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Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study Navani et al Thorax 2011. Journal Club 17/08/16 Matt Dickson ST3. Introduction . Background
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Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre studyNavaniet al Thorax 2011 Journal Club 17/08/16 Matt Dickson ST3
Introduction • Background • Tuberculous intrathoracic lymphadenopathy • EBUS TBNA • Aims and Method • Results • Discussion of findings • Limitations of study
Tuberculous intrathoracic lymphadenopathy • Incidence of TB has decreased since peak of 2011 • 2013 – 7855 (12.3 per 100,000)1 • 2014 – 6520 (12 per 100,000) 2 • Proportions of pulmonary and extra-pulmonary TB notifications shifting • Proportion of extra-pulmonary TB increasing • Intrathoracic TBLA: • 2013 – 916 • 2014 – 863 • Treated for 6 months with anti-tuberculous antibiotics (2 months quadruple therapy)
Importance of establishing firm diagnosis • Multiple causes of mediastinal lymphadenopathy • Bronchoscopy/sputum culture have low yield for isolated mediastinal TB3 • Isolating organism allows susceptibility testing • Avoid suboptimal/unnecessary antituberculous treatments • Intrathoracic TBLA may not alter radiologically on successful treatment (may even increase) • EBUS TBNA, conventional TBNA, EUS TBNA and mediastinoscopy
Endobronchial Ultrasound Guided TBNA • Alternative to conventional transbronchial needle aspiration, endoscopic ultrasound guided TBNA or mediastinoscopy • Less morbidity associated vs mediastinoscopy • More nodes/smaller nodes (<10mm) accessible • Outpatient procedure • Improves yield in lung cancer/sarcoidosis compared to standard bronchoscopic techniques
Aims and Method • The role of EBUS-TBNA in the diagnosis of intrathoracic TBLA not been established • Establish the diagnostic utility in this setting • Multicentre, retrospective study • Consecutive patients referred for EBUS between 1/1/08 and 1/2/10 • Excluded from study if: • Sputum/bronchial washing positive for AFBs prior to EBUS • Diagnosis available from sampling extrathoracic disease • Final diagnosis made by: • Positive pathology • Positive microbiology • Unequivocal clinical/radiological response to treatment • Demographic data and HIV status recorded • Patients followed up for 6 months
Intervention • CT Thorax • Outpatients, LA, midazolam and fentanyl • Same model of endo-bronchoscope used • Location, number and size of TBLA recorded • 22 or 21 gauge aspiration needle used • Two centres – on site evaluation of samples to influence number of passes • Other centres – at least 3 passes per node • Smear samples prepared • Samples expelled into formalin for cell block analysis • Samples from at least one pass sent for microbiological analysis
Assessment of samples • Pathological findings classified into five grades I) epithelioid granulomatous reaction with caseation II) epithelioid granulomatous reaction without caseation III) non-granulomatous reaction with necrosis IV) non-specific V) inadequate sample • I-III consistent with a diagnosis • Microbiological investigations considered positive for TB if: • smear positive for acid-fast bacilli • culture-isolated Mycobacterium tuberculosis
Statistical analysis • Sensitivity calculated • Predictors of a positive culture for TB were modelled using logistic regression • Significant variables in univariate analysis or those deemed clinically important were included in the multivariate model • Interactions were assessed for all covariates considered for inclusion in the multivariate analysis by including interaction variables in the multivariate model to see if the model could be improved • No questions please…
Results • 156 patients from 4 centres • Median age was 39 (range 18-86) • 51:49 Male to Female • Most common symptom was cough (60%) • Nodes of median size of 22mm (range 5-60mm) • Station 7 most commonly sampled • 39% of patients had ≥2 stations sampled
Results (2) • EBUS TBNA diagnostic in 94% (146) • Pathological assessment: • Findings consistentwith TB in 134 patients (86%); • 68 (44%) had granulomas with necrosis, • 58 (37%) had granulomas without necrosis • 8 (5%) had necrosis alone • 19(12%) had lymphocytes alone • 3 (2%) the sample was inadequate • Microbiological assessment: • Findings diagnostic of TB in 82 (53%) patients • 27 (17%) smear positive for AFBs • 74 (47%) had a positive culture, with a median time to positive culture of 16 days • 8 (5%) positive for AFBs but the culture was negative • 8 (5%) proven to have isoniazid-resistant TB • 15 (10%) pathology was negative, but firm diagnosis of TB was obtained on auramine/ZiehlNeelsenstain or culture
Results (3) • Presence of necrosis on pathology/sampling more than one lymph node both significant - may be associated with a positive culture • A significant interaction found between lymph node size and necrosis on pathology - positive culture less likely to occur in larger nodes with necrosis • No other significant interactions were identified • 10 (6%) did not have a specific diagnosis following EBUS-TBNA. • 4/10 underwent mediastinoscopy (all confirmed TB) • Remaining 6/10 received empirical treatment • One patient developed sepsis 2 days post-procedure
Discussion • 94% sensitivity • 47% had positive culture (similar to rates from other sites) • Slightly better sensitivity compared to EUS TBNA (90-93%)4,5 • Benefit of sampling right paratracheal and hilar nodes (47% of stations sampled in this study) • Can perform bronchial washings • EBUS procedures which obtained necrotic granulomas or necrosis alone were more likely to have a positive culture for TB
Limitations • High level of experience in EBUS in centres involved • Pathology consistent with TB (I-III), despite positive tuberculin/interferon gamma release assay may be sarcoidosis • Statement that 94% diagnostic is possibly misleading • Any difference is needle gauge used
References • 1. Public Health England: Tuberculosis (TB) in the UK: annual report data up to 2013 • 2. Public Health England. Tuberculosis in England 2015 report: presenting data from 2014 • 3. Codecasa LR, Besozzi G, De CL, et al. Epidemiological and clinical patterns of intrathoracic lymph node tuberculosis in 60 human immunodeficiency virus-negative adult patients. Monaldi Arch Chest Dis 1998;53:277e80 • 4. PuriR, Vilmann P, Sud R, et al. Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy. Endoscopy 2010;42:462e7. • 5. Song HJ, Park YS, Seo DW, et al. Diagnosis of mediastinal tuberculosis by using EUS-guided needle sampling in a geographic region with an intermediate tuberculosis burden. GastrointestEndosc 2010;71:1307e13.