We demonstrated that hydrophobic derivatives of the nonsteroidal anti-inflammatory drug (NSAID)flufenamic acid (FA), can be formed into stable nanometer-sized prodrugs (nanoprodrugs) that inhibit the ...growth of glioma cells, suggesting their potential application as anticancer agent. We synthesized highly hydrophobic monomeric and dimeric prodrugs of FA via esterification and prepared nanoprodrugs using spontaneous emulsification mechanism. The nanoprodrugs were in the size range of 120 to 140 nm and physicochemically stable upon long-term storage as aqueous suspension, which is attributed to the strong hydrophobic interaction between prodrug molecules. Importantly, despite the highly hydrophobic nature and water insolubility, nanoprodrugs could be readily activated into the parent drug by porcine liver esterase, presenting a potential new strategy for novel NSAID prodrug design. The nanoprodrug inhibited the growth of U87-MG glioma cells with IC50 of 20 μM, whereas FA showed IC50 of 100 μM, suggesting that more efficient drug delivery was achieved with nanoprodrugs.
Primary leiomyosarcoma of the inferior vena cava (IVC) is best managed with surgical resection when technically feasible. However, consensus is lacking regarding the best choice of conduit and ...reconstruction technique. The aim of the present multicenter study was to perform a comprehensive assessment through the VLFDC (Vascular Low Frequency Disease Consortium) to determine the most effective method for caval reconstruction after resection of primary leiomyosarcoma of the IVC.
A multicenter, standardized database review of patients who had undergone surgical resection and reconstruction of the IVC for primary leiomyosarcoma from 2007 to 2017 was performed. The demographics, periprocedural details, and postoperative outcomes were analyzed.
A total of 92 patients (60 women and 32 men), with a mean age of 60.1 years (range, 30-88 years) were treated. Metastatic disease was present in 22%. The tumor location was below the renal veins in 49 (53%), between the renal and hepatic veins in 52 (57%), and above the hepatic veins in 13 patients (14%). The conduits used for reconstruction included ringed polytetrafluoroethylene (PTFE; n = 80), nonringed PTFE (n = 1), Dacron (n = 1), autogenous vein (n = 1), bovine pericardium (n = 4), and cryopreserved tissue (n = 5). Complete R0 resection was accomplished in 73 patients (79%). In-hospital mortality was 2%, with a median length of stay of 8 days. The primary patency of PTFE reconstructed IVCs was 97% and 92% at 1 and 5 years, respectively, compared with 73% at 1 and 5 years for the non-PTFE reconstructed IVCs. The overall 1-, 3-, and 5-year survival for the entire cohort were 94%, 86%, and 65%, respectively
The findings from our multi-institutional study have demonstrated that complete en bloc resection of IVC leiomyosarcoma with vascular surgical reconstruction in selected patients results in low perioperative mortality and is associated with excellent long-term patency. A ringed PTFE graft was the most commonly used conduit for caval reconstruction, yielding excellent long-term primary patency.
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