Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review.

INTRODUCTION: New tools such as cryobiopsy of mediastinal lymph nodes (cryoEBUS) have been described to improve the diagnostic usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The literature suggests that this novel procedure could be associated with greater diagnostic usefulness than conventional EBUS-TBNA. METHODS: To develop a systematic analysis and meta-analysis on the diagnostic diagnostic yield and safety of cryobiopsy of hilar and mediastinal adenopathies compared to EBUS-TBNA. RESULTS: Seven studies that had included a total of 555 patients were considered in this review, with 365 (65.7%) of these patients having an etiology of malignant lymph node involvement. The overall diagnostic usefulness of cryoEBUS was higher compared to EBUS-TBNA (92% vs. 80%). However, when the results were analysed according to the specific aetiologies of the adenopathies, cryoEBUS was especially useful in cases of lymphomas or non-pulmonary carcinomas (83% vs. 42%) and in cases that were benign (87% vs. 60.1%), with no significant differences being found in specific cases of lung cancer. For lymphoma, cryoEBUS was diagnostic in 87% of cases compared to 12% for EBUS-TBNA and in addition, also allowed the characterisation of every lymphoma subtype. Genetic studies and immunohistochemical determination of PD-L1 was possible in almost all (97%) of the samples obtained by cryoEBUS, while this was only possible in 79% of those obtained by EBUS-TBNA. The most frequent complication was light bleeding, which was described in up to 85% of cases in some series. CONCLUSION: CryoEBUS could represent a promising technique in the diagnostic algorithm used for mediastinal and hilar involvement. Although cryoEBUS did not significantly improve the diagnosis of lung cancer compared to EBUS-TBNA, the results were significantly better in patients with benign pathologies and other tumour types, including lymphomas. In addition, it seems that the samples obtained by cryoEBUS better defined the histological subtypes of lymphoma and allowed complete molecular characterisation in cases of lung cancer. The technique has proven to be safe and no serious complications were described after the procedure.

Results from a Spanish national survey on the application of ultrasound in pulmonology services.

BACKGROUND: This was an observational, cross-sectional, and multicentre study carried out from October to December 2020, through a survey sent to Spanish Society of Pulmonology and Thoracic Surgery members in public hospitals with different levels of complexity. Our objective was to complete a national analysis of clinical practice, organisation, infrastructure, the services portfolio, teaching, and research activity related to ultrasound. RESULTS: Data from 104 hospitals were analysed. Ultrasound was used in 56.7% of cases, both in the area of bronchopleural techniques and on conventional wards, with no differences between centres. Lung ultrasound (LUS) was performed more often in the procedures area in intermediate-complexity centres compared to high- and low-complexity centres (36% vs. 31% and 6.25%, respectively). More high-complexity centres had three or more ultrasound scanners than intermediate-complexity centres (38% vs. 16%); 43% of low-complexity centres shared their ultrasound equipment with other specialties. Fewer than 6% of centres did not have an ultrasound machine. LUS was most often used during the treatment of pleural effusion (91.3%), in the differential diagnosis of dyspnoea (51.9%), and to rule out iatrogenic pneumothorax (50.9%). Only 5.7% of the centres had a pulmonologist specialised in LUS. Finally, fewer than 35% of the hospitals were teaching centres and fewer than 18% participated in research projects. CONCLUSIONS: The use and availability of LUS has grown in pulmonology services, however, still relatively few pulmonologists are specialised in its use. Moreover, teaching and research activity in this field is scarce. Strategies are necessary to improve physicians' skill at using LUS and to promote its use, with the ultimate goal of improving healthcare activity.

Transbronchial biopsy results according to diffuse interstitial lung disease classification. Cryobiopsy versus forceps: MULTICRIO study.

BACKGROUND: In recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification. OBJECTIVES: We compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient. METHOD: Prospective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB. RESULTS: Included were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB. CONCLUSIONS: Diagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02464592.

Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer.

The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging.

A Pseudo-Outbreak of Pseudomonas putida and Stenotrophomonas maltophilia in a Bronchoscopy Unit.

BACKGROUND: Endoscopes represent the medical devices most commonly linked to health care-associated outbreaks and pseudo-outbreaks. Most of the recent outbreaks and pseudo-outbreaks have resulted from contaminated automated endoscope reprocessors (AER) or the use of damaged or malfunctioning bronchoscopes or contaminated equipment. OBJECTIVES: We investigated a pseudo-outbreak of Pseudomonas putida and Stenotrophomonas maltophilia recovered from bronchial washing (BW) specimens obtained during bronchoscopy in a bronchoscopy unit. METHODS: Samples were obtained from environmental surfaces in the endoscopy suite, bronchoscopes, and bronchoscopic dispensable material, and specimens of cleaning solutions, cleaning brushes, the AER, and the ultrasound system were sent for bacterial culture. Medical records were reviewed to identify possible infections after a bronchoscopy. RESULTS: P. putida and S. maltophilia were isolated from BW samples of 39 patients. The bronchoscopy models Olympus BF-1T160 and BF-160 were contaminated. Both bronchoscopes and other contaminated material (cleaning brushes, diluted cleaning solutions, and the sink) were isolated, but new cases continued to appear. The AER was recently installed, and new connections were used for the water lines and new tubes were connected to the AER. Initially, specimens were obtained from the external circuits and the internal walls of the AER. Finally, cultures were made from the filters on the water lines, and growth of P. putida and S. maltophilia was found. The investigation revealed that the BW specimens were contaminated because sterile saline was injected by means of the biopsy port of the bronchoscope and was recovered through the same channel by means of the proximal suction port. No patients developed clinical signs or symptoms of infection, but the positive cultures did lead to treatment of 21 patients. CONCLUSIONS: We described a pseudo-outbreak related to a contaminated bronchoscope because of inadequate installation of the AER for used new water lines and because the new tubes were connected to the AER. The antibacterial filters of the AER used tap water, and this may have contained low levels of microorganisms. No serious clinical complications derived from this pseudo-outbreak.

Tumor, node and metastasis classification of lung cancer--M1a versus M1b--analysis of M descriptors and other prognostic factors.

INTRODUCTION: The current edition of the tumor, node and metastasis (TNM) classification of lung cancer (LC) divides the presence of metastasis (M1) into two categories: M1a and M1b, depending on its anatomical location. To assess this new classification, the survival and the M descriptors of LC patients with metastatic disease registered by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery II (GCCB-S-II), were analyzed. METHODS: Non-small cell lung cancer (NSCLC) patients, with M1a or M1b disease, included in the GCCB-S-II, from April 2009 to December 2010, staged in accordance with the prospective staging project protocol of the International Association for the Study of Lung Cancer (IASLC), and with complete TNM staging and follow-up data, were studied. The overall survival associated with each M1 category and each M descriptor, besides other prognostic factors (sex, age, performance status [PS] and others) were analyzed by univariate and multivariate models. RESULTS: 640 NSCLC patients (195 M1a and 445 M1b) were included. M1b tumors had significantly worse survival than M1a tumors (p < 0.001). The prognostic value of M1 category was independent from other prognostic variables such as PS, weight loss, and others. The number of metastatic sites (isolated versus multiple) and the number of lesions (single versus multiple) in patients with isolated metastasis showed prognostic value, especially in those with brain metastasis. CONCLUSION: The current division of the M1 category into two subsets (M1a and M1b) is warranted by their prognostic significance. The number of metastatic sites and the number of lesions in patients with isolated metastasis should be taken into account, because they also have prognostic relevance.

The contribution of cell blocks in the diagnosis of mediastinal masses and hilar adenopathy samples from echobronchoscopy.

BACKGROUND: Cell block material from puncture can be obtained with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in many cases. The aim of this study was to analyse the value of additional information from cell blocks obtained with EBUS-TBNA samples from mediastinal and hilar lymph nodes and masses. METHODS: Review of pathology reports with a specific diagnosis obtained from EBUS-TBNA samples of mediastinal or hilar lesions, prospectively obtained over a two-year period. The generation of cell blocks from cytology needle samples, the contribution to morphological diagnosis, and the possible use of samples for immunohistochemistry were analysed. RESULTS: One hundred and twenty-nine samples corresponding to 110 patients were reviewed. The diagnosis was lung cancer in 81% of cases, extrapulmonary carcinoma in 10%, sarcoidosis in 4%, lymphoma in 2.7%, and tuberculosis in 0.9%. Cell blocks could be obtained in 72% of cases. Immunohistochemistry studies on the cell blocks were significantly easier to perform than on conventional smears (52.6% vs. 14%, P<.0001). In 4cases, the cell block provided an exclusive morphological diagnosis (3sarcoidosis and one metastasis from prostatic carcinoma) and in 3carcinomas, subtype and origin could be identified. Exclusive diagnoses from the cell block were significantly more frequent in benign disease than in malignant disease (25% vs 0.9%, P=.002). CONCLUSIONS: Cell blocks were obtained from 72% of EBUS-TBNA diagnostic procedures. The main contributions of cell blocks to pathology examinations were the possibility of carrying out immunohistochemical staining for the better classification of neoplasms, especially extrapulmonary metastatic tumours, and the improved diagnosis of benign lesions.

Viability of lymph node samples obtained by echobronchoscopy in the study of epigenetic alterations in patients with lung cancer.

INTRODUCTION: The diagnosis of microscopic lymph node metastasis in lung cancer is challenging despite the constant advances in tumor staging. The analysis of the methylation status of certain genes in lymph node samples could improve the diagnostic capability of conventional cyto-histological methods. The aim of this study was to demonstrate the feasibility of methylation studies using cytological lymph node samples. METHODS: Prospective study including 88 patients with a diagnosis or strong suspicion of non-small cell lung cancer, in which an echobronchoscopy was performed on mediastinal or hilar lymph nodes for diagnostic and/or staging. DNA was extracted from cytological lymph node samples and sodium bisulfite modification was performed. Methylation studies for p16/INK4a and SHOX2 were accomplished by MS-qPCR and pyrosequencing. RESULTS: The methodology used in our study yielded optimal/good DNA quality in 90% of the cases. No differences in DNA concentration were observed with respect to the lymph node biopsied and final diagnosis. Methylation analyses using MS-qPCR and pyrosequencing were not possible in a small number of samples mainly due to low DNA concentration, inadequate purity, fragmentation and/or degradation as a consequence of bisulfite conversion. CONCLUSION: Methylation quantification using MS-qPCR and pyrosequencing of cytological lymph node samples obtained using echobronchoscopy is feasible if an appropriate DNA concentration is obtained, notably contributing to the identification of epigenetic biomarkers capable of improving decision-making for the benefit of potentially curable lung cancer patients.

The Spanish Society of Pulmonology and Thoracic Surgery Lung Cancer Cooperative Group-II registry. A descriptive study.

INTRODUCTION AND OBJECTIVES: The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included. MATERIALS AND METHODS: Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value. RESULTS: Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages (ia to iib), and 61.6% of those treated using other methods had stage iv. Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%). CONCLUSIONS: The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain.

Intra- and interobserver agreement among bronchial endosonographers for the description of intrathoracic lymph nodes.

Several sonographic features observed by endobronchial ultrasonography have been suggested to be useful to predict malignancy in mediastinal lymph nodes. To evaluate agreement to describe sonographic features, 28 video images were evaluated twice by eight expert bronchoscopists. The observers reviewed each case for the presence of coagulation necrosis sign (CNS), central hilar structure (CHS), heterogeneity, distinct margin, round shape, size >1 cm and malignancy. Intraobserver agreement was almost perfect for size (κ = 0.826), substantial for CNS (κ = 0.721) and shape (κ = 0.615), and moderate for CHS (κ = 0.565), heterogeneity (κ = 0.441) and margin (κ = 0.407). Interobserver agreement was substantial for size (κ = 0.641), moderate for shape (κ = 0.445), and fair for CNS (κ = 0.340) and margin (κ = 0.274). In conclusion, inter- and intraobserver agreement of the endosonographic features for mediastinal or hilar lymph nodes is good for shape or size but not good enough for the other ultrasonographic features.

Intramural hematoma of the pulmonary artery and hemopneumomediastinum after endobronchial ultrasound-guided transbronchial needle aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and effective technique for the sampling of mediastinal and hilar adenopathies. We describe the first reported case of pulmonary artery intramural hematoma after EBUS-TBNA puncture of this artery. The complication was visualized by ultrasound and resolved spontaneously.

Multivariate study of predictive factors for clearly defined lung lesions without visible endobronchial lesions in transbronchial biopsy.

BACKGROUND: Although the diagnostic validity and predictive factors for the diagnostic yield of transbronchial biopsy (TBB) of clearly defined pulmonary lesions with no visible endobronchial lesion have been analyzed in numerous studies, very few have used multivariate analysis techniques to evaluate the validity of TBB as a diagnostic tool or to analyze the independent influence of clearly dependent variables, such as the bronchus sign and lesion size. METHODS: We retrospectively analyzed all cases in which this type of lesion underwent TBB under fluoroscopic control between 2006 and 2008. The analyzed variables included lesion size, localization, the presence of the bronchus sign, and the final result obtained. We performed a descriptive analysis of the TBB results and a multivariate analysis of the predictive factors for the results using logistic regression techniques. RESULTS: A total of 273 patients (206 males, 75.5%) were included in the study. The average lesion diameter was 34 (± 16) mm, with 24% 2 cm or smaller. Twenty-eight percent of the lesions were localized in the lower lobes and 32% in the peripheral third of the lung. The bronchus sign was present in 28% of the patients. Seventy-eight percent of the patients had primary or metastatic malignant lung lesions, the rest were benign lesions of diverse etiology. TBB was diagnostic in 45.4% of cases. In the multivariate analysis, the only independent predictors of outcome were malignant etiology (OR = 4.8; 95% CI = 2.210.4), diameter >20 mm (OR = 3.6; 95% CI = 1.8-7.3), and the presence of the bronchus sign (OR = 2.4; 95% CI = 1.3-4.3). CONCLUSIONS: TBB of lesions clearly delimited without an endobronchial lesion can lead to diagnosis in almost half of the patients. The nature of the lesion, diameter >20 mm, and the presence of the bronchus sign are independent predictors of outcome.

[Pulmonary tuberculosis associated to adalimumab: a study of 3 cases]. / Tuberculosis pulmonar en relación con adalimumab: estudio de 3 casos.

Tumour necrosis factor-alpha antagonist drugs represent a significant advance in the treatment of inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies, and intestinal inflammatory disease. The increase in tuberculosis with infliximab is known, but there is less data available that specifically associates tuberculosis with adalimumab. We present the cases of 2 patients with rheumatoid arthritis and one patient with ankylopoietic spondylitis on treatment with adalimumab, who developed pulmonary and disseminated tuberculosis despite following the screening and prophylaxis measures recommended in guidelines. We also review the association between treatment with tumour necrosis factor-alpha antagonists and tuberculosis.