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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

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.

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.

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.

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.

Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated. We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the χ 2 test and Student’s t test; any p value ≤0.05 was considered as significant. Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p

Background: We aimed to evaluate whether EGFR mutations (mEGFR) and KRAS amino acid substitutions can predict first site of recurrence or metastasis after non-small-cell lung cancer (NSCLC) surgery. Methods: Data were reviewed from 481 patients who underwent thoracic surgery for NSCLC between 2007 and 2012. Results: Patients with KRAS G12C developed significantly more bone metastases compared with the remainder of the cohort (59% vs 16%, P

Resume Introduction La thoracotomie etait consideree comme la voie d'abord de reference pour la lobectomie. Cependant, les techniques video assistees, dites « VATS » ( Video-Assisted Thoracoscopic Surgery ), offrent une alternative utilisee de facon rapidement croissante. Etat des connaissances : Les techniques VATS sont actuellement indiquees dans les cancers bronchiques de stade I. Leur utilisation est associee a une diminution de la morbidite postoperatoire, permettant leur integration dans des programmes de recuperation rapide, dits « FastTrack ». La duree d'hospitalisation est reduite de facon significative. Ces techniques respectent les regles de resection oncologique, et notamment le curage ganglionnaire complet est realisable. La VATS semble egalement etre associee a une meilleure survie sans recidive, comme globale. Perspectives Du fait des avantages de cette voie d'abord, les resections pulmonaires par VATS pourraient a l'avenir s’etendre aux stades II et IIIA, aux pathologies pulmonaires benignes, mais egalement a la chirurgie des metastases. Conclusion La VATS, de par ses nombreux benefices, est en voie de se positionner comme technique de reference pour les cancers bronchiques de stade I.

Resume Introduction La chirurgie constitue le traitement de choix des CBNPC de stades precoces. Malgre une chirurgie a visee curative, il existe un risque non nul de recidive et de deces par cancer. Etat des connaissances La chimiotherapie adjuvante est indiquee pour les stades II et III, debattue dans les stades IB. Les meta-analyses publiees ont conclu a un benefice de survie absolu de 5 % a 5 ans. La place de la chimiotherapie neoadjuvante est moins codifiee. La seule meta-analyse publiee comparant les deux schemas n'a pas note de difference significative en termes de survie. Perspectives : Le benefice de l'utilisation des inhibiteurs de tyrosine kinase (ITK), chez les malades mutes Epidermal Growth Factor Receptor (EGFR) de stades avances, a fait se poser la question de l'interât de leur utilisation perioperatoire chez les stades precoces. A ce jour, peu de donnees sont disponibles dans la litterature, mais sont encourageantes quant a leur interât en situation neoadjuvante afin d'augmenter la resecabilite et, en adjuvant afin d'allonger la survie sans progression, chez des malades selectionnes. Conclusion Le moment de la chimiotherapie semble avoir peu d'importance sur la survie. La place des ITK, bien que prometteuse, reste a definir.

A best evidence topic was constructed according to a structured protocol. The question addressed was whether the administration of perioperative chemotherapy (CT) is effective in improving survival in patients with resectable lung metastases of colorectal cancer (CRC). Of the 44 papers found using a report search, 6 investigated the effect of perioperative CT (adjuvant-CT, preoperative-CT or both) on outcomes in patients undergoing lung metastasectomy for CRC. These 6 studies presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, study type, group studied, relevant outcomes and results of these papers are given. Overall, none of the studies were successful in demonstrating that CT had an independent effect on overall survival in patients undergoing lung resection surgery for CRC metastasis. Indeed, beneficial outcomes have been shown in particular sub-groups of patients: multiple metastases, metachronous lung metastasis, low-risk patients, particular molecular marker expression and oxaliplatin-based regimen. All the studies indicated a benefit in disease-free survival or progression-free survival. Administration of tailored perioperative CT might be effective after an accurate patient selection. We conclude that the current evidence does not support the administration of unselective perioperative CT in patients with resectable lung metastases of colorectal cancer.

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Objective To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. Material and Methods Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. Results DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. Conclusions Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.

Lung transplantation has become an efficient life-saving treatment for patients with end stage respiratory disease. The increasing good outcome following lung transplantation may be explained by growing experience of transplant teams and availability of potent immunosuppressive drugs. Nevertheless, the latter carries an inherent risk for malignancy besides other common side effects such as systemic hypertension, diabetes and renal dysfunction. Malignancies occur in a smaller proportion of patients but explain for a large proportion of deaths following transplantation. From the first year post-transplantation they will represent the third cause of death with an increasing incidence along post lung transplant survival. In this chapter, we will browse the different types of malignancies arising following lung transplantation. According to the different techniques for lung transplantation, specific types of bronchogenic carcinoma will be described in the explanted lung, in the native lung, and in the graft. Risk factors associated to immunosuppressive therapy, but also to occupational and environmental factors, especially smoking, will be discussed. Eventually, we will strive at integrating recommendations for the treatment of malignancies following lung transplantation.

Neutrophil to lymphocyte ratio (NLR) has been shown to be a promising biomarker in several cancers. Prognostic biomarkers are still needed to define good candidates for lung metastasectomy for colorectal cancer. We aimed to evaluate the role of NLR.Data from 574 patients who underwent lung metastasectomy for colorectal cancer in 3 departments of thoracic surgery from 2004 to 2014 were retrospectively reviewed. Overall survival (OS) and the time to pulmonary recurrence (TTPR) were the main end points.Correlations between NLR and OS (R2 = 0.53), and NLR and TTPR (R2 = 0.389) were significant (P 0.0001 for both), with corresponding Pearson R of -0.728 (P 0.0001) and -0.624 (P 0.0001), respectively. A receiver operating characteristic curve analysis highlighted an NLR cut-off value of 4.05 as the best predictor of OS and TTPR. NLR ≤4.05 was observed in 238 patients (41.4%). In the univariable analysis, the median OS was 117 months for patients with NLR ≤4.05 and decreased to 40 months for patients with NLR4.05 (P 0.0001). The median TTPR reached 52 months in case of NLR ≤4.05 and decreased to 12 months in patients with NLR4.05. In the multivariable analysis, NLR ≤4.05 remained an independent favourable prognostic factor on both OS [hazard ratio [HR] 0.29, 95% confidence interval (CI) 0.167-0.503; P 0.0001] and TTPR (HR 0.346, 95% CI 0.221-0.54; P 0.0001). Significant correlations between NLR4.05 and KRAS (Cramer's V = 0.241, P 0.0001) and BRAF (Cramer's V = 0.153, P = 0.003) mutations were observed.NLR is a simple and powerful predictor of outcomes in patients undergoing pulmonary metastasectomy for colorectal cancer.

Optimization of methods for diagnostics and prediction of lung cancer, which occupies a leading position in the structure of oncological diseases, still remains an important task. In this study we have investigated the level of cytokines and acute-phase proteins in saliva of patients with lung cancer in dependence on the tumor size, and distant and regional metastasis. The case-control study included 121 patients, which were divided into 3 groups: the main group (patients with diagnosed lung cancer, n = 70), the reference group (patients with non-malignant lung pathologies, n = 12) and the control group (conditionally healthy individuals, n = 39). All participants answered the questionnaire, underwent biochemical study of saliva and histological verification of the diagnosis. The content of IL-2 and IL-4 in saliva reduced in both lung cancer and inflammatory lung diseases, whereas the levels of IL-18, IL-8 and TNF-α decreasd in lung cancer and increased in non-malignant pathologies. Tumor progression was accompanied by an increase in the level of proinflammatory cytokines (IL-6, IL-8, IL-18, TNF-α), whereas the levels of IL-2, IL-4 and IL-10 decreased. Although saliva levels of C-reactive protein and tumor markers increased in lung cancer they did reach the level of statistical significance as compared with the reference group. Thus, with the only exception of IL-2 and IL-4, the saliva levels of cytokines in lung cancer patients insignificantly differ from the control group. However, the recognzied dynamics of the saliva cytokines level in patients with distant and regional metastasis opens the prospect of using these parameters for monitoring the treatment and controlling relapse occurrence., До настоящего времени остаются актуальными проблемы оптимизации методов диагностики и прогнозирования течения рака легкого, занимающего лидирующие позиции в структуре онкологических заболеваний. Цель исследования: изучение уровня цитокинов и острофазовых белков в слюне пациентов с раком легкого в зависимости от размера опухоли, а также на фоне отдаленного и регионарного метастазирования. В исследовании случай – контроль приняли участие 121 человек, которые были разделены на 3 группы: основную (с диагнозом рак легкого, n=70), группу сравнения (с незлокачественными патологиями легких, n=12) и контрольную группу (условно здоровые, n=39). Всем участникам было проведено анкетирование, биохимическое исследование слюны, гистологическая верификация диагноза. Межгрупповые различия оценены непараметрическим критерием. Показано, что что уровни цитокинов в слюне больных раком легкого и здоровых людей статистически достоверно не отличаются. Содержание ИЛ-2 и ИЛ-4 в слюне уменьшается как в случае рака легкого, так и при воспалительных заболеваниях легких, тогда как уровни ИЛ-8, ИЛ-18 и ФНО-α при раке легкого снижаются, а на фоне неопухолевых патологий растут. При прогрессировании опухоли уровень провоспалительных цитокинов (ИЛ-6, ИЛ-8, ИЛ-18, ФНО-α) растет, тогда как ИЛ-2, ИЛ-4 и ИЛ-10 уменьшается. Отмечено увеличение уровня С-реактивного белка и опухолевых маркеров в динамике рака легкого, однако достоверных отличий от воспалительных заболеваний легких не выявлено.

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Survival analysis refers to the statistical methods used for the analyzing of data where the outcome variable is the time until the occurrence of the event of interest. Survival analysis is also known as time to event analysis. Survival analysis applications are very large: For instance, they can be used for determining the survival rate of a population, or comparing the survival of two or more groups.

OBJECTIVE The aim of this study was to evaluate the benefit of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) harboring KRAS mutations SUMMARY BACKGROUND DATA:: KRAS mutations are related to high aggressiveness in the lung metastasis of CRC. It is unknown whether AR can lead to better outcomes than can non-AR (NAR) in KRAS patients. METHODS We retrospectively reviewed the data from 574 consecutive patients who underwent a LM for CRC. We focused on patients exhibiting 1 lung metastasis who underwent an AR (segmentectomy) or an NAR (wedge) and for whom the KRAS mutational status was known. Overall survival (OS) and time to pulmonary recurrence (TTPR) were analyzed. RESULTS We included 168 patients, of whom 95 (56.5%) harbored KRAS mutations. An AR was performed in 74 patients (44%). The type of resection did not impact the median OS in wild-type (WT) patients (P = 0.67) but was significantly better following AR in KRAS patients (101 vs 45 months, P = 0.02) according to the multivariate analysis [hazard ratio (HR): 6.524; 95% confidence interval (CI), 2.312-18.405; P < 0.0001). TTPR was not affected by the type of resection in WT patients (P = 0.32) but was significantly better for AR in KRAS patients (50 vs 15 months, P = 0.01) in the multivariate analysis (HR: 5.273; 95% CI, 1.731-16.064; P = 0.003). The resection-margin recurrence rate was significantly higher for NAR in KRAS patients (4.8% vs 54.2%, P = 0.001) but not in WT patients (P = 0.97). CONCLUSION AR seems to improve both the OS and TTPR in LM of CRC harboring KRAS mutations.

Summary Background Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. Methods In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434. Findings Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate −9·1%; 95% CI −∞ to −1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0–98·4) in the OCS group and 165 patients (100%; 97·8–100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1–93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8–92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate −0·045%; 95% CI −∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1). Interpretation The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation. Funding TransMedics Inc.