Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need.A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients. Caspase-4 quantification was also assessed in the lung tumor mass of 98 paired NSCLC patients compared to 10 non-tumor lung tissues (i.e. tuberculosis).Circulating caspase-4 was detected in both healthy and NSCLC patients; however at different range values: 2.603–3.372 ng/ml for NSCLC patients (95% CI) compared to 0.3994-0.6219 ng/ml for healthy subjects (95% CI). The sensitivity of the test ranged from 97.07% to 100%; the specificity was 88.1% with a positive predictive value of 92.54%, accuracy of 95.19% and AUC of 0.971. Smokers (95% CI, 0.3947–0.6197 ng/ml) and COPD patients (95% CI, 1.703–2.995 ng/ml) showed intermediate values of circulating caspase-4. Tissue levels of caspase-4 in the tumor mass showed that 72 (72.7%) out of 99 patients were positive. More importantly, higher levels (cut-off value = 0.307 ng/ml) of caspase-4 in the tumor mass were associated to reduced overall survival (median 0.92 years) compared to NSCLC patients with lower levels (median 3.02 years).We report for the first time caspase-4 as a novel diagnostic and prognostic biomarker, opening new therapeutic perspectives for NSCLC patients.

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AbstractThoracic surgery remains the better therapeutic option for non-small cell lung cancer patients that are diagnosed in early stage disease. Preoperative lung function assessment includes respiratory function tests (RFT) and cardio-pulmonary exercise testing (CPET). Vo2 peak, FEV1 and DLCO as well as recognition of performance status, presence of co-morbidities, frailty indexes, and age predict the potential impact of surgical resection on patient health status and survival risk. In this study we have retrospectively assessed the benefit of a high-intensity preoperative pulmonary rehabilitation program (PRP) in 14 patients with underlying lung function impairment prior to surgery. Amongst these, three patients candidate to surgical resection exhibited severe functional impairment associated with high score of frailty according CHS and SOF index, resulting in a substantial mortality risk.Our observations indicate that PRP appear to reduce the mortality and morbidity risk in frail patients with concurrent lung function impairment undergoing thoracic surgery. PRP produced improvement of VO2 peak degree and pulmonary function resulting in reduced postoperative complications in high-risk patients from our cases. Our results indicate that a preoperative training program may improve postoperative clinical outcomes in fraillung cancer patients with impaired lung function prior to surgical resection.

Background/Aims: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) exerts a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Epidemiological studies proved high levels of circulating S1P in non-small cell lung cancer (NSCLC) patients. Studies in literature suggest that high levels of S1P support carcinogenesis but the exact mechanism is still elusive. The aim of this study was to understand the mechanism/s underlying S1P-mediated lung tumor cell proliferation. Methods: We used human samples of NSCLC, a mouse model of first-hand smoking and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. Results: We found that the expression of S1PR3 was also into the nucleus of lung cells in vitro, data that were confirmed in lung tissues of NSCLC patients, smoking and tumor bearing BaP-exposed mice. The intranuclear, but not the membrane, localization of S1PR3 was associated to S1P-mediated proliferation of lung adenocarcinoma cells. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after Toll Like Receptor (TLR) 9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. Conclusion: These results prove that the nuclear S1PR3/SPHK II axis is involved in lung tumor cell proliferation, highlighting a novel molecular mechanism which could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Background: Patient satisfaction reflects the perception of the customer about the level of quality of care received during the episode of hospitalization. Objective: To compare the levels of satisfaction of patients submitted to lung resection in two different thoracic surgical units. Methods: Prospective analysis of 280 consecutive patients submitted to pulmonary resection for neoplastic disease in two centers (center A: 139 patients; center B: 141 patients; 2009–2010). Patients’ satisfaction was assessed at discharge through the EORTC-InPatSat32 module, a 32-item, multi-scale self-administered anonymous questionnaire. Each scale (ranging from 0 to 100 in score) was compared between the two units. Multivariable regression and bootstrap were used to verify factors associated with the patients’ general satisfaction (dependent variable). Results: Patients from unit B reported a higher general satisfaction (91.5 vs. 88.3, p = 0.04), mainly due to a significantly higher satisfaction in the doctor-related scales (doctors’ technical skill: p = 0.001; doctors’ interpersonal skill: p = 0.008; doctors’ availability: p = 0.005, and doctors information provision: p = 0.0006). Multivariable regression analysis and bootstrap confirmed that level of care in unit B (p = 0.006, bootstrap frequency 60%) along with lower level of education of the patient population (p = 0.02, bootstrap frequency 62%) were independent factors associated with a higher general patient satisfaction. Conclusion: We were able to show a different level of patient satisfaction in patients operated on in two different thoracic surgery units. A reduced level of patient satisfaction may trigger changes in the management policy of individual units in order to meet patients’ expectations and improve organizational efficiency.