Publications by authors named "Philippe Astoul"

98 Publications

Medical Thoracoscopy Implementation after a European Respiratory Society Course Held from 2003 to 2016: A Survey.

Respiration 2021 Apr 13:1-7. Epub 2021 Apr 13.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital NORD Aix-Marseille University, Marseille, France.

Background: Medical thoracoscopy (MT) is an important procedure in the management of patients with pleural diseases.

Objectives: We designed a survey to explore whether the participants of our courses implement MT at their hospital after attending the course as no real-life data exist.

Methods: We distributed by e-mail a questionnaire to the participants of the courses. The questionnaire included general information about the participants, the precourse experience on MT, the postcourse implementation of the technique, and the reasons for failure.

Results: Responses were obtained from 104 of 324 (32.3%) identified emails. Responders were males (76%), seniors (59.7%), respiratory physicians (91.3%), working in a public/university hospital (78.8%), and mostly beginners (65.3%) from 41 countries. Following the course, 58.6% of responders either created or modified a MT program in their workplace. The reasons for not performing MT before the course were as follows: patients' referral to a thoracic surgeon, not enough training, lack of funding, department understaffed, and refusal by the hospital/department. Overall, these reasons were significantly decreased (p = 0.002) after the course.

Conclusions: Real-life data of our survey suggest that more than half of the responders have implemented the technique or modified their practice according to the skills they got from the course.
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http://dx.doi.org/10.1159/000514317DOI Listing
April 2021

Advances in pleural infection and malignancy.

Eur Respir Rev 2021 Mar 13;30(159). Epub 2021 Jan 13.

Dept of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, North University Hospital, Marseille, France

Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas.
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http://dx.doi.org/10.1183/16000617.0002-2020DOI Listing
March 2021

Prolonged survival after multimodal therapy for pleural mesothelioma: Don't give up the follow-up. A case report.

Ann Med Surg (Lond) 2020 Dec 11;60:442-444. Epub 2020 Nov 11.

Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, Aix-Marseille University, Marseille, France.

Malignant Pleural mesothelioma (MPM) is a rare disease which is associated with a poor prognosis. Front line chemotherapy represents the cornerstone in the management of MPM, and the place of radical surgery is controversial and reserve in early-stage disease. However prolonged survival (more than 24 months) can be observed in rare cases and only in the context of multimodal treatment including surgical management. We report the case of a patient suffering from an epithelial MPM with a 14-years progression-free survival after trimodal treatment including extrapleural pneumonectomy followed by chemotherapy and radiotherapy. This case illustrates that despite being an aggressive disease, multimodal management including radical surgery may allow a prolonged response in MPM but requires a whole-life surveillance.
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http://dx.doi.org/10.1016/j.amsu.2020.11.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683176PMC
December 2020

A new hybrid immunocapture bioassay with improved reproducibility to measure tissue factor-dependent procoagulant activity of microvesicles from body fluids.

Thromb Res 2020 12 21;196:414-424. Epub 2020 Sep 21.

BioCytex, Research and Technology Department, Marseille, France. Electronic address:

Background: The procoagulant activity of tissue factor-bearing microvesicles (MV-TF) has been associated with the risk of developing venous thrombosis in cancer patients. However, MV-TF assays are limited either by i) a lack of specificity, ii) a low sensitivity, or iii) a lack of repeatability when high-speed centrifugation (HS-C) is used to isolate MV. Therefore, our objective was to develop a new hybrid "capture-bioassay" with improved reproducibility combining MV immunocapture from biofluids and measurement of their TF activity.

Materials And Methods: Factor Xa generation and flow cytometry assays were used to evaluate IMS beads performance, and to select the most effective capture antibodies. The analytical performance between IMS-based and HS-C-based assays was evaluated with various models of plasma samples (from LPS-activated blood, spiked with tumoral MV, or with saliva MV) and different biofluids (buffer, plasma, saliva, and pleural fluid).

Results: Combining both CD29 and CD59 antibodies on IMS beads was as efficient as HS-C to isolate plasmatic PS+ MV. The IMS-based strategy gave significantly higher levels of MV-TF activity than HS-C in tumor MV spiked buffer, and both pleural fluids and saliva samples. Surprisingly, lower TF values were measured in plasma due to TFPI (TF pathway inhibitor) non-specifically adsorbed onto beads. This was overcome by adding a TFPI-blocking antibody. After optimization, the new IMS-based assay significantly improved reproducibility of MV-TF bioassay versus the HS-C-based assay without losing specificity and sensitivity. In addition, this approach could identify the cellular origin of MV-TF in various biological fluids.

Conclusion: Compared to HS-C, the IMS-based measurement of MV-TF activity in body fluids improves reproducibility and makes the assay compatible with clinical practice. It can facilitate future automation.
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http://dx.doi.org/10.1016/j.thromres.2020.09.020DOI Listing
December 2020

Rethought histologic classification of pleural mesothelioma to better treat: go forward from looking back.

Authors:
Philippe Astoul

Transl Lung Cancer Res 2020 Aug;9(4):1613-1616

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology - Aix-Marseille University, Marseille, France.

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http://dx.doi.org/10.21037/tlcr-20-592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481632PMC
August 2020

Pulmonary cement embolism complicating percutaneous kyphoplasty: A case report.

Respir Med Case Rep 2020 13;31:101188. Epub 2020 Aug 13.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital Nord, Marseille, France.

Background: Vertebral cement augmentation procedures, as kyphoplasty (KP) or percutaneous vertebroplasty (PVP), are commonly used for the management of pain of the vertebral column usually due to fractures related to traumatic injury, osteoporosis or metastatic lesion. It is a useful and safe technique with few complications. Among them, symptomatic pulmonary cement embolism (PCE) can happened, even rarely described in the literature, leading to severe cardio-respiratory manifestations depending on the location and size of the cement emboli.

Case Presentation: A 55 yo woman presented with atypical chest pain and presyncope three weeks after a motor vehicle accident resulting in an L1 compression fracture treated with kyphoplasty. She was hemodynamically stable. Blood tests showed D-Dimer 0.29 μg/mL, troponin <5ng/mL, Brain Natriuretic Protein 14 ng/mL and a PaO2 of 99 mmHg on arterial blood gas analysis. A computed tomography scan of chest showed linear hyperdense foreign bodies in two segmental pulmonary arteries at the level of middle lobe and right lower lobe compatible with pulmonary cement embolism. Anticoagulation with rivaroxaban for sixth months resulted in resolution of symptoms.

Conclusions: In this case, the pulmonary cement embolism occurred after kyphoplasty, which is associated with less risk of PCE than vertebroplasty. The procedure was done under biplanar fluoroscopy and no leakage of cement was noted, which would raise suspicion for CPE. Repeat imagine after this procedure is not routinely done. This case demonstrates that systematic imaging post procedure should be considered.An anticoagulation with rivaroxaban seems to be effective in our patient.
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http://dx.doi.org/10.1016/j.rmcr.2020.101188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475197PMC
August 2020

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

Eur Respir J 2020 06 11;55(6). Epub 2020 Jun 11.

Dept of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including and () for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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http://dx.doi.org/10.1183/13993003.00953-2019DOI Listing
June 2020

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

Eur J Cardiothorac Surg 2020 07;58(1):1-24

Unit of Thoracic Surgery, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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http://dx.doi.org/10.1093/ejcts/ezaa158DOI Listing
July 2020

Cerebral Air Embolism After Pleural Lavage for Empyema.

Ann Thorac Surg 2020 10 1;110(4):e289-e291. Epub 2020 Apr 1.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology Assistance Publique, Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Aix-Marseille University, Marseille, France.

Percutaneous pleural maneuvers are performed routinely in the management of pleural diseases with a favorable safety profile. We report a case of cerebral air embolism during a pleural lavage for the management of an empyema. This severe complication is rarely reported in the literature, although it can happen after any percutaneous thoracic procedures. Asymptomatic arterial air emboli can occur in up to 5% of percutaneous thoracic maneuvers. Diagnosis should be made upon sudden neurologic signs and confirmed with brain imaging. Standard treatment is based on hyperbaric oxygen therapy, and it can be performed safely with an intrapleural catheter.
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http://dx.doi.org/10.1016/j.athoracsur.2020.02.068DOI Listing
October 2020

Novel pleural-bladder pump in malignant pleural effusions: from animal model to man.

Thorax 2020 05 12;75(5):432-434. Epub 2020 Mar 12.

North Bristol Lung Centre, Southmead Hospital, Bristol, UK.

Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients.
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http://dx.doi.org/10.1136/thoraxjnl-2019-214003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231434PMC
May 2020

miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma.

Int J Mol Sci 2020 Feb 26;21(5). Epub 2020 Feb 26.

Aix Marseille Univ, APHM, INSERM, MMG, Hôpital la Timone, Service de Biologie Cellulaire, 13005 Marseille, France.

In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the 'Low lamin A expression' group compared to patients from the 'High lamin A expression' group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A- carcinoma cells compared to lamin A+ carcinoma cells in patients from the 'Low lamin A expression' group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A- carcinoma cells in patients from the 'High lamin A expression' group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells.
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http://dx.doi.org/10.3390/ijms21051599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084260PMC
February 2020

Lateral decubitus chest radiography or chest ultrasound to predict pleural adhesions before medical thoracoscopy: a prospective study.

J Thorac Dis 2019 Oct;11(10):4292-4297

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Marseille, France.

Background: Medical thoracoscopy (MT) is the gold-standard to investigate unexplained pleural exudates. However, the major prerequisite is an easy pleural access obtained by creating an artificial pneumothorax at the beginning of the procedure which can be a challenge in case of pleural adhesions and make the procedure unsafe. The detection of pleural adhesions prior to MT is necessary. Nowadays chest ultrasonography (CUS) is considered the best procedure to detect pleural adhesions. However, this technique is not available in all countries where the assessment of the pleural cavity is only based on chest radiography. Therefore, we conducted this study to compare the performance of lateral decubitus chest radiography (LDCR) and CUS to predict pleural adhesions.

Methods: LDCR and CUS were performed prior MT in consecutive patients presenting exudative pleural effusion to detect pleural adhesions. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for each pre thoracoscopy procedure were calculated.

Results: Data analysis for the sixty-six enrolled patients showed a higher superiority to detect pleural adhesions for CUS in comparison to LDCR for all the parameters analyzed.

Conclusions: These results confirm that pre-MT CUS is the cornerstone to evaluate the access to the pleural cavity and justify educational program in this field in all centers which intends to develop interventional pulmonology.
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http://dx.doi.org/10.21037/jtd.2019.09.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837969PMC
October 2019

The necessity of a more aggressive initial surgical treatment in patients with mesothelioma of the testicular tunica vaginalis.

Ann Med Surg (Lond) 2019 Nov 12;47:57-60. Epub 2019 Oct 12.

Service d'Oncologie Thoracique, Maladies de la Plèvre et Pneumologie Interventionnelle, Centre Hospitalier Universitaire Nord, and, Aix-Marseille University, Marseille, France.

Mesothelioma of the tunica vaginalis of the testis (MTVM) is a rare tumor encountering for less than 1% of mesothelioma. Patients suffering from these tumors have poor survival due to local and distant metastasis despite treatment. Actually, no specific treatment recommendations exist for this tumor, yet radical orchidectomy is the gold standard in limited disease. We herein report the case of a 71 patient with MTVM who underwent radical orchidectomy without inguinal lymph node dissection and recurred 2 years later with metastasis in pelvic and mediastinal lymph nodes. Despite systemic chemotherapy combining pemetrexed, bevacizumab and Cisplatinum, the disease relapsed eight months later with multiple metastatic lung nodules leading to a treatment shift. We believe that systematic inguinal-iliac lymph node resection should be included in the initial treatment of this tumor.
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http://dx.doi.org/10.1016/j.amsu.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806379PMC
November 2019

Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.

Respiration 2020;99(1):28-34. Epub 2019 Oct 25.

Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonary Medicine, Hôpital Nord, Marseille, France.

Background: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only.

Objectives: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM.

Methods: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE.

Results: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM.

Conclusion: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.
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http://dx.doi.org/10.1159/000503239DOI Listing
April 2021

Anaplastic thyroid carcinoma mimicking a malignant pleural mesothelioma: Clues for diagnosis.

Thorac Cancer 2019 11 17;10(11):2175-2178. Epub 2019 Sep 17.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, North University Hospital, Marseille, France.

Pleural metastasis of thyroid carcinoma is very rarely encountered in the evaluation of pleural effusion and diagnosis may be challenging. However, an anaplastic transformation of papillary thyroid carcinoma (PTC), although a rare condition, should be considered even after a prolonged period of patient follow-up. Here we report a case of anaplastic thyroid carcinoma mimicking malignant pleural mesothelioma diagnosed nine years after the initial diagnosis of PTC and detail the clues used to orient and confirm the diagnosis.
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http://dx.doi.org/10.1111/1759-7714.13191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825913PMC
November 2019

Successful Lung Volume Reduction Surgery after Endobronchial Coils Treatment in a Severe Emphysematous Patient.

Respiration 2019;98(2):174-177. Epub 2019 May 22.

Department of Thoracic Surgery, North University Hospital, Marseille, France.

Lung volume reduction surgery (LVRS) in emphysema has demonstrated improvement in both overall survival and clinical/functional outcomes. Endobronchial coil treatment (ECT) has also demonstrated improvement in pulmonary function, exercise performance, and quality of life, although predictive factors of responders remain to be determined. We describe the first successful LVRS in an emphysematous patient who displayed no benefit, either clinically or functionally, from a previous ECT. LVRS was performed in the right lower lobe 4 years after ECT in the same lobe. An air leak persisted for 18 days after LVRS, with no requirement for surgery or endobronchial treatment. Six months after LVRS, the patient dramatically improved with a decrease in hyperinflation and dyspnea.
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http://dx.doi.org/10.1159/000499682DOI Listing
September 2020

Recent developments in pleurodesis for malignant pleural disease.

Clin Respir J 2018 Oct;12(10):2463-2468

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital Nord, Marseille, France.

Objective: Metastatic pleural effusion (MPE) is one of the most frequent causes of pleural effusion. The aims of the therapeutic management are palliation of symptoms and improvement in patient's quality of life. The first step is a therapeutic thoracentesis. In case of a recurrent MPE, pleural maneuvers can be used to manage symptoms based on either ambulatory pleural drainage or pleurodesis to prevent fluid accumulation. The aim of this review is to describe recent advances, according to the best available evidence, in the field of pleurodesis for the management of MPE.

Data Source And Study Selection: Three different searches of the most clinically relevant articles and up-to-date results in the field of pleurodesis for the management of MPE were performed using PubMed. Different indexing terms and time restriction were chosen. From these PubMed searches, 322 articles were respectively found. After cross-checking these three lists and the selection of articles published after January 2010 specially dedicated to the management of MPE by pleurodesis, the abstracts of 106 articles were extracted to feed the corpus of this review.

Results And Conclusion: Treatment approaches of recurrent MPE should take into account multiple factors in particular patient's life expectancy and preference. If talc is the best sclerosing agent alone or in combination with indwelling pleural catheter which is a promising strategy, the pathophysiology of MPE has to be revisited in order to propose a personalized management targeting intrapleural key molecules involved in the genesis of malignant process.
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http://dx.doi.org/10.1111/crj.12958DOI Listing
October 2018

Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

Cells 2018 Jul 16;7(7). Epub 2018 Jul 16.

Aix Marseille Université, APHM, INSERM, MMG, Hôpital la Timone, Service de Biologie Cellulaire, 13385 Marseille, France.

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear , where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9.
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http://dx.doi.org/10.3390/cells7070078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071028PMC
July 2018

Chest ultrasonography to assess the kinetics and efficacy of talc pleurodesis in a model of pneumothorax: an experimental animal study.

ERJ Open Res 2018 Apr 11;4(2). Epub 2018 Jun 11.

AP-HM, Hôpital Nord, Dept of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Marseille, France.

Talc pleurodesis is used to avoid recurrences in malignant pleural effusions or pneumothorax. The lack of lung sliding detected by chest ultrasonography (CUS) after talc application is indicative of the effectiveness of pleurodesis. The objective of our study was to explore, in an animal model, the capacity of CUS to predict the quality of a symphysis induced by talc poudrage (TP) and talc slurry (TS). We induced an artificial pneumothorax in six healthy pigs prior to talc application. TP was performed on one hemithorax, followed by TS on the other side 1 week later. 108 points on the chest were marked and evaluated by ultrasonography during the study. TP showed higher sonographic scores compared to TS starting from 72 h after talc administration. At autopsy, a higher grade of symphysis was observed for TP, and a high correlation rate was registered between CUS and macroscopic findings. Histological analysis also showed a higher grade of pleural symphysis for TP. CUS is a reliable tool to assess talc pleurodesis. The quality and kinetics of the pleural symphysis are also evaluable by ultrasonography. Pleurodesis by TP is more effective than TS in this experimental model of pneumothorax.
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http://dx.doi.org/10.1183/23120541.00158-2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994484PMC
April 2018

Diagnostic Accuracy of Lateral Decubitus Chest Radiography before Pleural Maneuvers for the Management of Pleurisies in the Era of Chest Ultrasound.

Respiration 2018;95(6):449-453. Epub 2018 May 3.

Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, Marseille, France.

Background: Chest ultrasound (CUS) is the gold standard to detect pleural adhesions before pleural maneuvers. However, the CUS technique is not available in all countries where the assessment is only based on clinical examination and chest radiography.

Objective: To assess the value of lateral decubitus chest radiography (LDCR) to detect pleural adhesions.

Methods: Consecutive patients with pleural effusions undergoing LCDR followed by medical thoracoscopy the day after were identified from an institutional database. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for LDCR were calculated.

Results: Eighty-six patients were included in the study. The sensitivity, specificity, PPV, and NPV of LDCR for the presence of adhesions taking into account the shape of the horizontal level were 71.2% (56.7-82.5), 44.1% (27.6-61.9), 66.1% (52.1-77.8), and 50% (31.7-68.3), respectively. The accuracy to predict pleural adhesions for the sign "incomplete horizontal level" was 60.5 (49.3-70.7). The accuracy to predict pleural adhesions in case of irregular aspect of the horizontal level was 53.5 (42.5-64.2).

Conclusions: The accuracy of LDCR for the detection of pleural adhesions is low in patients with pleural effusion and LDCR is not sufficient before pleural maneuvers. This has to be taken into account in countries with a high prevalence of pleural tuberculosis which usually lead to loculated pleural effusions. CUS has to be urgently included in dedicated educational programs in these areas in order to decrease the complications related to unexpected pleural adhesions and achieve better planning for the management of pleural effusions.
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http://dx.doi.org/10.1159/000487999DOI Listing
November 2018

"Kissing Nodules" in Saber-Sheath Trachea.

Respiration 2018;95(6):464. Epub 2018 Apr 25.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, North Hospital of Marseille, Aix-Marseille University, Marseille, France.

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http://dx.doi.org/10.1159/000488246DOI Listing
November 2018

Experience with Transcordal Silicone Stents in Adult Laryngotracheal Stenosis: A Bicentric Retrospective Study.

Respiration 2018;95(6):441-448. Epub 2018 Apr 5.

Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North Hospital of Marseille, Aix-Marseille University, Marseille, France.

Background: Benign stenosis involving laryngeal and upper tracheal structures represents a therapeutic challenge. Open surgery and endoscopic management have to be discussed by a multidisciplinary board in order to evaluate the risk and benefit for each patient.

Objective: The objective of this retrospective study was to report the experience of two French centers with transcordal silicone stents (TSS) in the endoscopic management of benign laryngotracheal stenosis (BLTS) in adults, with focus on efficacy, safety, and tolerability.

Methods: We performed a retrospective chart review of all cases of BLTS treated with TSS between January 2001 and June 2017 at two tertiary centers in France: the Centre Hospitalier Régional Universitaire de Strasbourg and the Hôpital Nord de Marseille.

Results: A total of 17 patients were included. Eleven had a tracheostomy at initial management which consisted of 8 T-tubes and 9 strictly endoluminal stents placements. The main complications were minor aspirations in 5 patients (29%), granulation in 3 patients (18%), migration in 2 patients (12%), and severe dysphonia in 3 patients (18%). After a mean duration of 18.3 months, 11 patients (65%) had had their TSS definitely removed, 13 patients were tracheostomy free (76%), and a TSS remained in place in 4 patients (24%).

Conclusions: Adult BLTS treatment with TSS placement is associated with low morbidity and excellent clinical outcomes, with a large proportion of patients free of airway instrumentation on long-term follow-up.
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http://dx.doi.org/10.1159/000487242DOI Listing
November 2018

Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid.

Clin Chem Lab Med 2018 04;56(5):851-856

APHM, Hôpital la Timone, Service de Biologie Cellulaire, Marseille, France.

Background: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed.

Methods: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF.

Results: Five patients showed mutations in one or two actionable genes, two harboured an EGFR mutation (exons 19 and 21), one only a KRAS mutation, one both EGFR and KRAS mutations and one a BRAF mutation. In all cases, the results of mutation testing provided new major information for patient management, leading to therapeutic adaptation. CSF molecular analysis identified mutations not detected in other neoplastic sites for two patients. In one case, the EGFR p.Thr790Met was identified. CSF was also the only sample available for genetic testing for almost all patients at the time of disease progression.

Conclusions: When cancer cells are present in the CSF, the molecular profiling from the cell pellets is relevant, as it can detect supplemental or different mutations compared to a previous analysis of the primitive tumour or plasma cell-free DNA and allows the adaptation of the treatment strategy.
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http://dx.doi.org/10.1515/cclm-2017-0527DOI Listing
April 2018

Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor Performance status.

PLoS One 2017 14;12(8):e0183136. Epub 2017 Aug 14.

Aix Marseille Univ, INSERM, GMGF, Marseille, France.

The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunofluorescence, western blotting, and flow cytometry. In a sub-group of lung adenocarcinomas, we found reduced expression of lamin A but not of lamin C. The reduction in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1, an epithelial marker that is involved in the epithelial to mesenchymal transition (EMT). Finally, the lamin A expression was inversely correlated with the number of metastatic sites and the WHO Performance status, and association of pleural, bone and lung metastatic localizations was more frequent when lamin A expression was reduced. In conclusion, low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis, associated with EMT and could account for a pejorative factor correlated with a poor Performance status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183136PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555706PMC
October 2017

Safety and Efficacy of a Fully Covered Self-Expandable Metallic Stent in Benign Airway Stenosis.

Respiration 2017 28;93(6):430-435. Epub 2017 Apr 28.

Department of Thoracic Oncology, Pleural Disease, and Interventional Pulmonology, North Hospital, Marseilles, France.

Background: The use of self-expandable metallic stents (SEMS) in benign airway disease was the object of a boxed warning from the United States Food and Drug Administration in 2005 due to the risk of stent-related complications and difficulties associated with their removal. Third-generation fully covered SEMS have been commercialized since this warning and theoretically should not present the same difficulties associated with removal as they cannot become embedded in the airway mucosa.

Objectives: We aimed to examine the safety and efficacy of a specific third-generation SEMS, the Silmet stent.

Methods: We reviewed the records of all patients treated for benign airway stenosis with third-generation Silmet SEMS from January 2011 to December 2015 at the North Hospital of Marseilles, France.

Results: Forty SEMS were inserted in 30 patients over this period. Twenty (50.0%) stents were removed because of stent-related complications after a median of 77.0 ± 96.6 days (migration 32.5%, granulation tissue formation 7.5%, subjective intolerance 5.0%, mucus plugging 2.5%, laryngeal edema 2.5%). There were no cases of stent-related mortality. All complications were managed successfully endoscopically. Thirty-six stents (90.0%) were removed successfully after a median of 122.0 ± 113.2 days without any complications. The clinical success rate of stent treatment was 40.7%.

Conclusion: Third-generation SEMS are a safe treatment option for complex benign airway stenosis, but complications requiring stent removal are frequent. Further studies are needed to compare the performance of third-generation SEMS and silicone stents in benign airway stenosis.
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http://dx.doi.org/10.1159/000472155DOI Listing
March 2018

Positive pleural cytology is an indicator for visceral pleural invasion in metastatic pleural effusions.

Clin Respir J 2018 Mar 15;12(3):1011-1016. Epub 2017 Mar 15.

Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital Nord, Aix-Marseille University, Marseille, France.

Introduction: In case of undiagnosed pleural effusions, it is necessary to conduct thoracentesis with pleural fluid (PF) cytology. Yet, sensitivity of PF cytology is widely variable as a result of sample size, experience, and preparation method.

Objectives: The aim of this study was to assess whether pleural fluid (PF) cytology is correlated to visceral or parietal pleural invasion as assessed by thoracoscopy in metastatic pleural effusions.

Methods: All records of patients with pleural effusion were reviewed. The inclusion criteria were as follows: PF cytology, reported appearance of macroscopic pleural invasion during thoracoscopy and malignant diagnosis. Patients with mesothelioma were excluded. Finally, 287 patients who met all criteria were selected. According to the thoracoscopy findings, the extent of the disease on the pleura was analyzed in relation to the PF cytology.

Results: In this study, 160 patients (55.7%) had a positive PF cytology (Group A) while 127 (44.3%) recorded negative PF cytology (Group B). From Group A, patients with visceral pleural invasion were 120 (75%) while only 49 patients (38.5%) were found from Group B and the difference was statistically significant (P < .00001). In univariate analysis, visceral pleural invasion was strongly associated with positive PF cytology (P < .001). Other significant associations with positive PF cytology included PF bloody aspect (P = .012), and endoscopic mixed pattern of pleural invasion (P = .0039). Only visceral pleural invasion was statistically significant in multivariate analysis (P < .001).

Conclusions: In patients with pleural metastatic disease, visceral pleural invasion is the only significant factor associated with positive pleural fluid cytology.
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http://dx.doi.org/10.1111/crj.12619DOI Listing
March 2018

Successful Late Removal of Endobronchial Coils.

Chest 2016 Dec;150(6):e143-e145

Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North University Hospital, Marseille, France.

Although endobronchial coils for the treatment of severe emphysema are associated with an acceptable safety profile, adverse events such as pneumothorax and thoracic pain may occur. The coils are indicated as a permanent implant and are deemed very difficult to remove. We describe the first successful removal of two coils 10 months after placement in a patient who experienced persistent thoracic pain. This case report highlights that very distal (subpleural) coil placement may induce pneumothorax and subsequent thoracic pain and that nonsurgical removal of coils up to 10 months after implantation is feasible.
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http://dx.doi.org/10.1016/j.chest.2016.03.026DOI Listing
December 2016

Pneumothorax.

Rev Prat 2016 Dec;66(10):e445-e452

Service d'oncologie thoracique, maladies de la plèvre et pneumologie interventionnelle, hôpital Nord, Marseille, France.

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December 2016

Pneumothorax : en bref.

Rev Prat 2016 Dec;66(10):e444

Service d'oncologie thoracique, maladies de la plèvre et pneumologie interventionnelle, hôpital Nord, Marseille, France.

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December 2016

Airway stenting in the management of iatrogenic tracheal injuries: 10-Year experience.

Respirology 2016 11 21;21(8):1452-1458. Epub 2016 Jul 21.

Thoracic Oncology, Pleural Diseases and Interventional Pulmonology Department, North University Hospital, Marseille, France.

Background And Objective: Iatrogenic tracheal injury (ITI) is a rare yet severe complication of endotracheal tube (ETT) placement or tracheostomy. ITI is suspected in patients with clinical and/or radiographic signs or inefficient mechanical ventilation (MV) following these procedures. Bronchoscopy is used to establish a definitive diagnosis.

Methods: We conducted a retrospective, single-centre chart review of 35 patients between 2004 and 2014. Depending on the nature and location of ITI and need for MV, patients were triaged to surgical repair, endoscopic management with airway stents or conservative treatment consisting of ETT or tracheotomy cannula (TC) placement distal to the wound and bronchoscopic surveillance.

Results: Three of the four patients (11.43%) presenting with tracheoesophageal fistula (TEF) underwent surgery. Seven patients (20%) who did not require MV underwent endoscopic surveillance. Of the 24 ventilated patients (68.57%), 7 with ITI in the lower trachea were treated with silicone Y-stent (ETT or TC was placed inside the stent) and 17 patients with ITI in the upper trachea were managed by placing ETT or TC cuff distal to the injury. Overall management success, defined as complete healing of the ITI, was seen in 88.57% of patients. Four patients (11.43%) died of non-ITI-related comorbidities.

Conclusion: Conservative management should be considered in non-ventilated patients with ITI and when ITI is located in the upper trachea of ventilated patients where ETT or TC bypasses the injury. Airway stenting should be considered in ventilated patients with ITI located in the lower trachea. Surgery should be reserved for TEF and conservative and endoscopic management failure.
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http://dx.doi.org/10.1111/resp.12853DOI Listing
November 2016