Publications (27) View all
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Article: Anti-tissue factor (TF9-10H10) treatment reduces tumor cell invasiveness in a novel migratory glioma model.
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ABSTRACT: In vitro and descriptive studies of human tissue samples revealed the pro-coagulant glycoprotein tissue factor (TF) as a potent player in glioma cell infiltration that is activated by hypoxia and has also been shown to be upregulated by mutations of TP53 or PTEN. Here we present the morphological and genetic characterization of a novel glioblastoma in vivo model and provide evidence that treatment with an antibody targeting TF leads to reduced glioma cell invasiveness. Therefore, we established a murine xenograft treatment model by transplanting the angiogenic and diffusely infiltrating human glioma cell line MZ-18 with endogenous TF expression into nude mice brains and treating these mice with an intracranial osmotic pump system continuously infusing a monoclonal antibody against TF (mAb TF9-10H10). The human MZ-18 cell line harbors two TP53 mutations resulting in a strong nuclear accumulation of p53, thereby facilitating the unambiguous identification of tumor cells in the xenograft model. Intracranial application of TF9-10H10 significantly reduced invasion of MZ-18 cells compared to mock-treated control animals. The extent of activated blood vessels was also reduced upon anti-TF treatment. Thus, targeting the TF pathway might be a promising treatment strategy for future glioblastoma therapies, by affecting both invading tumor cells and tumor vasculature.Neuropathology 02/2013; · 2.02 Impact Factor -
Article: On the value of routine prothrombin time screening in elective neurosurgical procedures.
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ABSTRACT: Object The authors performed a study to evaluate whether preoperative assessment of prothrombin time (PT) is mandatory in patients undergoing routinely planned neurosurgical procedures. Methods The charts of all patients admitted to general wards of the authors' department for routinely planned surgery (excluding trauma and ICU patients) between 2006 and 2010 were retrospectively reviewed. The authors assessed preoperative PT and the clinical courses of all patients, with special consideration for patients receiving coagulation factor substitution. All cases involving hemorrhagic complications were analyzed in detail with regard to pre- and postoperative PT abnormalities. Prothrombin time was expressed as the international normalized ratio, and values greater than 1.28 were regarded as elevated. Results Clinical courses and PT values of 4310 patients were reviewed. Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat surgery. Thirty-one patients (94%) had a normal PT before the initial operation, while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were anticipated based on the patient's history. In the latter 2 cases, surgery was performed without prior correction of PT. Preoperatively, PT was elevated in 78 patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected and explained by each patient's medical history. In only 5 (0.1%) of 4310 patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All 5 patients underwent surgery without complications, while 2 had received coagulation factor substitution preoperatively, as requested by the surgeon, because of an estimated risk of bleeding complications. None of the 5 patients received coagulation factor substitution postoperatively, and later detailed laboratory studies ruled out single coagulation factor deficiencies. There was no statistically significant association between preoperatively elevated PT levels and the occurrence of hemorrhagic complications (p = 0.12). Before the second procedure but not before the initial operation, 4 (12%) of the 33 patients had elevated PT. Conclusions The findings suggest that the value of preoperative PT testing is limited in patients in whom a normal history can be ascertained. Close postoperative PT control is necessary in every neurosurgical patient, and better tests need to be developed to identify patients who are prone to hemorrhagic complications.Neurosurgical FOCUS 11/2012; 33(5):E9. · 2.87 Impact Factor -
Article: Motor cortex evaluation by nTMS after surgery of central region tumors: a feasibility study.
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ABSTRACT: Largely discussed during the past decade, motor cortex reorganization in brain tumor surgery has been investigated only by few studies. We therefore aimed to investigate cortical motor representation after resection of perirolandic WHO grade II and III gliomas using navigated transcranial magnetic stimulation (nTMS). Five patients were examined before neurosurgery and after a follow-up period of 17.7 ± 6.8 months. As a control, five healthy age-matched subjects were equally studied by nTMS in two sessions spaced 12.6 (range 2-35) days apart. Resting motor thresholds (RMT), hotspots and centers of gravity (CoG) were identified for the first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum (EXT), tibialis anterior (TA) and abductor hallucis (AH) muscles. Euclidian distances, coefficients of variance and intraclass correlation coefficients (ICC) were calculated. Healthy subjects showed moderate to excellent reliability measurement of RMT (ICC = 0.69-0.94). Average displacement of CoGs across sessions was 0.68 ± 0.34 cm in the dominant and 0.76 ± 0.38 cm in the non-dominant hemisphere; hotspots moved 0.87 ± 0.51 cm and 0.83 ± 0.45 cm, respectively. In one patient these parameters differed significantly from the control group (p < 0.05 for both CoGs and hotspots). Overall, all patients' CoGs moved 1.12 ± 0.93 cm, and hotspots were 1.06 ± 0.7 cm apart. In both patients and healthy subjects, movement of assessed parameters was more important along the X- than the Y-axis. nTMS allows evaluating cortical reorganization after brain tumor surgery. It may contribute to the understanding of neurofunctional dynamics, thus influencing therapeutic strategy.Acta Neurochirurgica 06/2012; 154(8):1351-9. · 1.52 Impact Factor -
Article: Optimizing the extent of resection in eloquently located gliomas by combining intraoperative MRI guidance with intraoperative neurophysiological monitoring.
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ABSTRACT: Several methods have been introduced to improve the extent of resection in glioma surgery. Yet, radical tumor resections must not be attempted at the cost of neurological deterioration. We sought to assess whether the use of an intraoperative MRI (iMRI) in combination with multimodal neurophysiological monitoring is suitable to increase the extent of resection without endangering neurological function in patients with eloquently located gliomas. Fifty-four patients were included in this study. In 21 patients (38.9 %), iMRI led to additional tumor resection. A radiologically complete resection was achieved in 31 patients (57.4 %), while in 12 of these, iMRI had depicted residual tumor tissue before resection was continued. The mean extent of resection was 92.1 % according to volumetric analyses. Postoperatively, 13 patients (24.1 %) showed new or worsening of pre-existing sensory motor deficits. They were severe in 4 patients (7.4 %). There was no correlation between the occurrence of either any new (P = 0.77) or severe (P = 1.0) sensory motor deficit and continued resection after intraoperative image acquisition. Likewise, tumor location, histology, and tumor recurrence did not influence complication rate on uni- and multivariate analysis. We conclude that the combination of iMRI guidance with multimodal neurophysiological monitoring allows for extended resections in glioma surgery without inducing higher rates of neurological deficits, even in patients with eloquently located tumors.Journal of Neuro-Oncology 04/2012; 109(1):81-90. · 3.21 Impact Factor -
Article: Risk of ischemia in glioma surgery: comparison of first and repeat procedures.
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ABSTRACT: The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm(3). Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P = 0.77) or neurological deficits (10.0 vs. 10.6%, P = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.Journal of Neuro-Oncology 01/2012; 107(3):599-607. · 3.21 Impact Factor
