OBJECTIVE: Malignant pleural effusion (MPE) is a common complication of lung cancer with poor prognosis. Benign pleural effusion (BPE), such as tuberculous and pneumonic pleural effusion, usually has a good prognosis. Differential diagnosis between MPE and BPE remains a clinical challenge.
METHODS: 52 MPE, 93 BPE, and their corresponding serum samples were analyzed by hydrogen nuclear magnetic resonance (1HNMR) based metabolomics.
RESULTS: The 1HNMR study showed that some amino acids and betaine in MPE are significantly altered in pleural effusion and serum compared to BPE patients. Levels of serum glucose and glutamine have strong positive correlation with those in pleural effusion (r>0.6) for MPE patients. The area under the receiver operating characteristic curve (AUROC) values of metabolites in pleural effusion or serum were less than 0.805 in differentiating MPE from BPE. Improved an AUROC value of 0.901 was observed using pleural effusion-serum ratios of glutamic acid in differentiating MPE from BPE, which was further validated by 15 double-blind samples.
CONCLUSIONS: Compared with BPE patients, amino acids and betaine in MPE are significantly altered in pleural effusion and serum. Pleural effusion-serum ratio of glutamic acid may contribute to the rapid diagnosis of MPE from BPE by 1HNMR analysis.

The differential diagnosis of malignant pleural effusion (MPE) and benign pleural effusion (BPE) presents a clinical challenge. In recent years, the use of artificial intelligence (AI) machine learning models for disease diagnosis has increased.
This study aimed to develop and validate a diagnostic model for early differentiation between MPE and BPE based on routine laboratory data.
This was a retrospective observational cohort study.
A total of 2352 newly diagnosed patients with pleural effusion (PE), between January 2008 and March 2021, were eventually enrolled. Among them, 1435, 466, and 451 participants were randomly assigned to the training, validation, and testing cohorts in a ratio of 3:1:1. Clinical parameters, including age, sex, and laboratory parameters of PE patients, were abstracted for analysis. Based on 81 candidate laboratory variables, five machine learning models, namely extreme gradient boosting (XGBoost) model, logistic regression (LR) model, random forest (RF) model, support vector machine (SVM) model, and multilayer perceptron (MLP) model were developed. Their respective diagnostic performances for MPE were evaluated by receiver operating characteristic (ROC) curves.
Among the five models, the XGBoost model exhibited the best diagnostic performance for MPE (area under the curve (AUC): 0.903, 0.918, and 0.886 in the training, validation, and testing cohorts, respectively). Additionally, the XGBoost model outperformed carcinoembryonic antigen (CEA) levels in pleural fluid (PF), serum, and the PF/serum ratio (AUC: 0.726, 0.699, and 0.692 in the training cohort; 0.763, 0.695, and 0.731 in the validation cohort; and 0.722, 0.729, and 0.693 in the testing cohort, respectively). Furthermore, compared with CEA, the XGBoost model demonstrated greater diagnostic power and sensitivity in diagnosing lung cancer-induced MPE.
The development of a machine learning model utilizing routine laboratory biomarkers significantly enhances the diagnostic capability for distinguishing between MPE and BPE. The XGBoost model emerges as a valuable tool for the diagnosis of MPE.

OBJECTIVE: The aim of this study was to investigate the diagnostic potential of Krebs von den Lungen-6 (KL-6) in differentiating between malignant pleural effusion (MPE) induced by non-small cell lung cancer (NSCLC) and benign pleural effusion (BPE).
METHODS: We collected 143 pleural effusion samples from August 2018 to March 2021. The samples included 91 cases of MPE and 52 cases of BPE. The KL-6 and other indicators in pleural effusion were detected.
RESULTS: The level of pleural effusion KL-6 (pKL-6) in the MPE group was significantly higher than in the BPE group (Mann-Whitney U = 442.500, P = .000). The area under the curve (AUC) of pKL-6/pleural effusion adenosine deaminase (pADA) + pleural effusion carcinoembryonic antigen (pCEA)/pADA (AUC = 0.992) in diagnosing MPE was higher than that of pKL-6 alone (AUC = 0.903), with a sensitivity of 93.26% and specificity of 100%.
CONCLUSIONS: The measurement of pKL-6 can differentiate NSCLC-induced MPE from BPE. Furthermore, the combined detection of pKL-6/pADA and pCEA/pADA can significantly improve the diagnostic efficiency for distinguishing NSCLC-induced MPE.

UNASSIGNED: Occurrence of malignant pleural effusion (PE) is known to be associated with a poor prognosis, but the mortality of patients with non-malignant effusions has not been sufficiently studied. Our objective was to describe the clinical course and explore risk factors associated with all-cause mortality at 1, 5 and 10 years in patients who develop a PE.
UNASSIGNED: Retrospective observational study of patients undergoing diagnostic thoracentesis during the decade 2008-2017 in a pulmonology service. Demographic, biochemical, pathological and evolutionary variables were evaluated. The etiology of the effusions was determined using standardized criteria.
UNASSIGNED: Pleural fluid samples from 358 patients with a mean age of 68.9 years (SD 15.1 years), 69.2% males, were analyzed. Malignant (29.4%), parapneumonic (19.8%) and secondary to heart failure (18.9%) effusions predominated. Patients with malignant and heart failure related PE had 1-year mortality rates of 60.0% and 30.8%, respectively, and 85% and 64.7% at 5 years. Male gender (hazard ratio [HR] 1.46; 95% CI: 1.03-2.07), positive cytology for malignancy (HR 1.66; 95% CI: 1.03-2.68) and effusion recurrence (HR 1.61; 95% CI: 1.17-2.21) were associated with a worse prognosis and 5-year mortality.
UNASSIGNED: Patients undergoing thoracentesis for effusion have a high short and long-term mortality. In our series of hospitalized patients with PE, the factors associated with higher mortality at 1 and 5 years were age, male sex, recurrence of PE, and coexistence of malignancy.

The results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions.
We conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021.
One hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV>7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV>4.5 (5 points) and cardiomegaly (-1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients.
PET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.

Long-term follow-up course for patients with idiopathic pleural effusions has not been established.
From October 2013 to June 2021 all patients with idiopathic effusion were prospectively followed up with clinical examination and imaging at 1, 3, 6 and every 6 months for a minimum of 1 year.
Twenty-nine patients were diagnosed with idiopathic effusion and followed up. Mesothelioma was detected during the follow-up in two patients at 7 and 18 months, one of whom had blood-tinged pleural fluid and the other reported a 10% weight loss. Mesothelioma was not diagnosed in any of the patients with effusion covering less than two thirds of the hemithorax, and without constitutional symptoms or a blood-tinged fluid appearance. Most of the effusions resolved or showed a clear improvement in the first six months.
Patients without weight loss and with small, non-hematic effusions, may benefit from conservative treatment and clinical-radiological follow-up.

The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers.
This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients\' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy.
The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%).
The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

BACKGROUND: Malignant pleural effusion (MPE) causes substantial symptomatic burden in advanced malignancy. Although pleural fluid cytology is a commonly accepted gold standard of diagnosis, its low diagnostic yield is a challenge for clinicians. The aim of this study was to determine whether pro-cathepsin D can serve as a novel biomarker to discriminate between MPE and benign pleural effusion (BPE).
METHODS: This study included 81 consecutive patients with exudative pleural effusions who had underwent thoracentesis or pleural biopsy. Pleural fluid and serum were collected as a standard procedure for all individuals at the same time. The level of pro-cathepsin D was measured by the sandwich enzyme-linked immunosorbent assay method.
RESULTS: Though there were no significant differences in plasma pro-cathepsin D between the two groups, the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group (0.651 versus 0.590 pg/mL, P = 0.034). The discriminative power of pleural fluid pro-cathepsin D for diagnosing MPE was moderate, with 81% sensitivity and 53% specificity at a pro-cathepsin D cut-off ≥0.596 pg/mL (area under the curve: 0.656). Positive and negative predictive values for MPE were 38 and 89%, respectively, with pro-cathepsin D cut-off value (> 0.596 pg/mL).
CONCLUSIONS: The level of pleural fluid pro-cathepsin D was found to be significantly higher in MPE than in BPE. Although results of this study could not support the sole use of pleural fluid pro-cathepsin D to diagnose MPE, pleural fluid pro-cathepsin D can be added to pre-existing diagnostic methods for ruling-in or ruling-out MPE.

BACKGROUND: Indwelling pleural catheters (IPCs) are an emerging therapy for persistent benign pleural effusions. IPCs may achieve pleurodesis and be removed.
OBJECTIVE: We aimed to identify factors associated with higher pleurodesis rates and earlier IPC removal in benign pleural effusions.
METHODS: We reviewed a database of IPCs inserted for nonmalignant pleural effusions in the period August 2007 to June 2017 in patients who underwent medical thoracoscopy (MT). Clinical, radiologic, and pleural fluid data were recorded. Logistic regression and Cox proportional hazards were used to assess the rate of and time to pleurodesis.
RESULTS: 304 IPCs were reviewed. 52 were excluded from the pleurodesis analysis due to removal for another reason, or because of an eventual diagnosis of malignant disease. The overall pleurodesis rate was 74%, and median time to pleurodesis was 42 (IQR 18-93) days. Variables with increased pleurodesis rates in multivariate analysis include Eastern Cooperative Oncology Group performance status score of ≤2 (odds ratio [OR] 4.22, 95% confidence interval [CI] 1.75-10.16) and MT (OR 5.27, 95% CI 2.74-10.11). No variables were associated with reduced pleurodesis rates in multivariate analysis. Variables that predicted earlier removal in multivariate analysis included secondary pleural infection (hazard ratio [HR] 14.19, 95% CI 4.11-48.91), % eosinophils (HR 1.03, 95% CI 1.01-1.05), and connective tissue disease (HR 2.59, 95% CI 1.20-5.57). Variables that predicted delayed removal include pleural effusion above the hilum (HR 0.54, 95% CI 0.34-0.85), liver failure (HR 0.31, 95% CI 0.16-0.60), and heart failure (HR 0.32, 95% CI 0.20-0.52).
CONCLUSIONS: IPCs are safe in benign effusions. Clinicians should consider numerous factors when predicting the rate of and time to pleurodesis.

Thoracoscopy in the endoscopy suite, has a high diagnostic yield of undiagnosed pleural effusions with minimal and mild complications. Whereas relatively minimal invasive techniques, such as thoracentesis, image-guided pleural biopsy or blind pleural biopsy, can yield sufficient cell or tissue material to establish the diagnosis of the underlying condition, more definite invasive diagnostic and therapeutic procedure, such as thoracoscopy, may be required for accurate sampling and diagnosis, and further provide real-time treatment options in same procedure. If thoracoscopy is considered the gold standard for the diagnosis is a fact in case. The current review aims to provide informations on thoracoscopy indications in benign pleural diseases according to up to date publications.