Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons.Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT.Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin.Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.peer-reviewe

Endovascular Treatment of Anterior Circulation Cerebral Aneurysms by Using Guglielmi Detachable Coils: A 10-Year Single-Center Experience with Special Emphasis on the Use of Three-Dimensional GDC

Purpose:: To analyze the immediate, long-term angiographic and clinical results of endovascular treatment of anterior circulation aneurysms with special regard to the use of three-dimensional Guglielmi detachable coils (3D-GDC). Patients and Methods:: Between 1993 and 2003, 116 patients with 116 anterior circulation aneurysms were treated. 88 patients (75.9%) underwent embolization due to high surgical risk. To analyze the use of 3D-GDC, patients treated before (group 1) and after (group 2) implementation of 3D-GDC in 1999 were compared. Mean duration of angiographic follow-up was 13.9 months. Clinical follow-up was set at hospital discharge and using a questionnaire for long-term follow-up (mean 46.8 months). Results:: Overall, at initial intervention, complete occlusion was achieved in 65 aneurysms (56.0%), neck remnant in 42 (36.2%), and incomplete occlusion in nine (7.8%). Procedure-related permanent morbidity was 4.3% and mortality 2.6%. Recanalization rate at radiologic follow-up was 16.7%. Occlusion success at initial treatment correlated with aneurysm neck size (p = 0.001). Clinical outcome at hospital discharge was dependent on Hunt & Hess grade at presentation (p = 0.01). Subgroup analysis revealed that the use of 3D-GDC produced a higher initial obliteration rate compared to standard coils, but did not reach statistical significance (p = 0.059). Neither aneurysm neck size nor aneurysm dome size nor the use of 3D-GDC significantly influenced recanalization rate. Conclusion:: GDC technology is effective and safe, particularly in case of patients with high surgical risk. Aneurysm neck size was predictive of occlusion rate and Hunt & Hess grade of clinical outcome. Introduction of 3D-GDC probably improved occlusion rate, but did not significantly influence recanalization rat

Experimental determination of Lamb wave dispersion diagrams over large frequency ranges in fiber metal laminates

Fiber metal laminates (FML) are of high interest for lightweight structures as they combine the advantageous material properties of metals and fiber-reinforced polymers. However, low-velocity impacts can lead to complex internal damage. Therefore, structural health monitoring with guided ultrasonic waves (GUW) is a methodology to identify such damage. Numerical simulations form the basis for corresponding investigations, but experimental validation of dispersion diagrams over a wide frequency range is hardly found in the literature. In this work the dispersive relation of GUWs is experimentally determined for an FML made of carbon fiber-reinforced polymer and steel. For this purpose, multi-frequency excitation signals are used to generate GUWs and the resulting wave field is measured via laser scanning vibrometry. The data are processed by means of a non-uniform discrete 2d Fourier transform and analyzed in the frequency-wavenumber domain. The experimental data are in excellent agreement with data from a numerical solution of the analytical framework. In conclusion, this work presents a highly automatable method to experimentally determine dispersion diagrams of GUWs in FML over large frequency ranges with high accuracy

Endovascular and surgical treatment of spinal dural arteriovenous fistulas

Introduction: The aim of this retrospective study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas (SDAVFs) that were treated with surgery, catheter embolization, or surgery after incomplete embolization. Methods: The study included 21 consecutive patients with SDAVFs of the thoracic, lumbar, or sacral spine who were treated in our institution from 1994 to 2007. Thirteen patients were treated with catheter embolization alone. Four patients underwent hemilaminectomy and intradural interruption of the fistula. Four patients were treated by endovascular techniques followed by surgery. The clinical outcome was assessed using the modified Aminoff-Logue scale (ALS) for myelopathy and the modified Rankin scale (MRS) for general quality of life. Patient age ranged from 44 to 77years (mean 64.7years). Results: Surgical as well as endovascular treatment resulted in a significant improvement in ALS (−62.5% and −31.4%, respectively, p < 0.05) and a tendency toward improved MRS (−50% and −32%, respectively) scores. Patients that underwent surgery after endovascular treatment due to incomplete occlusion of the fistula showed only a tendency for improvement in the ALS score (−16.7%), whereas the MRS score was not affected. Conclusion: We conclude that both endovascular and surgical treatment of SDAVFs resulted in a good and lasting clinical outcome in the majority of cases. In specific situations, when a secondary neurosurgical approach was required after endovascular treatment to achieve complete occlusion of the SDAVF, the clinical outcome was rather poor. The best first line treatment modality for each individual patient should be determined by an interdisciplinary tea

Intracerebral delivery of Carboplatin in combination with either 6 MV Photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.

International audienceABSTRACT: BACKGROUND: The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. METHODS: Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6 days using AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8 keV synchrotron X-rays. RESULTS: Untreated control animals had a median survival time (MeST) of 33 days. Animals that received either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a MeSTs 38 and 33 days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons. CONCLUSIONS: These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays

Intracerebral delivery of 5-iodo-2'-deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma.

International audienceIodine-enhanced synchrotron stereotactic radiotherapy takes advantage of the radiation dose-enhancement produced by high-Z elements when irradiated with mono-energetic beams of synchrotron X-rays. In this study it has been investigated whether therapeutic efficacy could be improved using a thymidine analogue, 5-iodo-2'-deoxyuridine (IUdR), as a radiosentizing agent. IUdR was administered intracerebrally over six days to F98 glioma-bearing rats using Alzet osmotic pumps, beginning seven days after tumor implantation. On the 14th day, a single 15 Gy dose of 50 keV synchrotron X-rays was delivered to the brain. Animals were followed until the time of death and the primary endpoints of this study were the mean and median survival times. The median survival times for irradiation alone, chemotherapy alone or their combination were 44, 32 and 46 days, respectively, compared with 24 days for untreated controls. Each treatment alone significantly increased the rats' survival in comparison with the untreated group. Their combination did not, however, significantly improve survival compared with that of X-irradiation alone or chemotherapy alone. Further studies are required to understand why the combination of chemoradiotherapy was no more effective than X-irradiation alone

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients

Background: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature. Methods: From 1998 to 2009 we treated 586 consecutive patients with CEA. CEA was performed, under general anesthesia, with a surgical microscope using a non-patch technique. Somatosensory evoked potential and transcranial Doppler were continuously monitored. Cross-clamping was performed under EEG burst suppression and adaptive blood pressure increase. Follow-up was performed by an independent neurologist. Mortality at 30 days and morbidity such as major and minor stroke, peripheral nerve palsy, hematoma and cardiac complications were recorded. The restenosis rate was assessed using duplex sonography 1 year after surgery. Results: A total of 439 (75%) patients had symptomatic and 147 (25%) asymptomatic stenosis; 49.7% of the stenoses were on the right-side. Major perioperative strokes occurred in five (0.9%) patients [n = 4 (0.9%) symptomatic; n = 1 (0.7%) asymptomatic patients]. Minor stroke was recorded in six (1%) patients [n = 4 (0.9%) symptomatic; n = 2 (1.3%) asymptomatic patients]. Two patients with symptomatic stenoses died within 1 month after surgery. Nine patients (1.5%) had reversible peripheral nerve palsies, and nine patients (1.5%) suffered a perioperative myocardial infarction. High-grade (>70%) restenosis at 1 year was observed in 19 (3.2%) patients [n = 12 (2.7%) symptomatic; n = 7 (4.7%) asymptomatic patients]. Conclusions: The midterm rate of restenosis was low when using a microscope-assisted non-patch endarterectomy technique. The 30-day morbidity and mortality rate was comparable or lower than those in recently published surgical serie

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients

Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature