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Long-term outcome in anesthesia usually refers to 72 hours.An investigation of the effect of aprotinin on intraoperative hemorrhage during extrapleural pneumonectomy revealed that aprotinin decreased hemorrhage and decreased the need for transfusion.An unexpected finding when preparing for publication was an improved survival of the patients in the treatment arm despite some of these patients being inoperable.Conversely the entire placebo group was dead within 24 months.(Cancer 2009).A concurrent investigation of the effects of rofecoxib on shoulder pain after thoracotomy with epidural analgesia had to be discontinued when this COX-2 drug was withdrawn due to concerns over an increase in cardiovascular events with its use (APPROVE trial).In a Bayesian analysis, chosen due to small numbers, there was posterior probability of 0.99 that patients had less shoulder pain after receiving rofecoxib than placebo, and also had less overall pain (posterior probability 0.93).Survival also was better in the rofecoxib group (posterior probability 0.925).Three patients with later-determined benign tumors in the rofecoxib group did not have long-term follow up.With their exclusion,the posterior probability was still 0.88 for improved survival.Median survival in the benign-excluded rofecoxib group was 66.6 months versus 45.6 in the placebo group.This is an intriguing finding and if real many causal pathways could be hypothesized.Such an effect could be a function of decreased pain and stress which might affect overall survival even of patients with benign masses.Alternatively,it could be due to a specific anti-tumor effect of COX-2 inhibition.COX-2 catalyses the synthesis of prostaglandins and is frequently up-regulated in cancer..Prostaglandin E2 (PGE2) is a downstream product of COX-2 which promotes rumor growth by stimulating angiogenesis and invasiveness through VEGF.PGE2 inhibits apoptosis (cell death) and inhibits immune surveillance.It may be hypothesized that COX-2 blocking agents help in the chemoprevention of lung cancer and perhaps the perioperative use of these drugs decreases intraoperative metastasis or affects the ability of the tumor to grow.The K-RAS proto-oncogene has been implicated in the development of cancers of the pancreas,lung and colon.The K-RAS protein is a GTPase that acts as a self-inactivating signal transducer in response to stimulation of a cell surface receptor, including epidermal growth factor receptor (EGFR).One of the RAS-stimulated angiogenic factors is COX-2 though the relationship between these various associations is still being investigated.