Venous thromboembolism occurs infrequently in meningioma patients receiving combined modality prophylaxis

Abstract

The long‐term disease‐free survival in patients with metastatic transitional cell carcinoma (TCC) is still considerably low. Novel chemotherapeutic agents are needed to decrease the morbidity and mortality of TCC. In this study, we have evaluated several epigenetic modifiers for their therapeutic application in bladder cancer. Both histone deacetylase inhibitors (FK228, TSA) and DNA hypomethylating agent (5‐Azacytidine) were tested using in vitro assays such as cell viability, cell cycle analysis and western blot to determine their mechanisms of action. Drug combination experiments were also designed to study any additive or synergistic effects of these agents. In addition, two bladder cancer xenograft models (one subcutaneous and one orthotopic) were employed to assess the therapeutic efficacy of these agents in vivo. Three agents exhibited various growth inhibitory effects on 5 different TCC cell lines in a dose‐ and time‐dependent manner. In addition to G2/M cell cycle arrest, FK228 is more potent in inducting apoptosis than the two other single agents, and combination of both FK228 and 5‐Aza further enhances this effect. p21 induction is closely associated with FK228 or TSA but not 5‐Aza, which is mediated via p53‐independent pathway. Consistent with in vitro results, FK228 exhibited a significant in vivo growth inhibition of TCC tumor in both subcutaneous and orthotopic xenograft models. FK228 is a potent chemotherapeutic agent for TCC in vivo with minimal undesirable side effects. The elevated p21 level mediated via p53 independent pathway is a hallmark of FK228 mechanism of action. © 2007 Wiley‐Liss, Inc.

The incidence of postoperative thromboembolic complications following surgical resection of intracranial meningioma. A retrospective study of a large single center patient cohort

“…The primary prevention method for fatal PE, therefore, is averting the formation of DVT [2]. Preventive measures to lower the chance on postoperative VTE include compression stockings, early mobilization, and the prophylactic administration of low-molecular weight heparins [1,2,[4][5][6]8,15,[20][21][22][23][24][25][26][27]. There remains controversy over the use of VTE prophylaxis after meningioma resection with either or both mechanical and pharmacological means [2,20,22,25,28,29].…”

“…VTE may be treated either pharmacologically or by graduate compression stockings and the use of sequential compression devices in case of DVT [2,4,20,21]. Pharmacologic agents that have gained great importance in prophylaxis are low-molecular weight heparins, despite the potential risk of hemorrhage [5,6,15,[21][22][23][24][25][26][27].…”

“…Pharmacologic agents that have gained great importance in prophylaxis are low-molecular weight heparins, despite the potential risk of hemorrhage [5,6,15,[21][22][23][24][25][26][27]. There remains, however, controversy about the prophylactic treatment of VTE with either or both pharmacologic and mechanic means in the treatment of neurosurgical patients with meningioma, despite an increasing body of confirmatory evidence [1,2,8,20,22,25,28,29]. To determine the number of and the risk factors for VTE in a large cohort of consecutive intracranial meningioma patients undergoing surgery, we performed a retrospective single-center analysis.…”

Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas

“…Other contributing factors may include surgeon preference as well as conflicting studies some of which support anticoagulation in decreasing the risk of DVT and PE and others which show no difference in their occurrences [18,19]. Individual patient characteristics such as age, preexisting compromise of vascular integrity, use of lumbar drains or coagulopathies make each meningioma resection unique and therefore may prolong controversy in the field around adjuvant enoxaparin administration post meningioma resection [1,20,21]. Perhaps a large multi-center, randomized control trial is necessary to conclusively establish practice guidelines.…”

Association of methionine synthase rs1801394 and methionine synthase reductase rs1805087 polymorphisms with meningioma in adults: A meta-analysis

“…Meningioma is a complex multifactorial disease and is the second most common primary cerebral neoplasm in adults (2). The prevalence of meningioma was reported to be 6/100,000 individuals annually in the United States (3).…”