CEA and ADA in Pleural Fluid for Differential Malignant Pleural Effusion and Tuberculous Pleural Effusion

Diagnostic Value ◽

Diagnostic Model ◽

Diagnostic Efficacy ◽

Diagnostic Models ◽

Independent Risk Factors

Abstract Objective This study aimed to establish a predictive model based on the clinical manifestations and laboratory findings in pleural fluid of patients with pleural effusion for the differential diagnosis of malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE). Methods Clinical data and laboratory indices of pleural fluid were collected from patients with malignant pleural effusion and tuberculous pleural effusion in Zigong First People's Hospital between January 2019 and June 2020，and were compared between the two groups. Independent risk factors or Independent protective factors for malignant pleural effusion were investigated using multivariable logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of factors with independent effects, and combined diagnostic models were established based on two or more factors with independence effect. ROC curve was used to evaluate the diagnostic ability of each model, and the fit of the eath model was measured using Hosmer-Lemeshow goodness-of-fit test. Results Patients with MPE were older than those with TPE, the rate of fever of patients with MPE was lower than that of patients with TPE, and these differences were statistically significant (p < 0.05). Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin-19 fragment antigen (CYFRA21-1), cancer antigen 125 (CA125), and glucose (GLU) levels in the pleural fluid were higher, but total protein (TP), albumin (ALB) and Adenosine deaminase (ADA) levels in the pleural fluid were lower in MPE patients than in TPE patients, and the differences were statistically significant (P<0.05). In multivariate logistic regression analysis, CEA and NSE levels in the pleural fluid were independent risk factors for MPE, whereas ADA levels in pleural fluid and fever were independent protective factors for MPE. The differential diagnostic value of pleural fluid CEA and pleural fluid ADA for MPE and TPE were higher than that of pleural fluid NSE（p<0.05） and the area under the ROC curve was 0.901, 0.892, and 0.601, respectively. Four different binary logistic diagnostic models were established based on pleural fluid CEA combined with pleural fluid NSE, pleural fluid ADA or ( and ) fever. Among them, the model established with the combination of pleural fluid CEA and pleural fluid ADA (logit (P) = 0.513 + 0.457*CEA-0.101*ADA) had the highest diagnostic value for malignant pleural effusion, and its predictive accuracy was high with an area under the ROC curve of 0.968 [95% confidence interval (0.947, 0.988)]. But the diagnostic efficacy of the diagnostic model could not be improved by adding pleural fluid NSE and fever. Conclusion The model established with the combination of CEA and ADA in the pleural fluid has a high differential diagnostic value for malignant pleural effusion and tuberculous pleural effusion, and NSE in the pleural fluid and fever cannot improve the diagnostic efficacy of the diagnostic model.

Potential diagnostic value of pleural fluid cytokines levels for tuberculous pleural effusion

International Journal of Mycobacteriology ◽

10.4103/2212-5531.307124 ◽

2021 ◽

Vol 9 (5) ◽

pp. 71

Author(s):

Esmaeil Mortaz

Keyword(s):

Pleural Effusion ◽

Pleural Fluid ◽

Diagnostic Value ◽

Tuberculous Pleural Effusion

Proteome analysis of malignant pleural effusion

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22194 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22194-e22194

Author(s):

K. Lee ◽

J. Bang ◽

K. Kim

Keyword(s):

Pleural Effusion ◽

False Positive Rate ◽

Coagulation Factor ◽

Proteome Analysis ◽

Diagnostic Value ◽

Complement Factor ◽

Glycoprotein Precursor ◽

Potential Biomarker

e22194 Background: Because pleural effusion contains proteins of potential diagnostic value, a comprehensive proteomic analysis of the pleural effusion is worthy to discover a new biomarker. Malignant pleural effusion and tuberculous pleural effusion are sometimes diagnositc challenge due to their similarity like lymphocyte-dominant effusion. Herein, we tried to identify differentially expressed proteins in both effusion using proteomic anlaysis. Methods: Twenty microliters of pleural effusions(PEs) from 3 patients with non-small cell lung cancer(NSCLC) and 3 patients with tuberculous pleurisy(TBC) were used for proteome analysis. After depletion of high abundant proteins including albumin, IgG with MARS Hu-6(Agilent), proteins were separated by SDS-PAGE and subject to in-gel tryptic digestion. The resulting peptides were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The MS/MS spectra were analyzed by Spectrum Mill against normal and reversed human protein databases. Results: In the total of 6 samples, 90 proteins were identified with more than 2 peptides and less than 1% of false positive rate. Among the identified pleural proteins, 57 proteins were detected both in PEs of NSCLS and TBC, 19 and 14 proteins were identified only in the PE of NSCLC and TBC, respectively. We analysed molecular functions, molecular composition and molecular processes of identified proteins with FindGo software. Among the identified proteins, we found the biomarker candidates that significantly have different expression levels in malignant effusion; apolipoprotein B precursor, vitronectin, complement factor B, histidine-rich glycoprotein precursor, coagulation factor II precursor variant. Conclusions: We found that several pleural effusion proteins may serve as potential biomarker candidates for differential diagnosis between maligant and tuberculous pleural effusion. We'll confirm these proteins through the proteomic method(MRM) and immunological method(Western bolt). No significant financial relationships to disclose.

Potential diagnostic value of pleural fluid cytokines levels for tuberculous pleural effusion

Scientific Reports ◽

10.1038/s41598-020-79685-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neda Dalil Roofchayee ◽

Majid Marjani ◽

Neda K. Dezfuli ◽

Payam Tabarsi ◽

Afshin Moniri ◽

...

Keyword(s):

Differential Diagnosis ◽

Pleural Effusion ◽

Diagnostic Accuracy ◽

Pleural Fluid ◽

Diagnostic Value ◽

Parapneumonic Effusion ◽

Pleural Effusions ◽

New Biomarkers ◽

High Level

AbstractPatients with tuberculous pleural effusion (TPE) or malignant pleural effusions (MPE) frequently have similar pleural fluid profiles. New biomarkers for the differential diagnosis of TPE are required. We determined whether cytokine profiles in the PE of patients could aid the differential diagnosis of TPE. 30 patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP) and 14 patients with parapneumonic effusion (PPE) were enrolled between Dec 2018 and 2019. The levels of interleukin (IL)-6, IL-18, IL-27, CXCL8, CCL-1 and IP-10 were determined in PE by ELISA along with measurements of adenosine deaminase (ADA). The best predictors of TPE were combined ADA.IL-27 [optimal cut-off value = 42.68 (103 U ng/l2), sensitivity 100%, specificity 98.28%], ADA [cut off value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] and IL-27 [cut-off value = 2363 (pg/ml), sensitivity 96.7%, specificity 98.3%, p ≤ 0.0001]. A high level of IL-6 [cut-off value = 3260 (pg/ml), sensitivity 100%, specificity 67.2%], CXCL8 [cut-off value = 144.5 (pg/ml), sensitivity 93.3%, specificity 58.6%], CCL1 [cut-off value = 54 (pg/ml), sensitivity 100%, specificity 70.7%] and IP-10 [cut-off value = 891.9 (pg/ml), sensitivity 83.3%, specificity 48.3%] were also predictive of TPE. High ADA.IL-27, ADA and IL-27 levels differentiate between TPE and non-TPE with improved specificity and diagnostic accuracy and may be useful clinically.

Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion

Respiratory Research ◽

10.1186/s12931-020-01557-z ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Hai Zhang ◽

Changhui Li ◽

Fang Hu ◽

Xueyan Zhang ◽

Yinchen Shen ◽

...

Keyword(s):

Lung Cancer ◽

Pleural Effusion ◽

Pleural Fluid ◽

Compliance Rate ◽

Diagnostic Value ◽

Tumor Biomarkers ◽

Training Set ◽

Test Set ◽

Benign Pleural Effusion

Abstract Background Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio. Patients and method The study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators. Result In the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (all p < 0.001). In the test set, PF CEA at the cut-off value of 5.23 ng/ml showed the highest sensitivity, specificity and accuracy, positive and negative predictive value among other tumor biomarkers, which were 99.0%, 69.1%, 91.6%, 90.7%, and 95.9%, respectively. Conclusion PF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.

Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919850341 ◽

2019 ◽

Vol 11 ◽

pp. 175883591985034 ◽

Cited By ~ 5

Author(s):

Klaus Hackner ◽

Peter Errhalt ◽

Sabin Handzhiev

Keyword(s):

Pleural Effusion ◽

Carcinoembryonic Antigen ◽

Pleural Fluid ◽

Predictive Value ◽

Diagnostic Value ◽

Tumour Markers ◽

Operating Characteristics ◽

Characteristics Analysis ◽

Individual Marker

Background: Tumour markers in pleural fluid and their diagnostic value are subject to debate. Although there are several studies on this topic, standardized cut-off values do not exist. In this study we investigated the potential of a ratio of carcinoembryonic antigen (CEA) in pleural fluid and serum, serving as an individual marker for pleural cancer manifestation. Methods: A total of 201 consecutive patients with unclear pleural effusion were included in the study; 98 were diagnosed with malignant pleural effusion and 103 had an effusion due to other, benign reasons. CEA levels in pleural fluid and serum were measured. Results: By using receiver operating characteristics analysis, at the cut-off of 1.0, the CEA ratio showed a specificity of 92% and sensitivity of 85%, with a positive predictive value of 91% and a negative predictive value of 87%. These results are higher than in previous investigations on different pleural tumour markers and their combination. Conclusions: The CEA ratio is a useful tool in predicting pleural carcinosis. Elevated results in cytology-negative patients should lead to further investigations, such as repeated cytological examination or thoracoscopy.

Diagnostic value of ex vivo pleural fluid interferon-gamma versus adapted whole-blood quantiferon-TB gold in tube assays in tuberculous pleural effusion

Annals of Thoracic Medicine ◽

10.4103/1817-1737.102181 ◽

2012 ◽

Vol 7 (4) ◽

pp. 220 ◽

Cited By ~ 8

Author(s):

MahaK Ghanem ◽

Asmaa Omar ◽

AdelH.M Mekawy ◽

EmanN Eldin ◽

Mahmoud Khairy

Keyword(s):

Pleural Effusion ◽

Pleural Fluid ◽

Interferon Gamma ◽

Whole Blood ◽

Ex Vivo ◽

Diagnostic Value ◽

Tuberculous Pleural Effusion

Potential diagnostic value of pleural fluid cytokines levels for tuberculous pleural effusion

10.21203/rs.3.rs-68599/v1 ◽

2020 ◽

Author(s):

Neda Dalil Roofchayee ◽

Majid Marjani ◽

Neda K.Dezfuli ◽

Payam Tabarsi ◽

Afshin Moniri ◽

...

Keyword(s):

Differential Diagnosis ◽

Pleural Effusion ◽

Pleural Fluid ◽

Extrapulmonary Tuberculosis ◽

Clinical Manifestations ◽

Diagnostic Value ◽

Pleural Effusions ◽

New Biomarkers ◽

High Level

Abstract Background: Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. Patients with tuberculous or malignant pleural effusions (MPE) frequently have similar clinical manifestations and pleural fluid profile. New biomarkers for the differential diagnosis of TPE are required. Objective: We sought to determine of whether cytokine profiles in the pleural effusion of patients were suitable as tools for the differential diagnosis of TPE. Methods: 30 patients with TPE, 30 patients with MPE, 14 patients with empyema and 14 patients with parapneumonic effusion were enrolled consecutively from the Masih Daneshvari Hospital, Tehran, Iran between Dec 2018-Dec 2019. The levels of interleukin (IL)-6, IL-18, IL-27, CXCL-8, CCL-1 and IP-10 were determined in pleural effusions by ELISA along with measurements of adenosine deaminase (ADA). Results: The levels of all analytes measured except IL-18 were higher in TPE compared with non-TPE subjects (all p < 0.01). The best predictors of TPE were combined ADA.IL-27 (optimal cut-off value = 42.68 103.U.ng/L2, sensitivity 100%, specificity 98.28%, p ≤ 0.0001), ADA (optimal cut off value 27.5 IU/L, sensitivity 90%, specificity 96.5%, p ≤ 0.0001) and IL-27 (optimal cut-off value = 2363 pg/ml, sensitivity 96.7%, specificity 98.3%, p ≤ 0.0001). A high level of IL-6 (optimal cut-off value = 3260 pg/ml, sensitivity 100%, specificity 67.2%, p ≤ 0.0001), CXCL-8 (optimal cut-off value = 144.5 pg/m, sensitivity 93.3%, specificity 58.6%, p ≤ 0.0001), CCL-1 (optimal cut-off value = 54 pg/mL, sensitivity 100%, specificity 70.7%, p ≤ 0.0001) and IP-10 (optimal cut-off value = 891.9 pg/mL, sensitivity 83.3%, specificity 48.3%, p = 0.0001) were also predictive of TPE. Conclusion: High ADA.IL-27, ADA and IL-27 levels differentiate between TPE and non-TPE with improved specificity and diagnostic accuracy.

Diagnostic Value of Combined Pleural IL-33, ADA and Peripheral T-SPOT.TB for Tuberculous Pleurisy

10.21203/rs.3.rs-48549/v1 ◽

2020 ◽

Author(s):

Jin Fenhua ◽

Wang Daohui ◽

Lin Hui ◽

Xia Xiaodong ◽

wen huang

Keyword(s):

Pleural Effusion ◽

Pleural Fluid ◽

Peripheral Blood ◽

Diagnostic Value ◽

Diagnostic Efficacy ◽

Interleukin 33 ◽

Spot Detection ◽

Tuberculous Pleurisy ◽

Group 5 ◽

Combined Detection

Abstract Background To investigate the correlation between pleural fluid interleukin-33 (IL-33) and adenosine deaminase （ADA） and peripheral blood tuberculosis T cell spot detection (T-SPOT.TB), and the combined value of the three tests for the diagnosis of tuberculous pleurisy.Method 79 patients with pleural effusion admitted from June 2017 to December 2018 were enrolled. They were divided into tuberculous pleural effusion (TPE) group (57 cases, 72.2%) and malignant pleural effusion group (17 cases,21.5%), pneumonia-like pleural effusion group (5 cases, 6.3%). Correlation between pleural fluid IL-33,pleural effusion ADA and peripheral blood T-SPOT.TB was analyzed, comparison of the three separate and combined diagnostic efficacy was also performed.Result The levels of IL-33, ADA and peripheral blood T-SPOT.TB in patients with TPE were significantly higher than those in non-TPE (P<0.001). The level of pleural fluid IL-33 was positively correlated with pleural effusion ADA and peripheral blood T-SPOT.TB. The Area under the ROC curve（AUC）of TPE diagnosed by pleural IL-33, ADA and peripheral blood T-SPOT.TB were 0.753, 0.912 and 0.865, respectively. AUC for combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB is the largest, with a value of 0.962. Specificity is 100% and sensitivity is 88.5%.Conclusion Combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB can improve the diagnostic efficacy of tuberculous pleurisy.