtraction angiography (2D-DSA) was performed in 14 patients. Forty-five aneurysms (38 ruptured and 7 unruptured) were diagnosed. Six patients were found to have SAH of unknown origin (no aneurysm on CTA nor 2D-DSA). In 20 patients surgery was performed, in 10 patients endovascular coiling of the aneurysm was carried out, and 12 patients were treated conservatively. The findings on CTA and 2D-DSA could be compared for 26 patients (59%). Correlation between CTA and 2D-DSA was good in 25 of these cases (96%). Glasgow Outcome Scale scores of 4 or 5 were calculated for 37% of the operated patients, 27% of those treated with coils, and 36% of the patients treated conservatively. CONCLUSION: In older patients with degenerative vascular diseases, CTA can replace 2D-DSA in most cases if the image quality is excellent and analysis is performed carefully.

[Pigmented villonodular synovitis involving the thoracic spine: a case report]. / Pigmentierte villonoduläre Synovitis der thorakalen Wirbelsäule - operatives Langzeitergebnis: ein Fallbericht.

Spinal diffuse-type giant cell tumours (also known as pigmented villonodular synovitis [PVNS]) are benign. Their occurrence in the thoracic spine is a very rare entity, nevertheless it should be considered in the differential diagnosis. We report about the case of a 35-year-old male presenting with an osteolytic and expansive mass compressing the spinal cord from C7 to Th2. Surgical resection was performed. Histopathological diagnosis was PVNS. 2 years postoperatively the patient was without pain and fully reintegrated in his previous job as a physician.