Julien Guinde

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

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.

Pleuro-pneumopathie révélant une thrombophlébite septique de la veine jugulaire : pensez au syndrome de Lemierre

INTRODUCTION Infection by Fusobacterium necrophorum, a Gram negative anaerobic bacteria, can lead to the development of Lemierres syndrome, an uncommon but potentially fatal infection of the internal jugular vein. Since the introduction of antibiotics, the morbidity and mortality associated with this syndrome have been dramatically reduced. This syndrome is characterized by a pharyngeal infection, which leads to the development of septic thrombophlebitis of the internal jugular vein with septic emboli, which usually spread into the lung. Sometimes the syndrome can be revealed by other unusual clinical symptoms. CASE REPORT We present the case of a young patient with an atypical pleural infection associated with pharyngeal infection and thrombosis from the internal jugular vein. CONCLUSIONS The diagnosis of Lemierres syndrome is mainly clinical, based on a range of suggesting symptoms. Confirmation and monitoring of the condition can be done by ultra-sound and/or contrast enhanced computed tomography. Treatment is based on long-term, high-dose antibiotic therapy and eventually surgical drainage of the infected collection with surgical excision of the internal jugular vein where there is extensive thrombosis. The important message is that in the context of a young patient without comorbidity, who presents with a significant infectious pleurisy, it is important to consider this clinical complication.

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

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.

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

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.

“Kissing Nodules” in Saber-Sheath Trachea

Saber-sheath trachea (SST) was first described by Greene and Lechner in 1975 [1] and is characterized by the reduction of the coronal diameter and elongation of the sagittal diameter of the intrathoracic trachea. SST is most frequently associated with chronic obstructive pulmonary disease (COPD) but can also be seen in bronchiolitis obliterans syndrome following lung transplantation. Despite an unclear pathophysiology, SST seems to be related to the functional severity of airway obstruction and lung hyperinflation [2]. Elevated intrathoracic pressure induces chronic remodeling and bending of the tracheal cartilage rings without causing mucosal damage. STT diagnosis is made when the tracheal index, on computed tomography, is lower than 0.67. This index is defined as the ratio between coronal and sagittal tracheal diameters in the axial plane located 1 cm above the upper edge of the aortic arch. Bronchoscopy confirms the diagnosis and establishes the degree of expiratory collapse. There is no specific treatment for this entity. We present a 71-year-old male patient with severe COPD and uncommon SST in whom the lateral collapse of the cartilages induced chronic and repetitive mucosal contact points. This phenomenon created symmetrical mucosal nodules at the level of each tracheal ring (Fig. 1; online suppl. video, www.karger.com/doi/10.1159/000488246). These nodules are described as metaplasia by the pathologists. a b

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

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.

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

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. Quality of talc pleurodesis and kinetics of pleural symphysis can be evaluated by chest ultrasonography http://ow.ly/8Ejt30jVTjn

Recent developments in pleurodesis for malignant pleural disease: XXXX

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.

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

Abstract 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.

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

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 lamina, 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.