Project description:BACKGROUND:Pleural fluid homocysteine (HCY) can be useful for diagnosis of malignant pleural effusion (MPE). There are no published studies comparing the diagnostic accuracy of HCY with other tumour markers in pleural fluid for diagnosis of MPE. The aim was to compare the accuracy of HCY with that of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA19.9 and CA125 in pleural fluid and to develop a probabilistic model using these biomarkers to differentiate benign (BPE) from MPE. METHODS:Patients with pleural effusion were randomly included. HCY, CEA, CA15.3, CEA19.9 and CA125 were quantified in pleural fluid. Patients were classified into two groups: MPE or BPE. By applying logistic regression analysis, a multivariate probabilistic model was developed using pleural fluid biomarkers. The diagnostic accuracy was determined by receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). RESULTS:Population of study comprised 133 patients (72 males and 61 females) aged between 1 and 96 years (median = 70 years), 81 BPE and 52 MPE. The logistic regression analysis included HCY (p<0.0001) and CEA (p = 0.0022) in the probabilistic model and excluded the other tumour markers. The probabilistic model was: HCY+CEA = Probability(%) = 100×(1+e-z)-1, where Z = 0.5471×[HCY]+0.3846×[CEA]-8.2671. The AUCs were 0.606, 0.703, 0.778, 0.800, 0.846 and 0.948 for CA125, CA19.9, CEA, CA15.3, HCY and HCY+CEA, respectively. CONCLUSIONS:Pleural fluid HCY has higher accuracy for diagnosis of MPE than CEA, CA15.3, CA19.9 and CA125. The combination of HCY and CEA concentrations in pleural fluid significantly improves the diagnostic accuracy of the test.
Project description:BackgroundCytological examination of pleural fluid has good specificity, but imperfect sensitivity for the diagnosis of malignant pleural effusion (MPE). Published estimates of sensitivity vary and predictors of false negative cytology are not well established.AimsTo estimate pleural fluid cytology sensitivity and identify risk factors for false negative cytology.MethodsWe conducted a retrospective cohort study of patients who had cytology testing of pleural fluid at Christchurch Hospital, New Zealand, from July 2017 to October 2019. Data on clinical and pleural fluid characteristics were collected. MPE was defined by positive pleural fluid cytology, tissue histology or multidisciplinary meeting consensus. We estimated sensitivity of the first pleural cytology assessment. We performed multivariate logistic regression to ascertain patient groups at greatest risk of false negative results.ResultsInitial pleural fluid cytology was diagnostic in 117 of 156 patients, providing a sensitivity (95% confidence interval (CI)) of 75.0% (67.4-81.6%). The sensitivity was 79.0% (66.8-88.3%) for lung cancer, 91.3% (72.0-98.9%) for breast cancer and 33.3% (95% CI 11.8-61.6%) for mesothelioma. Cloudy appearance of pleural fluid (odds ratio (OR) 0.12; 95% CI 0.03-0.54) and yellow/gold pleural fluid (OR 0.24; 95% CI 0.06-0.96) reduced the odds of false negative pleural cytology. Pleural thickening on computed tomography scan (OR 3.3; 95% CI 1.2-9.4) was a risk factor for false negative cytology.ConclusionSensitivity of pleural fluid cytology was greatest in primary lung and breast cancer, and lowest in mesothelioma. Clinicians should be alert to false negative results when suspecting mesothelioma or if pleural thickening is present.
Project description:BackgroundThe prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE.ObjectiveWe aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE.DesignA prospective, preregistered, and double-blind diagnostic test accuracy study.MethodsWe prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA).ResultsIn all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67.ConclusionPleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.
Project description:BackgroundPleural 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 methodThe 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.ResultIn 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.ConclusionPF 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.
Project description:BackgroundSeveral studies have evaluated the diagnostic accuracy of pleural fluid carbohydrate antigen 72-4 (CA72-4) for malignant pleural effusion (MPE), but the results were diverse. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE.MethodsThe PubMed and Web of Science databases were searched to verify potential studies investigating the diagnostic accuracy of pleural fluid CA72-4 for MPE. The last search date was August 2024. The quality of the eligible studies was assessed by this study using the revised diagnostic accuracy study quality assessment tool-2 to assess the quality of the eligible studies. This study used a summary receiver operating characteristic (sROC) curve and a bivariate model to pool the findings and their 95% confidence intervals (CIs) of available studies.ResultsEight studies with 828 cases of MPEs and 963 cases of benign pleural effusion (BPE) were included in the present meta-analysis. The pooled sensitivity (95% CI) and specificity (95% CI) were 0.47 (0.39-0.55) and 0.98 (0.95-0.99). The area under sROC curves was 0.77 (95% CI: 0.73-0.80). The primary design weaknesses of the included studies were the representativeness of the participants and the data-driven threshold to define positive CA72-4. A significant publication bias was observed across the eligible studies.ConclusionsPleural fluid CA72-4 is an auxiliary diagnostic marker for MPE. However, its diagnostic accuracy may be overestimated by available studies.
Project description:Patients 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.
Project description:Malignant pleural effusion is associated with a poor prognosis and, while risk stratification models exist, prior studies have not evaluated pleural fluid resolution and its association with survival. We performed a retrospective review of patients diagnosed with malignant pleural effusion between 2013 and 2017, evaluating patient demographics, pleural fluid and serum composition, and procedural and treatment data using Cox regression analysis to evaluate associations with survival. In total, 123 patients were included in the study, with median survival from diagnosis being 4.8 months. Resolution of malignant pleural fluid was associated with a significant survival benefit, even when accounting for factors such as placement of an indwelling pleural catheter, anti-cancer therapy, pleural fluid cytology, cancer pheno/genotypes, and pleural fluid characteristics. Elevated fluid protein, placement of an indwelling pleural catheter, and treatment with targeted or hormone therapies were associated with pleural fluid resolution. We conclude that the resolution of pleural fluid accumulation in patients with malignant pleural effusion is associated with a survival benefit possibility representing a surrogate marker for treatment of the underlying metastatic cancer. These findings support the need to better understand the mechanism of fluid resolution in patients with malignant pleural effusion as well as the tumor-immune interplay occurring with the malignant pleural space.
Project description:Medical thoracoscopy has been shown to be an efficacious procedure in diagnosing unexplained exudative pleural effusions with excellent safety. This study aimed to assess the diagnostic significance of thoracoscopy in the management of patients with malignant pleural effusion (MPE).Consecutive patients with malignant pleural effusion were retrospectively reviewed, and their demographic, radiographic, thoracoscopic and histological data were collected.Between July 2005 and June 2014, 342 of 833 patients undergoing thoracoscopy were finally confirmed to suffer from MPE. The top three frequent causes of MPE were metastatic carcinoma (79.5%), malignant mesothelioma (10.2%), and lymphoma (2.9%). Among metastatic malignancies, the most common cancer was lung cancer (85.2%), followed by breast cancer (4.4%), ovarian cancer (2.2%), pancreatic cancer (1.8%), etc. No serious adverse events associated with thoracoscopy were recorded.Medical thoracoscopy is a valuable and safe tool in diagnosing malignant pleural effusion with minimal complication rates.
Project description:BackgroundThe diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE.MethodsWe prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI).ResultsThe area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively.ConclusionsPleural fluid sFasL has moderate diagnostic accuracy for TPE.