Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer.

OBJECTIVES: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear. MATERIAL AND METHODS: We conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. RESULTS: Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia. CONCLUSIONS: Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy.

Lung cancer survival in Spain and prognostic factors: a prospective, multiregional study.

Lung cancer survival varies greatly from one European country to another. Differences in data collection may account for some of the variations observed. The aim of this work was to ascertain the survival rate in diverse Spanish regions and to analyse the influence of age and other prognostic factors. This was a prospective, observational, multiregional study carried out in 10 hospitals from 8 different Spanish regions. Epidemiological and clinical data, diagnostic and therapeutic procedures, and 3-year survival were recorded according to a common protocol and uniform criteria in 1027 patients with lung cancer diagnosed in 2003. Thirteen (1.26%) were lost to follow-up. The average 3-year survival rate in the remaining 1014 patients was 13.8% with regional rates varying from 6.7% to 19.7%. The resection rate also varied greatly. Early TNM stage, surgical treatment, and asymptomatic status at diagnosis were good independent prognostic factors. Cardiovascular comorbidity and weight loss had an adverse influence on survival. Patients over the age of 70 years were more often asymptomatic at diagnosis; they had less advanced disease and more comorbidity, received less active treatment and had worse survival. The average long-term survival rate in this Spanish series was similar to that reported for other European countries. It varied widely between regions depending on the resection rate. We conclude that although older patients are diagnosed at less advanced stages of disease, they have worse survival because they are less likely to receive effective therapy.

Association between habitual naps and sleep apnea.

STUDY OBJECTIVES: Taking an afternoon nap (siesta) is a common habit. A number of studies have shown an increased cardiovascular mortality in habitual nappers. Afternoon nappers have anthropometric characteristics similar to those of patients with sleep apnea. Nappers appear to suffer from more sleep apnea, which could contribute to cardiovascular disorders. Our aim was therefore to determine the association between sleep apnea and napping, as well as to analyze the relationship of sleep apnea and napping with hypertension. DESIGN: Case-control study. SETTING: Residents in the town of Caceres (Spain) with a population of 100,000 inhabitants. PARTICIPANTS: Four hundred five individuals were initially selected (186 nappers and 219 nonnappers). INTERVENTIONS: Telephone interviews were conducted to contact habitual nappers and nonnappers. Out of the total population selected, 90 nappers and 88 nonnappers completed the study protocol (personal interview and polysomnography). MEASUREMENTS AND RESULTS: The nappers had a higher frequency of sleep apnea at the 3 cutoff points studied (apnea and hypopnea index > or = 5, > or = 10, > or = 15). The adjusted odds ratio was between 2.8 (confidence interval, 1.3-5.8) and 5.5 (confidence interval, 2.3-13). Napping was associated with hypertension in the univariate analysis (odds ratio: 2.1; confidence interval, 1.1-4), but this association disappeared once sleep apnea was included as a covariate in the multivariate modeling (odds ratio dropped to 1.1). CONCLUSIONS: Our findings suggest that napping could be regarded as a marker of sleep apnea, which could account for the cardiovascular diseases observed in nappers. Given that napping is common and that sleep apnea is treatable, more attention should be focused on this population.