Maribel Botana-Rial

The Endobronchial Ultrasound-Guided Transbronchial Needle Biopsy Learning Curve for Mediastinal and Hilar Lymph Node Diagnosis

The learning curve required for the endobronchial ultrasoundguided transbronchial needle biopsy (EBUS-TBNA) of mediastinal or hilar lymph nodes is unclear, and the evidence is scarce and contradictory. 1 4 Two of the evidentiary studies 2 , 3 only analyzed the learning curve of EBUS-TBNA for lung cancer diagnosis and staging and did not include the use of this technique in the study of lymph nodes affected by other pathologies. Other factors that might be infl uenced by learning have also not been examined. 2 4 To address these issues, we conducted a prospective study to describe the learning curve of an experienced bronchoscopy team in a unselected sample of patients with mediastinal or hilar lymph nodes. Team performance was analyzed not only in terms of the diagnostic yield of the procedure, but also to evaluate procedure length, number of lymph node passes performed to obtain adequate samples, and number of lymph nodes studied per patient. We included unselected consecutive patients with mediastinal or hilar lymph node . 10 mm in the short axis on CT scan or . 5 mm in the presence of PET scan-positive uptake. The study involved a team of two bronchoscopists with . 10 years experience in diagnostic bronchoscopy, including conventional transbronchial needle biopsy. The bronchoscopists had previously conducted extensive theoretical training and several practical workshops and performed between fi ve and 10 supervised procedures. The learning curve was evaluated by analyzing consecutive groups of 20 patients, the number of adequate samples obtained, and the diagnostic accuracy of the procedure. We also recorded the other variables shown in Table 1 . Over a period of 13 months, EBUS-TBNA was performed for 215 lymph nodes in 120 patients (71 with lung cancer, 16 with extrapulmonary carcinomas, seven with lymphomas, and 26 with several nonmalignant pathologies). Table 1 shows these values in groups of 20 consecutive patients. No serious complications were reported. The present study demonstrated that the diagnostic effectiveness of EBUS-TBNA clearly improved with an increasing number of procedures performed, allowing for access to a greater number of lymph nodes without increasing the length of the procedure by reducing the number of punctures in each nodal station. Analyzing the studies included in systematic reviews and published meta-analyses, 5 , 6 the diagnostic accuracy of EBUS-TBNA is between 85% and 98%. Accordingly, and based on our fi ndings, we could argue that the minimal diagnostic yield is achieved with procedure 60 but can be improved and even reach optimal results after 100 patients. We hope that this study and others in the same line help scientifi c societies to establish specifi c recommendations for learning linear EBUS-TBNA. 1 , 7

N-acetyltransferase 2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians.

OBJECTIVE To analyse slow-acetylation N-acetyltransferase 2 (NAT2) polymorphisms for their association with the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH). DESIGN A case-control study including Caucasian patients with tuberculosis (TB) treated with isoniazid, rifampicin and pyrazinamide. NAT2 genotype results were compared between ATDH cases and controls and with a healthy Spanish control population of Caucasian origin. RESULTS Fifty cases and 67 controls were included in the study. Slow, intermediate and rapid NAT2 genotypes were found in respectively 72%, 18% and 10% of cases compared with 65.7%, 25.4% and 9% of controls (P> 0.05). On comparing NAT2 genotypes among cases with those among healthy controls (n = 1312), we found more slow NAT2 genotypes and fewer intermediate genotypes among cases (respectively 72% and 18% in cases vs. 54.8% and 38.1% in controls; OR 2.07, 95%CI 1.12-2.79, P = 0.016 and OR 0.37, 95%CI 0.18-0.75, P = 0.003). CONCLUSIONS We could not demonstrate an increased risk of ATDH related to the presence of slow NAT2 polymorphisms among this Caucasian TB cohort. However, we found a significantly greater frequency of slow and a significantly lower frequency of intermediate NAT2 genotypes among the ATDH cases compared with the healthy control population.

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.

Calprotectin: a novel biomarker for the diagnosis of pleural effusion

Background:Novel non-invasive biomarkers for the precise diagnosis of malignancy in pleural effusion (PE) are needed. The aim of this study was to determine the diagnostic accuracy of calprotectin for predicting malignancy in patients with exudative PE.Methods:Calprotectin concentration was measured in 156 individuals diagnosed with exudative PE (67 malignant and 89 benign). Calprotectin accuracy for discriminating between malignant and benign PE was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression were performed to test the association between calprotectin levels and malignant PE.Results:Calprotectin levels were significantly lower in malignant pleural fluid (257.2 ng ml−1, range: 90.7–736.4) than benign effusions (2627.1 ng ml−1, range: 21–9530.1). The area under the curve was 0.963. A cutoff point of ⩽736.4 ng ml−1 rendered a sensitivity of 100%, with a specificity of 83.15%, which could prove useful to delimit those patients with negative cytology tests that should be referred for more invasive diagnostic procedures. Logistic regression demonstrated a strong association between calprotectin and malignancy (adjusted OR 663.14).Conclusion:Calprotectin predicts malignancy in pleural fluid with high accuracy and could be a good complement to cytological methods.

Screening for Chronic Obstructive Pulmonary Disease: Validity and Reliability of a Portable Device in Non-Specialized Healthcare Settings

Introduction and Objectives The underdiagnosis of chronic obstructive pulmonary disease (COPD) could be improved through screening using portable devices simpler than conventional spirometers in specific healthcare settings to reach a higher percentage of the at-risk population. This study was designed to assess the validity and reliability of the COPD-6 portable device to screen for COPD in non-specialized healthcare settings. Methods Prospective cohort study to validate a diagnostic test. Three cohorts were recruited: primary care (PC), emergency services (ES) and community pharmacies (CPh). Study population: individuals with risk factors for COPD (>40 years, smoking >10 pack-years, with respiratory symptoms). The values measured using the COPD-6 were FEV1, FEV6 and the FEV1/FEV6 ratio. Subsequently, participants underwent conventional spirometry at hospital, using a post-bronchodilator FEV1/FVC value <0.7 as the gold standard criterion for the COPD diagnosis. Results 437 participants were included, 362 were valid for the analysis. COPD was diagnosed in 114 patients (31.5%). The area under the ROC curve for the COPD-6 for COPD screening was 0.8.The best cut-off point for the FEV1/FEV6 ratio was 0.8 (sensitivity, 92.1%) using spirometry with the bronchodilator test as the gold standard. There were practically no differences in the COPD-6 performancein the different settings and also regarding age, gender and smoking status. Conclusions The COPD-6 device is a valid tool for COPD screening in non-specialized healthcare settings. In this context, the best cut-off point for the FEV1/FEV6 ratio is 0.8.

Thoracic Ultrasound-Assisted Selection for Pleural Biopsy With Abrams Needle

BACKGROUND: Closed pleural biopsy (CPB) in patients with malignant pleural effusion is less sensitive than cytology. Ultrasound-assisted CPB allows biopsies to be performed in the lower thoracic parietal pleura, where secondary spread from pleural metastases is initially more likely to be found. We analyzed whether choosing the point of entry for CPB with thoracic ultrasound assistance influences the diagnostic yield in malignant pleural effusion. METHODS: This prospective study included patients who underwent CPB performed by an experienced pulmonologist in 2008–2010 (group A) and thoracic ultrasound was used to select the biopsy site. The results were compared with a historical series of CPB performed by the same pulmonologist without the assistance of thoracic ultrasound (group B). An Abrams needle was used in all cases. We analyzed the obtaining of pleural tissue and the diagnostic yield. RESULTS: We included 114 CPBs from group A (23% tuberculous pleural effusion, 27% malignant pleural effusion) and 67 CPBs from group B (24% tuberculous pleural effusion, 30% malignant pleural effusion) (P = .70). Pleural tissue was obtained in 96.5% of the group A CPBs and 89.6% of the group B CPBs (P = .05). The diagnostic yields of CPB for tuberculous pleural effusion and malignant pleural effusion in group A were 89.5% and 77.4%, respectively, and 91.7% and 60%, respectively, in group B (P = .80 for tuberculous pleural effusion, and P = .18 for malignant pleural effusion). CONCLUSIONS: Selecting the point of entry for CPB using thoracic ultrasound increases the likelihood of obtaining pleural tissue and the diagnostic yield, but without statistical significance. We recommend ultrasound-assisted CPB to investigate pleural effusion, since the diagnostic yield of a pleural biopsy with an Abrams needle increased by > 17% in subjects with malignant pleural effusion.

Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARβ in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.

Update in the extraction of airway foreign bodies in adults

Foreign body (FB) aspiration into the airway is lees common in adults than children. Nevertheless its incidence does not decrease through time. We present clinical relevant aspects of airway FBs on the basis of a selective review of pertinent literature retrieved by a search in the PubMed database. The most common aspirated FBs by adults are organics, especially fragments of bones and seeds. Symptoms usually are cough, chocking and dyspnea. Right localization, especially bronchus intermedius and right lower lobe, is more frequent. Chest radiography can be normal in up to 20% of the cases and FBs can be detected in 26% of the patients. FBs can safely remove in the majority of patients under flexible bronchoscopy. Surgical treatment must be reserved for cases in which bronchoscope fails or there are irreversible bronchial or lung complications.

Aportación del bloque celular en el diagnóstico de adenopatías y masas mediastínicas o hiliares realizado por ecobroncoscopia

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.

Endobronchial fibroepithelial polyp.

Benign polypoid lesions are an uncommon finding on bronchoscopic examination. The histopathologic fibroepithelial subtype is very rare in this location. In this report, we describe a 77-year-old man diagnosed with a fibroepithelial polyp located at the bifurcation of the left main bronchus; this was completely removed using flexible bronchoscope.