Phenotypic diversity of the lung vasculature in experimental models of metastases.

In vivo phage display is a screening method in which peptides homing to specific vascular beds are selected after IV administration of a random peptide library. This strategy has revealed a vascular address system that allows tissue-specific targeting of normal blood vessels and angiogenesis-related targeting of tumor blood vessels by selected peptides. Many vascular receptors or "addresses" targeted by homing peptides have been identified. One such vascular receptor of normal lung endothelium is membrane dipeptidase (MDP), which was found by in vivo phage display to bind the tripeptide motif gly-phe-glu (GFE). Our studies with GFE peptide and lung vasculature suggest that MDP mediates cancer cell adhesion to lung vasculature and the development of lung metastases, but that MDP is not present in the vasculature of lung metastases. MDP appears to occupy a vascular distribution that is similar to the pulmonary artery circulation. These results demonstrate the promise of defining critical functional and anatomic characteristics of endothelial cells in lung and other organs by in vivo phage display.

Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.

BACKGROUND: The prevention of major pulmonary events (MPEs) after pneumonectomy may minimize postoperative mortality rates. The purpose of this study was to identify preoperative and perioperative factors associated with the development of MPEs after pneumonectomy to help predict which patients are at increased risk for MPEs. METHODS: We retrospectively reviewed the medical records of all patients (n = 261) who underwent pneumonectomies between January 1990 and May 1999. We analyzed preoperative and perioperative risk factors, the primary end point of an MPE and the secondary end points of mortality (in-hospital or 30 days postprocedure), length of stay, and hospital charges. A postoperative MPE included only pneumonia or acute respiratory distress syndrome as defined by the Centers for Disease Control and the American and European Consensus Conference's established criteria. Simple atelectasis that did not progress to pneumonia or a documented aspiration was not included. RESULTS: Four patients died within 12 hours of operation; the records of the remaining 257 patients were analyzed. An MPE occurred in 33 (12.8%) of 257 patients; 16 (6.2%) of 257 patients died. A multivariate analysis performed on relevant variables showed that only the timing of smoking cessation (1 month or sooner before operation) was a significant predictor of an MPE. Age, side of pneumonectomy, and the use of preoperative chemotherapy or combined chemotherapy and radiation therapy were not significant predictors of an MPE. An MPE significantly increased the mortality rate 2.1% versus 39.3%, p < 0.001). CONCLUSIONS: Mortality after pneumonectomy increased significantly with the development of an MPE. Patients who continue to smoke within 1 month of operation are at an increased risk for developing an MPE. Interventions to minimize MPEs may minimize the mortality rate after pneumonectomy.

Cost-effectiveness of initial diagnostic strategies for pulmonary nodules presenting to thoracic surgeons.

BACKGROUND: Patients presenting to thoracic surgeons with pulmonary nodules suggestive of lung cancer have varied diagnostic options including navigation bronchoscopy (NB), computed tomography-guided fine-needle aspiration (CT-FNA), (18)F-fluoro-deoxyglucose positron emission tomography (FDG-PET) and video-assisted thoracoscopic surgery (VATS). We studied the relative cost-effective initial diagnostic strategy for a 1.5- to 2-cm nodule suggestive of cancer. METHODS: A decision analysis model was developed to assess the costs and outcomes of four initial diagnostic strategies for diagnosis of a 1.5- to 2-cm nodule with either a 50% or 65% pretest probability of cancer. Medicare reimbursement rates were used for costs. Quality-adjusted life years were estimated using patient survival based on pathologic staging and utilities derived from the literature. RESULTS: When cancer prevalence was 65%, tissue acquisition strategies of NB and CT-FNA had higher quality-adjusted life years compared with either FDG-PET or VATS, and VATS was the most costly strategy. In sensitivity analyses, NB and CT-FNA were more cost-effective than FDG-PET when FDG-PET specificity was less than 72%. When cancer prevalence was 50%, NB, CT-FNA, and FDG-PET had similar cost-effectiveness. CONCLUSIONS: Both NB and CT-FNA diagnostic strategies are more cost-effective than either VATS biopsy or FDG-PET scan to diagnose lung cancer in moderate- to high-risk nodules and resulted in fewer nontherapeutic operations when FDG-PET specificity was less than 72%. An FDG-PET scan for diagnosis of lung cancer may not be cost-effective in regions of the country where specificity is low.