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Object The best approach to the management of vestibular schwannoma (VS) remains controversial. The aim of this study is to analyze the initial and follow-up costs of resection and stereotactic radiosurgery for patients with VS. Methods Initial and follow-up costs in 53 cases in which patients with unilateral, previously unoperated VSs > 3 cm underwent resection (21 cases) or radiosurgery (32 cases) at the Mayo Clinic from June 2000 until July 2002 were analyzed for 36 months. Follow-up treatment-specific utilization records were gathered prospectively for patients not returning to the Mayo Clinic after treatment. Six-month moving averages of incremental follow-up costs were calculated for the 2 patient groups. Results The mean cost of surgery in the microsurgery group was $23,788 (95% confidence interval $22,280–$24,842) compared with $16,143 (95% confidence interval $15,277–$17,545) for the radiosurgical group. Mean incremental follow-up costs per month for patients in the microsurgery group started just > $1000 per month, decreased steadily, and remained < $70 per month by the 10th month of follow-up. Mean incremental follow-up costs per month for patients in the radiosurgery group were <$10 per month for the first few months and thereafter increased to as much as $200 per month. Conclusions Although the total cost of microsurgery is higher due to the costs of hospitalization, follow-up costs for radiosurgery are greater in general. From a societal perspective, radiosurgery is less expensive than microsurgical resection provided that the rate of tumor progression after radiosurgery remains low with long-term follow-up.

Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.

Abstract Learning Objectives After reading this article, the reader should be able to: Monitor for and treat to prevent bone loss in postmenopausal breast cancer patients receiving an aromatase inhibitor.Describe the methodology of the Z-FAST and ZO-FAST clinical trials.Discuss the effectiveness and tolerability of zoledronic acid when administrated to prevent bone loss associated with aromatase inhibitors. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. The interim (12-month) results of two similarly designed, ongoing studies (the Zometa®-Femara® Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred. Methods. An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12. Findings. The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p &lt; .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group—seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported. Conclusions. The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor–associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.

The role of prostaglandin production in the control of regenerative function of endothelial progenitor cells (EPCs) has not been studied. We hypothesized that activation of cyclooxygenase (COX) enzymatic activity and the subsequent production of prostacyclin (PGI 2 ) is an important mechanism responsible for the regenerative function of EPCs. In the present study, we detected high levels of COX-1 protein expression and PGI 2 biosynthesis in human EPCs outgrown from blood mononuclear cells. Expression of COX-2 protein was almost undetectable under basal conditions but significantly elevated after treatment with tumor necrosis factor-α. Condition medium derived from EPCs hyperpolarized human coronary artery smooth muscle cells, similar to the effect of the PGI 2 analog iloprost. The proliferation and in vitro tube formation by EPCs were inhibited by the COX inhibitor indomethacin or by genetic inactivation of COX-1 or PGI 2 synthase with small interfering (si)RNA. Impaired tube formation and cell proliferation induced by inactivation of COX-1 were rescued by the treatment with iloprost or the selective peroxisome proliferator–activated receptor (PPAR)δ agonist GW501516 but not by the selective PGI 2 receptor agonist cicaprost. Downregulation of PPARδ by siRNA also reduced angiogenic capacity of EPCs. Iloprost failed to reverse PPARδ siRNA-induced impairment of angiogenesis. Furthermore, transfection of PGI 2 synthase siRNA, COX-1 siRNA, or PPARδ siRNA into EPCs decreased the capillary formation in vivo after transplantation of human EPCs into the nude mice. These results suggest that activation of COX-1/PGI 2 /PPARδ pathway is an important mechanism underlying proangiogenic function of EPCs.