Randomized Controlled Trial of Urokinase versus Placebo for Nondraining Malignant Pleural Effusion.

RATIONALE: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. MEASUREMENTS AND MAIN RESULTS: Co-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). CONCLUSIONS: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).

Understanding local performance data for EBUS-TBNA: insights from an unselected case series at a high volume UK center.

BACKGROUND: We reviewed the diagnostic performance of endobronchial ultrasound transbronchial aspiration (EBUS-TBNA) on an unselected large cohort of patients who underwent the procedure in our institution in the past 3 years and to compare against published standards and existing literature. METHODS: All consecutive patients who underwent EBUS from January 2013 to December 2015 were included in the retrospective analysis, with a minimum of 6 months of clinico-radiological follow up. For assessing EBUS-TBNA performance, patients were analysed in three subgroups based on the indication for the EBUS-TBNA: in investigation of isolated mediastinal and/or hilar lymphadenopathy (IMHL), in staging of suspected or confirmed non-small cell lung cancer (NSCLC) and in making a tissue diagnosis in suspected thoracic or extrathoracic cancer. For patients subjected to EBUS-TBNA for staging in suspected lung cancer, accuracy of EBUS was measured by its ability to determine the true N2 stage. RESULTS: A total of 1,656 lymph nodes and 138 peribronchial/peritracheal masses were sampled in 940 patients over the study period. The prevalence of reactive lymphadenopathy was 34%. The overall sensitivity to detect pathological disease was 81.6% (95% CI: 74.2-87.6%) whilst NPV was 74.8% (95% CI: 65.2-82.8%). Amongst patients who underwent EBUS-TBNA for staging purposes, the sensitivity for N2 staging was 83.7% (95% CI: 76.2-89.6%) and NPV was 81.6% (95% CI: 73.2-88.2%). The prevalence of N2 disease was 58%. In the subgroup of patients who proceeded to surgical sampling, the sensitivity was higher with the N2/N3 disease prevalence of 67.4%. The sensitivity of EBUS-TBNA to make a tissue diagnosis of thoracic or extrathoracic cancer was 88% (95% CI: 85.1-90.5%) and a NPV of 62% (95% CI: 54.7-69.0%). The disease prevalence was 83.6%. CONCLUSIONS: This retrospective study of a large volume of patients represents real life practice and provides an accurate representation of the typical cohort of patients referred in for EBUS-TBNA to the general respiratory physician in UK. Our study highlights the pitfalls in collecting and analyzing data but also demonstrates how they can be used to improve service performance.