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Gabrielle Drevet,1 Stéphane Collaud,1 François Tronc,1 Nicolas Girard2,3, Jean-Michel Maury1,3–41Department of Thoracic Surgery, Lung and Heart-Lung Transplantation, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France; 2Institute Curie, Institut du Thorax Curie Montsouris, 75248, Paris Cedex 05, France; 3National Expert Center for Thymic Malignancies, Réseau Tumeurs THYMiques et Cancer (RYTHMIC), Lyon, France; 4IVPC UMR754 INRA, Univ Lyon, Université Claude Bernard Lyon 1, EPHE, Lyon, FranceAbstract: Thymic epithelial tumors (TETs) belong to orphan oncology. The incidence of TETs is about 1.3–3.2 cases per million worldwide. Following pathology, evolution and prognosis are variable. The World Health Organization classification distinguishes thymomas and thymic carcinomas. TETs are composed of thymic epithelial tumoral cells and normal lymphocytes. The mean age at diagnosis is 50–60 years-old. There are no identified risk factors. TETs are frequently associated with paraneoplastic syndromes as myasthenia gravis. The complete R0 surgical resection is the most significant prognosis factor on survival. In 2010, the French National Institute of Cancer labeled the RYTHMIC network as a specific tumor board including thoracic surgeons, oncologist, and radiation therapist to define standard of care for the management of TETs. The aim of the review was to update knowledge to optimize the standard of care.Keywords: thymic epithelial tumors, thymomas, thymic carcinomas, surgery, radiation, chemotherapy

Introduction: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT., Methods: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement., Results: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years., Conclusion: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices., Competing Interests: Disclosure The authors have no conflict of interest to disclose concerning the current work., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France., Methods: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases., Results: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications., Conclusion: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis., Competing Interests: Declaration of Competing Interest Vincent COTTIN has no conflict of interest to disclose in relation with the content of the manuscript. Elodie BLANCHARD has no conflict of interest to disclose in relation with the content of the manuscript. Mallorie KERJOUAN declares research fees paid by Pfizer and Novartis to her institution. Romain LAZOR has no conflict of interest to disclose in relation with the content of the manuscript. Martine REYNAUD-GAUBERT has no conflict of interest to disclose in relation with the content of the manuscript. Romain LAZOR has no conflict of interest to disclose in relation with the content of the manuscript. Camille TAILLE declares consulting fees paid to her by Novartis. Yurdagül UZUNHAN has no conflict of interest to disclose in relation with the content of the manuscript. Lidwine WEMEAU has no conflict of interest to disclose in relation with the content of the manuscript. Claire ANDREJAK has no conflict of interest to disclose in relation with the content of the manuscript. Dany BAUD has no conflict of interest to disclose in relation with the content of the manuscript. Philippe BONNIAUD has no conflict of interest to disclose in relation with the content of the manuscript. Pierre-Yves BRILLET has no conflict of interest to disclose in relation with the content of the manuscript. Alain CALENDER has no conflict of interest to disclose in relation with the content of the manuscript. Lara CHALABREYSSE has no conflict of interest to disclose in relation with the content of the manuscript. Isabelle COURT-FORTUNE has no conflict of interest to disclose in relation with the content of the manuscript. Nicolas DESBAILLETS has no conflict of interest to disclose in relation with the content of the manuscript. Gilbert FERRETTI has no conflict of interest to disclose in relation with the content of the manuscript. Anne GUILLEMOT has no conflict of interest to disclose in relation with the content of the manuscript. Laurane HARDELIN has no conflict of interest to disclose in relation with the content of the manuscript. Marianne KAMBOUCHNER has no conflict of interest to disclose in relation with the content of the manuscript. Violette LECLERC (deceased). Mathieu LEDERLIN has no conflict of interest to disclose in relation with the content of the manuscript. Marie-Claire MALINGE has no conflict of interest to disclose in relation with the content of the manuscript. Alain MANCEL has no conflict of interest to disclose in relation with the content of the manuscript. Sylvain MARCHAND-ADAM declares consulting fees paid by Novartis. Jean-Michel MAURY has no conflict of interest to disclose in relation with the content of the manuscript. Jean-Marc NACCACHE has no conflict of interest to disclose in relation with the content of the manuscript. Mouhamad NASSER has no conflict of interest to disclose in relation with the content of the manuscript. Hilario NUNES has no conflict of interest to disclose in relation with the content of the manuscript. Gaële PAGNOUX has no conflict of interest to disclose in relation with the content of the manuscript. Grégoire PRÉVOT has no conflict of interest to disclose in relation with the content of the manuscript. Christine ROUSSET-JABLONSKI has no conflict of interest to disclose in relation with the content of the manuscript. Olivier ROUVIERE has no conflict of interest to disclose in relation with the content of the manuscript. Salim SI-MOHAMED has no conflict of interest to disclose in relation with the content of the manuscript. Renaud TOURAINE has no conflict of interest to disclose in relation with the content of the manuscript. Julie TRACLET has no conflict of interest to disclose in relation with the content of the manuscript. Ségolène TURQUIER has no conflict of interest to disclose in relation with the content of the manuscript. Stéphane VAGNARELLI has no conflict of interest to disclose in relation with the content of the manuscript. Kaïs AHMAD has no conflict of interest to disclose in relation with the content of the manuscript., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Surgical rib fixation for multiple rib fractures and flail chest has become more common in the 2000s with interesting results in selected patients. However, surgical rib fixation lacks a consensus on the delay to surgery and the benefits on postoperative clinical outcomes. Our goal was to determine if delay to surgery can affect postoperative outcomes., Methods: We analyzed a retrospective database including all consecutive patients referred for surgical rib fixation. All outcomes were explored according to trauma mechanism, associated lesions, initial ventilatory status, delay to surgery, surgical technique and a specific focus was made towards post-operative care and pulmonary complications. Logistic regressions were performed to evaluate the association between delay to surgery [before 48 hours (early group), 48 hours to 7 days (mid group), more than 7 days (late group)] and pneumonia and failure of extubating., Results: From 2010 to 2020, 159 patients underwent surgical rib fixation. The median hospital length of stay was 18 days (interquartile range, 13-30 days). Pulmonary infections were encountered in 67 patients (42.2%) with about two third of early pneumonia (<5 days). The one-month mortality rate was 1.9%. Delay to surgery was not associated with either pneumonia (P>0.05) or failure of extubating (P>0.05)., Conclusions: Surgical rib fixation can be delayed without increasing the risk of pulmonary complications. Stabilizing other clinical situations can be safely prioritized if needed. A global evaluation including characteristics of trauma and lung evaluation must be considered before surgical stabilization of rib fracture., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-735/coif). GD reports personnal fees from Astra Zeneca for presentations. JSD reports honoraria for lectures and expertise from LFB Laboratory, les Ullis, France outside the submitted work. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Diffuse interstitial lung diseases (ILD) constitute a heterogeneous group of conditions with complex etiological diagnoses requiring a multidisciplinary approach. Much is still unknown about them, particularly their relationship with occupational exposures. The primary objective of this study was to investigate the distribution of occupational exposures according to type of ILD. The secondary objectives were to estimate the proportion of ILDs possibly related to occupational exposure and to evaluate the added value of the participation of an occupational disease consultant in ILD multidisciplinary discussions (MDD)., Methods: From May to December 2020, all consecutive patients with ILD whose cases were reviewed during a MDD in a referral centre for ILD were prospectively offered a consultation with an occupational disease consultant., Results: Of the 156 patients with ILD whose cases were reviewed in MDD during the study period, 141 patients attended an occupational exposure consultation. Occupational exposure was identified in 97 patients. Occupational exposure to asbestos was found in 12/31 (38.7%) patients with idiopathic pulmonary fibrosis (IPF) and in 9/18 (50.0%) patients with unclassifiable fibrosis. Occupational exposure to metal dust was found in 13/31 (41.9%) patients with IPFs and 10/18 (55.6%) patients with unclassifiable fibrosis. Silica exposure was found in 12/50 (24.0%) patients with autoimmune ILD. The link between occupational exposure and ILD was confirmed for 41 patients after the specialist occupational consultation. The occupational origin had not been considered (n = 9) or had been excluded or neglected (n = 4) by the MDD before the specialised consultation. A total of 24 (17%) patients were advised to apply for occupational disease compensation, including 22 (15.6%) following the consultation. In addition, a diagnosis different from the one proposed by the MDD was proposed for 18/141 (12.8%) patients., Conclusions: In our study, we found a high prevalence of occupational respiratory exposure with a potential causal link in patients with ILD. We suggest that a systematic specialised consultation in occupational medicine could be beneficial in the ILD diagnostic approach., (© 2022. The Author(s).)

Introduction: Stage IVa thymoma is a rare disease without a standard of care. Subtotal pleurectomy and HITHOC introduced in highly selected patients may provide interesting oncologic results. The purpose of this study was to distinguish de novo stage IVa tumors (DNT) from distant relapse (DR) with respect to post-operative and long-term outcomes to provide the procedure efficacy., Methods: From July 1997-December 2021, 40 patients with IVa pleural involvement were retrospectively analyzed. The surgical procedure was subtotal pleurectomy and HITHOC (cisplatin 50 mg/m 2 , mitomycin 25 mg/m 2 , 42 °C, 90 min). The post-operative outcome, disease-free interval (DFI) and overall survival (OS) were analyzed., Results: Mean age was 52 ± 12 years. B2 and B3 thymomas were preponderant (27; 67.5%). The median number of pleural nodes were nine (4-81) vs. five (1-36); p = 0.004 * in DNT and DR, respectively. Hospital mortality rate was 2.5%. There were four specific HITHOC complications (10%). DFI were 49 and 85 months ( p = 0.02 *), OS were 94 and 118 months (NS), in DNT and DR, respectively., Conclusions: Subtotal pleurectomy with HITHOC in IVa offers satisfying results in highly selected patients, for both DNT and DR. Due to the disease rarity, multicentric studies are needed to define HITHOC as a standard of care.

Background: Lung cancer screening is correlated with an increase in detection of small indeterminate pulmonary nodules and these nodules often require operative resection to obtain the diagnosis. In suspected early-stage lung cancer, video-assisted thoracoscopic surgery (VATS) has become the preferred option. In this context of minimally invasive surgery, diagnostic wedge resection is sometimes difficult to perform for small deep impalpable nodules. So, our purpose was to determine whether performing VATS for indeterminate pulmonary nodule increases the risk of lobectomy for benign lesions., Methods: A retrospective analysis was carried out in our center from January 2013 to January 2019 on patients who underwent resection for a solitary pulmonary nodule suspicious for cancer. Resection method, frozen section analysis, post-operative outcomes, operative and pathology reports were reviewed., Results: Six hundred fifty-one patients underwent surgical exploration for a solitary pulmonary nodule. Thirty hundred and forty-five patients underwent VATS and 306 patients underwent thoracotomy. Patients in the VATS group underwent significantly more wedge resections (P=0.012) and diagnosis of lung cancer was significantly more frequent in the thoracotomy group (P<0.001). One hundred and thirty-two patients (38.3%) in the VATS group and 60 patients (19.6%) in the thoracotomy group underwent lobectomy without frozen section analysis of the pulmonary nodule. There was no significant difference in terms of lobectomy performed for a benign lesion between the two groups., Conclusions: VATS was associated with a higher rate of benign lesion resection but was not associated with a higher rate of lobectomies for benign lesion in our study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1789/coif). GD reports personal fees from ASTRA ZENECA, outside the submitted work. MD reports personal fees from ROCHE, PFIZER, MSD, Boerhinger Ingelheim, NOvartis, ABBVIE, TAKEDA, BMS and ASTRA ZENECA, outside the submitted work. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO 2 /FiO 2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO 2 /FiO 2 ratio ≤300 mmHg, and abnormal chest imaging., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the "one step" group tended to have more perioperative complications whereas patients in the "two step" group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers.

Background: Non-neoplastic thymic lesions are uncommon findings that corresponds to multiple histological and clinical entities that may be difficult to differentiate from thymic malignancies. In this study, our main objective was to describe the clinical, imaging and pathological characteristics of non-neoplastic thymic lesions in a large cohort of patients. We also aimed at understanding the key factors that led to a decision to surgically resect those lesions., Methods and Materials: This is an observational, retrospective study. We enrolled both patients with non-neoplastic thymic lesions - normal thymus, thymic lymphoid/non-lymphoid hyperplasia, and thymic cysts - that had been pathologically-confirmed after surgical resection - , and patients with a thymic lesion that was never operated, based on imaging follow-up., Results: A total of 128 patients were included, 88 of whom underwent surgical resection of the lesion (69%), and 40 patients (31%) had follow-up without surgery. Discovery of the lesion was incidental in 69 (54%) cases; thoracic magnetic resonance imaging was performed in 33 (26%) cases, 85% of which showed apparent decrease in the lesion signal intensity in phase opposition at chemical shift sequences. In the 88 operated patients, there were 34 (39%) normal thymuses, 29 (33%) lymphoid hyperplasias, 6 (7%) non-lymphoid thymic hyperplasias, and 19 (22%) thymic cysts. In the 40 non-operated patients, a major driver for the decision of follow-up was the decrease in the lesion signal intensity in phase opposition at chemical shift sequences, observed in 68% of cases; imaging follow-up of these lesions showed sustained regression in the majority of the cases., Conclusions: The management of benign thymic lesions requires multidisciplinary assessment. A strategy that integrates clinical and imaging features, including chemical-shift sequences at magnetic resonance imaging, as well as follow-up, allows a better selection of the patients for surgery., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Medical students experience rising rates of burnout throughout their training. Efforts have been made to not only mitigate its negative effects, but also prevent its development. Medical improv takes the basic ideas of improvisational theatre and applies them to clinical situations. Given improv's focus on self-awareness and reflection, in addition to its spontaneous nature, we hypothesized it had the potential to serve as a creative outlet, a way to prevent and/or mitigate the negative effects of stress, burnout, and fatigue, and provide a learning environment to develop skills necessary to succeed as a physician. University of California (UC) San Diego School of Medicine developed a medical improv elective for pre-clinical students and assessed its effects on student development and wellbeing. Students enrolled in the elective between Fall 2019 and Fall 2020 at UC San Diego School of Medicine were surveyed pre- and post- course completion using both qualitative and quantitative methods. Students noted significant improvement in domains related to proactivity in their professional career (3.15 to 4.00, p = 0.02), wellbeing (3.0 to 4.4, p < 0.001), engagement with their studies (3.85 to 4.52, p = 0.02), and communication (3.75 to 4.3, p = 0.04) after completion of the medical improv elective. We describe a pilot-study demonstrating the positive effects of improv on medical student wellbeing and professional development, laying the groundwork for both future study of improv on student wellness and its implementation in the pre-clinical curriculum.

Thymic epithelial tumors (TETs) are rare malignancies ranging from indolent thymoma A to aggressive thymic carcinomas (TCs). Brain metastases are extremely infrequent for TETs and have only been described in case reports or small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically review every TET case and prospectively includes all consecutive patients discussed by national or regional tumor boards. We analyzed patients with TETs and central nervous system (CNS) metastasis during their cancer history from this large French registry. In an 8-year period, 2909 patients were included in the database, including 248 TCs (8.5%). A total of 14 patients had CNS metastases, five (36%) at diagnosis and nine (64%) at relapse. Among them, 12 patients (86%) had a diagnosis of TC and two (14%) had thymoma A and B3. Surgical biopsies were performed, and the histologic subtype for non-TC tumors was centrally confirmed. Median overall survival was 22 months (95% confidence interval [CI]: 9.8-34.2), with longer, albeit not significant, overall survival when CNS metastases were present at diagnosis versus relapse (not reached versus 17 mo; p = 0.29); median progression-free survival was 13 versus 8 months (p = 0.06), respectively. A higher risk of death (hazard ratio = 5.34, 95% CI: 1.3-21.9, p = 0.02) and relapse (hazard ratio = 1.89, 95% CI: 0.9-3.7, p = 0.06) was observed for patients suffering from TC with brain metastases compared with those without CNS extension. CNS disease was extremely rare in our TET cohort (0.48%), reported at both diagnosis and progression, present primarily in TC, with prevalence rising to 4.9%., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: To increase the knowledge and communication skills of health professionals related to climate change and human health (CCHH)., Methods: From February to April 2021, Project ECHO (Extension for Community Healthcare Outcomes) created an 8-week, synchronous and virtual, CCHH ECHO telementoring series for health professionals. Didactics, simulated cases, and climate change tools were used to educate the interprofessional group of participants., Results: During this CCHH ECHO pilot series, 625 unique participants represented 45 US states and 25 countries. The participants reported that they increased their knowledge, skills, and communication techniques regarding climate change and health., Conclusions: The human health effects of climate change is an emerging field, and increasing knowledge and communication skills among health practitioners is of critical importance. The CCHH ECHO is one potential platform that may reach a diverse community of health professionals globally due to the diffusion and demonopolization of knowledge., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Case Presentation: A 74-year-old man, in excellent physical condition and doing regular intense cycling, was evaluated for transient episodes of thoracic discomfort over a period of several months. His medical history only included a right inguinal hernia, surgically treated, and an abdominal aortic aneurysm measured at 46 mm and treated medically. Physical examination did not reveal much information. The patient did not report gastroesophageal reflux, dysphagia, or history of digestive occlusion. The patient had normal weight and had no trauma history. He had no nicotine or alcohol-dependent behaviors. Vital signs were within normal values. Laboratory test results were normal. Functional status was normal, without anomalies of pulmonary function tests or arterial blood gases. The ECG did not reveal any anomaly., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas., Material and Methods: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017., Results: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11)., Conclusion: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Malignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE., Methods: PITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted-one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO 2 is established, and a combination of Cisplatin (10.5 mg/m 2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m 2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H 2 O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy., Results: In our hands, the technique above has shown to be feasible and safe., Conclusions: Further studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Gabrielle Drevet et al., published by De Gruyter, Berlin/Boston.)

Combined lung-liver transplantation is a rare life-saving procedure to treat concomitant end-stage lung and liver failure. In this report, we describe the first published case of single lung and liver transplantation in a cystic fibrosis patient who had previously undergone a pneumonectomy for the treatment of an infected and destroyed right lung. We detail the lung first, sequential transplant procedure and surgical difficulties due to mediastinal shift. Emergent intraoperative renal replacement therapy was carried out before liver transplantation to overcome pulmonary edema in the transplanted lung. After fluid balance equilibration, liver transplantation was performed in good conditions. The patient is currently alive with no signs of rejection 8 years after the procedure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: EGFR mutant non-small cell lung cancer (NSCLC) is a heterogeneous disease. The treatment for frequent EGFR mutations relies on tyrosine kinase inhibitors (TKIs); the clinical and therapeutic significance of uncommon EGFR mutations is uncertain., Methods: This is a single-center retrospective study of patients with EGFR -mutant lung cancer (2009-2017). Molecular analyses of EGFR exons 18-21 were performed. Only patients with uncommon mutations were included (p.Glu709X, p.Gly719X, p.Ala767&#95;Val769 dup, p.Ser768Ile, and p.Leu861Gln)., Results: Among 6,747 tumor samples, 95 out 820 patients (11.6%) harbored 113 uncommon EGFR mutations. There were 50 metastatic NSCLC patients for whom the median OS was 18.0 months (95% CI: 15, 32). In this population, the p.Leu861Gln uncommon exon 21 EGFR mutation was associated with poor prognosis (HR: 2.96, 95% CI: 1.39, 6.31; P=0.003). Among those harboring a single uncommon EGFR mutation, median OS was 27.6 months (95% CI: 10.8, not attained) in patients who were treated by chemotherapy only (n=13) versus 6.0 months (95% CI: 2.4, not attained) in patients exclusively treated with a first or second- EGFR -TKI (n=9; HR: 0.27, 95% CI: 0.09, 0.78; P=0.01. In patients with a single uncommon EGFR mutation, first-line chemotherapy was associated with a better overall survival than TKIs (HR: 0.31, 95% CI: 0.15, 0.68; P=0.002). In patients who received first or second- EGFR -TKI as first-line treatment (n=26), OS was significantly better for those with two uncommon EGFR mutations than those with a single uncommon mutation (HR: 0.07, 95% CI: 0.009, 0.54; P=0.001)., Conclusions: In conclusion, uncommon EGFR mutations may be associated with a poor outcome and the data challenge the use of first-generation TKI in such patients, however first-line TKI is more effective in cases of double uncommon mutations and such patients should be treated accordingly., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3790). AB reports grants from Boerhinger Ingelheim, during the conduct of the study; MB reports grants from Boerhinger Ingelheim, from null, outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Mesenchymal epithelial transition receptor ( MET ) alterations, including MET exon 14 skipping mutation, are oncogenic in non-small cell lung cancer (NSCLC) and may confer sensitivity to targeted therapy. Given the rarity and the diversity of exon 14 skipping mutations, diagnosis may be challenging on small-biopsy specimens., Methods: Between March 2014 and May 2018, tissue samples from patients with metastatic NSCLC were analysed for MET exon 14 skipping mutation as part of routine practice in the Pathology Department of the Hospices Civils de Lyon, France. Over the study period, Sanger sequencing and/or two different DNA-based next generation sequencing (NGS) assays were used., Results: Genomic alterations of MET exon 14 were detected in 2.6% (62/2,369) samples of NSCLC analysed for MET exon 14 mutations. Patients were mainly women (38/62, 61%) without smoking history (22/39, 56%) and the median age was 75 years. MET exon 14 skipping mutations were diagnosed by NGS in 50 cases and by classical Sanger sequencing in 12 cases. The frequency of MET mutations was 15.4% when Sanger sequencing was performed at the request of the clinician and 4.1% when the DNA-based NGS assay coverage included the 3' and 5' parts of the MET exon 14 and performed systematically., Conclusions: The frequency of genomic alterations is highly dependent on patient selection and the technical approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.04.21). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: After lung transplantation (LT), between 2% and 25% of bronchial anastomoses develop complications requiring therapeutic intervention. The status of healing of both bronchial anastomoses and downhill airways are well described by the French consensual MDS standardized grading system (Macroscopic, Diameter, Suture). We analyzed risks factors for airway complications (AC) after transplantation and the way we managed them. We report here our challenging method of early rigid bronchoscopic intervention with airway stenting on bronchial healing., Methods: All single center consecutives LTs were retrospectively analyzed between 2010-2016. Patient-level data (demographic, peri-operative data) and anastomosis-level data (surgical parameters, bronchoscopy findings) were monitored. The incidence and contributive factors of ACs are reported. We also reported modalities of the conservative treatment and outcome., Results: A total of 121 LTs were performed, 39 single-lung and 82 bilateral sequential LT. Main indication for LT were cystic fibrosis (45%) and emphysema (25%) and 58 were male patients (n=70). After a waiting period of healing, 28 patients presented AC on 41 anastomoses (prevalence: 23%). A multivariate analysis found as contributive factors of ACs, post-operative infection by Aspergillus [odds ratio (OR) 2.7, 95% confidence interval (CI): 1.08-6.75; P=0.033] at the patient level, and at the anastomosis level, emphysema (OR 2.4, 95% CI: 1.02-5.6; P=0.045), early dehiscence (OR 11.2, 95% CI: 1.7-76; P=0.01) and cold ischemia time >264 min (OR 2.45, 95% CI: 1.08-5.6; P=0.03). All the 41 ACs were managed conservatively with rigid bronchoscopy (range, 1-10), 41 stents (21 in silicone and 20 fully-covered Silicone Expandable Metallic Stents) without major complication. Two AC were still under regular bronchoscopic care and silicone stenting for long left bronchus reason. No surgical intervention was needed. The 2-years overall survival rate where not different between AC group and controls, respectively 85% and 81%., Conclusions: Airway healing after transplantation remains a scalable process and the French consensual MDS classification helped us for therapeutic decisions. Rigid bronchoscopy and safety use of current stenting devices may have the pivotal role in the conservative management of ACs, avoiding perilous situation of surgery for AC. Despite a high rate of AC, their favorable evolution may be explained by the cautious care of airway healing and maybe by the use of the Celsior antioxidant solution., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.21). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Introduction: Due to an increase in life expectancy, onco-pulmonologists and thoracic surgeons are more frequently faced with octogenarian patients with lung cancer. In this age group, treatment modalities may need to be revised because of the increasing presence of comorbidities. Surgery remains the reference treatment for early stage disease, but mortality rates and postoperative complications are higher in this group of patients. One of the solutions to reduce the operative risk would be to develop videoassisted thoracoscopic pulmonary resection surgery. The aim of this study was to evaluate the results of this form of lung cancer surgery in octogenarians., Methods: All patients 80 years old or more who underwent videoassisted lung cancer surgery from 2014 to 2018 at Lyon University Hospital were included. Wedge resections and diagnostic procedures were excluded., Results: Nineteen patients (13 men, 6 women) were included. The median age was 82 years old. All patients had undergone videoassisted lobectomy. Three patients required conversion to thoracotomy (15.8%). All patients underwent complete resection (R0). One patient had N1 lymph node involvement, all others were N0. The postoperative complication rate was 68.4%, the majority of which were grade II of the Clavien classification. Perioperative mortality was 5.3%., Conclusions: Videoassisted lung cancer resection in a selected population of octogenarians is associated with satisfactory short-term results. It is reasonable to favour minimally invasive techniques in this population, even if the proof of their superiority has not yet been firmly established., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

As for molecular alterations of lung adenocarcinoma, it is critical that pathologists are able to give PD-L1 expression status before first-line of treatment. The present study compared PD-L1 expression (clone 22-C3) in decalcified using EDTA or formic acid and non-decalcified lung cancer metastases bone samples. Amongst the 84 bone samples analysed for PD-L1 expression, and independently of decalcification, TPS ≥ 1% was 25.0% and ≥ 50% was 11.4%. There was no significant difference between decalcified samples ( n  = 45) and non-decalcified samples ( n  = 39) for both TPS ≥ 1% ( p  = 0.32) and TPS ≥ 50% ( p  = 1). To conclude, we confirm decalcified bone metastasis specimens may be used for PD-L1 IHC in routine practice. These results also highlight potentially interesting specificities of the bone microenvironment that should be further studied., Competing Interests: Authors did not declare any conflict of interest regarding to this research., (© 2020 The Authors.)

Background: Video-assisted surgical lung biopsy (SLB) is performed in 10-30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF)., Objectives: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF., Methods: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB., Results: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline., Conclusion: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year., (© 2020 S. Karger AG, Basel.)

Objectives: Solid organ transplantation is an accepted treatment for end-stage organ failure. Long-lasting immunosuppressive therapy may increase the risk ofde novo malignancies in transplant recipients. Increased risk of bronchogenic carcinoma in this population is controversial but prolonged transplant recipients' survival (obtained in modern transplantation era) may increase the need for lung cancer surgical resection in immunosuppressed patients. Our aim was to assess morbidity, mortality and long-term survival after lung cancer surgical treatment in this population., Materials and Methods: In an observational study, the medical charts of all consecutive patients who had undergone surgical treatment for lung cancer after solid organ transplantation were reviewed. These medical records were extracted from the University of Lyon (France) Transplantation database and Thoracic Surgery database. From 1986-2016, 61 patients underwent a surgical treatment for lung cancer after solid organ transplantation., Results: The surgical procedures consisted of 52 lobectomies, 7 pneumonectomies and 2 wedge-resections. 90-day post-operative complications, most of which were pneumonias, affected 31 patients (50.8 %). 90-day postoperative mortality was 9.8 %. Overall survival was 40.6 % at 5 years and 18 % at 10 years., Conclusion: Despite a higher rate of infectious complications and 90-day postoperative mortality, surgical treatment for lung cancer must be offered to these patients as it offers a chance to cure earlier- stage disease. Long-term survival rate is satisfactory and similar to that of the general population. In transplant recipients with former smoking history, close follow-up is mandatory to increase early lung cancer diagnosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database., Methods: All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models., Results: During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT., Conclusions: This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics., Competing Interests: Conflict of interest: A. Roussel has nothing to disclose. Conflict of interest: E. Sage has nothing to disclose. Conflict of interest: G. Massard has nothing to disclose. Conflict of interest: P-A. Thomas has nothing to disclose. Conflict of interest: Y. Castier has nothing to disclose. Conflict of interest: E. Fadel has nothing to disclose. Conflict of interest: F. Le Pimpec-Barthes has nothing to disclose. Conflict of interest: J-M. Maury has nothing to disclose. Conflict of interest: J. Jougon has nothing to disclose. Conflict of interest: P. Lacoste has nothing to disclose. Conflict of interest: J. Claustre has nothing to disclose. Conflict of interest: M. Dahan has nothing to disclose. Conflict of interest: A. Pirvu has nothing to disclose. Conflict of interest: A. Tissot has nothing to disclose. Conflict of interest: M. Thumerel has nothing to disclose. Conflict of interest: G. Drevet has nothing to disclose. Conflict of interest: C. Pricopi has nothing to disclose. Conflict of interest: J. Le Pavec has nothing to disclose. Conflict of interest: H. Mal has nothing to disclose. Conflict of interest: X-B. D'Journo has nothing to disclose. Conflict of interest: R. Kessler has nothing to disclose. Conflict of interest: A. Roux has nothing to disclose. Conflict of interest: R. Dorent has nothing to disclose. Conflict of interest: G. Thabut has nothing to disclose. Conflict of interest: P. Mordant has nothing to disclose., (Copyright ©ERS 2019.)

Objective: To describe the prevalence of cystic fibrosis-related diabetes (CFRD) before and after lung transplantation (LT); to analyse the survival and renal function after LT according to the CFRD status before LT., Methods: Sixty cystic fibrosis (CF) patients transplanted at the Lyon University Hospital between 2004 and 2014 were included. Genotype, pancreatic status, age at LT, survival were recorded. Glucose tolerance status, daily insulin dose requirement, glomerular filtration rate (GFR), and daily glucocorticoid (GC) dose were recorded before LT and until December 2016., Results: The median follow-up was 5.6 (3.8-8.2) years, and nine patients died. Survival was poorest for patients with CFRD before LT compared with those without CFRD (P = 0.03) but was not correlated with the GFR before LT, with sex, age at LT, or CF genotype. The prevalence of CFRD was 68% at 2 years and 54% at 5 years. For persistent insulin-treated CFRD, the insulin requirement decreased (-2.1 IU/d/y; P < 0.01) and was correlated with the daily GC dose (+0.4 IU/d for one additional milligram, P = 0.012). Seven (11%) patients who had insulin-treated CFRD before LT became nondiabetic after LT, with a median time of 2 (1-4) years. After LT, the GFR decreased (-5.3 ml/min/1.73 m 2 /y; P < 0.001) and was not correlated with the CFRD status before LT., Conclusions: CFRD before LT is associated with poor survival after LT, which should lead to better management of diabetes. Some patients with pre-LT CFRD became nondiabetic after LT. CFRD is not associated with renal insufficiency after LT., (© 2019 Wiley Periodicals, Inc.)

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system. We analyzed protein expression and activation of key players of the Akt/ mTOR pathway namely Akt, mTOR, and P70S6K in eleven A, B and AB thymomas as well as in normal thymuses. While only Akt and phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated in thymomas. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, we report the activation of Akt, mTOR and P70S6 proteins in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas. Finally, we showed that rapamycin (100 nM) significantly reduced proliferation of thymoma- derived epithelial cells without inducing cell death. Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities in rare thymic tumors., Competing Interests: The authors have declared that no competing interests exist.

A 75 year old man presented with left upper lobe squamous cell carcinoma. Severe aortic stenosis has been discovered during preoperative assessment. In this situation, two therapeutic strategies are described: concomitant or two-staged procedures. The debate has not yet led to the conclusion on whether preferably performing one or the other. Furthermore, in an oncologic context, using cardiopulmonary bypass is still controversial. So, thoracic and cardiac surgeons jointly proposed to the patient a transcatheter aortic valve implantation followed, 72 h later, by lung cancer resection. This case report describes a way to treat both diseases avoiding cardiopulmonary bypass adverse effects and without delaying lung cancer treatment.

Several surgical procedures, from debulking to extrapleural pneumonectomy, may be applied for stage IVa Masaoka thymomas, but their efficiency is still controversial. Case studies have favored R 0 resection as the cornerstone of multimodal therapy for locoregional metastatic extension. This report describes a standardized procedure combining a cytoreductive surgical procedure and intrathoracic chemohyperthermia on a 46-year-old patient presenting with B2 thymoma and synchronous unilateral pleural metastasis., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The benefit of adding opioid to a local anaesthetic for continuous thoracic paravertebral analgesia after video-assisted thoracic surgery (VATS) is unclear., Objectives: To analyse the analgesic efficacy of ropivacaine and sufentanil in combination compared with ropivacaine alone after VATS., Design: A randomised, double-blinded, single-centre clinical trial., Setting: A tertiary university hospital between March 2010 and April 2014., Patients: Ninety patients were recruited, two were not included leaving 88 randomised into two groups. Eighteen patients were excluded from analysis and 70 completed the study., Intervention: To receive thoracic paravertebral analgesia with either 2 mg ml ropivacaine and 0.25 μg ml sufentanil (ropivacaine + sufentanil group) or 2 mg ml ropivacaine alone (ropivacaine group) for 48 h postoperatively. Infusion rate was set at 0.15 ml kg h in both groups., Main Outcome Measures: The primary endpoint was the mean total amount of self-administered morphine by the patients in each group at 48 h postoperatively., Results: The mean ± SD total amount of self-administered morphine was not significantly different between groups (53.1 ± 27.2 mg in the ropivacaine + sufentanil group vs. 58.8 ± 34.3 mg in the ropivacaine group; P = 0.72). No significant differences were found between the two groups in either pain scores at rest or during movement, in opioid-related adverse reactions, in patient satisfaction or length of hospital stay., Conclusion: Adding 0.25 μg ml sufentanil to 2 mg ml ropivacaine in continuous thoracic paravertebral analgesia for VATS did not reduce morphine consumption or pain scores when compared with ropivacaine alone. We cannot recommend its use for routine clinical practice. Further studies analysing different concentrations and infusion rates of sufentanil are needed before a lack of efficacy can be confirmed., Trial Registration: Clinical trial registrations: EudraCT: 2009-014832-38. ClinicalTrials.gov: NCT 01082744.

Multiple lung carcinomas are 5 to 11,5% of lung carcinomas. The distinction between primary lung carcinomas from carcinomas with intrapulmonary metastasis is essential for optimal patient management. The histopathological analysis is very useful but it has to be completed by genotypic assessment using molecular biology (NGS). Molecular biology can also identify genetic alterations with therapeutic implications. We present the case of a patient with a history of surgery for multiple lung carcinomas diagnosed from 2013 to 2017., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: The systematic assessment of anti-programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in lung adenocarcinomas is becoming standard practice. However, the assessment of PD-L1 expression on small tissue specimens needs to be evaluated and the association with other features more thoroughly analyzed., Methods: This retrospective single center study evaluated the immunohistochemical expression of the SP263 anti-PD-L1 antibody on tissue microarrays (TMA) of 152 surgically resected lung adenocarcinomas, using a 25% positivity threshold. The positive cases and 50 randomly chosen negative cases in tissue microarray (TMA) were reassessed on whole tissue sections. The results were correlated to clinical, histopathological and to molecular data obtained through the screening of 214 mutations in 26 genes (LungCarta panel, Agena Biosciences)., Results: Among 152 primary lung adenocarcinomas, 19 cases (13%) showed PD-L1 expression. The agreement between TMA and whole tissue sections was 89%, specificity was 97%. PD-L1 expression was correlated to RAS mutations (p = .04), RAS/TP53 co-mutations (p = .01) and to the solid or acinar subtype (p = .048)., Conclusions: With the SP263 PD-L1 antibody, small samples appear as a reliable means to evaluate the PD-L1 status in lung adenocarcinoma. The association between PD-L1 expression and RAS/TP53 mutations may have clinical relevance to predict the efficacy of PD-1/PD-L1 immune checkpoints inhibitors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Introduction: Thymic epithelial tumors (TETs) are rare intrathoracic malignancies that are categorized histologically according to the WHO classification, which was recently updated in 2015 on the basis of a consensus statement of the International Thymic Malignancy Interest Group (ITMIG); at the same time, the standard Masaoka-Koga staging system is scheduled to be replaced by the eighth edition of the TNM staging classification by the American Joint Committee on Cancer/Union for International Cancer Control consortium. Our objectives were to analyze the feasibility of assessing ITMIG consensus major and minor morphological and immunohistochemical criteria and the eighth edition of the TNM staging classification in a routine practice setting., Methods: This is a single-center study conducted at the Louis-Pradel Hospital of Lyon University, one of the largest centers for TETs in France. Overall, a large surgical series of 188 TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed., Results: There were 89 men (49%) and 92 women (51%); 57 patients (31%) presented with myasthenia gravis at time of diagnosis. According to the WHO classification, there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1 thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20 thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100% of type A, AB, B1, and B2 thymomas. After restaging according to the eighth edition of the TNM staging classification, there were 127 stage I (84%), three stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three stage IVb (2%) thymomas. Significant correlation between histological type and stage at diagnosis was maintained after restaging according the TNM classification., Conclusion: Comprehensive analysis of our well-characterized surgical series of 188 TETs indicates the feasibility and the diagnostic value of the ITMIG consensus statement on WHO histological classification and highlights the major switch in staging when the eighth edition of the TNM staging classification is applied., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Opinion Statement: The management of thymic tumours is a paradigm of multidisciplinary collaboration. Chemotherapy may be administered part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy, or as an exclusive treatment if local treatment is not achievable. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Given the limited activity of cytotoxic agents in the advanced, refractory setting, novel and innovative agents are needed. The better understanding of thymic carcinogenesis may provide a rationale in this setting.Targeted agents approved for other solid tumors that have shown activity in thymic tumors include mTOR, KIT inhibitors, as well as somatostatin analogues. Anti-angiogenic agent sunitinib may be considered a standard in advanced lines of treatment. Ongoing studies are assessing the opportunity of targeting emerging targets, including PI3K, CDK, and immune checkpoint PD-1/PD-L1.

Introduction: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD., Materials and Methods: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis., Results: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation., Discussion and Conclusion: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: This retrospective study was undertaken to evaluate late results of lung cancer surgery in octogenerians., Methods: All patients 80years old or more who underwent a lung resection for cancer from 2000 to 2010 at Lyon University Hospital were included. No patients were treated with video-assisted surgery. Wedge resections were excluded., Results: Sixty-three patients (42 men, 21 women) were operated. The median age was 82years. Operative mortality was 4.7%. The rate of perioperative complications was 49%. The late survival was 34% at 5years. Five-year survival by nodal involvement was N0, 36%; N1, 29%; N2 20%, P<0.05. Patients with a squamous cell carcinoma (24) had a better long-term survival than patients with an adenocarcinoma (30), 33% and 25% respectively at 5years, P<0.05. The rate of recurrence was 33.9%., Conclusions: Surgical treatment of lung cancer in selected population of octogenerians is associated with satisfactory early and long-term results. Survival is influenced by nodal involvement and by the pathologic type of the cancer., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)