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This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

OBJECTIVES Since video-assisted thoracic surgery (VATS) was first performed in the early 1990s, there have been many developments, and the conversion rate has decreased over the years. This article highlights the specific outcomes of patients undergoing conversion to thoracotomy despite initially scheduled VATS lung resection. METHODS We retrospectively reviewed 501 patients who underwent thoracoscopic anatomic lung resection (i.e. lobectomy, segmentectomy or bilobectomy) between 1 January 2012 and 1 August 2017 at our institution. We explored the risk factors for surgical conversion and adverse events occurring in patients who underwent conversion to thoracotomy. RESULTS A total of 44/501 patients underwent conversion during the procedure (global rate: 8.8%). The main reasons for conversion were (i) anatomical variation, adhesions or unexpected tumour extension (37%), followed by (ii) vascular causes (30%) and (iii) unexpected lymph node invasion (20%). The least common reason for conversion was technical failure (13%). We could not identify any specific risk factors for conversion. The global complication rate was significantly higher in converted patients (40.9%) than in complete VATS patients (16.8%) (P = 0.001). Postoperative atrial fibrillation was a major complication in converted patients (18.2%) [odds ratio (OR) 5.09, 95% confidence interval (CI) 1.80–13.27; P = 0.001]. Perioperative mortality was higher in the conversion group (6.8%) than in the VATS group (0.2%) (OR 33.3, 95% CI 3.4–328; P = 0.003). CONCLUSIONS Through the years, the global conversion rate has dramatically decreased to

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), and restoring metabolic control in these patients may improve their management after lung transplantation. In this multicenter, prospective, phase 1-2 trial, we evaluate the feasibility and metabolic efficacy of combined pancreatic islet-lung transplantation from a single donor in patients with CFRD, terminal respiratory failure, and poorly controlled diabetes. Islets were infused via the portal vein under local anesthesia, 1 week after lung transplantation. At 1 year, the primary outcome was transplant success as evaluated by a composite score including four parameters (weight, fasting glycemia, HbA1c, and insulin requirements). Ten participants (age: 24 years [17-31], diabetes duration: 8 years [4-12]) received a combined islet-lung transplant with 2892 IEQ/kg [2293-6185]. Transplant success was achieved in 7 out of 10 participants at 1-year post transplant. Fasting plasma C-peptide increased from 0.91 μg/L [0.56-1.29] to 1.15 μg/L [0.77-2.2], HbA1c decreased from 7.8% [6.5-8.3] (62 mmol/mol [48-67]) to 6.7% [5.5-8.0] (50 mmol/mol [37-64]), with 38% decrease in daily insulin doses. No complications related to the islet injection procedure were reported. In this pilot study, combined pancreatic islet-lung transplantation restored satisfactory metabolic control and pulmonary function in patients with CF, without increasing the morbidity of lung transplantation.

Summary A best evidence topic was constructed according to a structured protocol. The question addressed was whether size-reduced or lobar lung transplantation (LLTx) offers the same benefit as classic lung transplantation (LTx). Of the 147 papers found using the reported search, 9 were selected to provide the best evidence. Details of the studies regarding authors, date, journal, country of publication, study type, group studied, relevant outcomes and results are given. All studies reported survival rates of LLTx and most compared it with classical LTx. No statistical differences were reported in medium term and long term. Two of the studies reported a higher incidence of postoperative complications, such as the need for cardiopulmonary bypass, reperfusion oedema or primary graft dysfunction, and longer intubation or intensive care unit stay times. Although the largest study showed a significantly worse 1-year survival in LLTx, a sub-analysis considering patients successfully discharged showed similar outcomes at 1, 3 and 5 years when compared with classic LTx patients. We conclude that LLTx is a valid therapeutic option for recipients with significant donor size mismatch, offering similar outcomes as classical LTx in the medium term and long term.

Specialist training is a critical issue in Europe and worldwide. The trainee is a future colleague from whom we expect that he will deliver the best ever possible quality of care. This best quality of care encompasses a huge number of prerequisites. On the front line appear knowledge and cognitive skills, and psychomotor procedural skills; competence is demonstrated by appropriate decision-making and application of technical skills. During his training, a trainee is expected to progressively escalate the top of the famous Miller’s pyramid (1). As opposed to technical skills, which are tested in national or European board examinations, best quality of care requires a broad spectrum of non-technical skills including empathy, team playing, leadership, cost control among other. The Royal College of Physicians of Canada has prepared and published a guideline document called “CanMEDS glossary”, which describes 7 fundamentals, yet overlapping areas of competence, centred by medical expertise: communicator, collaborator, leader, health advocate, scholar, and professional (2).

BACKGROUND Although central airway stenosis (CAS) is a common complication after lung transplantation, its consequences have been poorly evaluated. The objective of our study was to evaluate the impact of CAS on lung function after lung transplantation. MATERIAL AND METHODS All lung transplant recipients from June 2009 to August 2014 in a single center (Strasbourg, France) were retrospectively reviewed. RESULTS A total of 191 lung transplantations were performed: 175 bilateral, 15 single, and 1 heart-lung transplantation. Of the 161 bilateral lung-transplanted patients who survived >3 months, 22 (13.6%) developed CAS requiring endobronchial treatment. All these patients were treated by endoscopic balloon dilatation, and 9 additionally needed endobronchial stents. Respiratory function tests demonstrated persistent obstructive ventilatory pattern despite endoscopic treatment in recipients with CAS compared to those without CAS at 6, 12, and 18 months post-transplant. At 18 months, CAS patients had significantly lower post-transplant FEV1 (1.96±0.60 L versus 2.57±0.76 L, p=0.001) and FEV1/FVC (61±14% versus 81±13%, p

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Thoracic oncology encompasses a broad spectrum of primary tumour entities originating from various pulmonary, tracheobronchial, pleural, mediastinal and chest wall tissues or distinct cell types within these compartments. Lung cancer represents by far the most frequent malignant tumour within the thoracic cavity, and is the most common type and largest killer among all cancers worldwide. Lung cancer leads mortality statistics in Europe, accounting for at least one fifth of all cancer-related deaths [1]. In addition, lung cancer causes a significant burden of symptoms in a population of patients with high comorbidity, providing significant challenges to national healthcare systems in the European Union, with the highest overall costs among all cancer types [2–4]. Contrary to the general stigma applied to lung cancer patients, where they are often assumed to suffer from a self-inflicted disease, it is now estimated that up to 10–20% of lung cancer patients are never-smokers [5, 6]. Even if numerically far lower, the remaining, The @EuroRespSoc launches a new thoracic oncology continuous professional development programme http://bit.ly/31ShuTp

Objectives In case of inoperability or refusal of surgery, stereotactic body radiation therapy (SBRT) is the most effective treatment for a stage I non-small cell lung carcinoma (NSCLC). The results obtained by this irradiation technique are considerably superior to those observed in the time of conventional 3D irradiation and its toxicities are much less important, which makes it possible in elderly patients, or those presenting cardio-pulmonary comorbidities and a poor perfomance status. Materials and methods This study is a retrospective analysis of 90 patients who underwent SBRT for a stage I NSCLC between 2010 and 2015. Its purpose is to describe its effectiveness in term of overall survival (OS), specific survival (SS), local control (LC), regional control (RC) and metastatic control (MC) as well as their prognostic factors, and its tolerance. Results LC, RC, MC as well as OS and SS rate at 4 years were comparable to the main prospective studies, respectively 89%, 92%, 70%, 33% and 66%. No LC prognostic factor could be identified. Radiation pneumonitis was observed with a rate of 61.5%, of which 56% were asymptomatic, and 4% of the patients had a rib fracture. Conclusions SBRT is an efficient and well-tolerated treatment for stage I non-small cell lung carcinomas

Founded in 1958 the UEMS (Union Européenne des Médecins Spécialistes-European Union of Medical Specialists) has become the largest European Medical organization representing over 1.5 million specialists of 43 Specialties in 39 countries. The primary goal of UEMS is to defend the interests of Specialists in the broadest sense of the word. This includes promoting the highest quality of care, the highest standards of training, continuous professional development (CPD) and continuous medical education (CME). For the latter the European Accreditation Council for Continuous Medical Education (EACCME) is one of the main assets of UEMS. The UEMS Section of Thoracic Surgery was created in 2013 and has substantially contributed to the improvement of the identity of Thoracic Surgery as a specialty throughout Europe. Its main activities are focusing on harmonization of training and organization of the format of the UEMS Board in Thoracic Surgery as well as further molding of the specialty via an intense collaboration with all involved stakeholders over the specialty boundaries. ispartof: JOURNAL OF THORACIC DISEASE vol:13 issue:3 pages:2021-2028 ispartof: location:China status: published

Thoracic and cardiovascular surgery requires learning both theoretical knowledge and technical skills. In this surgical field, several disparities exist between the different training programs around the world. This report describes the implementation of a portfolio in the teaching and assessment of French trainees in Thoracic and Cardiovascular surgery, following an electronic logbook model, aiming to improve the training program. The French surgical course is a twelve semesters' curriculum divided in 3 parts, each part containing knowledge, technical skills and behaviors objectives to be validated, defined by the French College of Thoracic and Cardiovascular surgery. The competencies are marked in the logbook, following a declarative model where the surgical trainee fills every surgical procedure attended (all or part) if he/she has observed, partially or fully performed, or supervised another trainee. All the surgical procedures are linked to theoretical e-learning lessons and each e-learning lesson includes a self-evaluation. This constitutes a competency-based assessment model with milestones both for surgeon trainees and their mentors. This portfolio also contains complementary tools such as an automated publication point calculation, a formatted curriculum vitae generator, and several contact tools between trainees. Implementation of a dedicated portfolio following an electronic logbook model appears to be a relevant pedagogic tool and survey element in the thoracic and cardiovascular surgery training program. Its use may lead to potential educational benefits for the trainee, reliable competency assessment for the supervising surgeon and for scientific society or national college.

Background : We sought to evaluate prognostic value of neutrophil-to-lymphocyte ratio (NLR) in surgically resected non-small cell lung cancer (NSCLC) and its correlation to oncogenic drivers. We retrospectively reviewed data of patients who underwent anatomic lung resection for NSCLC and whose mutational status was known, from 4 department of thoracic surgery, over the period 2008 to 2019. Primary endpoints were overall survival (OS) and time to recurrence (TTR). Clinical and molecular factors were investigated in the univariate and multivariate analysis for their association with the primary endpoints. Results : 2027 patients were included in the analysis. Correlations between NLR and OS (R2=0.21), NLR and TTR (R2=0.085) were significant (P In the univariable analysis, the median OS was 66 months (95% CI: 62.94 – 69.06) in case of pre-operative NLR ≤ 4.07 and 38 months (95% CI: 36.73 – 39.27) in case of pre-operative NLR > 4.07 (P 4.07 (P 4.07 and KRAS (Cramer's V = 0.082, P Conclusions : Low pre-operative NLR is associated with longer OS in patients with resected NSCLC. Low pre-operative NLR is not associated with longer TTR in multivariate analysis. Correlation between the high NLR and KRAS/EGFR mutations were observed.

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.

Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1-2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT-TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10-5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFβ pathway. EMT-TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.

Training of European thoracic surgeons is subject to huge variations in terms of length of training, content of training and operative experience during training. Harmonization of training outcomes has been approached by creating the European Board of Thoracic Surgery, which has been accredited by the European Union of Medical Specialists (UEMS); however, a clear description of the content of training is lacking. Building on their recognized experience with curriculum building, task forces of the European Respiratory Society and the European Society of Thoracic Surgery agreed on a joint task force on training in thoracic surgery. The goal of this study is to report on the mission statement developed from the UEMS-driven survey, describe the Delphi method and the observed results and present the first large consensus-based syllabus. The working group is currently working on a description of the curriculum and assessment of learning outcomes. ispartof: EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY vol:54 issue:2 pages:214-220 ispartof: location:AUSTRIA, Innsbruck status: published

Respiratory complications are the leading causes of morbidity and mortality after lung cancer surgery. We hypothesized that oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate (CHG) would be an effective method to reduce these complications as reported in cardiac surgery. In this multicenter parallel-group randomized double-blind placebo-controlled trial, we enrolled consecutive adults scheduled for anatomical pulmonary resection for lung cancer. Perioperative decontamination consisted in oropharyngeal rinse solution (0.12% CHG) and nasopharyngeal soap (4% CHG) or a placebo. The primary outcome measure was the proportion of patients requiring postoperative invasive and/or noninvasive mechanical ventilation (MV). Secondary outcome measures included occurrence of respiratory and non-respiratory healthcare-associated infections (HAIs) and outcomes within 90 days. Between July 2012 and April 2015, 474 patients were randomized. Of them, 24 had their surgical procedure cancelled or withdrew consent. The remaining 450 patients were included in a modified intention-to-treat analysis: 226 were allocated to CHG and 224 to the placebo. Proportions of patients requiring postoperative MV were not significantly different [CHG 14.2%; placebo 15.2%; relative risks (RRs) 0.93; 95% confidence interval (CI) 0.59–1.45; P = 0.76]. Neither of the proportions of patients with respiratory HAIs were different (CHG 13.7%; placebo 12.9%; RRs 1.06; 95% CI 0.66–1.69; P = 0.81). The CHG group had significantly decreased incidence of bacteremia, surgical-site infection and overall Staphylococcus aureus infections. However, there were no significant between-group differences for hospital stay length, change in tracheal microbiota, postoperative antibiotic utilization and outcomes by day 90. CHG decontamination decreased neither MV requirements nor respiratory infections after lung cancer surgery. Additionally, CHG did not change tracheal microbiota or postoperative antibiotic utilization. This study is registered on ClinicalTrials.gov, number NCT01613365.

The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67–88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21–51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098–0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67–87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86–34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027–0.999; p = 0.05). The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.

A best evidence topic was constructed according to a structured protocol. The question addressed was whether pulmonary grafts from donors deceased from hanging offer the same benefit as grafts from donors deceased from other causes in lung transplantation. Of the 17 papers found, 4 provided the best evidence to answer the question. The authors, date, journal, country of publication, study type, group studied, relevant outcomes and results of these papers are tabulated. One study reported a large cohort of donors and analysed the outcomes by cause of death, reporting no differences in survival. The remaining 3 papers analysed observational studies on the outcomes of lung transplantation using pulmonary grafts from donors deceased from hanging, compared with donors deceased from other causes. No differences in the rates of post-transplantation pulmonary graft dysfunction and long-term overall survival were reported. Although the cohort of donors deceased from hanging is small, we conclude that these donors are an important contribution to the donor pool. Ex vivo lung perfusion may have a role in assessing graft viability in this scenario.

Il trauma toracico rimane la seconda causa di mortalita traumatica dopo il trauma cranico. Tre tipi di meccanismi possono essere descritti per i traumi chiusi del torace: le lesioni da compressione/schiacciamento, le lesioni da decelerazione e le lesioni da scoppio. I fattori di gravita da ricercare sono un’eta superiore ai 65 anni, una patologia cronica polmonare o cardiovascolare, un disturbo della coagulazione congenito o acquisito e un meccanismo a cinetica elevata. Questi fattori aumentano il rischio di decesso legato al trauma di un fattore 2-3. Una volta completato il bilancio lesionale e stabilizzato il paziente, le tecniche di osteosintesi toracica si applicano tanto ai traumi acuti che a quelli antichi (pseudoartrosi). I molteplici scopi dell’osteosintesi toracica comprendono il controllo del dolore, il ripristino dell’espansione toracica e della meccanica respiratoria normale e l’emostasi del sanguinamento dalla frattura.

Resume Introduction En chirurgie thoracique, l’ extracorporeal life support (ECLS) represente un arsenal therapeutique indique en cas de defaillance de l’appareil respiratoire ou comme support mecanique pour un acte therapeutique. Les objectifs de cette revue generale sur l’ECLS en chirurgie thoracique sont de decrire le rationnel des techniques d’ECLS disponibles, de presenter les indications d’ECLS lors de defaillances de l’appareil respiratoire et aussi de demontrer l’interet de l’ECLS pour pratiquer l’ECLS en chirurgie thoracique selon une medecine fondee sur les preuves. Etat des connaissances L’ECLS doit se pratiquer dans des centres experts. Dans le syndrome de defaillance respiratoire aigue severe et refractaire, l’ECLS permet de mettre au repos les poumons en pratiquant une ventilation protectrice. En transplantation pulmonaire, l’ECLS peut etre pratiquee avec de bons resultats en pont a la transplantation pulmonaire, en temps que support cardiorespiratoire peroperatoire et en pont a la recuperation en cas de dysfonction primaire du greffon pulmonaire. L’ECLS en tant que support a un acte therapeutique tracheobronchique et/ou chez un insuffisant respiratoire severe est faisable sans majorer significativement le risque perioperatoire. Perspectives Les indications d’ECLS vont accroitre dans le temps sous l’impulsion des centres experts. Dans les annees a venir, les progres des techniques et de l’ingenierie ainsi que des connaissances approfondies permettront l’amelioration du pronostic des patients atteints de defaillance respiratoire sous assistance mecanique. Des etudes prospectives multicentriques et randomisees affineront les indications et les strategies de prise en charge globale de ces patients. Conclusion L’ECLS est un moyen therapeutique ameliorant le pronostic de patients atteints ou soumis aux risques de defaillance respiratoire.

Duration and content of Thoracic surgery training differs considerably across Europe, leading to unequal levels of knowledge, skills and attitudes at the time of graduation as a specialist. The European Board of Thoracic Surgery examination strives to overcome these regional differences by offering a diploma to achieve harmonization and equal qualified certification. The HERMES initiative, driven by a joint task force from European Society of Thoracic Surgeons (ESTS) and European Respiratory Society (ERS) is currently establishing a consensual syllabus and curriculum for Thoracic Surgery to standardize content of training and achieve equal levels of qualification all-over Europe. In this context, new opportunities in teaching and learning have become available and should be considered to support and encourage for beneficial development in the future. International platforms are the key for connecting with experts and other trainees and are provided by annual meetings and within the ESTS School.

Despite several advances in the last decades in both medical and surgical management, with a 5-year overall survival (OS) not exceeding 15%, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide (1). The past few years have seen an increased understanding in the molecular alterations of several cancers, helping clinicians to guide medical treatment and offer more accurate prognosis to patients. NSCLC was not left behind (2). Indeed, the recent discovery of oncogenic drivers such as activating mutations in the tyrosine kinase domain of the Epidermal Growth Factor Receptor (EGFR) has led to a dramatic increase in survival of patients harboring these mutations (3). Meanwhile, the prognostic and predictive values of EGFR mutations seem to be largely established in metastatic NSCLC (4), only a fleeting glimpse of clinical implications of many other mutations has been offered so far by the published literature, and might need further researches. One of the most promising molecular markers seems to rely in the mutations of the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene. KRAS encodes for RAS proteins which are small GTPases bounding between inactive guanosine diphosphate (GDP) and active guanosine triphosphate (GTP) forms. RAS proteins are central mediators downstream of growth factor receptor signaling and therefore are critical for cell proliferation, survival, and differentiation. Approximately 15% to 25% of NSCLC adenocarcinomas exhibit KRAS mutations (5). In the very large majority of the cases, these mutations are missense mutations introducing an amino-acid substitution at codon 12, 13 or 61 of the exon 2 of the gene (6). This confers a constitutive activation of KRAS signaling pathways, including the PI3K-AKT-mTOR pathway, involved in cell survival, and the RAS-RAF-MEK-ERK pathway, involved in cell proliferation. The complexity of KRAS mutations is reflected by the difficulty to develop effective therapies for patients with NSCLC harboring such mutations, and so far KRAS mutations are related to a poor prognosis in both locally and advanced NSCLC patients (7,8).

Background Postpneumonectomy acute respiratory distress syndrome (ppARDS) is a life-threatening condition with a disastrous prognosis. This study assessed the efficacy of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with unresponsive severe ppARDS. Methods We retrospectively reviewed data of all patients treated with VV-ECMO for ppARDS from January 2009 to December 2015. We calculated the Sequential Organ Failure Assessment score before ECMO insertion and monitored the subsequent mechanical ventilation settings. The primary end point was hospital survival. The secondary end point was the ability to achieve a protective ventilatory strategy allowing lung recovery on ECMO. Results VV-ECMO was indicated in 8 ppARDS patients for refractory hypoxemia (median partial pressure of arterial oxygen/fraction of inspired oxygen: 68 [range, 60 to 75] mm Hg). Median Sequential Organ Failure Assessment before ECMO was 15 (range, 12 to 17), predicting a mortality rate greater than 80%. Median duration of ECMO was 9.5 (range, 5 to 16) days. Tidal volumes and plateau pressures both decreased on ECMO (pre-ECMO tidal volume: 412 [range, 250 to 450 mL] vs ECMO tidal volume: 277 [range, 105 to 367 mL], p = 0.0156; pre-ECMO plateau pressure: 34 [range, 32 to 40] cm H 2 O vs ECMO plateau pressure: 24.5 [range, 23.3 to 27.3] cm H 2 O, p = 0.0195). ECMO could be weaned in 7 patients (87.5%). Hospital survival was 50%. Conclusions Hospital survival was better than predicted before ECMO insertion. In severe and refractory ppARDS, VV-ECMO allows lung recovery and therefore increased survival.

Resume Introduction Dans certains cas de tumeur primitive intra-abdominale, la chirurgie de cytoreduction suivie d’une chimiotherapie hyperthermique peritoneale permet d’ameliorer la survie des patients se presentant au stade de carcinomatose peritoneale. Nous decrivons un cas de paralysie diaphragmatique consecutive a ce type d’intervention. Observation Dans les suites d’une chirurgie et d’une chimiotherapie hyperthermique pour un pseudomyxome intra-abdominal, une patiente de 60 ans a developpe une insuffisance respiratoire. Les explorations fonctionnelles respiratoires ont montre un syndrome restrictif. Des scanners thoraciques successifs ont mis en evidence un amincissement musculaire des coupoles diaphragmatiques. L’atteinte respiratoire a evolue vers le deces de la patiente. Conclusion Nous concluons a une degenerescence du muscle diaphragmatique liee a la reduction chirurgicale et a l’effet cytotoxique de la chimiotherapie. Devant le caractere unique de ce type de complication, nous n’avons pas evoque cette hypothese suffisamment tot dans l’histoire de notre patiente. Nous pensons que ce cas doit etre connu pour permettre un diagnostic plus precoce de ce type de complications et recommandons la realisation d’une biopsie musculaire pour attester l’atteinte du diaphragme.

Background After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. Methods After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). Results In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. Conclusions Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.

Background Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. Conclusions Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.

Chondroblastoma is a rare benign cartilage neoplasm that arises from the appendicular skeleton in the vast majority of the cases (80%). Chondroblastoma of the spine is an even more rare condition (30 cases reported), and vertebral chondroblastomas, unlike chondroblastomas of the extremities, present with the appearance of an aggressive tumor on CT and MR imaging and occur at least a decade later. Even though vertebral chondroblastomas are very uncommon tumors, they should nonetheless be included in the differential diagnosis when encountered with an aggressive vertebral mass, and a histological confirmation should be performed. We present a case of chondroblastoma of the thoracic spine of a 27-year-old female for which detailed radiologic-pathologic correlation was obtained.

The pathophysiological importance of the immunogenicity of damage-associated molecular patterns (DAMPs) has been pinpointed by their identification as triggers of allograft rejection following release from dying cells, such as after ischemia-reperfusion injury. In cancers, however, this strong trigger of a specific immune response gives rise to the success of cancer immunotherapy. Here, we review the recently literature on the pathophysiological importance of DAMP release and discuss the implications of these processes for allograft rejection and cancer immunotherapy, revealing a striking mechanistic overlap. We conclude that these two fields share a common mechanistic basis of regulated necrosis and inflammation, the molecular characterization of which may be helpful for both oncologists and the transplant community.

In origine, l’extracorporeal membrane oxygenation (ECMO) era una tecnica di assistenza respiratoria che utilizzava uno scambiatore gassoso a membrana. Per estensione, l’ECMO è diventata una tecnica respiratoria e cardiopolmonare utilizzata in caso di deficit respiratorio e/o cardiaco nell’attesa della restaurazione della funzione deficitaria o di un eventuale trapianto. Il supporto emodinamico può essere parziale o totale. Gli accessi vascolari possono essere periferici o centrali. Questo tipo di assistenza utilizza il concetto di circolazione extracorporea (CEC) sanguigna che in epoca moderna si è estesa con l’utilizzo di polmoni artificiali a membrana. Il circuito di base è semplice e comprende una pompa, un ossigenatore (che permette al sangue di caricarsi di O2 e di eliminare CO2) e delle vie d’accesso (una di drenaggio e una di reinfusione). La sua attuazione è facile, veloce e può essere avviata al letto del malato. Il miglioramento delle attrezzature, una migliore conoscenza delle tecniche e delle indicazioni, e le politiche di salute pubblica hanno reso popolare questa tecnica. Alcuni centri di chirurgia toracica la utilizzano di routine come assistenza alla realizzazione di un intervento terapeutico (soprattutto trapianto) assieme a team di rianimazione per il trattamento della sindrome da distress respiratorio acuto. Nel quadro della malattia polmonare dell’adulto, l’idea principale è quella di sviluppare il concetto di strategia minimalista con l’uso di una CEC adiuvante parziale – più che sostitutiva totale – che permetterebbe il recupero metabolico ad integrum del paziente. Nei prossimi anni, i progressi della tecnologia e dell’ingegneria così come le conoscenze approfondite permetteranno il miglioramento della prognosi dei pazienti colpiti da deficit respiratorio sotto assistenza meccanica.

Lung transplantation is the only life-saving treatment for end stage respiratory disease. The immediate outcome is still hampered by primary graft dysfunction. The latter is a form of acute lung injury occurring within the 30min following the unclamping of the pulmonary artery that prompts ischemia reperfusion injury. Severe forms may need prolonged mechanical ventilation and extra-corporeal membrane oxygenation. Overall, primary graft dysfunction accounts for at least one third of the deaths during the first post-operative month. Despite increasing experience and knowledge on the underlying cellular events, there is still a lack of an early marker of ischemia reperfusion graft injuries. Microparticles are plasma membrane vesicles that are released from damaged or stressed cells in biological fluids and remodeling tissues, among which the lung parenchyma during acute or chronic injury. We recently evidenced alveolar microparticles as surrogate markers of strong ischemia injury in ex-vivo reperfusion experimental models. We propose herein new insights on how microparticles may be helpful to evaluate the extent of lung ischemia reperfusion injuries and predict the occurrence of primary graft dysfunction.

Objective: Our study aims at assessing the outcomes and survival after completion pneumonectomy (CP) for non-small cell lung cancer (NSCLC). Methods: We restrospectively recorded all CP performed in our centre for NSCLC from January 1st,1999 to December 31st, 2015. Immediate post-operative outcome and overall survival were studied. Results: A total of 48 patients underwent CP. All patients had a previous pulmonary resection for NSCLC except for one with previous benign disease. Most of patients were male (81,3%), and weaned smoker (70.8%). Ten (20,8%) patients received neo-adjuvant chemotherapy. A post-operative complication occurred in 62,5% patients: haemorrhage requiring blood transfusion (33,3%), lung infection (16,7%), recurrent nerve paralysis (10,4%), and atrial fibrillation (8,3%). Only 6,3% of patients required a re-operation for bleeding. None of the patients presented with bronchopleural fistula as a post-operative complication of CP. Inhospital mortality occurred in four (8,3%) patients. Despite the need for CP, 35,4% of patients had a stage I disease, and 43.8% had a stage II disease. Recurrence occurred in 47,9% of patients with a mean disease-free survival of 11 months. Mean overall survival following CP reached 45 months (>3 years). Conclusions: In experienced hands, CP is a safe curative treatment for NSCLC. Despite its complications, the mortality rate was low. A further prolonged overall survival was offered by CP to patients who already had a previous NSCLC treated with surgery.

With survival after retransplant improving over the years, issues regarding multiple retransplant have emerged. Here, we report the 25-year follow-up of a 16-year-old male patient who received 4 successful lung transplant procedures in 1990, 1991, 1995, and 2005.

Background: Surgical repair has demonstrated a beneficial effect on outcome for patients presenting with flail chest or with multiple rib fractures. We hypothesized that benefit on outcome parameters concerns predominantly patients being extubated within 24 hours post-operatively. Methods: We prospectively recorded all patients presenting with chest traumatism eligible for surgical repair with anticipated early extubation according to our institutional consensus (flail chest, major deformity, poor pain control, associated lesions requiring thoracotomy). We compared outcomes of patients extubated within 24 hours post-operatively to those who required prolonged ventilator support. We tested predictive factors for prolonged intubation with univariate and multivariate analysis. Results: From 2010 to 2014, 132 patients required surgical repair. Two thirds were extubated within 24 hours following surgical repair. Pneumonia was the main complication and occurred in 30.3% of all patients. Patients extubated within 24 hours following surgical repair had significantly shorter ICU stay and shorter in-hospital stay (P

The purpose of the study was to study parameters of the antioxidant protection system in saliva for non-small cell lung cancer. In the case-control study, included 683 volunteers, which were divided into 3 groups: primary (lung cancer patients, n = 290), comparison group (patients with nonmalignant pulmonary pathologies, n = 178) and control (conditionally healthy individuals, n = 215). Biochemical examination of saliva, histological verification of the diagnosis were carried out for all participants. The parameters of the antioxidant defense was determined spectrophotometrically. Intergroup differences were estimated by a nonparametric criterion. Saliva of lung cancer patients was characterized by imbalance in the antioxidant defense. It is shown that the activity of the enzymes of the first link of antioxidant protection (catalase, SOD) was significantly reduced (p ˂ 0.0001), whereas activity of salivary peroxidases increase (p = 0.0037). The parameters of non-enzymatic protection varied in opposite directions: the level of uric acid in lung pathologies decreases (p = 0.0399), whereas albumin concentration increased, under these conditions, it begins to exhibit prooxidant properties. Differences between adenocarcinoma and squamous cell lung cancer have been found in terms of the mode of the dynamics of antioxidant protection parameters. Probably, against the background of squamous cell lung cancer, an enzymatic link (catalase, SOD) contributes to the antioxidant protection system, whereas against adenocarcinoma - nonenzymatic (uric acid, albumin)., Цель исследования – изучение показателей системы антиоксидантной защиты в слюне при немелкоклеточном раке легкого. В исследовании «случай – контроль» приняли участие 683 добровольца, которые были разделены на 3 группы: основную (рак легкого, n = 290), группу сравнения (незлокачественные легочные патологии, n = 178) и контрольную (условно здоровые, n = 215). Всем участникам было проведено биохимическое исследование слюны, гистологическая верификация диагноза. Параметры антиоксидантной защиты определены спектрофотометрически. Межгрупповые различия оценены непараметрическим критерием. В образцах слюны пациентов с раком легких отмечено нарушение баланса антиоксидантной защиты в слюне. Активность ферментов первого звена антиоксидантной защиты (каталаза, SOD) существенно снижается (р ˂ 0.0001), тогда как активность пероксидаз слюны растет (р = 0.0037). Показатели неферментативной защиты меняются разнонаправленно: уровень мочевой кислоты при патологиях легких снижается (р = 0.0399), тогда как концентрация альбумина растет; в данных условиях он начинает проявлять прооксидантные свойства. Выявлены различия между аденокарциномой и плоскоклеточным раком легкого по характеру динамики показателей антиоксидантной защиты. Вероятно, на фоне плоскоклеточного рака легких больший вклад в систему антиоксидантной защиты вносит ферментативное звено (каталаза, SOD), тогда как на фоне аденокарциномы – неферментативное (мочевая кислота, альбумин).

Background: This study evaluates the number of video-assisted thoracic surgery-lobectomies (VATS-lobectomies) required for an experienced consultant thoracic surgeon to obtain competence and to perform standard quality surgery. Methods: We have analysed the initial VATS-experience (January 2012 to September 2014) of a confirmed senior consultant who has performed 145 consecutive anatomic resections by thoracoscopy. After excluding bilobectomies, segmentectomies, and lobectomies for infectious disease, we have focused into 119 consecutive lobectomies, classified into 4 chronologic groups of 30 each. We have considered: demographics; pathology; postoperative outcomes; conversion rate; morbidity. We compared the 4 groups in a Bayesian inference model (very strong probability of a difference if Pr>95% or Pr>80% or 5% Results: There was a very strong probability of difference of group 1 (first 30 lobectomies) compared to the 3 other groups: less incomplete fissures (Pr 1 =0.019, Pr 1 =0.037, Pr 1 =0.046), more node samplings (Pr 1>2 =0.977, Pr 1>3 =0.96, Pr 1>4 =0.997) and, conversely, less radical dissections (Pr 1 =0.022, Pr 1 =0.039, Pr 1 =0.003), less harvested nodes (Pr 1 ≤0.001, Pr 1 ≤0.001, Pr 1 ≤0.001), less pleural adhesions (Pr 1 =0.077, Pr 1 =0.044). Instead, there was a very strong probability of difference of group 4 compared to the first three groups (first 90 lobectomies): lower conversion rate (Pr 1>4 =0.992, Pr 3>4 =0.996, Pr 2>4 =0.995), lower duration of the operation (Pr 1>4 =0.946, Pr 2>4 =0.901, Pr 3>4 =0.932), less air leak (Pr 1>4 =0.936, Pr 2>4 =0.97) and shorter chest tube drainage (Pr 1>4 =0.94, Pr 2>4 =0.94, Pr 3>4 =0.937), as well as shorter hospital stay (Pr 2>4 =0.94, Pr 3>4 =0.937). Conclusions: The learning curve was bimodal. After the initial 30 lobectomies, oncologic quality of the procedure improved and stabilized. The surgeon became less selective and accepted to proceed with more complex cases (incomplete fissures, pleural adhesions). Efficiency was obtained after 90 lobectomies (shorter operative time and lower conversion rate).

The HERMES (Harmonising Education in RespiratoryMedicine for European Specialists) project is fundedby the European Respiratory Society (ERS) andhas the declared aims of harmonising educationin thoracic medicine, recognising diplomas andcertificates of qualification, and improving freeaccess and mobility for medical specialists acrossthe European Union (EU). This takes into accountDirective 2013/55/EU of the European Parliamentand of the Council [1] on the recognition ofprofessional qualifications, one of the pillars of EUlegislation. Moreover, it conforms to the fact thatthere is a shortage of medical/surgical specialists inseveral European countries, which means that morephysicians of other Europeanand non-Europeancountries will be needed to sustain the functioningand development of health services in future yearsand decades [2]. HERMES is working towardsthe development of harmonised and structuredprogrammes for education across respiratoryspecialties to ensure that the best care is deliveredfor those suffering from respiratory diseases., SCOPUS: re.j, info:eu-repo/semantics/published

OBJECTIVES Epidermal growth factor receptor (mEGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue (mKRAS) mutations are the two main oncogenic drivers in resected non-small-cell lung cancer (NSCLC). We aimed to evaluate the correlation between histopathological prognostic factors and these mutations in resected NSCLC. METHODS We retrospectively reviewed data from 841 patients who underwent a surgical resection with a curative intent for NSCLC between 2007 and 2012. RESULTS KRAS mutations were observed in 255 patients (32%) and mEGFR in 103 patients (12%). A correlation was observed between mKRAS patients and lymph node involvement [Cramer's V: 0.451, P < 0.001, OR: 7.5 (95% CI: 5.3-10.7), P < 0.001]. Otherwise, a correlation was observed between mKRAS and the risk of harbouring 2 N2 stations [Cramer's V: 0.235, P = 0.02, OR: 3.04 (95% CI: 1.5-6.3), P = 0.004]. High lymph node ratio and angioinvasion were also significantly more frequent in mKRAS [Cramer's V: 0.373, P < 0.001, OR: 6.37 (95% CI: 3.9-10.5), P < 0.001; and Cramer's V: 0.269, P < 0.001, OR: 3.25 (95% CI: 2.4-4.4), P < 0.001, respectively]. Skip N2 and microscopic N2 were significantly more frequent in mEGFR [Cramer's V: 0.459, P < 0.001, OR: 18 (95% CI: 5.6-57.8), P < 0.001; and (Cramer's V: 0.45, P < 0.001 OR: 21.14 (95% CI: 9.2-48.3), P < 0.001, respectively]. CONCLUSIONS We observed a correlation between mKRAS and negative histopathological prognostic factors and between mEGFR and positive prognostic factors. One can wonder whether histopathological prognostic factors are only clinical reflections of molecular alterations.

A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand, soluble TNF-related apoptosis-inducing ligand and TNF-α, was associated with the occurrence of a reduced skeletal mass and osteoporosis in male patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study was to explore the associations between serum biomarkers of tumor necrosis factor (TNF) superfamily and body and bone compositions in end-stage COPD males. Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass, serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), TNF-α and its receptors (sTNFR-I, sTNFR-II) and soluble TNF-related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in male COPD patients than in control subjects, whereas sRANKL, TNF-α and its receptors were higher. The serum sTRAIL level showed a tendency to increase compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive correlation with bone density. In contrast, serum TNF-α, sRANKL and sTRAIL were inversely associated with pretransplant bone density. We have noted the appearance of statistically significant inverse relationships between lean mass values and TNF-α, sTNFR-I and II and sRANKL levels in male COPD patients. Moreover, there was a negative correlation between sTRAIL levels with airway obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients. Through a multiple linear regression analysis, our study revealed that a disequilibrium of TNF family members was strongly associated with the occurrence of a reduced skeletal mass and osteoporosis. These results provide further evidence that abnormal levels of TNF superfamily molecules may cause not only a decrease in BMD, but also lower muscle mass in end-stage COPD.