Objective Thoracoscopic Criteria in Differentiation between Benign and Malignant Pleural Effusions

<b><i>Background:</i></b> Thoracoscopy is the “gold standard” diagnostic modality for investigation of suspected pleural malignancy. It is postulated that meticulous assessment of the pleural cavity may be adequate to indicate malignancy through the macroscopic findings of nodules, pleural thickening, and lymphangitis. We attempted to critically assess this practice, by precisely defining objective macroscopic criteria which might differentiate benign from malignant pleural diseases according to intrapleural pattern and anatomical location, and thereby to explore the predilection of abnormalities to specific sites on pleural surfaces. <b><i>Methods:</i></b> A structured review of recorded video footage from medical thoracoscopy procedures in 96 patients was conducted by 2 independent assessors. Abnormalities were scored on agreed, objective criteria for the presence of nodules, lymphangitis and inflammation on each of the costoparietal, visceral and diaphragmatic surfaces. The costoparietal pleura was divided into 6 levels (apical, middle, and inferior surfaces of the lateral and posterior parietal pleura). The anterior surface of the costoparietal pleura was excluded from analysis after interim review as this surface was rarely seen. <b><i>Results:</i></b> In the benign group, inflammation was the predominant finding in 65% (<i>n</i> = 33; costoparietal), 44% (<i>n</i> = 21; visceral), and 42% (<i>n</i> = 15; diaphragmatic). Nodules were detected in 24% (<i>n</i> = 12; costoparietal), 8% (<i>n</i> = 4; visceral), and 8% (<i>n</i> = 3; diaphragmatic). The most affected surfaces with inflammation were the middle lateral (60%) and the inferior lateral (57.8%) parts of the costoparietal pleura. In the malignant group, nodules were the predominant finding according to surface in 73% (<i>n</i> = 33; costoparietal), 32% (<i>n</i> = 13; visceral) and 48% (<i>n</i> = 17; diaphragmatic). Inflammation was detected in 44% (<i>n</i> = 20; costoparietal), 25% (<i>n</i> = 10; visceral), and 29% (<i>n</i> = 10; diaphragmatic). The most affected surfaces with nodules were the middle lateral (67.4%) and inferior lateral (66.7%) costoparietal pleural surfaces. <b><i>Conclusion:</i></b> This is the first detailed, anatomical description of abnormalities in the pleural space during thoracoscopy. While nodules were the predominant pattern in malignant pleural effusion, they were detected in 24% of benign diagnoses. Detection of nodules in &#x3e;1 area of the costoparietal pleura was in favor of a malignant diagnosis. Inflammation was the predominant pattern in benign pleural effusion. Our results suggest that macroscopic nodules in malignant diagnoses have a predilection for the middle and inferior surfaces of the lateral costoparietal pleura.

Assessment of a panel of miRNAs in serum and pleural fluid for the differential diagnosis of malignant and benign pleural effusion

BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for MPE of diagnosis.

A rapid calprotectin test for the diagnosis of pleural effusion

In previous studies, measuring the levels of calprotectin in patients with pleural effusion (PE) was an exceptionally accurate way to predict malignancy. Here, we evaluated a rapid method for the measurement of calprotectin levels as a useful parameter in the diagnosis of malignant pleural effusion (MPE) in order to minimise invasive diagnostic tests. Calprotectin levels were measured with Quantum Blue® sCAL (QB®sCAL) and compared with the gold standard reference ELISA method. Calprotectin levels in patients with benign pleural effusion (BPE) were significantly higher (p < 0.0001) than for MPE patients. We measured the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LRs) for a cut-off value of ≤ 14,150 ng/mL; the diagnostic accuracy was 64%. The odds ratio for PE calprotectin levels was 10.938 (95% CI [4.133 − 28.947]). The diagnostic performance of calprotectin concentration was better for predicting MPE compared to other individual parameters. Comparison of two assays showed a slope of 1.084, an intercept of 329.7, and a Pearson correlation coefficient of 0.798. The Bland–Altman test showed a positive bias for the QB®sCAL method compared to ELISA fCAL®. Clinical concordance between both these methods was 88.5% with a Cohen kappa index of 0.76 (95% CI [0.68 − 0.84]). We concluded that QB®sCAL is a fast, reliable, and non-invasive diagnostic tool for diagnosing MPE and represents an alternative to ELISA that could be implemented in medical emergencies.

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

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.

Pro-cathepsin D as a diagnostic marker in differentiating malignant from benign pleural effusion: A retrospective cohort study

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.

Pro-cathepsin D as a diagnostic marker in differentiating malignant from benign pleural effusion: A retrospective cohort study

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 71% sensitivity and 73% specificity at a pro-cathepsin D cut-off ≥ 0.651 pg/mL (area under the curve: 0.698). Positive and negative predictive values for MPE were 39% and 92%, respectively, with pro-cathepsin D cut-off value (> 0.651 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.

Asbestos-related diseases

Knowledge of asbestos-related diseases has been accumulating for over one hundred years as the industrial value of asbestos was recognised for the strength of its fibres and their resistance to destruction, resulting in increasing production and use until the multiple health effects have become apparent. Deposition in the lung parenchyma results in an inflammatory/progressively fibrotic response, with impaired gas exchange and reduced lung compliance (‘asbestosis'), causing progressive dyspnoea and respiratory failure for which only palliation is indicated, although anti-fibrotic agents used for idiopathic usual interstitial pneumonitis remain to be evaluated. Benign pleural effusion, diffuse pleural fibrosis (occasionally with associated rolled atelectasis) and pleural plaques are the non-malignant pleural diseases that result from fibres reaching the pleura. But the main issues that led to the ban on asbestos in industry are those of malignancy: lung cancer, malignant mesothelioma (MM) of the pleura and MM of the peritoneum. Bronchogenic carcinoma risk from asbestos exposure is dose-dependent and multiplies the risk attributable to tobacco smoking. The principles of treatment are as for all cases of lung cancer. Low-dose computed tomography screening of exposed people can detect early-stage, non-small cell cancers, with improved survival. The amphibole varieties of asbestos are much more potent causes of MM than chrysotile, and the risk increases exponentially for 40–50 years following first exposure. As MM is non-resectable and poorly responsive to chemotherapy and radiotherapy, curative treatment is not possible and screening not justified.

Pro-cathepsin D as a diagnostic marker in differentiating malignant pleural effusion from benign pleural effusion: A retrospective cohort study

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). The diagnostic sensitivity and negative predictive value for MPE were 81% and 89%, respectively, at the pro-cathepsin D cut-off >0.596 pg/mL. Conclusions : The level of pleural fluid pro-cathepsin D was found to be significantly higher in MPE than in BPE; thus, pleural fluid pro-cathepsin D may be useful for discriminating MPE from BPE.

Pro-cathepsin D as a diagnostic marker in differentiating malignant pleural effusion from benign pleural effusion: A retrospective cohort study

Background Malignant pleural effusion (MPE) is a common complication of lung cancer and intrathoracic spreading or metastasis of extra-thoracic malignancy. The aim of the present study was to evaluate the levels of pro-cathepsin D from plasma and pleural fluid in patients with MPE and those in patients with benign pleural effusion (BPE) including pleural tuberculosis and parapneumonic effusion.Methods This study included 81 patients with pleural effusion who underwent thoracentesis and 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) (Table 1). In addition, there were no differences in pleural fluid pro-cathepsin D level according to causative malignancy of MPE. On receiver operating characteristic curve analysis, the optimal discrimination point between the MPE group and BPE group was defined as a cut-off value of 0.5960 pg/mL for pleural fluid pro-cathepsin D (81.0% sensitivity; 53.0% specificity) and 0.4335 pg/mL for plasma pro-cathepsin D (71.4% sensitivity; 61.7% specificity).Conclusions We found that the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group. Pro-cathepsin D could be a novel and potential biomarker to discriminate MPE from BPE.