Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls.

BACKGROUND: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis. METHODS: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database. RESULTS: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways. CONCLUSIONS: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.

Prophylactic continuous positive airway pressure after pulmonary lobectomy: a randomized controlled trial.

BACKGROUND: Despite advances in perioperative care and surgical techniques, patients undergoing pulmonary lobectomy are still at high risk for postoperative complications. Among interventions expected to reduce complications, continuous positive airway pressure (CPAP) is a discussed option. This trial aims to test the hypothesis whether prophylactic application of CPAP following pulmonary lobectomy can reduce postoperative complications. METHODS: The study was designed as a prospective, randomized, controlled trial. Patients with clinical stage I non-small cell lung cancer scheduled for pulmonary lobectomy were eligible and were trained for the use of CPAP interface. The control group received standard postoperative pain management and physiotherapy; in addition, the study group received CPAP (PEEP 8-12 cmH2O, 2 hours thrice daily for three days). RESULTS: After the appropriate selection, 163 patients were considered for the analysis: 82 patients constituted the control group, 81 the study group. The two groups were substantially comparable for preoperative parameters. The rate of postoperative complications was lower in the study group (24.7% vs. 43.9%; P=0.015) as well as the hospital stay (6 vs. 7 days; P=0.031). The stepwise logistic regression model identified: CPAP [odd ratio (OR): 0.3026, CI: 0.1389-0.6591], smoke habits [OR: 2.5835, confidence interval (CI): 1.0331-6.4610] and length of surgery in minutes (OR: 1.0102, CI: 1.0042-1.0163) as regressors on postoperative complications. CONCLUSIONS: The present trial demonstrated that prophylactic application of CPAP during the postoperative period after pulmonary lobectomy for stage I non-small cell lung cancer was effective in prevent postoperative complications.

Ten-year experience with endobronchial ultrasound-guided transbronchial needle aspiration: single center results in mediastinal diagnostic and staging.

BACKGROUND: Endobronchial ultrasonography with transbronchial needle aspiration (EBUS-TBNA) is recognized as an accurate and minimal invasive procedure for diagnosis and staging of lung cancer and lymph nodal malignancies. EBUS is recommended as the first choice procedure for mediastinal staging in lung cancer in international guidelines. METHODS: A retrospective evaluation was performed on single center experience with EBUS-TBNA in our thoracic surgery department in a 10-year time frame. Main indication for the procedure was suspected non-lymphomatous malignancy in intrathoracic lymph-nodes on computed tomography (CT) or positron emission tomography (PET) scan. All procedures were performed under conscious sedation in a day-hospital setting. All the aspirated specimens were obtained with a 22-gauge needle and were fixed in 10% formalin and paraffin embedded. Sections of 3 micron in thickness were cut and hematoxylin-eosin stained. RESULTS: From October 2005 to August 2016, 496 patients were submitted to EBUS-TBNA. Number of nodal stations punctured was 592 with a mean of 2.25 punctures per patient. Diagnosis of malignancy was obtained in 291 patients (58.6%). In 25 cases a nodal metastasis from an extrathoracic primary tumor was diagnosed. Sensitivity, specificity and diagnostic accuracy were 95%, 100% and 96% respectively. Negative predictive value was 90% and positive predictive value (PPV) was 100%. When molecular tests were requested, mutational analysis was successfully performed on cell block derived material in 55 out of 56 cases (98.2%), and fluorescence in situ hybridization (FISH) analysis in 26 out of 27 cases (96.2%). CONCLUSIONS: EBUS-TBNA in our setting was an accurate and safe tool to diagnose non-lymphomatous nodal malignancies. Interestingly, in our series EBUS-TBNA has demonstrated to yield sufficient tissue for molecular analysis.

Argon and xenon ventilation during prolonged ex vivo lung perfusion.

BACKGROUND: Evidence supports the use of ex vivo lung perfusion (EVLP) as a platform for active reconditioning before transplantation to increase the potential donor pool and to reduce the incidence of primary graft dysfunction. A promising reconditioning strategy is the administration of inhaled noble gases based on their organoprotective effects. Our aim was to validate a porcine warm ischemic lung injury model and investigate postconditioning with argon (Ar) or xenon (Xe) during prolonged EVLP. METHODS: Domestic pigs were divided in four groups (n = 5 per group). In the negative control group, lungs were flushed immediately. In the positive control (PC) and treatment (Ar, Xe) groups, lungs were flushed after a warm ischemic interval of 2-h in situ. All grafts were evaluated and treated during normothermic EVLP for 6 h. In the control groups, lungs were ventilated with 70% N2/30% O2 and in the treatment groups with 70% Ar/30% O2 or 70% Xe/30% O2, respectively. Outcome parameters were physiological variables (pulmonary vascular resistance, peak airway pressures, and PaO2/FiO2), histology, wet-to-dry weight ratio, bronchoalveolar lavage, and computed tomography scan. RESULTS: A significant difference between negative control and PC for pulmonary vascular resistance, peak airway pressures, PaO2/FiO2, wet-to-dry weight ratio, histology, and computed tomography-imaging was observed. No significant differences between the injury group (PC) and the treatment groups (Ar, Xe) were found. CONCLUSIONS: We validated a reproducible prolonged 6-h EVLP model with 2 h of warm ischemia and described the physiological changes over time. In this model, ventilation during EVLP with Ar or Xe administered postinjury did not improve graft function.