Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

Management of Malignant Pleural Effusion: Where Are We Now?

Pleural malignancies are among the most common causes of pleural disease and form the basis of our daily pleural practice. There has been significant research and increase in both diagnostic and therapeutic management of malignant pleural diseases in the last decade. Good-quality data have led to a paradigm shift in the management options of pleural malignancies, and indwelling pleural catheter is now recommended and widely used as first-line intervention. Several trials compared different treatment modalities for pleural malignancies and continue to emphasize the need to reduce hospital length of stay and unnecessary pleural intervention, and the importance of patient choice in clinical decision making. This practical review aims to summarize the current knowledge for the management of pleural malignancies, and the understanding of the steps that we still have to climb to optimize management and reduce morbidity.

Bifurcated Silicone Stents for the Management of Anastomotic Complications in Lung Transplanted Patients: Ten Years' Experience.

BACKGROUND: In lung transplantation (LT), the actual surgical practice is to cut the donor bronchus as short as possible in order to reduce anastomotic complications (AC). Consequently, the anastomosis is very close to the secondary carina. If AC occur, regular straight stents may be unsatisfactory and on-site modified bifurcated stents may represent an alternative. OBJECTIVES: This retrospective study sought to assess the short- and long-term outcomes of patients treated with customized bifurcated stent (CBS) for the management of AC following LT. METHODS: Data from patients with AC following LT requiring CBS placement between June 2010 and June 2020 were analyzed. RESULTS: Four hundred patients underwent lung transplant. AC requiring airway stenting occurred in 32 patients (8%), and CBS were inserted in 15 patients (3.5%). Indications were stenosis (n = 12; 80%) and bronchial dehiscence (n = 3; 20%). CBS were successfully deployed in 14 patients and failed in 1 patient. No migration was recorded during the follow-up. The median number of complication was 1 per patient (0-5). CBS could be removed in 11 patients (78.6%), and 3 died with their stents in place. AC recurrence or complications requiring new stenting occurred in 4/11 patients (36.3%), with a median time of 7 days (0-29). Seven patients (63.7%) had no AC recurrence, with a median follow-up of 925 days (118-3,249). CONCLUSIONS: The actual surgical anastomotic technique in LT provides new endoscopic challenges. CBS seem ideally positioned to address these difficulties safely and effectively but are associated with stent related complications requiring further endoscopic management.

Comparison between Immunocytochemistry, FISH and NGS for ALK and ROS1 Rearrangement Detection in Cytological Samples.

The detection of ROS1 and ALK rearrangements is performed for advanced-stage non-small cell lung cancer. Several techniques can be used on cytological samples, such as immunocytochemistry (ICC), fluorescence in situ hybridization (FISH) and, more recently, next-generation sequencing (NGS), which is gradually becoming the gold standard. We performed a retrospective study to compare ALK and ROS1 rearrangement results from immunocytochemistry, FISH and NGS methods from 131 cytological samples. Compared to NGS, the sensitivity and specificity of ICC were 0.79 and 0.91, respectively, for ALK, and 1 and 0.87 for ROS1. Regarding FISH, the sensitivity and specificity were both at 1 for ALK and ROS1 probes. False-positive cases obtained by ICC were systematically corrected by FISH. When using ICC and FISH techniques, results are very close to NGS. The false-positive cases obtained by ICC are corrected by FISH, and the true-positive cases are confirmed. NGS has the potential to improve the detection of ALK and ROS1 rearrangements in cytological samples; however, the cost of this technique is still much higher than the sequential use of ICC and FISH.

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

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.

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

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.

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

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 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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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.

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

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.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.

Biodegradable Airway Stents - Bench to Bedside: A Comprehensive Review.

Airway stents are indicated to treat symptomatic narrowing or to close fistulas of the central airways. They are generally divided into two types: the silicone stents and the metallic stents. Unlike in malignancies, removability is a major objective of temporary stenting in benign conditions, which poses the challenge of a new rigid bronchoscopic procedure under general anesthesia and stent removal with all its attendant risks and costs. The concept of a biodegradable (BD) stent that could maintain the patency of an airway for a predetermined duration of time is very appealing. These BD stents would gradually degrade and eventually vanish from the airway once they are no longer needed. Such stents are currently an area of intense research. Another very promising concept of drug delivery with such stents is also a very exciting area of current research. The aim of this comprehensive review is to discuss all pertinent available literature on the use of BD materials in various clinical applications and to extensively review all animal and humans trials involving BD airway stents.

Positron Emission Tomography/Computed Tomography for the Pleural Staging of Malignant Pleural Mesothelioma: How Accurate Is It?

BACKGROUND: Careful clinical staging in patients with malignant pleural mesothelioma (MPM) is fundamental in management planning. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an important staging modality. OBJECTIVES: The purpose of this study was to assess whether the metabolic activity of the pleural tumor detected with PET/CT correlates with specific endoscopic features and pleural distribution of the lesions as assessed by medical thoracoscopy. METHODS: Consecutive patients with MPM and available PET/CT performed before thoracoscopy were separated into 2 groups, according to their standardized uptake value (SUV). Kaplan-Meier-analysis for survival was performed on groups with low and high SUV. Agreement between PET/CT and thoracoscopy evaluation was analyzed using Cohen's kappa coefficient. The Wilcoxon test was used to compare the median SUV, and the χ(2) test was used to evaluate differences in endoscopic findings. RESULTS: A total of 32 patients were included. The median maximum SUV (SUV max) was 6.1 and patients were separated into 2 groups based on this cutoff. Patients with SUV max <6.1 had a better survival than those with SUV max ≥6.1 (p = 0.005). The comparison between PET/CT and thoracoscopy showed a fair agreement for visceral and diaphragmatic pleural involvement and moderate agreement for the presence of nodular lesions. There was a statistically significant association between median SUV max and visceral pleural involvement; nodular lesions and visceral pleural involvement were more common in the high-SUV group than in the low-SUV group (p = 0.0012 and p = 0.03, respectively). CONCLUSIONS: PET/CT data may be predictive of thoracoscopic features of MPM associated with prognosis and staging, but the correlation is moderate at best. A degree of disagreement exists between these two modalities, which supports thoracoscopy as the gold standard for assessment of local invasion in MPM.