RESUMEN
Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood-brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma.
RESUMEN
OBJECTIVES: Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. METHODS: Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. RESULTS: 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinson's medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; p<0.001). INTERPRETATION: We show for the first time that there is a survival advantage of DBS surgery in advanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These findings are of great interest to both patients with PD and the health professionals considering the treatment options for patients with severe PD.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Anciano , Antiparkinsonianos/uso terapéutico , Causas de Muerte , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Estimación de Kaplan-Meier , Levodopa/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/mortalidad , Enfermedad de Parkinson/psicología , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Núcleo Subtalámico/fisiología , Sobrevida , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND. Chronic subdural haematoma (CSDH) is a common condition that increases in incidence with rising age. Evacuation of a CSDH is one of the commonest neurosurgical procedures; however the optimal peri-operative management, surgical technique, post-operative care and the role of adjuvant therapies remain controversial. AIM. We propose a prospective multi-centre audit in order to establish current practices, outcomes and national benchmarks for future studies. METHODS. Neurosurgical units (NSU) in the United Kingdom and Ireland will be invited to enrol patients to this audit. All adult patients aged 16 years and over with a primary or recurrent CSDH will be eligible for inclusion. OUTCOME MEASURES AND ANALYSIS. The proposed outcome measures are (1) clinical recurrence requiring re-operation within 60 days; (2) modified Rankin scale (mRS) score at discharge from NSU; (3) morbidity and mortality in the NSU; (4) destination at discharge from NSU and (5) length of stay in the NSU. Audit standards have been derived from published systematic reviews and a recent randomised trial. The proposed standards are clinical recurrence rate < 20%; unfavourable mRS (4-6) at discharge from NSU < 30%; mortality rate in NSU < 5%; morbidity rate in NSU < 10%. Data will be submitted directly into a secure online database and analysed by the study's management group. CONCLUSIONS. The audit will determine the contemporary management and outcomes of patients with CSDH in the United Kingdom and Ireland. It will inform national guidelines, clinical practice and future studies in order to improve the outcome of patients with CSDH.