A Prospective Study to Evaluate a Diagnostic Algorithm for the Use of Fluid Lymphocyte Subset Analysis in Undiagnosed Unilateral Pleural Effusions.

BACKGROUND: Haematological malignancy is an important cause of pleural effusion. Pleural effusions secondary to haematological malignancy are usually lymphocyte predominant. However, several other conditions such as carcinoma, tuberculosis, and chronic heart failure also cause lymphocytic effusions. Lymphocyte subset (LS) analysis may be a useful test to identify haematological malignancy in patients with lymphocytic effusions. However, research into their utility in pleural effusion diagnostic algorithms has not yet been published. OBJECTIVES: We aimed to determine the clinical utility of pleural fluid LS analysis and whether it can be applied to a diagnostic algorithm to identify effusions secondary to haematological malignancy. The secondary aim was to evaluate the diagnostic value of pleural fluid differential cell count. METHODS: Consecutive consenting patients presenting to our pleural service between 2008 and 2013 underwent thoracentesis and differential cell count analysis. We proposed an algorithm which selected patients with lymphocytic effusions (>50%) to have further fluid sent for LS analysis. Two independent consultants agreed on the cause of the original effusion after a 12-month follow-up period. RESULTS: A total of 60 patients had samples sent for LS analysis. LS analysis had an 80% sensitivity (8/10) and a 100% specificity for the diagnosis of haematological malignancy. The positive and negative predictive values were 100 and 96.1%, respectively. Overall 344 differential cell counts were analysed; 16% of pleural effusions with a malignant aetiology were neutrophilic or eosinophilic at presentation. A higher neutrophil and eosinophil count was associated with benign diagnoses, whereas a higher lymphocyte count was associated with malignant diagnoses. CONCLUSIONS: LS analysis may identify haematological malignancy in a specific cohort of patients with undiagnosed pleural effusions. A pleural fluid differential cell count provides useful additional information to streamline patient pathway decisions.

The effect of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration biopsies on characterisation of malignant and benign disease. The Bristol experience.

EBUS-TBNA is a recent mediastinal staging and diagnostic technique. We have previously reported superior characterisation with 21G biopsies over 22G biopsies for benign and malignant mediastinal nodes. A new 19G needle now exists but there are limited studies. We hypothesised 19G biopsies would improve both benign and malignant characterisation due to larger samples. We retrospectively analysed sequential patients referred for EBUS-TBNA with unexplained mediastinal adenopathy performed with 19G, 21G and 22G needles respectively (100 patients each). Contingency table analysis was performed.  There were no complications. Sensitivity for malignancy was highest in the 19G group (95.7% versus 94.7% and 87.5%, respectively). The 19G group had higher mean lymph node size (19.4mm versus 18.6mm and 13.5mm, respectively), the highest proportion of lymphoma (9% versus 5% and 0%, respectively), the lowest proportion of NSCLC-NOS (2% versus 12% and 5%, respectively), the highest proportion of subcharacterised benign disease (89.6% versus 69.8% and 37.9%, respectively). This large single centre retrospective UK study suggests the 19G needle appears safe with the suggestion of better sensitivity for malignancy subcharacterisation of benign disease but this requires further study in adequately powered comparative controlled studies with univariate and multivariate analysis.

Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection.

Pleural infection is increasing in incidence. Despite optimal medical management, up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial.A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Secondary outcomes included surgical referral rate, hospital stay and adverse events.35 patients were randomised. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care (median (interquartile range) 32.3% (19.6-43.7%) reduction versus 15.3% (-5.5-28%) reduction) (p<0.04). Significantly fewer patients in the irrigation group were referred for surgery (OR 7.1, 95% CI 1.23-41.0; p=0.03). There was no difference in length of hospital stay, fall in C-reactive protein, white cell count or procalcitonin or adverse events between the treatment groups, and no serious complications were documented.Saline irrigation improves pleural fluid drainage and reduces referrals for surgery in pleural infection. A large multicentre randomised controlled trial is now warranted to evaluate its effects further.

Differentiating benign from malignant mediastinal lymph nodes visible at EBUS using grey-scale textural analysis.

BACKGROUND AND OBJECTIVE: Recent data suggest that grey-scale textural analysis on endobronchial ultrasound (EBUS) imaging can differentiate benign from malignant lymphadenopathy. The objective of studies was to evaluate grey-scale textural analysis and examine its clinical utility. METHODS: Images from 135 consecutive clinically indicated EBUS procedures were evaluated retrospectively using MATLAB software (MathWorks, Natick, MA, USA). Manual node mapping was performed to obtain a region of interest and grey-scale textural features (range of pixel values and entropy) were analysed. The initial analysis involved 94 subjects and receiver operating characteristic (ROC) curves were generated. The ROC thresholds were then applied on a second cohort (41 subjects) to validate the earlier findings. RESULTS: A total of 371 images were evaluated. There was no difference in proportions of malignant disease (56% vs 53%, P = 0.66) in the prediction (group 1) and validation (group 2) sets. There was no difference in range of pixel values in group 1 but entropy was significantly higher in the malignant group (5.95 vs 5.77, P = 0.03). Higher entropy was seen in adenocarcinoma versus lymphoma (6.00 vs 5.50, P < 0.05). An ROC curve for entropy gave an area under the curve of 0.58 with 51% sensitivity and 71% specificity for entropy greater than 5.94 for malignancy. In group 2, the entropy threshold phenotyped only 47% of benign cases and 20% of malignant cases correctly. CONCLUSIONS: These findings suggest that use of EBUS grey-scale textural analysis for differentiation of malignant from benign lymphadenopathy may not be accurate. Further studies are required.

Advances in understanding of the pathogenesis of acute respiratory distress syndrome.

The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. The resulting loss of gas exchange leads to acute respiratory failure and typically catastrophic illness, termed acute respiratory distress syndrome (ARDS), requiring ventilatory and critical care support. There remains a significant disease burden, with some estimates showing 200,000 cases each year in the USA with a mortality approaching 50%. In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.

Foamy Macrophage Deposition in Lymph Nodes Mimicking Lung Cancer Recurrence Diagnosed via Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

The radiological finding of mediastinal lymph node enlargement following surgery for lung cancer often signifies locoregional recurrence. The use of oxidised cellulose haemostatic agents (OCHAs) during staging mediastinoscopy is common. We report a case of 18-fluorodeoxyglucose-avid subcarinal lymphadenopathy in a patient in whom OCHAs had been used at mediastinoscopy 5 months earlier. Histopathological examination of suspected nodal recurrence is facilitated by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The technique is particularly useful after previous mediastinoscopy, when repeat surgical exploration can be challenging. EBUS-TBNA samples showed extensive foamy macrophage deposition, with no evidence of malignancy. The association between the use of OCHAs and subsequent intranodal foamy macrophage deposition is new. Clinicians should consider this possibility in the differential diagnosis of mediastinal lymphadenopathy after surgical exploration, where OCHAs have been left in situ; it remains important to resample the lymph nodes before assuming disease recurrence to prevent unnecessary treatment.

Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score.

BACKGROUND: Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. METHODS: Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. RESULTS: Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). CONCLUSIONS: The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

Impact of needle gauge on characterization of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) histology samples.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive mediastinal node sampling technique used for lung cancer staging and diagnosis of mediastinal lesions. The four published studies assessing sampling with 21-G or 22-G needles conflict. The study objective is to evaluate the diagnostic utility of 21-G versus 22-G EBUS-TBNA needles, and the ability to subcharacterize both benign and malignant lesions using histopathological assessment only. METHODS: A retrospective analysis was performed from 303 patients referred for EBUS-TBNA between January 2011 and July 2013. Sampling needle gauge was selected at the discretion of the operator. Samples were assessed by histopathologists blinded to the needle gauge without rapid on-site evaluation for cytology. Contingency table analysis was performed to compare diagnostic utility and ability to subcharacterize malignant and benign lesions. RESULTS: No difference in diagnostic ability was seen for malignancy (96.6% vs. 95.3% accuracy, 21-G vs. 22-G). Subgroup analysis of benign 21-G tissue samples revealed superior characterization compared with 22-G samples (63/76, 83%, vs. 31/52, 60%, P < 0.01). Characterization of non-small cell lung cancer (NSCLC) was also significantly better with samples obtained with 21-G needles versus 22-G needles (57/65, 88% vs. 34/52, 65%, P < 0.01). CONCLUSIONS: This large UK single-centre study suggests 21-G EBUS-TBNA needles are superior to 22-G in characterizing benign lesions (especially sarcoidosis) and NSCLC when using histopathological assessment. Making a positive benign diagnosis may avoid the need to perform mediastinoscopy. Obtaining sufficient histological material to subcharacterize NSCLC and particularly lung adenocarcinoma allows appropriate testing for genetic mutations facilitating targeted oncological therapy.

Endobronchial ultrasound-guided transbronchial needle aspiration: patient satisfaction under light conscious sedation.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an increasingly used mediastinal sampling technique. Many centres use conscious sedation in an ambulatory setting to optimise the flow of patients, save costs and shorten recovery time. The only EBUS-TBNA patient satisfaction study published so far used deep conscious sedation with propofol. To our knowledge, ours is the largest prospective study evaluating the experience of patients undergoing EBUS-TBNA using light conscious sedation without propofol. OBJECTIVES: To evaluate the patient tolerability of EBUS-TBNA under mild conscious sedation. METHODS: Eighty-two consecutive patients between January 2011 and November 2011 requiring EBUS-TBNA under light conscious sedation for either mediastinal staging of lung cancer or the diagnosis of suspected mediastinal disease due to malignancy or granulomatous disease were invited to complete a questionnaire after the intervention. The collection of data included the diagnostic yield, the number and size of nodes sampled and the dose of sedative medication administered. RESULTS: The average dose of sedative agents administered was 59.4 µg fentanyl and 3.2 mg midazolam. The sensitivity of EBUS-TBNA for the cancer staging, cancer diagnosis and granulomatous disease cohorts was 90.0, 94.1 and 87.5%, respectively. The most commonly reported symptom was a cough in 65 (93%) patients. Of these patients, 46 (71%) described the severity as being mild. All but 9 patients (61/70 or 87%) stated that they would definitely or probably undergo a repeat EBUS-TBNA. CONCLUSIONS: This single-centre UK study confirms that EBUS-TBNA under light conscious sedation is a well-tolerated procedure maintaining the expected diagnostic performance, with patients reporting a high degree of satisfaction with both the test and the information received beforehand.

A Retrospective Analysis of 2-Year Follow-Up of Patients with Incidental Findings of Sarcoidosis.

INTRODUCTION: Sarcoidosis is a multi-system granulomatous disease most commonly involving the lungs. It may be incidentally diagnosed during imaging studies for other conditions or non-specific symptoms. The appropriate follow-up of incidentally diagnosed asymptomatic stage 1 disease has not been well defined. OBJECTIVE: To define the clinical course of incidentally diagnosed asymptomatic stage 1 sarcoidosis and propose an algorithm for the follow-up of these patients. METHODOLOGY: A retrospective case note analysis was performed of all EBUS-TBNA (endobronchial ultrasound-guided transbronchial needle aspiration)-confirmed cases of stage 1 sarcoidosis presenting incidentally to Bristol and Liverpool Interstitial Lung Disease services. Clinical history, serology results, imaging scans, and lung function parameters were examined at baseline, 12, and 24 months. A cost analysis was performed comparing the cost of the current 2-year follow-up guidance to a 1 year follow-up period. RESULTS: Sixty-seven patients were identified as the final cohort. There was no significant change in the pulmonary function tests over the two-year follow-up period. Radiological disease stability was observed in the majority of patients (58%, n = 29), and disease regression was evidenced in 40% (n = 20) at 1 year. Where imaging was performed at 2 years, the majority (69.8%, n = 37) had radiological evidence of disease regression, and 30.2% (n = 16) showed radiological evidence of stability. All patients remained asymptomatic and did not require therapeutic intervention over the study period. CONCLUSIONS: Our results show that asymptomatic patients with incidental findings of thoracic lymph nodal non-caseating granulomas do not progress over a 2-year period. Our results suggest that the prolonged secondary-care follow-up of such patients may not be necessary. We propose that these patients are followed up for 1 year with a further year of patient-initiated follow-up (PIFU) prior to discharge.

Greater physician involvement improves coding outcomes in endobronchial ultrasound-guided transbronchial needle aspiration procedures.

BACKGROUND: Correct coding is essential for accurate reimbursement for clinical activity. Published data confirm that significant aberrations in coding occur, leading to considerable financial inaccuracies especially in interventional procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Previous data reported a 15% coding error for EBUS-TBNA in a U.K. service. OBJECTIVES: We hypothesised that greater physician involvement with coders would reduce EBUS-TBNA coding errors and financial disparity. METHODS: The study was done as a prospective cohort study in the tertiary EBUS-TBNA service in Bristol. 165 consecutive patients between October 2009 and March 2012 underwent EBUS-TBNA for evaluation of unexplained mediastinal adenopathy on computed tomography. The chief coder was prospectively electronically informed of all procedures and cross-checked on a prospective database and by Trust Informatics. Cost and coding analysis was performed using the 2010-2011 tariffs. RESULTS: All 165 procedures (100%) were coded correctly as verified by Trust Informatics. This compares favourably with the 14.4% coding inaccuracy rate for EBUS-TBNA in a previous U.K. prospective cohort study [odds ratio 201.1 (1.1-357.5), p = 0.006]. Projected income loss was GBP 40,000 per year in the previous study, compared to a GBP 492,195 income here with no coding-attributable loss in revenue. CONCLUSIONS: Greater physician engagement with coders prevents coding errors and financial losses which can be significant especially in interventional specialties. The intervention can be as cheap, quick and simple as a prospective email to the coding team with cross-checks by Trust Informatics and against a procedural database. We suggest that all specialties should engage more with their coders using such a simple intervention to prevent revenue losses.

A woman with breathlessness: a practical approach to diagnosis and management.

Worsening breathless in a patient with severe chronic obstructive pulmonary disease (COPD) is a common diagnostic and management challenge in primary care. A systematic approach to history-taking and examination combined with targeted investigation of pulmonary, cardiovascular, thromboembolic and systemic causes is essential if co-morbidities are to be identified and managed. Distinguishing between heart failure and COPD is a particular challenge as symptoms and signs overlap. In low and middle income countries additional priorities are the detection of infections such as tuberculosis and human immunodeficiency virus (HIV). Clinicians need to be alert to the possibility of atypical presentations (such as pain-free variants of angina) and less common conditions (including chronic thromboembolic pulmonary hypertension) in order not to overlook important potentially treatable conditions.

ANCA-negative ANCA-associated vasculitis: pitfalls of the 'vasculitis screen'.

Despite its recognition as an 'ANCA-associated vasculitis' (AAV), eosinophilic granulomatosis with polyangiitis (EGPA) is ANCA negative in up to 60% of cases. Herein, we report the case of a young man with a clinical syndrome highly suggestive of EGPA but with repeated negative ANCA serology, ultimately presenting with cardiac arrest before recognition of the primary systemic vasculitis, whereupon he received successful induction therapy with high dose glucocorticoids and cyclophosphamide. The case illustrates the importance of awareness of ANCA negative AAV among general physicians in order to minimise morbidity and mortality.

Suitability of endobronchial ultrasound-guided transbronchial needle aspiration samples for programmed death ligand-1 testing in non-small cell lung cancer, the Bristol experience.

Treatment for non-small cell lung cancer (NSCLC) is now personalised using molecular mutation testing. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy suitability for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation testing is established. Less is currently known about EBUS-TBNA suitability for PD-L1 (programmed death ligand-1) testing. To assess EBUS-TBNA biopsy adequacy for ALK, EGFR and PD-L1 testing, we conducted a prospective study of 279 consecutive NSCLC patients referred to a tertiary EBUS-TBNA centre in South West England. One hundred eight-four (62.6%) patients were found to have adenocarcinoma, 83 (28.2%) had squamous cell carcinoma, and 27 (9.2%) were identified as NSCLC-not otherwise specified. EGFR testing was successful in 166 of 168 patients (98.8%), ALK testing in all 115 and PD-L1 testing in 43 of 49 patients (88.2%). Previous EGFR and ALK testing did not affect biopsy PD-L1 testing success. PD-L1 testing failures occurred in three of five (60.0%) of 22G needle biopsies, one of five (20.0%) of 21G needle biopsies and two of 39 (5.1%) of 19G needle biopsies, P = .016. EBUS-TBNA biopsies are mostly suitable for PD-L1 testing. Larger needle size may improve PD-L1 (but not EGFR and ALK) testing success but requires further study in a controlled trial.

Is Systemic Anticancer Therapy Associated With Higher Rates of Malignant Pleural Effusion Control in People With Pharmacologically Sensitive Tumors?: A Retrospective Analysis of Prospectively Collected Data.

BACKGROUND: Malignant pleural effusions (MPEs) often cause symptoms, and guidelines recommend early definitive intervention. However, observational data suggest that systemic anticancer treatment (SACT) may control MPE caused by certain pharmacologically sensitive tumors. RESEARCH QUESTION: Is SACT associated with higher rates of MPE resolution in people with pharmacologically sensitive tumors? STUDY DESIGN AND METHODS: This was a retrospective analysis of prospectively collected data from an observational cohort study of people diagnosed with MPE from lung, breast, ovarian, and hematologic malignancy between May 11, 2008, and August 6, 2017. MPE resolution (defined as radiologic resolution with removal of drain or catheter and cessation of interventions) was compared in pharmacologically sensitive (high-grade lymphoma, small cell or target-mutation-positive lung cancer, and hormone-receptor-positive breast or ovarian cancer) and nonsensitive (remainder of cohort) tumors, with and without SACT. Secondary outcomes included time to resolution, 3-month resolution rates, and total pleural interventions. RESULTS: Of 280 patients, 127 had sensitive and 153 had nonsensitive tumors. One hundred seventy-one received SACT, and 109 did not. More patients with sensitive tumors achieved MPE resolution than those with nonsensitive tumors (53/127 [41.7%] vs 42/153 [27.5%]; P = .01), and this occurred predominantly after receipt of SACT. However, hematologic malignancies were overrepresented in the sensitive group, with high rates of SACT use and MPE resolution. After adjustment for this and other confounders, no relationship was found among pharmacologic sensitivity, SACT, and MPE resolution (adjusted OR, 1.4; 95% CI, 0.5-4.1). The strongest predictor of MPE resolution was administration of chemical pleurodesis (adjusted OR, 6.2; 95% CI, 3.3-11.7). In sensitive tumors, MPE resolution occurred without chemical pleurodesis in 14 of 52 patients (26.9%; 95% CI, 15.6%-41.1%) after SACT and in 5 of 22 patients (22.7%; 95% CI, 8.2%-47.2%) without SACT. INTERPRETATION: In this observational study, SACT was not associated independently on MPE resolution in pharmacologically sensitive tumors. Randomized trials are required, but with current data, patients with symptomatic MPE should receive early definitive pleural intervention regardless of underlying tumor or intended treatment.

VEGF in the lung: a role for novel isoforms.

Vascular endothelial cell growth factor (VEGF) is a potent mitogen and permogen that increases in the plasma and decreases in the alveolar space in respiratory diseases such as acute respiratory distress syndrome (ARDS). This observation has led to controversy over the role of this potent molecule in lung physiology and disease. We hypothesized that some of the VEGF previously detected in normal lung may be of the anti-angiogenic family (VEGF(xxx)b) with significant potential effects on VEGF bioactivity. VEGF(xxx)b protein expression was assessed by indirect immunohistochemistry in normal and ARDS tissue. Expression of VEGF(xxx)b was also detected by immunoblotting in normal lung tissue, primary human alveolar type II (ATII) cells, and bronchoalveolar lavage (BAL) fluid in normal subjects and by ELISA in normal, "at risk," and ARDS subjects. The effect of VEGF(165) and VEGF(165)b on both human primary endothelial cells and alveolar epithelial cell proliferation was assessed by [(3)H]thymidine uptake. We found that VEGF(165)b was widely expressed in normal healthy lung tissue but is reduced in ARDS lung. VEGF(121)b and VEGF(165)b were present in whole lung, BAL, and ATII lysate. The proliferative effect of VEGF(165) on both human primary endothelial cells and human alveolar epithelial cells was significantly inhibited by VEGF(165)b (P < 0.01). These data demonstrate that the novel VEGF(xxx)b family members are expressed in normal lung and are reduced in ARDS. A specific functional effect on primary human endothelial and alveolar epithelial cells has also been shown. These data suggest that the VEGF(xxx)b family may have a role in repair after lung injury.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): applications in chest disease.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) offers a minimally invasive option for staging the mediastinum in suspect lung cancer but also in the diagnosis of mediastinal lesions accessible from the airway. This review is aimed at centres considering establishing an EBUS service that may not be so familiar with the technique. It focuses primarily on technical aspects of EBUS-TBNA, training issues, cost considerations, indications, advantages and disadvantages compared with other mediastinal sampling techniques as well as some reference to its performance in clinical studies. In summary, EBUS-TBNA is primarily used for staging non-small cell lung cancer, especially for bulky mediastinal disease and discrete N2 or N3 disease on CT, but also used for the diagnosis of unexplained mediastinal lymphadenopathy. For radical treatment staging, mediastinoscopy is still used at many centres and negative EBUS-TBNA results should be corroborated by mediastinoscopy. In the future, EBUS-TBNA may be used for staging the radiologically normal mediastinum and in re-staging. It is a procedure that can be taught with ease by an experienced operator, has numerous advantages over mediastinoscopy and is potentially cost saving by reducing the number of mediastinoscopies and associated peri-operative support required.