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OBJECTIVES To determine safety and survival outcomes associated with lobectomy, segmentectomy and wedge resection for early-stage lung cancer by quiring the French population-based registry EPIdemiology in THORacic surgery (EPITHOR). METHODS Retrospective analysis of 19 452 patients with stage c IA lung carcinoma who underwent lobectomy, segmentectomy or wedge resection between 2016 and 2022 with curative-intent. Main outcome measures were 90-day mortality and 5-year overall survival estimates. Proportional hazards regression and propensity score matching were used to adjust outcomes for key patient, tumour and practice environment factors. RESULTS The treatment distribution was 72.2% for lobectomy, 21.5% for segmentectomy and 6.3% for wedge. Unadjusted 90-day mortality rates were 1.6%, 1.2% and 1.1%, respectively (P  = 0.10). Unadjusted 5-year overall survival estimates were 80%, 78% and 70%, with significant inter-group survival curves differences (P  < 0.0001). Multivariable proportional hazards regression showed that wedge was associated with worse overall survival [adjusted hazard ratio (AHR), 1.23 (95% confidence interval 1.03–1.47); P  = 0.021] compared with lobectomy, while no significant difference was disclosed when comparing segmentectomy to lobectomy (1.08 [0.97–1.20]; P  = 0.162). The three-way propensity score analyses confirmed similar 90-day mortality rate for wedge resection and segmentectomy compared with lobectomy (hazard ratio: 0.43; 95% confidence interval 0.16–1.11; P  = 0.081 and 0.99; 0.48–2.10; P  = 0.998, respectively), but poorer overall survival (1.45; 1.13–1.86; P  = 0.003 and 1.31; 1–1.71; P  = 0.048, respectively). CONCLUSIONS Wedge resection was associated with comparable 90-day mortality but lower overall survival when compared to lobectomy. Overall, all types of sublobar resections may not offer equivalent oncologic effectiveness in real-world settings. [ABSTRACT FROM AUTHOR]

Background: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. Methods: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan–Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. Results: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2–7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010–6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021–1.905; p = 0.036). Conclusions: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification. [ABSTRACT FROM AUTHOR]

We prove that if |$D$| is a strongly pseudoconvex domain with |$\mathcal C^{2, \alpha }$| -smooth boundary, then the length of a geodesic for the Kobayashi–Royden infinitesimal metric between two points is bounded by a constant multiple of the Euclidean distance between the points. [ABSTRACT FROM AUTHOR]

Background: Few epidemiological data are available on surgically treated Caucasian patients with non-small-cell lung cancers (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations. The main objective of this study was to describe, in the real-world setting, these patients' incidence, clinical, and tumoral characteristics. Methods: The participating centers included all consecutive localized non-squamous NSCLC patients undergoing surgery between January 2018 and December 2019 in France. EGFR status was determined retrospectively when not available before surgery. Results: The study includes 1391 no squamous NSCLC patients from 16 centers; EGFR status was determined before surgery in 692 (49.7%) of the cases and conducted as part of the study for 699 (50.3%); 171 (12.3%) were EGFR mutated; median age: 70 (range: 36–88) years; female: 59.6%; never smokers: 75.7%; non-squamous histology 97.7%, programmed death ligand-1 expression 0%/1–49%/⩾50 in 60.5%/25.7%/13.8%, respectively. Surgery was predominantly lobectomy (81%) or segmentectomy (14.9%), with systematic lymph node dissection in 95.9%. Resection completeness was R0 for 97%. Post-surgery staging was as follows: IA: 52%, IB: 16%, IIA: 4%, IIB: 10%, IIIA: 16%, and IIIB: 0.05%; EGFR mutation exon was Del19/exon 21 (L858R)/20/18 in 37.4%/36.8%/14%, and 6.4% of cases, respectively; 31 (18%) patients received adjuvant treatment (chemotherapy: 93%, EGFR tyrosine kinase inhibitor: 0%, radiotherapy: 20%). After a median follow-up of 31 (95% confidence interval: 29.6–33.1) months, 45 (26%) patients relapsed: 11/45 (24%) locally and 34 (76%) with metastatic progression. Median disease-free survival (DFS) and overall survival were not reached and 3-year DFS was 60%. Conclusion: This real-world analysis provides the incidence and outcomes of resected EGFR -mutated NSCLCs in a European patient cohort. [ABSTRACT FROM AUTHOR]

We introduce the notion of locally visible and locally Gromov hyperbolic domains in \mathbb {C}^d. We prove that a bounded domain in \mathbb {C}^d is locally visible and locally Gromov hyperbolic if and only if it is (globally) visible and Gromov hyperbolic with respect to the Kobayashi distance. This allows to detect, from local information near the boundary, those domains which are Gromov hyperbolic and for which biholomorphisms extend continuously up to the boundary. [ABSTRACT FROM AUTHOR]

Introduction: The influence of lung disease on the diaphragm has been poorly studied. The study aimed to evaluate the diaphragm morphology (height and thickness) in single-lung transplantation (SLTx), using computed tomography (CT), by assessing the evolution of the hemidiaphragm of the transplanted and the native side. Methods: Patients who underwent single lung transplantation in our center (Marseille, France) between January 2009 and January 2022 were retrospectively included. Thoracic or abdominal CT scans performed before and the closest to and at least 3 months after the surgery were used to measure the diaphragm crus thickness and the diaphragm dome height. Results: 31 patients mainly transplanted for emphysema or pulmonary fibrosis were included. We demonstrated a significant increase in diaphragm crus thickness on the side of the transplanted lung, with an estimated difference of + 1.25 mm, p = <0.001, at the level of the celiac artery, and + 0.90 mm, p < 0.001, at the level of the L1 vertebra while no significant difference was observed on the side of the native lung. We showed a significant reduction in the diaphragm height after SLTx on the transplanted side (-1.20 cm, p = 0.05), while no change on the native side (+0.02 cm, p = 0.88). Conclusion: After a SLTx, diaphragmatic morphology significantly changed on the transplanted lung, while remaining altered on the native lung. These results highlights that an impaired lung may have a negative impact on its diaphragm. Replacement with a healthy lung can promote the recovery of the diaphragm to its anatomical morphology, reinforcing the close relationship between these two organs. [ABSTRACT FROM AUTHOR]

The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing complications. From its early attempts to modern minimally invasive approaches, the journey has been marked by perseverance and innovation. Franz J. A. Torek's 1913 successful esophageal resection marked a milestone, demonstrating the feasibility of transthoracic esophagectomy and the potential for esophageal cancer cure. However, its high mortality rate posed challenges, and it took almost two decades for similar successes to emerge. Surgical techniques evolved with the left thoracotomy, right thoracotomy, and transhiatal approaches, expanding the indications for resection. Mechanical staplers introduced in the early 20th century transformed anastomosis, reducing complications. The advent of minimally invasive techniques in the 1990s aimed to minimize complications while maintaining oncological efficacy. Robot-assisted esophagectomy further pushed the boundaries of minimally invasive surgery. Collaborative efforts, particularly from the Worldwide Esophageal Cancer Collaboration and the Esophageal Complications Consensus Group, standardized reporting and advanced the understanding of outcomes. The introduction of risk prediction models aids in making informed decisions. Despite significant improvements in survival rates and postoperative mortality, anastomotic leaks remain a concern, with recent rates showing an increase. Prevention strategies include microvascular anastomosis and ischemic preconditioning, yet challenges persist. [ABSTRACT FROM AUTHOR]

Introduction: Chronic lung allograft dysfunction (CLAD) can take two forms: bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The aim was to determine if chest-CT abnormalities after lung transplantation (LTx) could predict CLAD before respiratory functional deterioration. Materials and methods: This monocentric retrospective study analyzed consecutive patients who underwent LTx from January 2015 to December 2018. Initial CT post-LTx (CTi) and a follow-up CT at least 9 months post-LTx (CTf) were reviewed. CLAD was defined as a persistent respiratory functional decline (> 20% of basal FEV1) outside acute episode. A Cox regression was performed in univariate, then in multivariate analysis (including features with p < 0.01 in univariate or of clinical importance) to determine risk factors for CLAD. Subgroup analyses were made for BOS, RAS, and death. Results: Among 118 LTx patients (median (min–max) 47 (18–68) years), 25 developed CLAD during follow-up (19 BOS). The median time to CLAD since LTx was 570 days [150–1770]. Moderate pulmonary artery stenosis (30–50%) was associated with the occurrence of CLAD on CTi (hazard ratio HR = 4.6, CI [1.6–13.2]) and consolidations and pleural effusion on CTf (HR = 2.6, CI [1.3–4.9] and HR = 4.5, CI [1.5–13.6] respectively). The presence of mosaic attenuation (HR = 4.1, CI [1.4–12.5]), consolidations (HR = 2.6, CI [1.3–5.4]), and pleural effusions (p = 0.01, HR = 5.7, CI [1.4–22.3]) were risk factors for BOS on CTf. The consolidations (p = 0.029) and pleural effusions (p = 0.001) were risk factors for death on CTf. Conclusions: CTi and CTf in the monitoring of LTx patients could predict CLAD. Moderate pulmonary artery stenosis, mosaic pattern, parenchyma condensations, and pleural effusions were risk factors for CLAD. Critical relevance statement: There is a potential predictive role of chest CT in the follow-up of LTx patients for chronic lung allograft dysfunction (CLAD). Early chest CT should focus on pulmonary artery stenosis (risk factor for CLAD in this study). During the follow-up (at least 9 months post-LTx), parenchymal consolidations and pleural effusions were shown to be risk factors for CLAD, and death in subgroup analyses. Key points: • Pulmonary artery stenosis (30–50%) on initial chest-CT following lung transplantation predicts CLAD HR = 4.5; CI [1.6–13.2]. • Pleural effusion and consolidations 1 year after lung transplantation predict CLAD and death. • Early evaluation of lung transplanted patients should evaluate pulmonary artery anastomosis. [ABSTRACT FROM AUTHOR]

Background: Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context. Methods: Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method. Results: The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months). Conclusions: Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds. Trial registration: NCT02502318. [ABSTRACT FROM AUTHOR]

Objectives: Lung carcinoids and atypical hamartomas may be difficult to differentiate but require different treatment. The aim was to differentiate these tumors using contrast-enhanced CT semantic and radiomics criteria. Methods: Between November 2009 and June 2020, consecutives patient operated for hamartomas or carcinoids with contrast-enhanced chest-CT were retrospectively reviewed. Semantic criteria were recorded and radiomics features were extracted from 3D segmentations using Pyradiomics. Reproducible and non-redundant radiomics features were used to training a random forest algorithm with cross-validation. A validation-set from another institution was used to evaluate of the radiomics signature, the 3D 'median' attenuation feature (3D-median) alone and the mean value from 2D-ROIs. Results: Seventy-three patients (median 58 years [43‒70]) were analyzed (16 hamartomas; 57 carcinoids). The radiomics signature predicted hamartomas vs carcinoids on the external dataset (22 hamartomas; 32 carcinoids) with an AUC = 0.76. The 3D-median was the most important in the model. Density thresholds < 10 HU to predict hamartoma and > 60 HU to predict carcinoids were chosen for their high specificity > 0.90. On the external dataset, sensitivity and specificity of the 3D-median and 2D-ROIs were, respectively, 0.23, 1.00 and 0.13, 1.00 < 10 HU; 0.63, 0.95 and 0.69, 0.91 > 60 HU. The 3D-median was more reproducible than 2D-ROIs (ICC = 0.97 95% CI [0.95‒0.99]; bias: 3 ± 7 HU limits of agreement (LoA) [− 10‒16] vs. ICC = 0.90 95% CI [0.85‒0.94]; bias: − 0.7 ± 21 HU LoA [− 4‒40], respectively). Conclusions: A radiomics signature can distinguish hamartomas from carcinoids with an AUC = 0.76. Median density < 10 HU and > 60 HU on 3D or 2D-ROIs may be useful in clinical practice to diagnose these tumors with confidence, but 3D is more reproducible. Critical relevance statement: Radiomic features help to identify the most discriminating imaging signs using random forest. 'Median' attenuation value (Hounsfield units), extracted from 3D-segmentations on contrast-enhanced chest-CTs, could distinguish carcinoids from atypical hamartomas (AUC = 0.85), was reproducible (ICC = 0.97), and generalized to an external dataset. Key points: • 3D-'Median' was the best feature to differentiate carcinoids from atypical hamartomas (AUC = 0.85). • 3D-'Median' feature is reproducible (ICC = 0.97) and was generalized to an external dataset. • Radiomics signature from 3D-segmentations differentiated carcinoids from atypical hamartomas with an AUC = 0.76. • 2D-ROI value reached similar performance to 3D-'median' but was less reproducible (ICC = 0.90). [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Despite an improvement in surgical abilities, the need for an intraoperative switch from a minimally invasive procedure towards an open surgery (conversion) still remains. To anticipate this risk, the Epithor conversion score (ECS) has been described for video-assisted thoracoscopic surgery (VATS). Our objective was to determine if this score, developed for VATS, is applicable in robotic-assisted thoracoscopic surgery (RATS). METHODS This was a retrospective monocentric study from January 2006 to June 2022, and data were obtained from the EPITHOR database. Patients included were those who underwent anatomic lung resection either by VATS or RATS. The ECS was calculated for all patients studied. Discrimination and calibration of the test were measured by the area under the curve and Hosmer–Lemeshow test. RESULTS A total of 1685 were included. There were 183/1299 conversions in the VATS group (14.1%) and 27/386 conversions in the RATS group (6.9%). Patients in the RATS group had fewer antiplatelet therapy and peripheral arterial disease. There were more segmentectomies in the VATS group. As for test discrimination, the area under the curve was 0.66 [0.56–0.78] in the RATS group and 0.64 [0.60–0.69] in the VATS group. Regarding the calibration, the Hosmer–Lemeshow test was not significant for both groups but more positive (better calibrated) for the VATS group (P  = 0.12) compared to the RATS group (P  = 0.08). CONCLUSIONS The ECS seems applicable for patients operated with RATS, with a correct discrimination but a lower calibration performance for patients operated with VATS. A new score could be developed to specifically anticipate conversion in patients operated on by RATS. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES A lung transplant is the final treatment option for end-stage lung disease. We evaluated the individual risk of 1-year mortality at each stage of the lung transplant process. METHODS This study was a retrospective analysis of patients undergoing bilateral lung transplants between January 2014 and December 2019 in 3 French academic centres. Patients were randomly divided into development and validation cohorts. Three multivariable logistic regression models of 1-year mortality were applied (i) at recipient registration, (ii) the graft allocation and (iii) after the operation. The 1-year mortality was predicted for individual patients assigned to 3 risk groups at time points A to C. RESULTS The study population consisted of 478 patients with a mean (standard deviation) age of 49.0 (14.3) years. The 1-year mortality rate was 23.0%. There were no significant differences in patient characteristics between the development (n  =   319) and validation (n  =   159) cohorts. The models analysed recipient, donor and intraoperative variables. The discriminatory power (area under the receiver operating characteristic curve) was 0.67 (0.62–0.73), 0.70 (0.63–0.77) and 0.82 (0.77–0.88), respectively, in the development cohort and 0.74 (0.64–0.85), 0.76 (0.66–0.86) and 0.87 (0.79 – 0.95), respectively, in the validation cohort. Survival rates were significantly different among the low- (< 15%), intermediate- (15%–45%) and high-risk (> 45%) groups in both cohorts. CONCLUSIONS Risk prediction models allow estimation of the 1-year mortality risk of individual patients during the lung transplant process. These models may help caregivers identify high-risk patients at times A to C and reduce the risk at subsequent time points. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener’s syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27–3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14–1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population. [ABSTRACT FROM AUTHOR]

Purpose: Since 2014, a trauma system (TS) for the Provence-Alpes-Cote-d'Azur (PACA) region has been set up with protocols based on the European guidelines for the management of bleeding trauma patients. The present study aims to assess compliance with protocols in penetrating thoracic trauma on admission to a level I trauma centre and to determine whether compliance impacts morbidity and mortality. Methods: This multicentric pre–post study included all penetrating thoracic trauma patients referred to Marseille area level I centres between January 2009 and December 2019. On the basis of the European guidelines, eight objectively measurable recommendations concerning the in-hospital trauma care for the first 24 h were analysed. Per-patient and per-criterion compliance rates and their impact on morbidity and mortality were evaluated before and after TS implementation. Results: A total of 426 patients were included. No differences between the two groups (before and after 2014) were reported for demographics or injury severity. The median (interquartile range) per-patient compliance rate increased from 67% [0.50; 0.75] to 75% [0.67; 1.0] (p < 0.01) after implementation of a TS. The 30-day morbidity–mortality was, respectively, of 17% (30/173) and 13% (32/253) (p = 0.18) before and after TS implementation. A low per-patient compliance rate was associated with an increase in the 30-day morbidity–mortality rate (p < 0.01). Severity score-adjusted per-patient compliance rates were associated with decreased 30-day morbidity–mortality (odds ratio [IC 95%] = 0.98 [0.97; 0.99] p = 0.01). Conclusion: Implementation of a TS was associated with better compliance to European recommendations and better outcomes for severe trauma patients. These findings should encourage strict adherence to European trauma protocols to ensure the best patient outcomes. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The aim of this study was to describe the epidemiology of patients undergoing diagnostic and/or curative surgical pulmonary resections for lung opacities suspected of being localized primary lung cancers without preoperative tissue confirmation. METHODS We performed a single-centre retrospective study of a prospectively implemented institutional database of all patients who underwent pulmonary resection between January 2010 and December 2020. Patients were selected when surgery complied with the Fleischner society guidelines. We performed a multivariable logistic regression to determine the preoperative variables associated with malignancy. RESULTS Among 1392 patients, 213 (15.3%) had a final diagnosis of benignancy. We quantified futile parenchymal resections in 29 (2.1%) patients defined by an anatomical resection of >2 lung segments for benign lesions that did not modified the clinical management. Compared with patients with malignancies, patients with benignancies were younger (57.5 vs 63.9 years, P  < 0.001), had lower preoperative risk profile (thoracoscore 0.4 vs 2.1, P  < 0.001), had a higher proportion of wedge resection (50.7% vs 12.2%, P  < 0.01) and experienced a lower burden of postoperative complication (Clavien–Dindo IV or V, 0.4% vs 5.6%, P  < 0.001). Preoperative independent variables associated with malignancy were (adjusted odd ratio [95% confident interval]) age 1.02 [1.00; 1.04], smoking (year-pack) 1.005 (1.00; 1.01), history of cardiovascular disease 2.06 [1.30; 3.30], history of controlled cancer 2.74 [1.30; 6.88] and clinical N involvement 4.20 [1.11; 37.44]. CONCLUSIONS Futile parenchymal lung resection for suspicious opacities without preoperative tissue diagnosis is rare (2.1%) while surgery for benign lesions represented 15.3% and has a satisfactory safety profile with very low postoperative morbi-mortality. [ABSTRACT FROM AUTHOR]

We obtain explicit bounds on the difference between “local” and “global” Kobayashi distances in a domain of C n as the points go toward a boundary point with appropriate geometric properties. We use this for the global comparison of various invariant distances. We provide some sharp estimates in dimension 1. [ABSTRACT FROM AUTHOR]

Uncontrolled inflammation of the airways in chronic obstructive lung diseases leads to exacerbation, accelerated lung dysfunction and respiratory insufficiency. Among these diseases, asthma affects 358 million people worldwide. Human bronchial epithelium cells (HBEC) express both anti‐inflammatory and activating molecules, and their deregulated expression contribute to immune cell recruitment and activation, especially platelets (PLT) particularly involved in lung tissue inflammation in asthma context. Previous results supported that HLA‐G dysregulation in lung tissue is associated with immune cell activation. We investigated here HLA‐F expression, reported to be mobilised on immune cell surface upon activation and displaying its highest affinity for the KIR3DS1‐activating NK receptor. We explored HLA‐F transcriptional expression in HBEC; HLA‐F total expression in PBMC and HBEC collected from healthy individuals at rest and upon chemical activation and HLA‐F membrane expression in PBMC, HBEC and PLT collected from healthy individuals at rest and upon chemical activation. We compared HLA‐F transcriptional expression in HBEC from healthy individuals and asthmatic patients and its surface expression in HBEC and PLT from healthy individuals and asthmatic patients. Our results support that HLA‐F is expressed by HBEC and PLT under healthy physiological conditions and is retained in cytoplasm, barely expressed on the surface, as previously reported in immune cells. In both cell types, HLA‐F reaches the surface in the inflammatory asthma context whereas no effect is observed at the transcriptional level. Our study suggests that HLA‐F surface expression is a ubiquitous post‐transcriptional process in activated cells. It may be of therapeutic interest in controlling lung inflammation. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The aim of this study was to analyse the outcomes of an international cohort of patients affected by Masaoka stage III thymic epithelial tumours with vascular involvement and treated by surgery. METHODS Study design was the observational multicentre retrospective cohort study. Data were extracted from the European Society of Thoracic Surgeons thymic database; additional variables were collected. Inclusion criteria were as follows: stage III (Masaoka–Koga) thymic epithelial tumours; surgery with radical intention; clinical or pathological great vessels involvement; and radiologically suspected or diagnosed intraoperatively. Outcome items were analysed. RESULTS Sixty-five patients submitted to surgery from 2001 to 2017 fulfilled inclusion criteria. Thymoma and thymic carcinoma patients did not differ for demographics and clinical characteristics. The majority of great vessel treated were superior vena cava or innominate veins (72.3%). Eleven patients (16.9%) had postoperative cardiopulmonary complications; vascular stenosis was observed in 3 patients (4.6%). The multivariable Cox analysis for disease-free survival showed an increased hazard of recurrence for thymic carcinoma (hazard ratio = 3.59; 95% confidence interval: 1.66–7.78, P = 0.001). The 1-, 3-, 5- and 10-year overall survival rates were 0.86, 0.84, 0.81, and 0.53, respectively. There was no significant difference in overall survival according to resection status or between thymoma and thimic carcinoma. The univariable Cox regression model did not show an increased hazard of death for myasthenic patients considering all resection status and for patients who received neoadjuvant therapy. CONCLUSIONS We observed that clinical outcomes of patients treated for stage III thymic epithelial tumours with vascular involvement are satisfactory suggesting to increase the confidence in dealing with these complex surgeries. Complete resection should be achieved, even though extensive vascular reconstructions are required. [ABSTRACT FROM AUTHOR]

Background: Thymic carcinoma is a rare and highly malignant tumor with a dismal prognosis, which occasionally coexists with myasthenia gravis (MG). This study aims to investigate the MG incidence on a surgical cohort of patients with thymic carcinoma and to explore its influence on long-term survival. Methods: the prospectively collected data from the ESTS database on thymic epithelial tumors were reviewed. Clinical, pathological, and survival information on thymic carcinoma were analyzed. Results: the analysis was conducted on 203 patients, with an equal gender distribution (96 males and 107 females). MG was detected in 22 (10.8%) patients, more frequently elderly (>60 years, p = 0.048) and male (p = 0.003). Induction therapy was performed in 22 (10.8%) cases. After surgery, 120 (59.1%) patients had a Masaoka stage II–III while complete resection (R0) was achieved in 158 (77.8%). Adjuvant therapy was performed in 68 cases. Mean follow-up was 60 (SD = 14) months. The 3-year, 5-year and 10-year survival rates were 79%, 75% and 63%, respectively. MG did not seem to influence long-term survival (5-year survival in non-MG–TCs 78% vs. 50% in MG–TCs, p = ns) as age < 60 years, female gender, early Masaoka stage, and postoperative radiotherapy did, conversely. Conclusions: myasthenia occurred in about 10% of thymic carcinomas and it did not seem to affect significantly the long-term prognosis in surgically treated thymic carcinoma-patients. [ABSTRACT FROM AUTHOR]

Background: In lung transplantation (LT), the actual surgical practice is to cut the donor bronchus as short as possible in order to reduce anastomotic complications (AC). Consequently, the anastomosis is very close to the secondary carina. If AC occur, regular straight stents may be unsatisfactory and on-site modified bifurcated stents may represent an alternative. Objectives: This retrospective study sought to assess the short- and long-term outcomes of patients treated with customized bifurcated stent (CBS) for the management of AC following LT. Methods: Data from patients with AC following LT requiring CBS placement between June 2010 and June 2020 were analyzed. Results: Four hundred patients underwent lung transplant. AC requiring airway stenting occurred in 32 patients (8%), and CBS were inserted in 15 patients (3.5%). Indications were stenosis (n = 12; 80%) and bronchial dehiscence (n = 3; 20%). CBS were successfully deployed in 14 patients and failed in 1 patient. No migration was recorded during the follow-up. The median number of complication was 1 per patient (0–5). CBS could be removed in 11 patients (78.6%), and 3 died with their stents in place. AC recurrence or complications requiring new stenting occurred in 4/11 patients (36.3%), with a median time of 7 days (0–29). Seven patients (63.7%) had no AC recurrence, with a median follow-up of 925 days (118–3,249). Conclusions: The actual surgical anastomotic technique in LT provides new endoscopic challenges. CBS seem ideally positioned to address these difficulties safely and effectively but are associated with stent related complications requiring further endoscopic management. [ABSTRACT FROM AUTHOR]

Background Physiotherapy is a major cornerstone of enhanced rehabilitation after surgery (ERAS) and reduces the development of atelectasis after thoracic surgery. By initiating physiotherapy in the post-anaesthesia care unit (PACU), the aim was to evaluate whether the ultra-early initiation of rehabilitation (in the first hour following tracheal extubation) would improve the outcomes of patients undergoing elective thoracic surgery. Methods A case–control study with a before-and-after design was conducted. From a historical control group, patients were paired at a 3:1 ratio with an intervention group. This group consisted of patients treated with the ultra-early rehabilitation programme after elective thoracic surgery (clear fluids, physiotherapy, and ambulation). The primary outcome was the incidence of postoperative atelectasis and/or pneumonia during the hospital stay. Results After pairing, 675 patients were allocated to the historical control group and 225 patients to the intervention group. A significant decrease in the incidence of postoperative atelectasis and/or pneumonia was found in the latter (11.4 versus 6.7 per cent respectively; P  = 0.042) and remained significant on multivariate analysis (OR 0.53, 95 per cent c.i. 0.26 to 0.98; P  = 0.045). A subgroup analysis of the intervention group showed that early ambulation during the PACU stay was associated with a further significant decrease in the incidence of postoperative atelectasis and/or pneumonia (2.2 versus 9.5 per cent; P  = 0.012). Conclusions Ultra-early rehabilitation in the PACU was associated with a decrease in the incidence of postoperative atelectasis and/or pneumonia after major elective thoracic surgery. [ABSTRACT FROM AUTHOR]

Let D ⊂ C n be a bounded domain. A pair of distinct boundary points { p , q } of D has the visibility property provided there exist a compact subset K p , q ⊂ D and open neighborhoods U p of p and U q of q, such that the real geodesics for the Kobayashi metric of D which join points in U p and U q intersect K p , q . Every Gromov hyperbolic convex domain enjoys the visibility property for any couple of boundary points. The Goldilocks domains introduced by Bharali and Zimmer and the log-type domains of Liu and Wang also enjoy the visibility property. In this paper we relate the growth of the Kobayashi distance near the boundary with visibility and provide new families of convex domains where that property holds. We use the same methods to provide refinements of localization results for the Kobayashi distance, and give a localized sufficient condition for visibility. We also exploit visibility to study the boundary behavior of biholomorphic maps. [ABSTRACT FROM AUTHOR]

Purpose: An assessment of the impact of functional status (FS) evaluated using a combination of Activities of Daily Living (ADL) and the short version of the Instrumental Activities of Daily Living (IADL), on 3- and 6- month mortality and on 3-month unplanned hospitalizations in older patients treated for lung cancers.Method and Objectives: This observational retrospective study was conducted between September 2015 and January 2019 at Marseille University Hospital (AP-HM). During this period, all consecutive outpatients aged 70 years or older referred for a comprehensive geriatric assessment (CGA) before the initiation of lung cancer treatment were enrolled.Results: Two hundred twenty-seven patients were analyzed: the median age was 78.7 years and 74.0% were male. Almost half of the patients were metastatic (45.4%). Concerning FS, 41.9% of patients had no ADL-IADL impairment, 30.0% had either IADL or ADL impairment, and both ADL-IADL were impaired for 28.1%. Impaired ADL-IADL was associated with poor nutritional status, depression, mobility, and cognitive disorders. In a logistic regression model, ADL or IADL impairment (aOR = 2.1; 95% CI [1.0-4.2]; p = 0.037) and impaired ADL-IADL (aOR = 2.6; 95% CI [1.2-5.3]; p = 0.012) were independently associated with a higher risk of unplanned hospitalizations within 3 months. In the multivariate Cox model, 6-month mortality risk was independently associated with impaired ADL-IADL (aHR = 2.3; 95% CI [1.3-4.4]; p = 0.008).Conclusion: The combination of ADL and IADL scales to assess FS is a prognostic marker of the mortality risk at 6 months in older patients with lung cancer and should be more largely used by oncologists in treatment decision making. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Pulmonary retransplant (ReTx) is considered a controversial procedure. Despite literature reporting outcomes following ReTx, limited data exist in recipients bridged to their ReTx on extracorporeal life support (ECLS). The goal of this study was to investigate the outcomes of recipients bridged to a first-time ReTx by ECLS. METHODS We performed a retrospective multicentre cohort analysis from 10 centres in Europe, Asia and North America. The primary outcome was overall survival. Risk factors were analysed using Cox regression models. RESULTS ECLS as a bridge to a first-time ReTx was performed in 50 recipients (ECLS-ReTx). During the study period, 210 recipients underwent a first-time ReTx without bridging on ECLS (regular-ReTx) and 4959 recipients had a primary pulmonary transplant (index-Tx). The overall 1-year (55%) and 5-year (29%) survival was significantly worse for the ECLS-ReTx group. Compared to the index-Tx group, the mortality risk was significantly higher after ECLS-ReTx [hazard ratio 2.76 (95% confidence interval 1.94–3.91); P  < 0.001] and regular-ReTx [hazard ratio 1.65 (95% confidence interval 1.36–2); P  < 0.001]. In multivariable analysis, recipient age ≥35 years, time interval <1 year from index-Tx, primary graft dysfunction as transplant indication, venoarterial-extracorporeal membrane oxygenation and Zurich donor score ≥4 points were significant risk factors for mortality in ECLS-ReTx recipients. CONCLUSIONS Recipients for ECLS-ReTx should be carefully selected. Risk factors, such as recipient age, intertransplant interval, primary graft dysfunction as transplant indication and type of ECLS should be kept in mind before bridging these patients on ECLS to ReTx. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES To compare outcomes at 12 months between video-assisted thoracic surgery (VATS) and open thoracotomy (OT) in patients with non-small-cell lung cancer (NSCLC) using real-world evidence. METHODS We did a nationwide propensity-matched cohort study. We included all patients who had a diagnosis of NSCLC and who benefitted from lobectomy between 1 January 2015 and 31 December 2017. We divided this population into 2 groups (VATS and OT) and matched them using propensity scores based on patients' and hospitals' characteristics. Unplanned readmission, mortality, complications, length of stay and hospitalization costs within 12 months of follow-up were compared between the 2 groups. RESULTS A total of 13 027 patients from 180 hospitals were included, split into 6231 VATS (47.8%) and 6796 OT (52.2%). After propensity score matching (5617 patients in each group), VATS was not associated with a lower risk of unplanned readmission compared with OT [20.7% vs 21.9%, hazard ratio 1.03 (0.95–1.12)] during the 12-months follow-up. Unplanned readmissions at 90 days were mainly due to pulmonary complications (particularly pleural effusion and pneumonia) and were associated with higher mortality at 12 months (13.4% vs 2.7%, P  < 0.0001). CONCLUSIONS VATS and OT were both associated with high incidence of unplanned readmissions within 12 months, requiring a better identification of prognosticators of unplanned readmissions. Our study highlights the need to improve prevention, early diagnosis and treatment of pulmonary complications in patients with VATS and OT after discharge. These findings call for improving the dissemination of systematic perioperative care pathway including efficient pulmonary physiotherapy and rehabilitation. [ABSTRACT FROM AUTHOR]

Background: The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. Methods: This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. Results: The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4–7.5 versus 4.8, 95% CI: 2.4–6.5 months, for median OS: 8.5, 95% CI:.6–11.1 versus 8.3, 95% CI:4.5–11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable. Conclusion: The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR. [ABSTRACT FROM AUTHOR]

Background: The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. Methods: This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. Results: The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4–7.5 versus 4.8, 95% CI: 2.4–6.5 months, for median OS: 8.5, 95% CI:.6–11.1 versus 8.3, 95% CI:4.5–11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable. Conclusion: The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR. [ABSTRACT FROM AUTHOR]

In the spirit of Kobayashi's applications of methods of invariant metrics to questions of projective geometry, we introduce a projective analogue of the complex squeezing function. Using Frankel's work, we prove that for convex domains it stays uniformly bounded from below. In the case of strongly convex domains, we show that it tends to 1 at the boundary. This is applied to get a new proof of a projective analogue of the Wong–Rosay theorem. [ABSTRACT FROM AUTHOR]

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended. [ABSTRACT FROM AUTHOR]

Background: Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices.Methods: We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period.Results: We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%).Conclusion: Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES To evaluate the postoperative complications and 30-day mortality rates associated with neoadjuvant chemotherapy before major anatomic lung resections registered in the European Society of Thoracic Surgeons (ESTS) database. METHODS Retrospective analysis on 52 982 anatomic lung resections registered in the ESTS database (July 2007–31 December 2017) (6587 pneumonectomies and 46 395 lobectomies); 5143 patients received neoadjuvant treatment (9.7%) (3993 chemotherapy alone and 1150 chemoradiotherapy). To adjust for possible confounders, a propensity case-matched analysis was performed. The postoperative outcomes (morbidity and 30-day mortality) of matched patients with and without induction treatment were compared. RESULTS 8.2% of all patients undergoing lobectomies and 20% of all patients undergoing pneumonectomies received induction treatment. Lobectomy analysis: propensity score analysis yielded 3824 pairs of patients with and without induction treatment. The incidence of cardiopulmonary complications was higher in the neoadjuvant group (626 patients, 16% vs 446 patients, 12%, P  < 0.001), but 30-day mortality rates were similar (71 patients, 1.9% vs 75 patients, 2.0%, P  = 0.73). The incidence of bronchopleural fistula and prolonged air leak >5 days were similar between the 2 groups (neoadjuvant: 0.5% vs 0.4%, P  = 0.87; 9.2% vs 9.9%, P  = 0.27). Pneumonectomy analysis: propensity score analysis yielded 1312 pairs of patients with and without induction treatment. The incidence of cardiopulmonary complications was higher in the treated patients compared to those without neoadjuvant treatment (neoadjuvant 275 cases, 21% vs 18%, P  = 0.030). However, the 30-day mortality was similar between the matched groups (neoadjuvant 68 cases, 5.2% vs 5.3%, P  = 0.86). Finally, the incidence of bronchopleural fistula was also similar between the 2 groups (neoadjuvant 1.8% vs 1.4%, P  = 0.44). CONCLUSIONS Neoadjuvant chemotherapy is not associated with an increased perioperative risk after either lobectomy or pneumonectomy, warranting a more liberal use of this approach for patients with locally advanced operable lung cancer. [ABSTRACT FROM AUTHOR]