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BACKGROUND: Patients with non-small cell lung cancer (NSCLC) receiving curative surgery have a risk of relapse, and adjuvant treatments only translate into a 5% increase in 5-year survival. We assessed the clinical significance of epithelial–mesenchymal transition (EMT) and explored its association with the [SNAIL/miR-34]:[ZEB/miR-200] regulation hub to refine prognostic information. METHODS: We validated a 7-gene EMT score using a consecutive series of 176 resected NSCLC. We quantified EMT transcription factors, microRNAs (miRs) of the miR-200, miR-34 families and miR-200 promoter hypermethylation to identify outcome predictors. RESULTS: Most tumours presented with an EMT-hybrid state and the EMT score was not predictive of outcome. Individually, all miR-200 were inversely associated with the EMT score, but only chromosome-1 miRs, miR-200a, b, 429, were associated with disease-free survival (p = 0.08, 0.05 and 0.025) and overall survival (p = 0.013, 0.003 and 0.006). We validated these associations on The Cancer Genome Atlas data. Tumour unsupervised clustering based on miR expression identified two good prognostic groups, unrelated to the EMT score, suggesting that miR profiling may have an important clinical value. CONCLUSION: miR-200 family members do not have similar predictive value. Core EMT-miR, regulators and not EMT itself, identify NSCLC patients with a low risk of relapse after surgery.

Donor to recipient (D-R) matching in lung transplantation (LTx) is firstly directed by blood group (identity or compatibility), immunological status and morphological criteria. Sex matching is ignored and impact on outcome less investigated.Systematic review of English literature using PubMed (1990-2019) was performed to evaluate the potential role of D-R matching in determining long-term outcome in patients after LTx. Search terms included (LTx) AND (sex) OR (gender) OR (matching) OR (mismatch) OR (donor characteristics) and were restricted to articles' title. Only articles directly reporting LTx survival outcome according to gender match/mismatch and D-R gender combination in LTx were included. Two authors independently extracted articles using predefined data fields, including study quality indicators. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies applied.Nine articles were analyzed and included into this study. All studies analyzed the effect of the different D-R gender combinations on survival while seven of them investigated exclusively the role of sex matching on LTx outcome. In this latter group two out of seven showed a trend towards an overall survival advantage for sex matching LTx combination. The worst survival results were reported for F to M gender combination in 3 studies and for M to F gender combination by 1 study. No differences were reported in remaining 4 studies.This systematic review suggests that sex matching and several gender combinations could play a role in determining overall survival rate after LTx. Data deriving from unbiased studies supported that matching female-female (F-F) and male-male (M-M) could improve LTx outcome while FD-MR combination should be avoided. Unfortunately, a good part of the analyzed data are affected by bias due to confounding factors. Up-to-date immunological, hormonal and morphological factors could explain the gender-based difference in LTx outcome. Further investigations should clarify their role and importance to define the effects of gender combinations on survival.

Case: We report a case of a metallic foreign body migration from the lower limb to the right ventricle. A metal tip of 5x3mm was discovered during a cardiac investigation for a ventricular extrasystole. A few months earlier, the patient had a tibia osteosynthesis for fracture. Conclusion: We propose guidelines in case of a cardiac foreign body detection. A conservative treatment or surgical removal can be discussed depending on the clinical features, the anatomical situation and the shape of the foreign body.

Inflammation, oxidative stress, and protease/protease inhibitor imbalance with excessive production of proteases are factors associated with pathogenesis of the chronic obstructive pulmonary disease (COPD). In this study, we report that kallikrein-related peptidase 5 (KLK5) is a crucial protease involved in extracellular matrix (ECM) remodeling and bronchial epithelial repair after injury. First, we showed that KLK5 degrades the basal layer formed by culture of primary bronchial epithelial cells from COPD or non-COPD patients. Also, exogenous KLK5 acted differently on BEAS-2B cells already engaged in epithelial-to-mesenchymal transition (EMT) or on 16HBE 14o- cells harboring epithelial characteristics. Indeed, by inducing EMT, KLK5 reduced BEAS-2B cell adherence to the ECM. This effect, neutralized by tissue factor pathway inhibitor 2, a kunitz-type serine protease inhibitor, was due to a direct proteolytic activity of KLK5 on E-cadherin, beta-catenin, fibronectin, and alpha 5 beta 1 integrin. Thus, KLK5 may strengthen EMT mechanisms and promote the migration of cells by activating the mitogen-activated protein kinase signaling pathway required for this function. In contrast, knockdown of endogenous KLK5 in 16HBE14o- cells, accelerated wound healing repair after injury, and exogenous KLK5 addition delayed the closure repair. These data suggest that among proteases, KLK5 could play a critical role in airway remodeling events associated with COPD during exposure of the pulmonary epithelium to inhaled irritants or smoking and the inflammation process.

BACKGROUND: The assessment before surgical plication for unilateral hemidiaphragm (HD) eventration is not clearly defined and no precise criteria exist to really understand which patient is operated with which results depending on the technique used. The goal of this study was to evaluate the place of dynamic magnetic resonance imaging (dMRI) before and after plication by developing measurement criteria. METHODS: Between 2006 and 2017, 18 patients (group1: Gp1) were operated for eventrations, 15 left-sided (Gp1L) and 3 right-sided (Gp1R). All had preoperative and postoperative evaluations including dMRI and pulmonary function tests. Five healthy volunteer subjects (group2: Gp2) had the same imaging protocol. For each HD, we measured the respiratory excursion at three fixed points (S1, S2, S3) and the height of curvature on sagittal plane. We also searched for upward paradoxical diaphragm movements. RESULTS: Before surgery, no excursion (n=13) or extremely reduced excursion (n=5) was detected on the injured HD (IHD) in Gp1. Upward paradoxical movements were identified only in Gp1L (n=6). Compared with Gp2 subjects, the healthy HD for Gp1L patients had significantly reduced excursion values at three sites S1 (P=0.038), S2 (P=0.006), and S3 (P=0.004). After plication, the decreasing height of curvature confirmed a tightening of the IHD in all patients (median value from 100 to 39.5 mm in Gp1L and 92 to 74 mm in Gp1R, P=0.0001). All upward paradoxical movements disappeared. Healthy HD excursions in Gp1L normalised their values. All those imaging improvements were correlated with postoperative improvements of dyspnoea score (P

Background Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat EGFR mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown. Methods The effect of ferroptosis inducers on a panel of EGFR mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment. Results Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in EGFR mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation. Conclusions Ferroptosis-inducing therapy shows promise in EGFR-activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression.

The ADAURA trial has been significant for the perception of EGFR tyrosine kinase inhibitors (TKIs) as a tool for early stage non-small-cell lung cancer (NSCLC). It produced such great insight that the main TKI, Osimertinib, was rapidly integrated into international guidelines for adjuvant use. However, EGFR-mutant NSCLC is a complex entity and has various targeting drugs, and the benefits for patients might not be as clear as they seem. We reviewed trials and meta-analyses considering TKI adjuvant and neoadjuvant use. We also explored the influence of mutation variability and financial evaluations. We found that TKIs often show disease-free survival (DFS) benefits, yet studies have struggled to improve the overall survival (OS); however, the results from the literature might be confusing because of variability in the stages and mutations. The safety profiles and adverse events are acceptable, but costs remain high and accessibility might not be optimal. TKIs are promising drugs that could allow for tailored treatment designs.

Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor growth and aggressiveness. Endoplasmic Reticulum (ER) stress has been documented in most major cancers, and the ability to tolerate persistent ER stress through an effective unfolded protein response enhances cancer cell survival, angiogenesis, metastasis, drug resistance and immunosuppression. The ER stress sensor IRE1α contributes to tumor progression through XBP1 mRNA splicing and regulated IRE1α-dependent decay of mRNA and miRNA. The aim of this study was to perform a molecular characterization of series of tumor samples to explore the impact of intratumoral IRE1 signaling in non-small cell lung cancer characteristics. To monitor IRE1 splicing activity, we adopted a fragment length analysis to detect changes in the length of the XBP1 mRNA before and after splicing as a method for measuring sXBP1 mRNA levels in tumors because sXBP1 mRNA is not probed by standard transcriptomic analyses. We demonstrate for the first time that XBP1 splicing is a valuable marker of lung cancer aggressiveness, and our results support a model in which IRE1 downstream signaling could act as a regulator of Epithelial to Mesenchymal Transition (EMT). Our findings study highlights the role of IRE1α downstream signaling in non-small cell lung cancer and opens a conceptual framework to determine how IRE1α endoribonuclease activity shapes the EMT program.

Theranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non–small-cell lung cancers (n = 1343). The R2 correlation between expected and measured allelic ratio, using commercial samples, was >0.96. Mutation detection threshold was 2% for 10 ng of DNA input. κ Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97–1.00) for EGFR and 0.98 (95% CI, 0.97–1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associations were found between EGFR and PI3KCA or CTNNB1 and between KRAS and STK11. Potential oncogenic driver mutations or gene amplifications were more frequent in validated oncogenic driver nonmutated samples. This work is a proof of concept that targeted NGS is accessible in routine screening, including large screening, at reasonable cost. Clinical data should be collected and implemented in specific databases to make molecular data meaningful for direct patients' benefit.

Background: Unicentric mediastinal Castleman disease (CD) is a rare condition, poorly characterized due to the small number of cases and the absence of genomic study. We analyzed clinical, radiological, histological and genomic patterns associated with mediastinal CD in a substantial case series. Methods: We retrospectively reviewed cases of unicentric mediastinal CD managed in 2 French thoracic surgery departments between 1988 and 2012. Clinical, radiological, surgical and pathological data were recorded. On available FFPE blocks we performed mutation screening by next-generation-sequencing, using AmpliSeq™ Cancer Hotspot v2 (Life Technologies) and immunohistochemistry (IHC) (AKT-mTOR pathway). Results: Eleven patients were identified (mean age 41±15 years, sex-ratio 0.8, median follow-up 78 months). Surgical approach was thoracotomy (n=6), sternotomy (n=4), and VATS (n=1). Additional procedures included thymectomy in three cases, mediastinal lymphadenectomy in two cases, and bilobectomy in one case. One patient presented local relapse as a follicular dendritic cell sarcoma, leading to death 48 months after the first resection. Within 9 patients whose FFPE blocks were available, 2 mutations were found: VHL (p.F119L, 35%, n=1) and JAK3 (p.V718L, 53%, n=1). Phospho-AKT and phospho-mTOR stainings were negative in all cases, whereas phospho-S6RP staining was positive in eight cases, mainly in interfollicular cell cytoplasm. Conclusions: From this series of patients with unicentric mediastinal CD, we observed 2 cases of potential driver mutations and 8 cases of phospho-S6RP activation not related to AKT-mTOR. Larger studies are required to decipher more precisely the molecular abnormalities and potential therapeutic targets underlying this uncommon condition.

Non-small cell lung cancer (NSCLC) is today the first cancer worldwide and represents the first cause of cancer-related death. The identification of EGFR activating mutations and development of specific EGFR inhibitors (EGFRi) such as tyrosine kinase inhibitor (TKI) has changed the management of metastatic NSCLC. However, TKI resistance progressively appeared and EGFR secondary resistance mutation have been identified such as the most frequent T790M (1).

La pleurite purulenta (PP) o empiema pleurico e un’urgenza terapeutica, perche puo essere fatale in caso di gestione insufficiente o ritardata. Nel 70-80% dei casi, questa infezione del liquido pleurico e secondaria a un’infezione polmonare vicina (parapneumonica, ascesso polmonare, cancro sovrainfetto, bronchiectasia, sequestro, ecc.). Puo anche essere di origine iatrogena (postchirurgica con o senza fistola, post-traumatica) o, raramente, da cause extratoraciche (sottodiaframmatiche, oto-rino-laringoiatrica o stomatologica). Qualunque sia il meccanismo causale, l’urgenza consiste nel realizzare allo stesso tempo la diagnosi, attraverso una toracentesi, e il trattamento iniziale con un drenaggio pleurico per evacuare il liquido purulento. L’agente eziologico puo essere difficile da identificare se e gia stata instaurata precedentemente una terapia antibiotica o se si tratta di un microrganismo anaerobio, il che puo giustificare il ricorso alla biologia molecolare. A seconda dell’antichita della PP, si osservano diversi stadi della malattia, con conseguenze sul polmone sottostante che giustificano una gestione diversa. Il semplice drenaggio permette, in genere, un miglioramento clinico spettacolare, ma non e sufficiente di per se. E necessario associarvi una detersione locale, che puo essere chimica mediante fibrinolitici locali e/o strumentale attraverso videotoracoscopia. Proprio come la terapia antibiotica per via endovenosa rivolta contro la malattia responsabile della PP, la kinesiterapia respiratoria pluriquotidiana e un elemento indispensabile per la guarigione. Essa mira a favorire la riespansione polmonare e la mobilita diaframmatica per eliminare la tasca pleurica infetta. Alcuni gesti possono essere associati, a seconda della causa: chiusura di una fistola bronchiale o esofagea, recentazione di una distruzione di una struttura vicina, rimozione di materiale infetto e cosi via. La fenestrazione deve essere ipotizzata in caso di sepsi persistente nonostante il drenaggio. Infine, nelle forme incistate di scoperta tardiva, il deficit di riespansione polmonare richiede un trattamento specifico di decorticazione pleuropolmonare mediante toracotomia e/o un gesto parietale a volte complesso di toracoplastica, mioplastica od omentoplastica. I ritardi nella presa in carico spiegano gli alti tassi di mortalita, che possono arrivare fino al 41%. Tuttavia, in caso di diagnosi precoce e di trattamento ben condotto, la guarigione e quasi costante. I fattori prognostici sfavorevoli sono le comorbilita multiple, l’immunosoppressione, la necessita di un cambiamento di terapia antibiotica in corso di trattamento, l’identificazione di un microrganismo e, anche se in modo controverso, l’eta avanzata.

The greater the number of lymph node (LN) sampled (NLNsS) during lung cancer surgery, the lower the risk of underestimating the pN-status and the better the outcome of the pN0-patients due to stage-migration. Thus, regarding LN sampling “to be or not to be”, number is the question. Recent studies advocate removing 10 LNs. The most suitable NLNsS is unfortunately impossible to establish by mathematics. A too high NLNsS variability exists, based on anatomy, surgery and pathology. The methodology may vary according to Inter-institutional differences in the surgical approach regarding LN inspection and number sampling. The NLNsS increases with the type of resection: sublobar, lobectomy or pneumonectomy. Concerning pathology, one LN may be divided into several pieces, leading to number overestimation. The pathological examination is limited by the number of slices analyzed by LN. The examined LNs can arbitrarily depend on the probability of detecting nodal metastasis. In fact, the only way to ensure the best NLNsS and the best pN-staging is to remove all LNs from the ipsilateral mediastinal and hilar LN-stations as they are discovered by thoroughly dissecting their anatomical locations. In doing so, a deliberate lack of harvest of LNs is unlikely, number turns out not to be the question anymore and a low NLNsS no longer means incomplete surgery. This prevents from judging as incomplete a complete LN dissection in a patient with a small NLNsS and from considering as complete a true incomplete one in a patient with a great NLNsS. Precise information describing the course of the operation and furnished in the surgeon's reports is also advisable to further improve the quality of LN-dissection, which ultimately might be beneficial in the long-term to patients. However, that procedure is of limited interest in pN-staging if LNs are not thoroughly examined and also described by the pathologist.

International audience; Notre objectif était de faire un état des lieux des connaissances sur la prise en charge médicamenteuse des douleurs neuropathiques chez les patients avec cancer. Alors que le nombre de patients avec cancer ne cesse d’augmenter et que les douleurs sont très fréquentes lors de cancer, peu d’articles s’intéressent à la prise en charge médicamenteuse des douleurs, notamment neuropathiques, chez les patients ayant ou ayant eu un cancer. Cette revue systématique de l’ensemble des études publiées entre décembre 2012 et août 2018 devait permettre d’estimer l’ampleur du manque. Au total, 27 articles ont été identifiés sur la base d’une recherche systématique de la littérature (PubMed) et des connaissances des auteurs. Ces résultats confirment que peu de données ont été publiées. L’hétérogénéité des patients cancéreux, du cancer, et de la douleur expliquent en partie ce manque. Les recommandations, qui s’appuient sur des résultats obtenus auprès de patients généralement non cancéreux, suggèrent l’utilisation des antidépresseurs tricycliques et des antiépileptiques ; les traitements locaux sont appréciés pour leur bonne tolérance systémique. Des études incluant un plus grand nombre d’individus et tenant compte de l’étiologie de la douleur neuropathique, de ses caractéristiques (neuropathiques ou mixtes), et de la place de l’individu dans le parcours de soins (patient devant être traité, patient sous traitement anticancéreux, survivant récent ou ancien, ou patient en phase terminale) sont nécessaires pour pouvoir améliorer la connaissance. Les résultats de cette analyse de la littérature peuvent guider les chercheurs pour leurs futures études.

The objective of the present systematic literature review was to provide an update on medical treatment of neuropathic pain in cancer patients. The number of cancer patients is steadily increasing. Pain is frequent in cancer patients. Few studies have focused on medical treatment of pain, and especially of neuropathic pain, in current or former cancer patients. The present systematic review of all studies published between December 2012 and August 2018 was intended to estimate the scale of this lack. In all, 27 articles were identified on a systematic PubMed search and from the authors' personal knowledge, confirming that scant data have been published. The heterogeneity of cancer patients, of cancer, and of pain go some way toward explaining this scarcity. Guidelines, founded mainly on results from non-cancer patients, recommend tricyclic antidepressants and antiepileptic drugs; local treatments have the advantage of good systemic tolerance. Larger-scale studies taking account of the etiology of neuropathic pain, its characteristics (strictly neuropathic or mixed) and patient characteristics (awaiting treatment, under treatment, recent or non-recent survivor, or in terminal phase) along the care pathway are needed to improve knowledge. The results of the present literature analysis can help future research.

Diaphragm disorders in adults. Diaphragm diseases, functional particularly, are little known and often underestimated by clinicians. Whether a fortuitous discovery on a chest x-ray showing an elevation of the hemidiaphragm or revealed by dyspnea, these abnormalities of the diaphragm require further investigations. The objective is to confirm the diagnosis, understanding the mechanism, to clarify the functional consequences and to consider treatment. Some dysfunctions may be temporary, contraindicating any emergency treatment apart from acute ruptures. Only symptomatic cases require a surgical treatment. The type of surgery depends on the cause and can range from simple repair of a diaphragmatic defect, diaphragm plication to restore tensioning and even phrenic pacing in very rare cases.Pathologies diaphragmatiques de l’adulte. Les pathologies du diaphragme, en particulier fonctionnelles, sont peu connues et souvent sous-estimées par les cliniciens. Qu’elles soient de découverte fortuite sur une radiographie thoracique montrant une surélévation de la coupole diaphragmatique ou révélées par une dyspnée, ces anomalies du diaphragme nécessitent des explorations complémentaires. L’objectif est d’affirmer le diagnostic, de comprendre le mécanisme en cause, de préciser les conséquences fonctionnelles et d’envisager un traitement. Certains dysfonctionnements peuvent être temporaires ce qui contre-indique tout traitement en urgence en dehors des ruptures « aiguës ». Seules les formes responsables d’une symptomatologie invalidante justifie d’une prise en charge chirurgicale. Le type de chirurgie dépend de la cause et peut aller de la simple réparation d’un défect diaphragmatique, à la remise en tension de la coupole par une plicature et même l’implantation d’un stimulateur phrénique dans de très rares cas.

Resume Introduction Les prises en charge des cancers bronchiques non a petites cellules (CBNPC) n’ont cesse de progresser et les resultats sur la survie de s’ameliorer. Nous avons revu les changements apparus en chirurgie sur une periode de 32 ans. Patients et methodes Les donnees de 6105 patients operes de 1979 a 2010 ont ete analyses sur trois periodes egales : sexe, âge, type de chirurgie, histologie, pTNM, tabagisme, comorbidites, et periodes de temps. Resultats L’âge, le nombre de femmes, les patients avec co-morbidites et antecedents de cancer et les cancers non epidermoides ont augmente entre la premiere et la troisieme periode. Le nombre des thoracotomies exploratrices a diminue (7,7 % a 1,6 %), ainsi que celui des pneumonectomies (48 % a 18 %) alors que celui des wedges (0,5 % a 6 %) et des lobectomies (42 % a 64 %) s’est accru. Les traitements neo-adjuvants representaient dans la derniere periode plus d’un patient sur cinq. La mortalite postoperatoire (4 %) ne variait pas mais le taux des complications non letales s’est aggrave (16,9 % a 27,7 %). Les taux de survie globale a 5 ans sont passes de 37,4 % a 49,8 % ( p −6 ). L’allongement de survie a interesse les differents composants du pTNM et s’observait quelles que soient les modalites therapeutiques. L’accroissement de l’âge et des comorbidites affectaient le pronostic. Conclusion Les caracteristiques des CBNPC et des patients, leurs prises en charge diagnostiques et therapeutiques ont evolue avec le temps. La survie s’ameliore sur l’ensemble des facteurs consideres. Le facteur periodes de temps est tres important et devrait etre inclus dans l’analyse des etudes cliniques sur le CBNPC.

Diaphragm pacing (DP) is an orphan surgical procedure that may be proposed in strictly selected ventilator-dependent patients to get an active diaphragm contraction. The goal is to wean from mechanical ventilation (MV) and restore permanent efficient breathing. The two validated indications, despite the lack of randomised control trials, concern patients with high-level spinal cord injuries (SCI) and central hypoventilation syndromes (CHS). To date, two different techniques exist. The first, intrathoracic diaphragm pacing (IT-DP), based on a radiofrequency method, in which the electrodes are directly placed around the phrenic nerve. The second, intraperitoneal diaphragm pacing (IP-DP) uses intradiaphragmatic electrodes implanted through laparoscopy. In both techniques, the phrenic nerves must be intact and diaphragm reconditioning is always required after implantation. No perioperative mortality has been reported and ventilator-weaning rate is about 72% to 96% in both techniques. Improvement of quality of life, by restoring a more physiological breathing, has been almost constant in patients that could be weaned. Failure or delay in recovery of effective diaphragm contractions could be due to irreversible amyotrophy or chest wall damage. Recent works have evaluated the interest of IP-DP in amyotrophic lateral sclerosis (ALS). After some short series were reported in the literature, the only multicentric randomized study including 74 ALS patients was prematurely stopped because of excessive mortality in paced patients. Then, another trial analysed the place of IP-DP in peripheral diaphragm dysfunction but, given the multiple biases, the published results cannot validate that indication. Reviewing all available literature as in our experience, shows that DP is an effective method to wean selected patients dependent on ventilator and improve their daily life. Other potential indications will have to be evaluated by randomised control trials.

Molecular screening has become a standard of care for patients with advanced cancers and impacts on how to treat a patient. Advances in genomic technologies with the development of high throughput sequencing methods will certainly improve the possibilities to access a more accurate molecular diagnosis and to go beyond the identification of validated targets as a large number of genes can be screened for actionable changes. Moreover, accurate high throughput testing may help tumor classification in terms of prognosis and drug sensitivity. Finally, it will be possible to assess tumor heterogeneity and changes in molecular profiles during follow-up using ultra-deep sequencing technologies and circulating tumor DNA characterization. The accumulation of somatic ADN alterations is considered as the main contributing factor in carcinogenesis. The alterations can occur at different levels: mutation, copy number variations or gene translocations resulting in altered expression of the corresponding genes or impaired protein functions. Genes involved are mainly tumor suppressors, oncogenes or ADN repair genes whose modifications in tumors will impinge cell fate and proliferation from tumor initiation to metastasis. The entire genome of various tumor types, have now been sequenced. In lung cancer, the average number of mutations is very high with more than 8.9 mutations/Mb (Network TCGAR, 2014) that is to say more than 10,000 mutations/genome. These alterations need to be classified, indeed, some are true drivers that directly impact proliferation and some are passenger mutations linked to genetic instability. The development of targeted therapies relies on the identification of oncogenic drivers. The identification of genotype-phenotype associations as in the case of EGFR-TKI (Epidermal growth factor receptor-tyrosine kinase inhibitor) and EGFR mutations in lung cancer led to the restriction of drugs to patients for which tumor genotype predicts efficacy. Tumor-molecular directed therapy based on validated targets (EGFR, ALK) is in the clinics, rapidly, with the developments of multi-targets or multi-drug assays there will be a need for tumor-molecular-profile directed therapy. Today, there are practical challenges to a successful implementation of NGS technologies for clinical applications. Broadly, some are linked to the tumor (heterogeneity), to the tissue (availability, storage, fixative), to the design of specific assays or set of genes, to the interpretation of non-driver mutations and to a possible access to drugs once a target is identified. Technical challenges are solved, NGS (at least targeted-NGS) plateforms have been validated by INCa labeled laboratories, in this context, we will address different questions: How, for whom, what kind of profiling and what can we expect?

Postoperative systemic artery to pulmonary vein fistula is very rare. In this report, we describe an exceptional condition of both intrapulmonary arteriovenous fistula and systemic artery to pulmonary vein fistula, involving all right hemithoracic systemic arteries, inducing left-to-left shunt. This condition was responsible for heart failure, 24 years after a right upper lobectomy for inflammatory tumor. Investigations included computed tomographic angiography, arteriography, and four-dimensional flow magnetic resonance imaging. Differential diagnosis and management are discussed.

// Nicolas Pecuchet 1,2 , Pierre Laurent-Puig 1,3 , Audrey Mansuet-Lupo 4,5 , Antoine Legras 1 , Marco Alifano 6 , Karine Pallier 1 , Audrey Didelot 1 , Laure Gibault 7 , Claire Danel 8 , Pierre-Alexandre Just 4 , Marc Riquet 9 , Francoise Le Pimpec-Barthes 9 , Diane Damotte 4,5,* , Elisabeth Fabre 1,2,* and Helene Blons 1,3,* 1 INSERM UMR-S1147, Paris Sorbonne Cite Universite, Paris, France 2 Department of Medical Oncology, Hopital Europeen Georges Pompidou (HEGP), Assistance Publique, Hopitaux de Paris, Paris, France 3 Department of Biochemistry, Pharmacogenetic and Molecular Oncology Unit, Hopital Europeen Georges Pompidou (HEGP), Assistance Publique, Hopitaux de Paris, Paris, France 4 Department of Pathology, Hopital Cochin, Assistance Publique, Hopitaux de Paris, Paris, France 5 INSERM U1138, Paris Sorbonne Cite Universite, Paris, France 6 Department of Thoracic Surgery, Hopital Cochin, Assistance publique Hopitaux de Paris, Paris, France 7 Department of Pathology, Hopital Europeen Georges Pompidou (HEGP), Assistance Publique, Hopitaux de Paris, Paris, France 8 Department of Pathology, Hopital Bichat, Assistance Publique, Hopitaux de Paris, Paris, France 9 Department of Thoracic Surgery, Hopital Europeen Georges Pompidou (HEGP), Assistance Publique, Hopitaux de Paris, Paris, France * These authors share senior authorship for this manuscript Correspondence: Helene Blons, email: // Keywords : lung cancer, STK11, LKB1, isoforms, prognosis Received : July 20, 2015 Accepted : October 09, 2015 Published : November 25, 2015 Abstract STK11 is commonly mutated in lung cancer. In light of recent experimental data showing that specific STK11 mutants could acquire oncogenic activities due to the synthesis of a short STK11 isoform, we investigated whether this new classification of STK11 mutants could help refine its role as a prognostic marker. We conducted a retrospective high-throughput genotyping study in 567 resected non-squamous non-small-cell lung cancer (NSCLC) patients. STK11 exons 1 or 2 mutations (STK11 ex1-2 ) with potential oncogenic activity were analyzed separately from exons 3 to 9 (STK11 ex3-9 ). STK11 ex1-2 and STK11 ex3-9 mutations occurred in 5% and 14% of NSCLC . STK11 mutated patients were younger ( P = .01 ) and smokers ( P< .0001 ) . STK11 mutations were significantly associated with KRAS and inversely with EGFR mutations. After a median follow-up of 7.2 years (95%CI 6.8-.4), patients with STK11 ex1-2 mutation had a median OS of 24 months (95%CI 15-57) as compared to 69 months (95%CI 56-93) for wild-type (log-rank, P = .005 ) and to 91 months (95%CI 57-unreached) for STK11 ex3-9 mutations ( P = .003 ). In multivariate analysis, STK11 ex1-2 mutations remained associated with a poor prognosis ( P = .002 ). Results were validated in two public datasets. Western blots showed that STK11 ex1-2 mutatedtumors expressed short STK11 isoforms. Finally using mRNAseq data from the TCGA cohort, we showed that a stroma-derived poor prognosis signature was enriched in STK11 ex1-2 mutated tumors. All together our results show that STK11 ex1-2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.

OBJECTIVES: Lung transplantation (LTx) is an accepted therapy for selected infants, children and adolescents with end-stage lung and pulmonary vascular disease. It remains a challenge for a selected group of patients. In 2011, the number of paediatric lung transplantations (PLTxs) worldwide was 107. In France, a total of 131 PLTxs have been performed since 2000 (data from ABM: Agence de biomedecine), 65 of which were conducted at our institution. METHODS: All patients under 18 (4.8–17.11) years of age matching inclusion and exclusion criteria, who underwent LTx at our institution were included in this study (n= 58). We analysed the outcomes of these patients in terms of survival rates, controlling for indications for transplantations and surgical procedures. Secondary outcomes were analysis of surgical and medical complications and identification of prognostic factors in the field of LTx in these categories of ages. RESULTS: The 30-day mortality rate was 10%. Kaplan–Meier survival rates at 1 month, 1, 3, 5 and 10 years were 90, 81, 66, 60 and 57%, respectively; the median survival was 91 months. Reduced-size transplantation was performed in 33% of double-lung transplantation (DLTx) patients without negatively impacting survival. In our series, female sex, the presence of a sex mismatching and, in particular, the occurrence of a male donor to a female recipient (F/M group) have been poor prognostic factors after PLTx. CONCLUSIONS: The overall survival after PLTx was encouraging (57% at 10 years). A PLTx should be offered to the small number of patients with end-stage pulmonary disease. The limited number of paediatric donor organs can be overcome by using reduced-size organs without a survival disadvantage to the patients. In our series, male sex and sex matching seemed to be positive predictive prognostic factors after PLTx but further studies are required to confirm these results and to also clarify the role of age of donor, time of cold ischaemia and body mass index in PLTx.

Objectives: Non-small cell lung carcinoma (NSCLC) with N1 involvement is associated with 5-year survival rates ranging from 7% to 55%. Numerous factors have been independently reported to explain this heterogeneous prognosis, but their relative weight on long-term survival is unknown. Methods: Patients who underwent surgical resection for NSCLC in two French centers from 1993 to 2010 were prospectively recorded and retrospectively reviewed. The overall survival (OS) of patients undergoing first-line surgery for pN1 disease was analyzed according to the type of extension, number of metastatic LN, number and anatomic location of metastatic stations. Results: The study group included 450 patients (male 80.2%, mean age 63.3 � 9.9 years, 5-year overall survival 46%). The number of metastatic station was 1 in 340 (75.6%, single-station disease) and � 2 in 110 patients (24.4%, multi-station disease). The number of metastatic stations was correlated with the number of metastatic LN (p < .001), and associated with adverse OS (p ¼ .0014). The presence of intralobar metastatic LN (station 12e13e14) was associated with a mechanism of direct extension (p < .001), but did not impact OS (p ¼ .71). The location of metastatic stations was of prognostic significance only in case of multi-station disease, with hilar (station 10) involvement being associated with adverse OS (p ¼ .005). The 110 patients with multi-station pN1 disease and the 134 patients operated on for single-station pN0N2 (skip-N2) disease during the study period yield comparable outcome (p ¼ .52). Conclusions: In patients with resected pN1 NSCLC, the number of metastatic stations and their location in case of multi-station disease have a prognostic value. 2014 Published by Elsevier Ltd.

A 64-year-old man complained of persistent dyspnea and bilateral basi-thoracic pain with shoulder irradiation. Chest computed tomography revealed a heterogeneous left diaphragmatic mass, while magnetic resonance imaging showed hypo-T1 and hyper-T2 signal. Positron-emission tomography did not show any hypermetabolism. Video-assisted thoracic surgery was decided. At inspection, tumour appeared within the posterior costal part of the diaphragmatic muscle. Tumour resection was extended to a 8-cm-long portion of the lumbar part of diaphragm. Diaphragm was repaired with non-absorbable interrupted sutures. Postoperative course was uneventful. Final pathology revealed an intra-diaphragmatic bronchogenic cyst, which is an exceptional condition. Primary diaphragmatic tumours are very rare and preoperative diagnosis cannot be affirmed. Embryologic hypotheses (migration along the oesophagus or envelopment within diaphragmatic precursors of an abnormal supernumerary lung bud) including recent molecular findings of deregulated pathways (fibroblast growth factor-10 and NOTCH) are discussed.

Theranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non-small-cell lung cancers (n = 1343). The R

Background Thoracic endometriosis syndrome refers to a broad spectrum of clinical manifestations related to the presence of ectopic intrathoracic endometrial tissue. Few studies have reported on manifestations other than pneumothorax. Methods Clinical, surgical, and pathology records of all consecutive women of reproductive age referred to our institution from September 2001 to August 2016 for clinically suspected thoracic endometriosis syndrome were retrospectively reviewed. After excluding women with pneumothorax, we enrolled 31 patients, divided into three subgroups: catamenial chest pain (n = 20), endometriosis-related diaphragmatic hernia (n = 6), and endometriosis-related pleural effusion (n = 5). Results Surgery was performed in 11 patients with catamenial thoracic pain (median age, 30 years; range, 23 to 42). Median pain intensity assessed on the 0 to 10 Visual Analogue Scale was 8 (range, 8 to 9) before surgery. At surgery, 8 patients had diaphragmatic endometriosis implants, which were resected with direct suture of diaphragm. At follow-up, median pain score was 3 (range, 0 to 8). In the group presenting with diaphragmatic hernia (median age, 36 years; range, 29 to 50), diaphragm was repaired by direct suture or placement of prosthesis in 4 and 2 cases, respectively. At follow-up, no sign of recurrent hernia was observed. Finally, among women with endometriosis-related pleural effusion (median age, 30 years; range, 25 to 42), surgical treatment was represented by evacuation of the pleural effusion and biopsy (n = 4) or removal (n = 1) of visible endometrial foci. Conclusions Thoracic endometriosis syndrome is a poorly recognized entity responsible for various manifestations other than pneumothorax. In case of catamenial thoracic pain, diaphragmatic hernia and catamenial pleural effusion surgery should be advised in a multidisciplinary setting.

N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned.The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S).All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8±48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients (p0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p0.001).Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients.

Background A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known. Methods Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed. Results Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n = 80, 34.9%) were endometriosis related in 50% of cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of patients (n = 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis (all, P P Conclusions In women with surgically treated pneumothorax, prevalence of catamenial/endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a difficult diagnosis.

Introduction Il n’existe pas de recommandation concernant l’evaluation preoperatoire des eventrations diaphragmatiques. L’objectif de cette etude a ete d’evaluer l’interet de l’IRM dynamique du diaphragme faite avant et apres plicature de coupole, en developpant des criteres standardises d’analyse. Methodes De 2006 a 2017, 18 patients (Gp1) operes d’une eventration diaphragmatique unilaterale gauche (Gp1L, n = 15) ou droite (Gp1R, n = 3) ont eu une evaluation pre- et post-operatoire incluant une IRM dynamique. Cinq volontaires sains ont aussi eu cet examen. La course diaphragmatique au niveau de 3 points fixes (S1-S2-S3) et l’evolution perioperatoire de la fleche de chaque coupole (n = 41) en vue sagittale ont ete les 2 criteres principaux d’analyse. Resultats Sur l’IRM preoperatoire, toutes les coupoles avec une eventration (Gp1) avaient une course significativement reduite voire nulle en comparaison avec leur cote sain (p Figure 1 ). Conclusion L’IRM dynamique est un examen non invasif qui parait utile pour ameliorer nos connaissances en eventrations unilaterales du diaphragme et evaluer nos resultats chirurgicaux. Bien qu’il s’agisse d’une petite serie de patients, cet examen nous permet de valider l’existence d’un impact negatif significatif de l’eventration unilaterale sur la coupole saine controlaterale. Il met en lumiere le benefice local et controlateral de la plicature diaphragmatique. La grille standardisee que nous avons developpee peut aider les cliniciens dans leur approche chirurgicale et leurs futures evaluations.

Resume Les pathologies primitives des lymphatiques thoraciques sont rares et probablement sous-diagnostiquees. Les deux principales formes nosologiques sont les lymphangiomes et les lymphangiectasies. Les lymphangiomes sont des tumeurs benignes isolees composees de vaisseaux lymphatiques. Les lymphangiomes de l’enfant semblent d’origine congenitale, alors que les lymphangiomes de l’adulte suivent le plus souvent une obstruction lymphatique secondaire a une pathologie extra-lymphatique. Les lymphangiomes kystiques typiques en scanner et IRM peuvent etre surveilles, mais les lymphangiomes doivent etre operes en cas de doute diagnostique ou de complication. Les lymphangiectasies sont des dilatations congenitales ou acquises des vaisseaux lymphatiques de la plevre et des septa interlobulaires sans processus proliferatif. Ces pathologies rares peuvent etre localisees a un lobe pulmonaire ou etendues a l’ensemble du systeme lymphatique sus- et sous-diaphragmatique. En cas de communication avec un canal thoracique permeable, les lymphangiectasies peuvent etre a l’origine de chyloptysies, chylothorax et chylopericarde. La lymphangio-IRM permet de preciser au mieux l’etendue des lymphangiectasies et l’anatomie du canal thoracique. De premiere intention, le traitement comprend une prise en charge medicale et le drainage d’eventuels epanchements. De seconde intention, une prise en charge specialisee par une equipe entrainee reste souhaitable.

This study was undertaken to identify perioperative risk factors for hospital death in patients undergoing surgery for acute type A aortic dissection. Between 2000 and 2009, 101 consecutive patients underwent emergency surgery for acute type A aortic dissection. Four patients died before institution of cardiopulmonary bypass or completion of the procedure. In the remaining 97 (68 men; mean age, 63.4 ± 16.7 years), proximal repair was performed using ascending aortic replacement with valve re-suspension in 52 (53.6%) and composite valve graft replacement in 44 (45.4%). Distal repair required hemi- or total arch replacement in 42 (43.3%) patients. Overall hospital mortality reached 25.8% (25/97 patients). Logistic regression analysis revealed that advanced age, location of an intimal tear in the arch or more distally, and preoperative coronary malperfusion were significant independent risk factors for hospital death. No procedure-related variables were significant risk factors. Current hospital mortality in patients undergoing emergency surgery for acute type A aortic dissection remains high, but seems to be mainly determined by preoperative variables. More aggressive proximal or distal repairs were not associated with increased mortality.

Molecular screening has become a standard of care for patients with advanced cancers and impacts on how to treat a patient. Advances in genomic technologies with the development of high throughput sequencing methods will certainly improve the possibilities to access a more accurate molecular diagnosis and to go beyond the identification of validated targets as a large number of genes can be screened for actionable changes. Moreover, accurate high throughput testing may help tumor classification in terms of prognosis and drug sensitivity. Finally, it will be possible to assess tumor heterogeneity and changes in molecular profiles during follow-up using ultra-deep sequencing technologies and circulating tumor DNA characterization. The accumulation of somatic ADN alterations is considered as the main contributing factor in carcinogenesis. The alterations can occur at different levels: mutation, copy number variations or gene translocations resulting in altered expression of the corresponding genes or impaired protein functions. Genes involved are mainly tumor suppressors, oncogenes or ADN repair genes whose modifications in tumors will impinge cell fate and proliferation from tumor initiation to metastasis. The entire genome of various tumor types, have now been sequenced. In lung cancer, the average number of mutations is very high with more than 8.9 mutations/Mb (Network TCGAR, 2014) that is to say more than 10,000 mutations/genome. These alterations need to be classified, indeed, some are true drivers that directly impact proliferation and some are passenger mutations linked to genetic instability. The development of targeted therapies relies on the identification of oncogenic drivers. The identification of genotype-phenotype associations as in the case of EGFR-TKI (Epidermal growth factor receptor-tyrosine kinase inhibitor) and EGFR mutations in lung cancer led to the restriction of drugs to patients for which tumor genotype predicts efficacy. Tumor-molecular directed therapy based on validated targets (EGFR, ALK) is in the clinics, rapidly, with the developments of multi-targets or multi-drug assays there will be a need for tumor-molecular-profile directed therapy. Today, there are practical challenges to a successful implementation of NGS technologies for clinical applications. Broadly, some are linked to the tumor (heterogeneity), to the tissue (availability, storage, fixative), to the design of specific assays or set of genes, to the interpretation of non-driver mutations and to a possible access to drugs once a target is identified. Technical challenges are solved, NGS (at least targeted-NGS) plateforms have been validated by INCa labeled laboratories, in this context, we will address different questions: How, for whom, what kind of profiling and what can we expect?

Intraosseous haemangioma is a rare and benign primary tumour of the bone. We report the case of a 76-year old woman who presented the exceptional condition of multifocal cavernous haemangiomas involving the spine and the ribs, requiring spinal and chest wall resections to confirm the diagnosis and treat the symptoms.

Scimitar syndrome is one of the large congenital pulmonary venolobar syndromes and is defined as hypogenetic lung associated with partial anomalous pulmonary venous return. We report the case of a 25-year-old man with complex and exceptional variant scimitar syndrome. A chest CT scan with three-dimensional (3-D) reconstruction led us to identify hypoplastic right lung with homolateral hemidiaphragm agenesis and hypogenetic right pulmonary artery. There was a large and sinuous systemic arterial supply and anomalous venous return directed into the left atrium (venous return being usually directed into the right atrium or inferior vena cava in scimitar syndrome). Hyperoxia test showed no shunt. This variant scimitar syndrome has been previously reported and anomalous venous return called "meandering" pulmonary vein. Diagnosis and management of these patients with complex congenital anomalies are difficult because of their exceptional condition. Chest CT scan with 3-D reconstruction offers an accurate noninvasive diagnosis.

Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT. Understanding the biology of EMT will help to define reversing process and treatment strategies. We will see that this complex mechanism is related to inflammation, cell mobility and stem cell features and that it is a dynamic process. The existence of intermediate phenotypes and tumour heterogeneity may be debated in the literature concerning EMT markers, EMT signatures and clinical consequences in NSCLC. However, given the role of EMT in metastasis and in drug resistance the development of EMT inhibitors is an interesting approach to counteract tumour progression and drug resistance. This review describes EMT involvement in cancer with an emphasis on NSCLC and microRNA regulation.

Background It has been proposed that examining a greater number of lymph nodes (LNs) in patients with non–small-cell lung cancer (NSCLC) treated by surgical resection may increase the likelihood of proper staging and affect outcome. Our purpose was to evaluate the interindividual variability and prognostic relevance of the number of LNs harvested during complete pulmonary and mediastinal lymphadenectomy performed for NSCLC. Methods We prospectively collected and retrospectively reviewed the data from 1,095 patients who underwent lung cancer resection in association with systematic lymphadenectomy and pulmonary and mediastinal LN counts from 2004 to 2009. We analyzed the interindividual variability and prognostic impact of the number of LNs on overall survival (OS). Results The mean number of harvested pulmonary and mediastinal LNs was 17.4 ± 7.3 (range, 1–65) and was higher in male patients, right lung surgical procedures, lobectomy and pneumonectomy, N2 disease, and pIII stage. The mean number of harvested mediastinal LNs was 10.7 ± 5.6 and was normally distributed (range, 0–49; median, 10). The 5-year survival rate was 53.8%. Overall survival was influenced by the number of involved stations (single-station versus multi-station disease, 5-year survival rates 31.5% versus 16.9%, respectively; p =0.041) but not by the number of harvested LNs, the number of harvested mediastinal LNs, or the number of positive mediastinal LNs. Conclusions After lung cancer resection and complete lymphadenectomy, the number of LNs is subject to normally distributed interindividual variability, with no significant impact on OS. Recommending an optimal number of nodes is therefore arbitrary. Instead, our recommendation is to perform a complete systematic pulmonary and mediastinal lymphadenectomy following established anatomical boundaries.

OBJECTIVES: During the last decades, pneumonectomy has been increasingly seen as a risky procedure, first reserved for tumours not amenable to lobectomy, and now discouraged even in advanced stages of non-small-cell lung cancer (NSCLC). Our purpose was to assess the long-term survival following pneumonectomy for NSCLC and its prognostic factors. METHODS: We set a retrospective study including every patient who underwent a pneumonectomy for NSCLC in 2 French centres from 1981 to 2002. We then described the demographic and pathological characteristics of patients who survived >10 years, and studied the prognostic factors of long-term survival. RESULTS: During the study period, 1466 pneumonectomies were performed for NSCLC, including 1121 standard and 345 extended, and accounted for the overall population. Postoperative complications occurred in 396 patients (27%), including 93 deaths (6.3%). Five- and 10-year survival rates were 32 and 19%, respectively. Two-hundred and fifty patients survived >10 years after surgery, and accounted for the study group. The study group included a majority of males (n= 230, 92%), a mean age of 57 ± 9.2 years and a majority of clinical stage IIIA (n= 117, 46.8%). Induction, right-sided pneumonectomy, extended resection and adjuvant therapy were performed in 41 (16.4%), 109 (43.6%), 40 (16%) and 97 patients (38.8%), respectively. Histology revealed a majority of squamous cell carcinoma (n= 181, 72.4%), T2 tumours (n= 117, 36.8%) and N1 disease (n= 105, 42%). In multivariate analysis, factors associated with adverse outcomes included older age, advanced stage, extended resection, non-lethal postoperative complication, adenocarcinoma, lymphatic vessel microinvasion, N1 and N2 disease and R1 and R2 resection. CONCLUSIONS: During the last 30 years, pneumonectomy was effectively performed for advanced NSCLC, allowing a 10-year survival rate of 19%. Such results have not been reported with other non-surgical treatments and confirm that pneumonectomy is still an essential weapon in the armamentarium against lung cancer.

A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known.Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed.Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n = 80, 34.9%) were endometriosis related in 50% of cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of patients (n = 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis (all, Plt; .02). Apical emphysema-like changes were found in 184 of the 213 patients (86%) with apical resection and were significantly associated with the absence of thoracic endometriosis (Plt; .001).In women with surgically treated pneumothorax, prevalence of catamenial/endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a difficult diagnosis.