Stefano Gasparini

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study

BACKGROUND Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

Efficacy predictors of lung volume reduction with zephyr valves in a european cohort

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean±sd change in forced expiratory volume in 1 s (7±20% versus 0.5±19%; p=0.067), cycle ergometry (2±14 W versus -3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 points versus 0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean±sd lobar volume reduction of -80±30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.

Transbronchial and transoesophageal (ultrasound-guided) needle aspirations for the analysis of mediastinal lesions

A tissue diagnosis of mediastinal nodes is frequently needed for accurate lung cancer staging as well as the assessment of mediastinal masses. Transbronchial needle aspiration (TBNA) is a safe procedure that is performed during routine bronchoscopy. Provided mediastinal metastases are confirmed, TBNA has a high impact on patient management. Unfortunately, TBNA remains underused in current daily practice, mainly due to the lack of real-time needle visualisation. The introduction of echo-endoscopes has overcome this problem. Endobronchial ultrasound-guided TBNA (EBUS-TBNA) allows real-time controlled tissue sampling of paratracheal, subcarinal and hilar lymph nodes. Mediastinal lymph nodes located adjacent to the oesophagus can be assessed by transoesophageal ultrasound-guided fine needle aspiration (EUS-FNA). Owing to the complementary reach of EBUS-TBNA and EUS-FNA in assessing different regions of the mediastinum, recent studies suggest that complete and accurate mediastinal staging can be achieved by the combination of both procedures. It is expected that implementation of minimally invasive endoscopic methods of endobronchial ultrasound-guided transbronchial needle aspiration and transoesophageal ultrasound-guided fine needle aspiration will reduce the need for surgical staging of lung cancer significantly.

Safety and Diagnostic Yield of Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Diseases: A Comparative Study versus Video-Assisted Thoracoscopic Lung Biopsy and a Systematic Review of the Literature.

Background: A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. Objectives: The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. Methods: We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). Results: A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11). Conclusion: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.

Sarcoidosis and Cancer Risk : Systematic Review and Meta-analysis of Observational Studies

BACKGROUND An increased cancer risk in patients with sarcoidosis has been suggested, although results are conflicting in a number of case-control and cohort studies. We conducted a systematic review of all available data and performed a meta-analysis to better define and quantify the association between sarcoidosis and cancer. METHODS We searched Medline and Embase for all original articles on cancer and sarcoidosis published up to January 2013. Two independent authors reviewed all titles/abstracts to identify studies according to predefined selection criteria. We derived summary estimates using a random-effects model and reported them as relative risk (RR). Publication bias was evaluated using a funnel plot and was quantified by the Egger test. RESULTS Sixteen original studies, involving > 25,000 patients, were included in the present review. The summary RR to develop all invasive cancers was 1.19 (95% CI, 1.07-1.32). The results for selected cancer sites indicated a significantly increased risk of skin (RR, 2.00; 95% CI, 1.69-2.36), hematopoietic (RR, 1.92; 95% CI, 1.41-2.62), upper digestive tract (RR, 1.73; 95% CI, 1.07-2.79), kidney (RR, 1.55; 95% CI, 1.21-1.99), liver (RR, 1.79; 95% CI, 1.03-3.11), and colorectal cancers (RR, 1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (P = .9), nor for any specific cancer site. CONCLUSIONS The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.

Bronchoscopic Treatment of Emphysema: State of the Art

In recent years, different bronchoscopic techniques have been proposed for the treatment of emphysema, with the aim of obtaining the same clinical and functional advantages of lung volume reduction surgical techniques while reducing risks and costs. Such techniques can be classified into: methods employing devices that block the airways (e.g. spigots and unidirectional valves), methods that have a direct effect on the lung parenchyma (polymeric lung volume reduction, coils and thermal vapor ablation) and procedures that facilitate the expiration of trapped air from the emphysematous lung (airway bypass). This review aimed to evaluate the indications, outcomes and safety of the different techniques, based on the evidence from the available literature. Results obtained by these methods are encouraging, but they are still based mainly on studies with small groups of patients. However, several trials are ongoing and in the near future we will acquire more knowledge which should lead to a better optimization of these procedures. Meanwhile, the bronchoscopic treatment of emphysema cannot yet be considered a standard of care and patients should be treated in the context of clinical trials or controlled registries, with well-defined programs of evaluation and follow-up.

Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study

One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes. Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed. 50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkins lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin’s lymphoma: n=2).No clinically significant procedure-related complications were encountered. This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.

Original Research: Diffuse Lung DiseaseSarcoidosis and Cancer Risk: Systematic Review and Meta-analysis of Observational Studies

BACKGROUND An increased cancer risk in patients with sarcoidosis has been suggested, although results are conflicting in a number of case-control and cohort studies. We conducted a systematic review of all available data and performed a meta-analysis to better define and quantify the association between sarcoidosis and cancer. METHODS We searched Medline and Embase for all original articles on cancer and sarcoidosis published up to January 2013. Two independent authors reviewed all titles/abstracts to identify studies according to predefined selection criteria. We derived summary estimates using a random-effects model and reported them as relative risk (RR). Publication bias was evaluated using a funnel plot and was quantified by the Egger test. RESULTS Sixteen original studies, involving > 25,000 patients, were included in the present review. The summary RR to develop all invasive cancers was 1.19 (95% CI, 1.07-1.32). The results for selected cancer sites indicated a significantly increased risk of skin (RR, 2.00; 95% CI, 1.69-2.36), hematopoietic (RR, 1.92; 95% CI, 1.41-2.62), upper digestive tract (RR, 1.73; 95% CI, 1.07-2.79), kidney (RR, 1.55; 95% CI, 1.21-1.99), liver (RR, 1.79; 95% CI, 1.03-3.11), and colorectal cancers (RR, 1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (P = .9), nor for any specific cancer site. CONCLUSIONS The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.

The role of the pulmonologist in rapid on-site cytologic evaluation of transbronchial needle aspiration: a prospective study.

BACKGROUND Rapid on-site cytologic evaluation (ROSE) of cytologic specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions. ROSE is not a widespread technique, however, because of a lack of time and resources. Our aim was to verify whether, in comparison with a board-certified cytopathologist, a pulmonologist could evaluate the adequacy of transbronchial needle aspiration (TBNA) specimens on-site to diagnose hilar/mediastinal adenopathies/masses after receiving training in cytopathology. Our secondary aim was to assess and compare the accuracy of ROSE as performed by both physicians. METHODS A pulmonologist and a cytopathologist, the latter deemed the gold standard, performed ROSE and classified specimens into five diagnostic categories. Agreement between clinicians was assessed through κ statistics. The accuracy of ROSE was established according to definitive cytologic assessment. RESULTS A total of 362 TBNAs were performed on 84 patients affected by hilar/mediastinal lymphadenopathies. There was an 81% overall substantial agreement between observers (κ, 0.73; 95% CI, 0.61-0.86; P , 0.001), which became excellent in cases of malignant disease (κ, 0.81; 95% CI, 0.70-0.90; P , 0.001). The accuracy of ROSE performed by the pulmonologist (80%; 95% CI, 77-90) was not statistically different from that provided by the cytopathologist (92%; 95% CI, 85-94). CONCLUSIONS Our study provides the first evidence, to our knowledge, that a trained pulmonologist can assess the adequacy of cytologic smears on-site. Training pulmonologists to have a basic knowledge of cytopathology could obviate most difficulties related to the involvement of cytopathologists in routine diagnostic activities and may reduce the costs of the procedure.

It Is Time for This ‘ROSE’ to Flower

tochemistry or microbiological studies, or to repeat the sample using histology needles, if histological material is considered useful for perfecting the diagnosis. A ‘ROSE’ is a fl ower, but it is also the acronym frequently employed to indicate Rapid On-Site Evaluation of the material obtained by needle aspiration techniques; other authors use the less romantic acronym ICA, which stands for Immediate Cytological Assessment [3] . In recent years, in an effort to improve the sensitivity and the diagnostic yield of the needle aspiration techniques, new technologies of guidance have been proposed (endobronchial ultrasound, virtual bronchoscopy, CT fl uoroscopy, 3D navigation systems) [4–6] , but only few papers have focused on the role of correct management, preparation and examination of the sampled material which is an essential point to achieve good results. In 1993, analyzing data from 55 patients who underwent percutaneous fi ne-needle aspiration from a lung lesion suspected for cancer, Austin and Cohen [7] obtained a sensitivity of 100% in 25 cases performed with ROSE and of 80% in 30 cases where the biopsy was performed without the cytopathologist. In the same paper, the metaanalysis of the previously published data showed that the immediate cytological assessment was associated with a statistically signifi cant increase in diagnostic accuracy compared with the procedures performed when a cytopathologist was not present. In 1998, in a series of 207 TBNA performed on 161 patients, comparing 73 aspirates using ROSE with 134 routinely processed samples, Davenport [8] showed that the percentage of specimens containing malignant cells increased from 31 to 56% and that the inadequate TBNA decreased from 56 to 18% In the last decades, needle aspiration techniques have gained ground in respiratory medicine, especially for the diagnosis and staging of lung cancer. Techniques such as percutaneous fi ne-needle aspiration and transbronchial needle aspiration (TBNA) have been demonstrated to be reliable sampling tools in clinical practice. Their use allows cytohistological diagnosis of malignancy and numerous benign conditions with good sensitivity and excellent specifi city, avoiding more invasive surgical procedures such as mediastinoscopy, video-assisted thoracoscopic surgery or thoracotomy [1, 2] . One of the advantages of the cytological aspiration techniques is the possibility to immediately evaluate the material with rapid stain methods to defi ne the adequacy of the sample and to obtain a preliminary diagnosis, if the cytopathologist is present in the diagnostic room. The presence of a cytopathologist during the needle aspiration procedures also ensures that the material will be treated and prepared in the best way. The results obtained by the immediate cytological assessment provides the operator with invaluable information on how to carry on with the procedure that can be stopped if the material is diagnostic, avoiding further and useless passes with the needle, thereby reducing time and risks. On the contrary, if the sample is not diagnostic, other needle passes can be performed by the operator who, on the basis of the information provided by the cytopathologist, could modify the technique of sampling or the point of punction. Furthermore, if required by the immediate assessment and deemed necessary by the cytopathologist, the operator could be invited to sample additional material for ancillary techniques, such as electron microscopy, immunocy-