Procalcitonin as preoperative marker for surgery in advanced parapneumonic empyema

BACKGROUND The optimal time point for surgical management of advanced parapneumonic empyema in need of open pleurectomy and decortication remains unclear. We hypothesized that surgical outcomes will be better when procalcitonin (PCT) levels have dropped to normal ranges as evidence for resolution of the underlying pneumonia. METHODS We retrospectively analyzed outcomes of 38 patients with advanced parapneumonic empyema who underwent open decortication and pleurectomy with available preoperative PCT (pPCT) values. Patients were divided into two groups based on the pPCT cut-off of 0.25 µg/L. Total length of stay was the primary endpoint. Secondary endpoints included postoperative length of stay, surgery-related complications and death. RESULTS Patients with a pPCT ≥0.25 µg/L had a significantly longer total length of stay compared to patients with a pPCT level <0.25 µg/L [mean 22.4 vs. 15.0 days, difference -7.4 days (95% CI: -12.8 to -2.0), P=0.009]. This was also confirmed in linear regression analysis adjusting for age, gender and comorbidities [adjusted regression coefficient for log-transformed length of stay -0.27, 95% CI: -0.02 to -0.52, P=0.037]. Results for postoperative length of stay were similar. Eight patients in the pPCT ≥0.25 µg/L group had postoperative complications with two deaths while no complications occurred in the PCT <0.25 µg/L group (38% vs. 0%, P=0.004). CONCLUSIONS These data suggest better surgical outcomes in advanced parapneumonic empyema when pneumonia has resolved with a pPCT drop of <0.25 µg/L. A larger, prospective study is needed to confirm these results

Induction chemotherapy followed by parenchyma-sparing surgery in medically inoperable NSCLC-results of a feasibility study

PURPOSE: Feasibility trial to test the toxicity and outcome of three cycles of induction chemotherapy followed by limited surgery in medically inoperable early stage NSCLC patients. PATIENTS AND METHODS: Thirteen patients with NSCLC (stages I-IIIB) with insufficient cardio-respiratory reserves for the oncologically required lung resection, received three cycles of induction chemotherapy with cisplatin (100mg/m(2)) and docetaxel (85mg/m(2)) followed by parenchyma-sparing lung surgery. Operability was evaluated with pulmonary function tests, perfusion scintigraphy and cardiopulmonary exercise testing. In selected patients coronary angiography or myocardial perfusion scintigraphy was performed. Rate of R0-resections was taken as primary outcome. RESULTS: Twelve of 13 patients received the three cycles of chemotherapy as planned. The main grade 3/4 hematological toxicity was neutropenia (62%), non-hematological toxicity was neutropenic fever (23%) and cough/dyspnea (31%). Complete, partial and stable responses to chemotherapy were seen in 1, 10 and 2 patients, respectively-the overall response rate was 85%. No patient had tumor progression. Eleven/13 (85% (CI 95% 54, 97) %) patients underwent surgery (4 lobectomies, 2 segmentectomies, and 5 wedge resections), all had a pathologically complete resection of the tumor. There was one postoperative death due to myocardial infarction. The median disease-free and overall survivals were 57(CI 95% 36-78) months and 66(CI 95% 40-92) months, with a median follow up time of 58 months. The 1-, 2- and 4-year OS was 85%, 85% and 67%, respectively. There were no significant changes in any lung function parameter compared to the preoperative assessment. The FEV(1) showed a trend for improved values after surgery. CONCLUSION: Induction chemotherapy in medically inoperable patients followed by parenchyma-sparing surgery is feasible and yields very promising results

Curative resection for lung cancer in octogenarians is justified

BACKGROUND: Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). METHODS: In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. RESULTS: Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell carcinoma [33], adenocarcinoma [41], large cell carcinoma [5] or other histological types [9]. Lung cancer stage distribution was 0 [1], I [53], II [17] and IIIA [14]. The overall 90-day mortality was 1.1%. The median hospitalisation and chest drainage times were 10 days (range, 5-27 days) and 5 days (range, 0-17 days), respectively. Thirty-six patients were complication-free (41%). In particular, pulmonary complications occurred in 25 patients (28%). In addition, 23 patients (26%) developed cardiovascular complications requiring medical intervention, while 24 patients (27%) had cerebrovascular complications, urinary tract infection and others. The median survival time was 51 months (range, 1-110 months), and the 5-year overall survival reached 45% without significance between tumour stages. CONCLUSIONS: Curative lung resections in selected octogenarians can be safely performed up to pneumonectomy for all tumour stages with a perioperative mortality, morbidity, and 5-year survival rate comparable to younger cohorts

Cytokine & chemokine response in the lungs, pleural fluid and serum in thoracic surgery using one-lung ventilation

BACKGROUND: Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the operated lung and ventilation of the non-operated lung. These procedures trigger a substantial inflammatory response. The aim of this study was to analyze the cytokine and chemokine reaction in both lungs, pleural space and blood in patients undergoing lung resection with OLV with special interest in the chemokine growth-regulated peptide alpha (GROα) which is the human equivalent to the rat cytokine-induced neutrophil chemoattractant-1 (CINC-1). METHODS: Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated lung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6, IL-1RA and GROα were determined with enzyme-linked immunosorbent assays in 15 patients. RESULTS: Substantial inter-individual differences in the BAL fluid between patients in cytokine and chemokine levels occurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the lung were affected and showed a significant increase in IL-6 and IL-1RA concentrations over time but not in GROα concentrations. Except for IL-6, which increased more in the collapsed, operated lung, no difference between the collapsed, operated and the ventilated, non-operated lung occurred. In the blood, IL-6 and IL-1RA increased early, already at the end of surgery. GROα was not detectable. In the pleural fluid, both cytokine and chemokine concentrations increased by day one. The increase was significantly higher in the pleural fluid compared to the blood. CONCLUSION: The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, non-operated lungs. The difference in extent of response underlines the complexity of the inflammatory processes during OLV. In contrast to the cytokines, the chemokine GROα concentrations did not react in the BAL fluid or in the blood. This indicates that GROα might not be useful as marker for the inflammatory reaction in complex surgical procedures

Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide-mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma

Increased levels of NO in exhaled air in association with increased NO synthetase (NOS)2 expression in bronchial epithelial are hallmark features of asthma. It has been suggested that NO contributes to asthma pathogenesis by selective down-regulation of TH1 responses. We demonstrate, however, that NO can reversibly limit in vitro expansion of both human TH1 and TH2 CD4+ T cells. Mechanistically, NO induces cGMP-mediated reversible STAT5 dephosphorylation and therefore interferes with the IL-2R activation cascade. Human bronchial epithelial cells (HBEC) up-regulate NOS2 after stimulation with IFN-gamma secreted by TH1 CD4+ T cells and release NO, which inhibits both TH1 and TH2 cell proliferation. This reversible T cell growth arrest depends on NO because T cell proliferation is completely restored after in vitro blocking of NOS2 on HBEC. HBEC thus drive the effector end of a TH1-controlled feedback loop, which protects airway mucosal tissues at the potential lesional site in asthma from overwhelming CD4+ TH2 (and potentially TH1) responses following allergen exposure. Variations in the efficiency of this feedback loop provides a plausible mechanism to explain why only a subset of atopics sensitized to ubiquitous aeroallergens progress to expression of clinically relevant levels of airways inflammation