Role of Medical Thoracoscopy and Closed-Blind Pleural Biopsy in Undiagnosed Exudative Pleural Effusions

Maturu, Venkata Nagarjuna; Dhooria, Sahajal; Bal, Amanjit; Singh, Navneet; Aggarwal, Ashutosh N.; Gupta, Dheeraj; Behera, Digamber; Agarwal, Ritesh

doi:10.1097/lbr.0000000000000145

Cited by 53 publications

(41 citation statements)

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“…Estimation of adenosine deaminase or interferon gamma and detection of the mycobacterial genome in pleural fluid are used as diagnostic surrogates (2). Pleural biopsies may improve the diagnostic yield; however, these procedures are invasive, require expertise, and are not free from complications (3)(4)(5).…”

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Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

et al. 2015

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The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active extrapulmonary tuberculosis. We systematically evaluated the diagnostic performance of blood-and pleural fluid-based IGRAs in tuberculous pleural effusion (TPE). We searched the PubMed and Embase databases for studies evaluating the use of commercially available IGRAs on blood and/or pleural fluid samples for diagnosing TPE. The quality of the studies included was assessed through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity with 95% confidence intervals (95% CI) were generated using a bivariate random-effects model and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Indeterminate IGRA results were included for sensitivity calculations. Heterogeneity was explored through subgroup analysis and meta-regression based on prespecified covariates. We identified 19 studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14 evaluations, respectively, of whole-blood and pleural fluid assays, involving 1,085 and 727 subjects, respectively. There was only one good-quality study, and five studies used nonstandard assay thresholds. The pooled sensitivity and specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95% CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to 0.87), respectively. There was considerable heterogeneity; however, multivariate meta-regression did not identify any covariate with significant influence. There was no publication bias for blood assays. We conclude that commercial IGRAs, performed either on whole-blood or pleural fluid samples, have poor diagnostic accuracy in patients suspected to have TPE.T uberculosis (TB) is a common etiology of pleural effusion, especially in developing countries (1). A definitive microbiological diagnosis is achieved by tuberculous pleural effusion (TPE) in only a few patients, and the diagnostic accuracy of other pleural fluid investigations is suboptimal (1, 2). Estimation of adenosine deaminase or interferon gamma and detection of the mycobacterial genome in pleural fluid are used as diagnostic surrogates (2). Pleural biopsies may improve the diagnostic yield; however, these procedures are invasive, require expertise, and are not free from complications (3-5).In recent years, interferon gamma release assays (IGRAs) have emerged as an immunodiagnostic tool to detect tuberculous infection. IGRAs quantify interferon gamma released by T-lymphocytes in response to stimulation by specific antigens encoded in region of difference 1 (RD1) of the Mycobacterium tuberculosis genome. An enzyme-linked immunosorbent spot (ELISpot) assay (T-SPOT.TB; Oxford Immunotec Limited, United Kingdom) and an enzyme-linked immunosorbent assay (ELISA) (QuantiFERON; Cellestis Limited, Australia) are commercially avail...

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Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

et al. 2015

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“…However, conventional methods have been shown to have lower sensitivity and are inadequate (12). Although thoracoscopy and thoracotomy present approximately 90% diagnostic sensitivity for malignant patients (13), they are expensive and have a risk of death (14). The use of TMs offers the potential for a cost-effective and minimally invasive alternative in the diagnosis of pleural malignancy.…”

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Diagnostic accuracy of tumor markers for malignant pleural effusion: a derivation and validation study

Zhai¹,

Wang²,

Wang³

et al. 2017

J. Thorac. Dis.

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Background: The utility of tumor markers (TMs) for differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) has been a subject of controversy. The majority of published studies are single center designed and lack validation. We performed a derivation and validation study in China to evaluate the diagnostic value of carcinoembryonic antigen (CEA) as well as carbohydrate antigen (CA) 15-3, CA 19-9 and CA 125 to differentiate between MPE and BPE. Methods: Three hundred and twenty seven pleural effusion (PE) and paired serum samples were collected from consecutive patients with MPE or BPE in Beijing (174 patients, derivation) and Wuhan (153 patients, validation) during the same period. The concentrations of four TMs were tested using chemiluminescent microparticle immunoassay technology. The performance of the TMs was analyzed by standard receiver operating characteristic (ROC) curves. Results: The levels of four TMs were significantly higher in MPE than in BPE and the corresponding serum. The concentrations of CEA and CA 15-3 were more stable than the concentrations of CA 125 and CA 19-9. CEA was the best single marker for discriminating MPE from BPE. With a specificity of 100% in the total population, the highest sensitivity (37.8%) using serum was found in CEA. In addition, CEA presented 19.8% sensitivity in PE and 18.0% sensitivity in the ∆(PE-serum). For CA 15-3, the sensitivity was 32.4% in PE, 15.3% in the PE/serum ratio and 25.2% in the ∆(PE-serum).Conclusions: CEA and CA 15-3 rather than CA 125 and CA 19-9 are more reliable to differentiate between MPE and BPE. The use of the ∆(PE-serum) value in TMs, such as CEA and CA 15-3, may improve the sensitivity and specificity of the diagnosis etiology of PE.Keywords: Pleural effusion (PE); tumor marker (TM); diagnosis; carcinoembryonic antigen (CEA); CA 125; CA Submitted Jan 13, 2017. Accepted for publication Aug 15, 2017Aug 15, . doi: 10.21037/jtd.2017 View this article at: http://dx.doi.org/10.21037/jtd.2017.11.62 5221 Journal of Thoracic Disease, Vol 9, No 12 December 2017 © Journal of Thoracic Disease. All rights reserved.J Thorac Dis 2017;9(12):5220-5229 jtd.amegroups.com IntroductionMalignant pleural effusion (MPE) is frequently observed in some malignancies, implying systemic spread of cancer and reduction of life expectancy and quality (1). The initial diagnostic approaches to differentiation between benign pleural effusions (BPEs) and MPEs include thoracocentesis and cytological, histological and biochemical examinations; however, the sensitivity of these non-invasive techniques is only 40-70% (2). Many studies have investigated the usefulness of a number of tumor markers (TMs), including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3, and CA 19-9, in pleural fluid for the diagnosis of MPE (3). Our previous meta-analyses indicated that current evidence does not recommend using a single TM for the diagnosis of MPE; a combination of two or more TMs seemingly is more sensitive (4,5). We, along with oth...

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“…The true sensitivity of Xpert MTB/RIF is expected to lie somewhere between the two estimates when an ideal reference standard such as thoracoscopic biopsy specimens with histopathology is used (4,5). The specificity of Xpert MTB/RIF was very high with either reference standard, making it an excellent "rule-in" test.…”

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“…Currently, the best tool for diagnosing TPE is a thoracoscopic pleural biopsy, an invasive procedure, with sensitivity ranging from 93 to 100% (2)(3)(4)(5). The most widely used diagnostic test for TPE is the pleural fluid adenosine deaminase (ADA) level, which has variable sensitivity ranging from 47 to 100% (6).…”

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Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis

et al. 2016

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A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE.T uberculous pleural effusion (TPE) is the second most common site of extrapulmonary tuberculosis (EPTB) (1). Currently, the best tool for diagnosing TPE is a thoracoscopic pleural biopsy, an invasive procedure, with sensitivity ranging from 93 to 100% (2-5). The most widely used diagnostic test for TPE is the pleural fluid adenosine deaminase (ADA) level, which has variable sensitivity ranging from 47 to 100% (6). The sensitivities of pleural fluid microscopy and culture in TPE are about 10% and 20%, respectively (5, 7, 8). The absence of a simple reference standard makes the treatment of TPE empirical (nonmicrobiological) in most circumstances.Xpert MTB/RIF (GeneXpert) has not only high sensitivity and specificity in smear-positive pulmonary tuberculosis (TB) (98% and 98%, respectively) but also reasonable diagnostic performance in smear-negative pulmonary tuberculosis (67% and 99%, respectively) (9). However, a recent meta-analysis reported the pooled sensitivity and specificity of GeneXpert in TPE as 46.4% and 99.1%, respectively, compared with those of pleural fluid mycobacterial culture (10). Since then, several new studies evaluating GeneXpert in TPE have been published. Herein, we perform an updated meta-analysis on the role of Xpert MTB/RIF in the diagnosis of TPE.The systematic review was conducted using the standard methodology for systematic reviews of diagnostic test accuracy (see the detailed methodology in the supplemental material) (11,12). Institutional ethics committee approval was not required as this was a systematic review of published data.Our search yielded 155 citations, of which 24 studies (2,486 patients) were included in the current analysis (see Fig. S1 in the supplemental material) (7,8,. There were equal numbers of studies from the developed and the developing countries (see Tables S1 and S2 in the supplemental material) (8, 14, 16-22, 24, 32, 33). Only two studies included children (13,15). Seven studies included people living with HIV infection (8,17,18,(20)(21)(22)27). Twenty-one studies (2,167 patients) and 10 studies (937 patients) used a microbiological standard (mycobacterial culture) (7, 8, 13-16, 19, 20, 22-34) or a composite reference standard (CRS) (7, 14-18, 21, 22, 24, 28), respectively, to assess the diagnostic accuracy of GeneXpert (see Table S3). Seven studies performed Xpert MTB/RIF on frozen pleural fluid (7,15,19,21,23,28,30), while the remaining used fresh samples (see Table S4). Nine studies concentrated the pleural fluid sample by centrifugation before performance of GeneXpert (7, 8, 16-18, 20, 22, 24, 29). The ov...

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Role of Medical Thoracoscopy and Closed-Blind Pleural Biopsy in Undiagnosed Exudative Pleural Effusions

Abstract: MT is the procedure of choice in the evaluation of undiagnosed EPE, due to its higher success rate and an acceptable safety profile. However, in centers where thoracoscopy is not feasible, CBPB should be performed in preference to initiating empiric treatment.

Cited by 53 publications

References 44 publications

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

Diagnostic accuracy of tumor markers for malignant pleural effusion: a derivation and validation study

Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis

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