Etude de la résistance à l'anoïkis au cours des adénocarcinomes pulmonaires avec progression aérogène

Une propagation aérogène est observée dans 50 % des adénocarcinomes pulmonaires et caractérise le type bronchioloalvéolaire (CBA). Elle implique des cellules tumorales (CT) capables de décollement/ré-adhésion et de résistance à l'anoïkis (apoptose des cellules épithéliales normales détachées de la membrane basale). Objectifs : le but de notre travail était de montrer que les CT décollées de leur membrane basale étaient capables de résister à l'anoïkis in vivo, et de mettre au point un modèle d'étude de la résistance à l'anoïkis, in vitro. Matériel et méthodes : Les tumeurs et lavages bronchioloalvéolaires de 12 malades opérés d'un ADC pulmonaire avec composante CBA ont servi à l'étude (groupe ADC-CBA). 9 malades opérés d'un ADC pulmonaire invasif (groupe ADC-Inv) ont servi de témoins. Les expériences in vitro ont été réalisées avec la lignée A549. Le support a été recouvert de polyHEMA pour obtenir une culture en condition de suspension. Les méthodes utilisées avaient pour but l'étude de la viabilité cellulaire, de l'apoptose et du cycle cellulaire. Résultats : In vivo, les CT présentent dans la lumière alvéolaire se regroupent en amas et forment des jonctions adhérentes prenant parfois l'aspect de micropapilles. 1.2 % des cellules endoluminales sont Tunel positives ; elles résistent donc à l'anoïkis. Les ADC-CBA sont des tumeurs diploïdes (9/12), peu cyclantes (fraction de cellules en phase S (FPS) à 2.2 %) avec 81.8 % des cellules en phase G0. A l'opposé, 37 % des ADC-Inv sont diploïdes (p < 0.002) ; la FPS et la proportion de cellules en G0 sont plus élevées (p < 0.01 et p < 0.001 respectivement). In vitro, les cellules A549 cultivées en suspension avec du sérum s'agrègent, forment des jonctions adhérentes et résistent à l'apoptose (3.74 % des cellules Tunel positives à J2).Sans sérum, l'apoptose augmente (28.47 %, p <0.01). Le cycle cellulaire des cellules en suspension est ralenti, probablement par allongement de la phase G1. Discussion : Ces résultats pourraient expliquer la progression aérogène de ces tumeurs et leur fréquente chimiorésistance.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Granulomatoses diagnostiquées par cytoponctions ganglionnaires trans-bronchiques

Objectif: décrire la population présentant des granulomes épithélioïdes sur les cyto-ponctions ganglionnaires transbronchiques et analyser leurs significations cliniques. Méthode: inclusion prospective monocentrique de tous les patients ayant bénéficié de ponctions ganglionnaires transbronchiques, échoguidées ou non, sur 3 ans. Résultats: sur 329 patients, 59 présentaient des granulomes (18%) : 43 cas de sarcoïdose (73%), 8 cas de tuberculose (14%) et 8 autres diagnostics. Etaient réalisées 5,7 ponctions par patients, sans complication. Les sarcoïdoses étaient de stade I et II pour plus de 90% des patients, 32% avaient d autres organes atteints, et 42% ont nécessité un traitement spécifique. La sensibilité de la technique pour le diagnostic de granulomatose était de 89%. Conclusion: des granulomes, correspondant surtout à des sarcoïdoses, sont fréquemment retrouvés lors des ponctions ganglionnaires transbronchiques. Cet examen pourrait être intégré dans le bilan diagnostique des granulomatoses.Purpose: the aim of our study was to define the frequency of granulomatosis diagnosed by transbronchial needle aspiration (TNBA), assess the clinical meaning of this result and describe technical details of the procedure. Methods: in a monocentricprospective study, we included all patients who underwent a TNBA with or without endobronchial ultrasound (EBUS), over three years. An extemporaneous cytological examination by an on site cytologist was mandatory. At least six months follow-up were needed to confirm the diagnosis. Results: during this period, 329 patients underwent a TBNA, without any complication. A median of five fine needle aspiration (FNA) per endoscopy were performed, and granulomas were found in 59 cases. In seven false-negative cases, the granulomatous disease could not be diagnosed by the procedure. The sensitivity of TNBA in diagnosing granulomatosis was 89%. Diagnoses were as follow: 49 sarcoidosis (74%), 9 tubercolosis (14%) and 8 other granulomatosis including three sarcoidal reactions in regional lymph nodes of a malignant disease. Sarcoidosis were stage I and II in over 90% of patients, 32% had at least another organ affected, and 42% required a specific treatment. The CD4/CD8 lymphocyte rate in lymph node aspirates had no diagnostic value. Conclusion: granulomatosis, consisting mainly in sarcoidosis, are frequently found during TBNA procedures. Cytological diagnosis of granulomas on FNA is reliable and can be integrated in the diagnostic workup of granulomatosis.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Endobronchial ultrasound-guided transbronchial needle aspiration is feasible, safe, and reaches a 90 % diagnostic yield in patients with hypoxemic acute respiratory failure

International audienceAdverse events are common during conventional invasive lung sampling procedures [1] and may be particularly detrimental in critically ill patients [2]. We sought to describe the feasibility, safety, and diagnostic accuracy of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) in the intensive care unit (ICU).Between May 2011 and May 2015, nine consecutive patients with acute respiratory failure (ARF) and mediastinal or hilar involvement were selected from a prospective cohort [3] that comprehensively describes all EBUS-TBNA procedures in Tenon hospital, a tertiary university teaching hospital in Paris, France. EBUS-TBNA was performed using a 6.7-mm-outer-diameter, real-time, bronchoscope with a 7.5-MHz linear ultrasound transducer

Safe and effective use of nivolumab for treating lung adenocarcinoma associated with sporadic lymphangioleiomyomatosis: a rare case report

Abstract Background Sporadic lymphangioleiomyomatosis (LAM) is a rare form of diffuse parenchymal lung disease. PD-1 blocking antibodies constitute an essential treatment option for advanced non-small-cell lung cancer (NSCLC). The effect of immune checkpoint inhibitors in lymphangioleiomyomatosis patients with non-small cell lung cancer is unknown: concomitant symptomatic interstitial lung disease or the use of immunosuppressors was a key exclusion criterion in the original studies of immune checkpoint inhibitors, especially regarding the risk of interstitial lung disease exacerbation. Case presentation A 48-year-old female, active smoker (36 pack-years), diagnosed with sporadic LAM since 2004 suffered from metastatic adenocarcinoma of the lung. Third-line therapy with nivolumab was started in 2015, with a major partial response. Due to pulmonary function alterations, sirolimus was also reinitiated in 2017 in conjunction with nivolumab, without any undesirable effects and a major partial response continuing up to May 2018. Conclusions This case highlights the safe and effective use of nivolumab for managing metastatic lung adenocarcinoma that occurred in a patient with sporadic LAM. In the current case, immunotherapy proved highly successful in managing the NSCLC tumor that occurred upon LAM follow-up, with both a significantly prolonged partial response and acceptable safety profile

Nebulised liposomal amphotericin B for Aspergillus lung diseases: case series and literature review

International audienc

Minimal Change Disease Induced by Lorlatinib

International audienc

Release of metal particles from needles used for transbronchial needle aspiration

Background: Although mediastinoscopy is still the gold standard for diagnosis of mediastinal lymphadenopathy, minimally invasive procedures have been developed: transbronchial needle aspiration (TBNA) using a flexible bronchoscope (conventional TBNA) or linear echoendoscope (endobronchial ultrasound [EBUS]) allowing real-time guided lymph node aspiration. The observation of contamination of samples by foreign particles led us to determine the frequency and the nature of this material and to identify its origin. Methods: From June 2007 to November 2008, 141 consecutive patients underwent conventional TBNA (n = 84) or EBUS-guided TBNA (EBUS-TBNA) (n = 57). All cytologic samples were reviewed in blinded fashion, and contamination was assessed semiquantitatively. Mineral analysis using a transmission electron microscope equipped with an energy dispersive x-ray spectrometer was performed on the solution obtained after rinsing unused needles and on four samples of calf thymuses punctured with EBUS needles. Results: Foreign material, different from anthracosis, was identified in samples obtained with five different batches of needles, only from EBUS-TBNA(P<.0001). The contamination score was correlated to the number of passes(P =.035). Mineral analyses of the rinsing solutions from conventional TBNA needles were negative, whereas metal alloys of iron, titanium, nickel, and chromium were released with EBUS needles. The same contamination was identified in three of the four punctured calf thymuses. Conclusions: Dedicated EBUS-TBNA needles are able to release metal particles, probably by friction between the stylet and the needle, with a potential risk to inject particles into nodes. The long-term consequences are unknown, but the need for safety measures should be evaluated. © 2011 American College of Chest Physicians.SCOPUS: ar.jinfo:eu-repo/semantics/publishe