Successful factor XIII treatment of refractory chylothorax in tuberous sclerosis complex-associated lymphangioleiomyomatosis, multifocal multinodular pneumocyte hyperplasia and mediastinal lymphadenopathy.

Tuberous sclerosis complex (TSC) or Bourneville disease is a rare autosomal dominant neurocutaneous disorder that affects various organs. Pulmonary involvement in TSC may consist of lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH), occurring together or alone. In patients with TSC-LAM, chylous pleural effusion (CPE) is a rare, though well-recognized, complication with an unpredictable clinical course. In refractory or persistent CPE, optimal management remains a clinical challenge. We report the unique case of a 29-year-old Caucasian female, neversmoker, with definite TSC since infancy, characterized by seizures, facial angiofibromas ("adenoma sebaceum"), bilateral renal angiomyolipomas, hepatic angiomyolipomas, subcortical/cortical tubers, and subependymal nodules. At 27 years old, due to bleeding from the renal angiomyolipomas, she underwent nephrectomy, first of the right, and then a year and 9 months later, of the left kidney. She was hemodialysis dependent for the next five years until cadaveric kidney transplantation. The medical history was also remarkable for recurrent exudative lymphocytic PE despite repeated therapeutic thoracenteses, with first presentation at 23.5 years of age. Chylothorax was initially diagnosed at 24 years and 8 months old (PE triglycerides 4.53 mmol/L), and reconfirmed at age 29 (PE triglycerides 12.46-15.30 mmol/L). Computerized tomography scan of the thorax showed a large encapsulated PE in the left lung field, multiple thin walled cysts (≤ 5 mm in diameter) in the lung parenchyma bilaterally, and mediastinal lymphadenopathy - all prominent features of LAM - as well as nodular pulmonary lesions (≤ 3 mm in diameter) consistent with MMPH. Given the persistent nature of the CPE, a five-day course of recombinant human factor XIII (FXIII) was administered intravenously. The chylothorax completely resolved within three months. There has been no recurrence of CPE on follow-up chest X-rays (i.e., total follow-up period of 53 months). This report suggests that the transglutaminase FXIII, a blood coagulation factor, may have an important clinical benefit in treating recurrent or thoracentesis-refractory CPE in TSC-LAM. To our knowledge, this is the first known case in the literature describing the successful treatment of CPE with FXIII in TSC-LAM. Because CPE is rare and there is currently no gold standard for its management, regardless of etiology, further research is warranted to investigate the potential clinical use of FXIII as an effective and safe treatment strategy in selected patients.

Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

AIM: We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. METHODS: Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. RESULTS: Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). CONCLUSION: Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Differentiating Malignant from Tubercular Pleural Effusion by Cancer Ratio Plus (Cancer Ratio: Pleural Lymphocyte Count).

Background. We performed prospective validation of the cancer ratio (serum LDH : pleural ADA ratio), previously reported as predictive of malignant effusion retrospectively, and assessed the effect of combining it with "pleural lymphocyte count" in diagnosing malignant pleural effusion (MPE). Methods. Prospective cohort study of patients hospitalized with lymphocyte predominant exudative pleural effusion in 2015. Results. 118 patients, 84 (71.2%) having MPE and 34 (28.8%) having tuberculous pleural effusion (TPE), were analysed. In multivariate logistic regression analysis, cancer ratio, serum LDH : pleural fluid lymphocyte count ratio, and "cancer ratio plus" (ratio of cancer ratio and pleural fluid lymphocyte count) correlated positively with MPE. The sensitivity and specificity of cancer ratio, ratio of serum LDH : pleural fluid lymphocyte count, and "cancer ratio plus" were 0.95 (95% CI 0.87-0.98) and 0.85 (95% CI 0.68-0.94), 0.63 (95% CI 0.51-0.73) and 0.85 (95% CI 0.68-0.94), and 97.6 (95% CI 0.90-0.99) and 94.1 (95% CI 0.78-0.98) at the cut-off level of >20, >800, and >30, respectively. Conclusion. Without incurring any additional cost, or requiring additional test, effort, or time, cancer ratio maintained and "cancer ratio plus" improved the specificity of cancer ratio in identifying MPE in the prospective cohort.

Research: Why and how to write a paper?

In this article, an internationally renowned pulmonologist with extensive experience in teaching and publishing gives practical advice to young physicians and/or residents on the importance of doing research, the steps for planning a project and also some do's and don'ts of writing and publishing a scientific paper.

Comparison of polymorphonuclear- and lymphocyte-rich tuberculous pleural effusions.

SETTING: Most patients with tuberculous pleural effusions (TPE) have more than 50% lymphocytes in the pleural fluid. Data on patients in whom polymorphonuclear leukocytes (PMNLs) are the predominant cell type are scarce. OBJECTIVE: To compare the clinical, biochemical, microbiological and radiological characteristics between patients with predominantly PMNL and those with lymphocytic TPE. DESIGN: Retrospective analysis of 214 consecutive patients with TPE. RESULTS: The pleural fluid was PMNL-rich in 24 (11%) cases at the time of first thoracocentesis. Compared with those whose pleural fluid was predominantly lymphocytic, these patients showed a higher yield of mycobacteria in culture of sputum (50% vs. 25%, P = 0.03) and pleural fluid (50% vs. 10%, P < 0.01) on solid media, as well as higher pleural adenosine deaminase (ADA) levels (80 vs. 62 U/l, P = 0.02) at the expense of both ADA1 and ADA2 isoenzymes. A shift towards pleural lymphocytic predominance was observed in more than half of the PMNL-predominant patients subjected to repeat thoracocentesis. CONCLUSIONS: The finding of a predominantly PMNL exudate should not rule out TPE, particularly when pleural ADA activity is elevated. The collection of sputum and pleural fluid samples for mycobacterial culture should be encouraged in the case of suspected PMNL-rich TPE, as they are frequently positive in this early stage.

[Parapneumonic pleural effusions and empyema in adults:current practice]. / Derrame pleural paraneumónico y empiema en adultos: guía práctica.

About 20% of hospitalized patients with bacterial pneumonia have an accompanying pleural effusion. Parapneumonic effusions (PPE) are associated with a considerable morbidity and mortality. The main decision in managing a patient with a PPE is whether to insert a chest tube (complicated PPE). Imaging (i.e., chest radiograph, ultrasound and computed tomography) and pleural fluid analysis (i.e., pH, glucose, lactate dehydrogenase, bacterial cults) provide essential information for patient management. Therefore, all PPEs should be aspirated for diagnostic purposes. This may require image-guidance if the effusion is small or heavily loculated. According to the current guidelines, any PPE that fulfills at least one of the following criteria should be drained: size > or = 1/2 of the hemithorax, loculations, pleural fluid pH < 7.20 (or alternatively pleural fluid glucose < 60 mg/dl), positive pleural fluid Gram stain or culture, or purulent appearance. The key components of the treatment of complicated PPE and empyema are the use of appropriate antibiotics, provision of nutritional support, and drainage of the pleural space by one of the following methods: therapeutic thoracentesis, tube thoracostomy, intrapleural fibrinolytics, thoracoscopy with breakdown of adhesions or thoracotomy with decortication. The routine use of intrapleural fibrinolytic therapy remains controversial. (c) 2009 Elsevier España, S.L. All rights reserved.

Incidence and aetiology of eosinophilic pleural effusion.

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed. We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (< or =40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample. Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.

Antinuclear antibody testing in pleural fluid for the diagnosis of lupus pleuritis.

We sought to determine whether measuring antinuclear antibodies (ANA) and their specificities [dsDNA, extractable nuclear antigens (ENA)] on pleural fluid may contribute to the differential diagnosis of pleural effusions. ANA were tested by indirect immunofluorescence on Hep-2 cells in the pleural fluid of 266 patients with effusions of different etiologies, including 15 lupus pleuritis. The cutoff value for diagnostic use was set at 1:160. Pleural fluid analysis of specific autoantibodies, such as anti-dsDNA and anti-ENA, was also performed if a positive ANA test was obtained. All patients with lupus pleurisy and 16 of 251 (6.4%) patients with pleural effusions secondary to other causes were ANA positive. Fifty-six percent of the positive ANAs in non-lupus pleural fluids were due to neoplasms. The pleural fluid ANA titers were low (< or = 1:80) or absent in two patients with systemic lupus erythematosus (SLE) and effusions due to other factors. Whereas ANA staining patterns in pleural fluid did not help to discriminate lupus pleuritis from non-lupus etiologies, the absence of pleural fluid anti-dsDNA or anti-ENA favored the latter. ANAs in pleural fluid provided no additional diagnostic information beyond that obtained by the measurement in serum and, therefore, these tests need not be routinely performed on pleural fluid samples. However, in patients with SLE and a pleural effusion of uncertain etiology, lack of ANAs or specific autoantibodies in pleural fluid argues against the diagnosis of lupus pleuritis.

Iatrogenic bilateral pneumothorax following unilateral transbronchial lung biopsy.

Bilateral pneumothoraces are recognized complications of thoracic procedures in patients who have undergone heart or heart-lung transplantation. Bilateral simultaneous pneumothoraces developing following a unilateral transbronchial lung biopsy in the absence of previous thoracic surgery has not been reported previously.

Routine use of pleural fluid cultures. Are they indicated? Limited yield, minimal impact on treatment decisions.

In pleural infection, it has been recommended that Gram stain and cultures should be obtained on a routine basis. However, this recommendation has not been tested prospectively. We evaluated the yield of microbiological studies in 259 patients with parapneumonic pleural effusion. Microbiological studies were positive on the pleural fluid of 50 patients (19.3%). In 48 of the 50 patients with positive microbiological results (96%), the need for pleural drainage was correctly predicted by pleural fluid parameters. There were no differences in hospital stay (9.5+/-2.5 days versus 9.9+/-3.2 days, P=0.68) or in mortality (2 deaths in each group, P=0.58) between the group of patients in which antibiotic treatment was changed according to microbiological results and the group of patients in which it is not. In conclusion, this study demonstrates that, at least in our institution, routine microbial investigation of pleural fluid adds very little to the standard management of parapneumonic effusions.

D-dimer levels in pleural effusions.

INTRODUCTION: D-dimer is a degradation product of cross-linked fibrin. We hypothesized that hemorrhagic pleural effusions would have greater D-dimer levels than non-hemorrhagic pleural effusions, and that persistently bloody effusions would be distinguishable from thoracentesis-induced bloody effusions by the D-dimer level. METHODS: Forty pleural effusions were studied. D-dimer levels (measured by ELISA), red blood cell (RBC) count, white blood cell (WBC) count, lactate dehydrogenase (LDH), and protein level was measured for each effusion. Ten effusions, five non-bloody, and five bloody were studied for each of the following disease states: parapneumonic effusion, congestive heart failure, post-coronary artery bypass grafting, and lung cancer. RESULTS: No significant difference of the D-dimer level was noted between bloody and non-bloody effusions of different disease states (P=0.286). There was no significant difference in the median D-dimer levels between all the bloody and all the non-bloody effusions (P=0.88). There was no significant difference (P=0.51) in D-dimer levels between five diseases groups when the bloody and non-bloody fluids were combined. The D-dimer levels did not correlate with the RBC count (r=0.11, P=0.48), WBC count (r=0.13, P=0.53), LDH (r=0.01, P=0.93), or protein levels (r=-0.01, P=0.93) in any of the groups. CONCLUSION: Measurement of pleural fluid D-dimer levels does not distinguish persistently bloody effusions from non-bloody effusions, and does not aid in narrowing the differential diagnosis of an effusion.

Pleural fluid parameters identifying complicated parapneumonic effusions.

BACKGROUND: Controversy exists regarding the clinical utility of pleural fluid parameters as prognosticators of complicated parapneumonic effusions that require drainage. OBJECTIVES: The purpose of this prospective study is to further assess the utility of these parameters in the management of a larger series of parapneumonic effusions and to determine appropriate binary decision thresholds. METHODS: We studied 238 consecutive patients with parapneumonic effusions who underwent diagnostic thoracentesis. RESULTS: We found that pleural fluid pH had the highest diagnostic accuracy (area under the curve, AUC: 0.928; 95% confidence interval, CI: 0.894-0.963) compared with pleural fluid glucose (AUC: 0.835; 95% CI: 0.773-0.897), LDH (AUC: 0.824; 95% CI: 0.761-0.887) or pleural fluid volume (AUC: 0.706; 95% CI: 0.634-0.777). The optimal binary decision threshold for pleural fluid pH identifying complicated effusions requiring drainage was 7.15. Binary, multilevel and continuous likelihood ratios (LRs) for pH were calculated to estimate the likelihood of complication of the pleural effusion. Values for the LRs were compared for each of the three strategies, and relative clinical and statistical significances were assessed. Binary LRs provided significantly less information than continuous strategies. CONCLUSION: The pH has the highest diagnostic accuracy for identifying complicated parapneumonic pleural effusions. The binary decision threshold determining the need for chest drainage is 7.15 in our patient series. We recommend continuous LRs to estimate the post-test probability of the complication as they provide the most information compared with binary LRs. Our results do not support the use of pleural fluid LDH as independent predictor of complicated parapneumonic effusions.

Penetration of clarithromycin in experimental pleural empyema model fluid.

BACKGROUND: The degree of penetration of clarithromycin into the pleural fluid has not been studied. OBJECTIVE: To determine the degree to which clarithromycin penetrates into empyemic pleural fluid using a new rabbit model of empyema. METHODS: An empyema was created via the intrapleural injection of 1 ml turpentine followed 24 h later by instillation of 5 ml (10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg was administered intravenously. Antibiotic levels were determined on samples of pleural fluid and blood samples collected serially over 12 h. Antibiotic levels were estimated using HPLC. RESULTS: The antibiotic penetrated well into the empyemic pleural fluid (AUC(PF)/AUC(serum) ratio of 1.57). The time to equilibration between the pleural fluid and blood antibiotic levels was 8 h. The peak pleural fluid level (Cmax(PF) of 2.88 microg/ml) occurred 1 h (Tmax(PF) of 1 h) after infusion and decreased thereafter. The Cmax(serum) was 3.53 microg/ml at 1 h after administration. CONCLUSION: The levels of clarithromycin in the pleural fluid after intravenous administration are inhibitory for most of the usual pathogens causing empyema. The degree of penetration of clarithromycin should be considered when macrolides are selected for the treatment of patients with empyema.

Penetration of newer quinolones in the empyema fluid.

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema. An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1 x 10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg.kg(-1) for both, i.v.) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC. Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUCPF/AUCblood) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (Cmax,PF) was 2.77 microg.mL(-1) and occurred at a time to maximum pleural fluid concentration (Tmax,PF) of 6 h after infusion and decreased thereafter. The peak blood concentration (Cmax,blood) was 4.81 microg.mL(-1) at 1 h after administration. With levofloxacin, the peak pleural fluid level (Cmax,PF=1.39 microg.mL(-1)) occurred at 6 h (Tmax,PF=6 h) after infusion. The Cmax,blood was 1.88 microg.mL(-1) at 1 h after administration. In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans.

Transforming growth factor-beta induces collagen synthesis without inducing IL-8 production in mesothelial cells.

Conventional pleurodesing agents often provoke acute pleural inflammation followed by fibrosis. The inflammation frequently causes pain and fever. Transforming growth factor (TGF)-beta is a pro-fibrotic but anti-inflammatory cytokine. Intrapleural TGF-beta2 administration produces effective pleurodesis in animals, but its effects on mesothelial cells are unknown. The authors hypothesised that, unlike conventional pleurodesing agents, TGF-beta2 can induce collagen synthesis without stimulating pleural inflammation. In the in vitro studies, TGF-beta2, talc and doxycycline were administered to rabbit mesothelial cells for 24 h. These agents were also injected intrapleurally in rabbits and the induced pleural fluids collected at 24 h. TGF-beta2 was as potent as talc and doxycycline in upregulating mesothelial cell collagen expression. Talc and doxycycline both induced significant increases in interleukin (IL)-8 production from mesothelial cells in vitro and in rabbit pleural fluids in vivo. TGF-beta2, however, did not stimulate mesothelial cell IL-8 release in vitro and induced a dose-dependent suppression of pleural fluid IL-8. Pleural fluid IL-8 levels correlated significantly with leukocyte and lactate dehydrogenase concentrations in the fluids. In summary, transforming growth factor-beta was a potent inducer of mesothelial cell collagen synthesis. Unlike talc and tetracycline, which provoked pleural inflammation, transforming growth factor-beta2 suppressed pleural inflammation in vivo. Transforming growth factor-beta2 can produce effective pleural fibrosis without necessitating acute pleural inflammation.

Prognostic features of residual pleural thickening in parapneumonic pleural effusions.

The objective of the study was the identification of predictive factors for the development of residual pleural thickening (RPT) in patients with parapneumonic effusion. The design of the prospective study involved investigating patients with parapneumonic pleural effusions diagnosed between March 1991 and December 2000 in the respiratory department of Hospital Ramón y Cajal (Madrid, Spain) which is a 1,500 tertiary-care hospital. The clinical and radiological characteristics and measurements of microbiological and biochemical variables in the pleural fluid taken from the patients were studied. RPT was defined in a posteroanterior chest radiograph as pleural thickening of > or = 10 mm measured at the lateral chest wall at the level of an imaginary line, tangent to the diaphragmatic dome. A total of 48 of the 348 patients studied (13.79%) were found to have RPT. Among the factors studied, only presence of pus in the pleural space, Fine classes IV and V, temperature > or = 38 degrees C and delayed resolution of pleural effusions after diagnosis (> 15 days) were independently associated with the risk of RPT. This study showed that significant residual pleural thickening was not a common complication of parapneumonic pleural effusions. There are certain risk factors for the development of residual pleural thickening. However, this complication was not associated with long-term functional repercussions in the series of patients involved in this study.

Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions.

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count > 50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n = 221), idiopathic effusions (n = 76), parapneumonic effusions (n = 35), postcoronary artery bypass graft surgery effusions (n = 6), miscellaneous exudative effusions (n = 21) and transudative effusions (n = 51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U x L(-1)) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADA(p) correctly classified these lymphocytic effusions as nontuberculous (ratio < 0.42). This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level < 40 IU x L(-1) virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminase(p) correctly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.

Determining the optimal number of specimens to obtain with needle biopsy of the pleura.

The aim of this study was to define the number of pleural biopsy samples necessary for optimum diagnostic performance and determine to what extent they are complementary. Eighty-four closed pleural biopsies were performed in our department between June 1996 and January 1998 on 55 males and 29 females with an average age of 64.4 +/- 16.7 years. The study of the pleural fluid included: pH, biochemical testing of pleura/serum (proteins, lactate dehydrogenase, glucose, cholesterol, triglycerides, albumin and adenosine deaminase), haemogram, cytology and microbiological testing (Gram-staining, aerobes, anaerobes and mycobacteriae cultures). The biopsies were performed using a Cope needle, with a total of five biopsies for each patient: four for pathological examination (taken numerically in the order in which they were performed: D1, D2, D3 and D4) and one for microbiological testing. In those cases in which the diagnosis was uncertain or effusion persisted, a thoracoscopy or thoracotomy was performed. There were no significant differences in the diagnostic yield of each individual sample (D1, D2, D3 and D4), but there were differences in the sum of the samples, depending on the number of biopsies performed.This was true for total group and the group with carcinomas, but not for the group with tuberculosis. The increase in diagnostic yield with the number of biopsies was more remarkable in the carcinoma cases, where it increased by 35% when four biopsies were performed (54% with one biopsy versus 89% with four biopsies, P < 0.002). In conclusion, the diagnostic yield increased with the number of biopsy samples in the total group and the group with malignancy but not in the group with tuberculous effusions. The best diagnostic performance for malignant pathology was obtained with four samples. In pleural tuberculosis, the diagnostic yield did not increase with more biopsy samples. One high quality sample should be enough to obtain a diagnosis.