[Transbronchial cryobiopsy in diffuse interstitial lung diseases]. / Cryobiopsies trans-bronchiques au cours des pneumopathies interstielles diffuses ­ expériences préliminaires.

INTRODUCTION: In the diagnostic approach to interstitial lung disease (ILD), the use of transbronchial cryobiopsy (TBC) may offer an alternative to surgical lung biopsy (SLB). We report the diagnostic effectiveness and the safety of TBC in ILD based on the preliminary experience in two French university centers. METHODS: Twenty four patients underwent TBC for the diagnosis of ILD in the operating room between 2014 and 2017. All the histological diagnoses obtained were then reviewed and validated during multidisciplinary discussions (MDD). RESULTS: Patients had an average of 3 TBC.TBC samples were analyzable in 22/24 (91.7%) patients. In these, samples allowed a histological diagnosis to be made in 14/22 (63.6%) patients and a diagnosis with certainty in 13/22 (59%) after MDD. The overall diagnostic yield from TBC was 13/24 (54.2%). Nine (37.5%) patients had a pneumothorax. Five (20.8%) patients had a bleeding. There were no deaths. Taking into account a possible initial learning curve and considering only the 15 patients who had their TBC after 2015, we note that a diagnosis could be made after MDD for 12 of them, that is, 80%. CONCLUSION: A prospective randomized study is needed to evaluate the technique in France in order to specify its diagnostic performance and its safety profile in comparison to SLB.

[Anti-tumor immunotherapy in malignant pleural mesothelioma]. / Immunothérapie anti-tumorale dans le mésothéliome pleural malin.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged. BACKGROUND: Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure. OUTLOOK AND CONCLUSIONS: However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.

[Treatment of malignant central airways obstruction by rigid bronchoscopy]. / Traitement par bronchoscopie rigide de l'obstruction maligne des voies aériennes centrales.

INTRODUCTION: Endobronchial resection is now the standard treatment for tracheobronchial narrowing due to malignancy. The clinical and functional respiratory improvement has been evaluated previously but only in heterogeneous population. METHODS: Between February 2009 and February 2011, we conducted a prospective single centre study at the University Hospital of Lille. Twenty-five patients with malignant tracheobronchial stenosis received a clinical and functional respiratory evaluation before and after a rigid bronchoscopy procedure to reduce the obstruction followed where appropriate by placement of an endobronchial stent. RESULTS: Thirteen patients (52%) had primary lung cancer and in 12 the tumor had another origin. Nineteen patients (76%) received a stent after bronchial unblocking. Clinically, all patients felt an improvement in their dyspnea estimated by the Borg score with a median improvement of -2 points [-1; -4] following the procedure (P<0.001). In 96% the dyspnea visual analogic scale improved by 40 mm [27; 67] (P<0.0001). The FEV1 increased significantly after unblocking by 9% [-3.5; 28.5] (P<0.05). The Rint decreased significantly by -0.19 kPa/L per second [-0.06; -0.023] (P=0.001). Correlations between scales of dyspnea and spirometric values were not significant (P>0.05). The survival rate at 1 year was 29%. CONCLUSION: Interventional bronchoscopy decreases dyspnea. It modestly improves respiratory function and decreases the Rint. However, lung function and dyspnea scales are not correlated. No spirometry factor can predict clinical dyspnea response but an elevated Borg dyspnea scale might be a good indicator.

[Diagnostic performance of EBUS-TBNA in patients with mediastinal lymphadenopathy and extrathoracic malignancy]. / Performance diagnostique de l'EBUS-PTBA chez des patients aux antécédents néoplasiques extrapulmonaires adressés pour adénopathies médiastinales.

INTRODUCTION: There is limited data about the diagnostic performance of EBUS-TBNA in patients with mediastinal lymphadenopathy and extrathoracic malignancy. METHODS: From January 2007 to July 2011, EBUS-TBNA was performed in 68 patients with a history of extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases. RESULTS: Thirty-one patients had a final diagnosis of cancer. In nineteen patients, the same histology was identified in the mediastinal nodes as in their prior extrathoracic cancer (colorectal cancer, esophageal cancer and lymphoma). In 12, the diagnosis was not "as expected" (ten lung cancers, one colorectal cancer, one unidentified cancer). Among 37 patients without diagnosis, biopsies in 27 showed normal lymphoid material, two had non-specific inflammation and eight had no contributory results. It was noted that procedures were reported to have been more difficult in these patients. CONCLUSIONS: Diagnostic performance of EBUS-TBNA in the context of extrathoracic malignancy is very variable depending on the origin of the cancer. Nevertheless, a diagnosis is concluded in almost 50% of the cases. These results underline the necessity to select carefully the indications of EBUS-TBNA in extrathoracic cancer.

[Feasibility of assessing EGFR mutation and others using samples obtained by EBUS transbronchial needle aspiration]. / Faisabilité de la recherche de mutations EGFR et KRAS sur des prélèvements obtenus par EBUS-PTBA.

INTRODUCTION: Assessment of mutation status in patients with non-small cell lung cancer (NSCLC) is often required. The aim of this study was to confirm the feasibility of molecular mutation analysis in cytologic specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS: Patients with an EBUS-TBNA positive for adenocarcinoma or NSCLC (squamous cell carcinoma excluded) were included retrospectively from January to December 2010, and prospectively from January to August 2011. Specimens were collected on liquid based preparation and processed on paraffin-embedded cell blocks after ThinPrepÒ procedure. Molecular analysis was performed by a SnaPshot assay for EGFR and by pyrosequencing for KRAS on suitable samples (>5% tumor cells). RESULTS: Eighty-two patients were included (63 adenocarcinoma). Molecular analysis for EGFR was feasible in 80 (97.6%) patients and for KRAS in 78 (95.1%) patients. Molecular analysis identified EGFR and KRAS mutations in tumor samples from four (5%) and 18 (23%) patients respectively. All EGFR mutations were found in women. CONCLUSIONS: Molecular analysis mutations can be performed routinely in cytologic specimens obtained by EBUS-TBNA.

[Castleman's disease: unusual presentation of Castleman's disease and review of literature]. / La maladie de Castleman : observations inhabituelles et revue de la littérature.

Castleman disease is a rare disorder of the lymphoid system which can be classified into two clinical groups, monocentric disease versus multicentric disease, and two histological types, the hyaline vascular form versus the plasma cell form. We report three cases of monocentric Castleman disease. The first one is a classical form of Castleman's disease. The second one is characterized by an uncommon radiological presentation, with a calcification within the tumor. The third one is a plasma cell form with monoclonal proliferation associated with a monoclonal gammapathy. These three cases highlight the polymorphic clinical and radiological features of Castleman disease. They underlie the difficulty of surgical resection due to the tumor vascularization. Other diagnosis hypothesis and associated diseases will also be discussed (HIV, Kaposi's sarcoma, POEMS syndrome).

[Should elevated beta-HCG levels be an exclusion criteria in clinical trials? A case report of paraneoplastic secretion associated with lung adenocarcinoma]. / L'élévation du taux de bêta-HCG doit-elle être un critère d'exclusion des essais thérapeutiques ? À propos d'un cas de sécrétion paranéoplasique associée à un adénocarcinome bronchique.

We report the case of a 55-year-old woman with pulmonary adenocarcinoma and bone metastases who was diagnosed with paraneoplastic secretion of the beta subunit of human chorionic gonadotropin (beta-HCG) while being screened for inclusion in a clinical trial. Immunohistochemistry analysis of a bone biopsy revealed strong staining of cancer cells with anti-beta HCG antibodies. Serial measurements of circulating Beta HCG seemed to be influenced by antineoplastic treatments, although they were not strictly associated with tumour evolution assessed by CT scans. Little is known about paraneoplastic secretion of beta HCG, although it has been found in 12% to 24% of non-small cell lung cancers. Usefulness of serial measurements of beta HCG for monitoring NSCLC has yet to be demonstrated, but its use as a criterion for inclusion in clinical trials needs to be questioned.

[Malignant pleural mesothelioma: diagnosis and treatment]. / Prise en charge diagnostique et thérapeutique du mésothéliome pleural malin.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor issued from the mesothelial surface of the pleural space. A previous exposure to asbestos is the main risk factor of mesothelioma. Clinical signs are most of the time late and unspecific. Chest CT-scan, a key imaging procedure, usually shows a (unilateral) pleurisy associated with pleural nodular thickening. PET-scan associated with CT-scan may help to differenciate MPM from pleural benign tumors but it is not recommended for the diagnosis of MPM, as well as chest resonance magnetic imaging and blood or pleural fluid biomarkers, including soluble mesothelin still under investigation. The diagnosis of MPM is based on histology using essentially immunohistochemistry on pleural biopsies best obtained by thoracoscopy. The treatment of MPM relies mostly on chemotherapy. Surgery, pleurectomy/decortication or extrapleural pneumonectomy, is not recommended outside a clinical trial, as well as adjuvant chest radiotherapy. Prophylactic irradiation of chest scars and drains, validated by the French guidelines in 2005, is however highly discussed at the international level. Finally, numerous research studies presently assess the value of targeted therapies and biomarkers in MPM, opening new perspectives in the management of this cancer.

Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study.

No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy. In vitro data suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum-based chemotherapy. Treatment consisted of doxorubicin (60 mg·m⁻²) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed. From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) ≥ 80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3-25%), all in patients with PS 80-100. The best disease control rate was 36% (95% CI 22-51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60-70). Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80-100) patients with refractory or recurrent MM, for which no standard therapy was available.

Treatment of malignant pleural mesothelioma: current status and future directions.

Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.