Neurosurgery
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Emergent neurosurgery may be precipitated or complicated by previous or concomitant administration of anticoagulants, thrombolytic medications, or antiplatelet agents. Recommendations are presented to reverse or counteract the effects of those drugs before or during neurosurgical interventions. ⋯ Other clinical experience based on mechanisms of drug action within the coagulation process confirm that single or combined administration of platelet transfusions, fresh frozen plasma, cryoprecipitate, vitamin K, protamine, desmopressin, and recombinant activated factor VII can treat coagulopathies caused by warfarin, heparin, aspirin, adenosine diphosphate-receptor antagonist, glycoprotein IIb/IIIa receptor blocking agents, and thrombolysis. Specific interventions and recommended dosages are reviewed.
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Review Comparative Study
Current strategies in whole-brain radiation therapy for brain metastases.
Whole-brain radiation therapy (WBRT) has been the primary treatment for patients with brain metastases for more than 50 years and provides effective palliative relief in most patients. Although advancements in radiotherapeutic technique continue to improve local and locoregional control, median survival for patients treated with WBRT monotherapy remains fixed at approximately 4 to 6 months. Key issues in the use of WBRT include optimizing its efficacy when it is used in conjunction with surgery, radiosurgery, radiosensitizers, and new chemotherapeutic agents. ⋯ Newer radiosensitizing agents (e.g., efaproxiral [RSR-13] and motexafin gadolinium) have shown promise in the treatment of brain tumors, especially in specific patient subsets. Recently developed systemic chemotherapy agents, such as temozolomide, which crosses the blood-brain barrier, have a synergistic effect on brain metastases when used in conjunction with radiation. In addition, the use of interstitial chemotherapy agents provides highly focused local chemotherapy in the brain without increasing systemic toxicity; carmustine polymer wafer, in combination with WBRT, has shown promising results in treating brain metastases.
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Comparative Study
Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3.
To identify the CCM3 gene in a population of 61 families with a positive family history of cerebral cavernous malformations (CCM), 8 of which had suggestive linkage to the CCM3 locus. ⋯ Our data establish PDCD10 as the gene responsible for CCM in families linking to the CCM3 locus. The discovery of the third gene involved in inherited forms of CCM, after KRIT1 and Malcavernin, is an important step toward dissecting the molecular pathophysiology of this disease.
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Comparative Study
Local delivery of a synthetic endostatin fragment for the treatment of experimental gliomas.
Endostatin is an anti-angiogenic agent that blocks matrix-metalloproteinase-2 and inhibits endothelial cell proliferation. Currently, endostatin is available through recombinant technology, which limits its broader use. In this study, a synthetic endostatin fragment (EF) was analyzed to determine its anti-angiogenic properties when locally delivered by controlled-release polymers and to establish its effect as a treatment for experimental gliomas. ⋯ Controlled-release polymers can effectively deliver a biologically active EF in a sustained fashion. EF inhibits angiogenesis in vitro and in vivo, and even though EF does not prolong survival as a single agent, it exhibits a synergistic effect when combined with systemic bischloroethylnitrosourea (carmustine) in the intracranial 9L gliosarcoma model.
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The role for surgical treatment of brain metastases continues to evolve. Data have demonstrated survival and quality-of-life benefits for surgical treatment of appropriate lesions in selected patients. With improvements in surgical technique, along with therapeutic improvements in the management of systemic cancers, more patients are now eligible for surgical resection. ⋯ Although surgery has traditionally been performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. Surgical techniques, such as image guidance, intraoperative ultrasound, functional neuronavigation, cortical mapping, and awake craniotomies, have expanded the scope of lesions that can be removed safely to optimize outcomes. Seizures, peritumoral edema, and venous thromboembolic disease all contribute significantly to surgical morbidity and mortality and thus require aggressive treatment around the time of the surgical procedure to improve the quality of life and maximize survival time.