Usefulness of thoracic ultrasound in the assessment of removal of indwelling pleural catheter in patients with malignant pleural effusion.

INTRODUCTION: There are no defined criteria for deciding to remove a non-functioning indwelling pleural catheter (IPC) when lung re-expansion on chest X-ray is incomplete. Chest computed tomography (chest CT) is usually used. The objective of this work is to validate the usefulness of chest ultrasound performed by a pulmonologist and by a radiologist compared to chest CT. PATIENTS AND METHODS: Prospective, descriptive, multidisciplinary and multicenter study including patients with malignant pleural effusion and non-functioning IPC without lung reexpansion. Decisions made on the basis of chest ultrasound performed by a pulmonologist, and performed by a radiologist, were compared with chest CT as the gold standard. RESULTS: 18 patients were analyzed, all of them underwent ultrasound by a pulmonologist and chest CT and in 11 of them also ultrasound by a radiologist. The ultrasound performed by the pulmonologist presents a sensitivity of 60%, specificity of 100%, PPV 100% and NPV 66% in the decision of the correct removal of the IPC. The concordance of both ultrasounds (pulmonologist and radiologist) was 100%, with a kappa index of 1. The 4 discordant cases were those in which the IPC was not located on the ultrasound. CONCLUSIONS: Thoracic ultrasound performed by an expert pulmonologist is a valid and simple tool to determine spontaneous pleurodesis and remove a non-functioning IPC, which would make it possible to avoid chest CT in those cases in which lung reexpansion is observed with ultrasonography.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Myelomatous pleural effusion in multiple myeloma- A rare presentation.

Multiple myeloma is a malignant plasma cell condition that mostly affects the skeletal system and bone marrow. Pleural effusions are uncommon and typically result from other conditions coexisting with multiple myeloma. Malignant myelomatous pleural effusions are rare complications of multiple myeloma, occurring in less than 1% of patients and are associated with poor prognosis having mean survival of less than 4 months. The present case report is a 41-year-old multiple myeloma patient who developed bilateral pleural effusion at a disease relapse. Chemotherapeutic regimen of cyclophosphamide, bortezomib, and dexamethasone given. Despite a positive response to treatment, the patient's condition worsened over the course of following month and he eventually passed away. Myelomatous pleural effusion indicates poor prognosis and early consideration helps in quick diagnosis and initiation of treatment which may help in improving prognosis.

Engineered lactococcus lactis intrapleural therapy promotes regression of malignant pleural effusion by enhancing antitumor immunity.

Intrapleural immunotherapies have emerged as a prominent field in treating malignant pleural effusion (MPE). Among these, bacteria-based intrapleural therapy has exerted an anti-MPE effect by immuno-stimulating or cytotoxic properties. We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. FOLactis activates tumor antigen-specific immune responses and displays systemic antitumor efficacy via intratumoral delivery. However, no available lesions exist in the pleural cavity of patients with MPE for intratumoral administration. Therefore, we further optimize FOLactis to treat MPE through intrapleural injection. Intrapleural administration of FOLactis (I-Pl FOLactis) not only distinctly suppresses MPE and pleural tumor nodules, but also significantly extends noticeable survival in MPE-bearing murine models. The proportion of CD103+ dendritic cells (DCs) in tumor-draining lymph nodes increases three-fold in FOLactis group, compared to the wild-type bacteria group. The enhanced DCs recruitment promotes the infiltration of effector memory T and CD8+ T cells, as well as the activation of NK cells and the polarization of macrophages to M1. Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of I-Pl FOLactis. In summary, we first develop an innovative intrapleural strategy based on FOLactis, exhibiting remarkable efficacy and favorable biosafety profiles. These findings suggest prospective clinical translation of engineered probiotics for managing MPE through direct administration into the pleural cavity.

Cytomorphology of metastatic malignant peripheral nerve sheath tumour present in pleural fluid: Case study and literature review.

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

Cell-free DNA methylation analysis as a marker of malignancy in pleural fluid.

Diagnosis of malignant pleural effusion (MPE) is made by cytological examination of pleural fluid or histological examination of pleural tissue from biopsy. Unfortunately, detection of malignancy using cytology has an overall sensitivity of 50%, and is dependent upon tumor load, volume of fluid assessed, and cytopathologist experience. The diagnostic yield of pleural fluid cytology is also compromised by low abundance of tumor cells or when morphology is obscured by inflammation or reactive mesothelial cells. A reliable molecular marker that may complement fluid cytology for the diagnosis of malignant pleural effusion is needed. The purpose of this study was to establish a molecular diagnostic approach based on pleural effusion cell-free DNA methylation analysis for the differential diagnosis of malignant pleural effusion and benign pleural effusion. This was a blind, prospective case-control biomarker study. We recruited 104 patients with pleural effusion for the study. We collected pleural fluid from patients with: MPE (n = 48), indeterminate pleural effusion in subjects with known malignancy or IPE (n = 28), and benign PE (n = 28), and performed the Sentinel-MPE liquid biopsy assay. The methylation level of Sentinel-MPE was markedly higher in the MPE samples compared to BPE control samples (p < 0.0001) and the same tendency was observed relative to IPE (p = 0.004). We also noted that the methylation signal was significantly higher in IPE relative to BPE (p < 0.001). We also assessed the diagnostic efficiency of the Sentinel-MPE test by performing receiver operating characteristic analysis (ROC). For the ROC analysis we combined the malignant and indeterminate pleural effusion groups (n = 76) and compared against the benign group (n = 28). The detection sensitivity and specificity of the Sentinel-MPE test was high (AUC = 0.912). The Sentinel-MPE appears to have better performance characteristics than cytology analysis. However, combining Sentinel-MPE with cytology analysis could be an even more effective approach for the diagnosis of MPE. The Sentinel-MPE test can discriminate between BPE and MPE. The Sentinel-MPE liquid biopsy test can detect aberrant DNA in several different tumor types. The Sentinel-MPE test can be a complementary tool to cytology in the diagnosis of MPE.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. METHODS: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. RESULTS: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. CONCLUSION: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Efficacy of osimertinib in patients with EGFR-mutation positive non-small cell lung cancer with malignant pleural effusion.

BACKGROUND: As an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), osimertinib has emerged as a standard EGFR-mutation positive treatment for non-small cell lung cancer (NSCLC). However, the efficacy of osimertinib for malignant pleural effusion (MPE) remains understudied. This study aimed to evaluate the impact of osimertinib on time to treatment failure (TTF) and overall survival (OS) in patients with EGFR-mutation positive NSCLC, comparing those with and without MPE. METHODS: This retrospective analysis included patients with advanced or recurrent NSCLC treated with osimertinib at our hospital between April 2016 and June 2021. TTF was defined as the duration from osimertinib initiation to discontinuation, and OS as the duration until death, irrespective of the reason. RESULTS: Among 229 patients receiving osimertinib, 84 had MPE before administration, 39 acquired EGFR exon20 T790M mutation following previous EGFR-TKI therapy, and 45 were EGFR-TKI-naive. Among EGFR-TKI-naive patients, median TTF was 14.8 and 19.8 months for those with and without MPE, respectively (hazard ratio [HR] 1.40; 95% confidence interval [CI]: 0.90-2.18; p = 0.12). Median OS was 32.0 and 42.0 months for patients with and without MPE, respectively (HR 1.43; 95% CI: 0.86-2.38; p = 0.16). Among patients with T790M mutation, median TTF was 12.3 and 13.1 months for patients with and without MPE, respectively (HR 1.03; 95% CI: 0.69-1.55; p = 0.88). Median OS for patients with and without MPE was 23.2 and 24.7 months, respectively (HR 1.09; 95% CI: 0.72-1.67; p = 0.68). CONCLUSION: Among patients with EGFR-mutation positive NSCLC, the evidence of MPE has little effect on survival with osimertinib.

Ultrasound in the Study of Thoracic Diseases: Innovative Aspects

Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training programmes are educating trainees in this technique, and ultrasound can be done rapidly without exposure to radiation.The aim of this review is to present the most interesting and innovative aspects of the use of TU in the study of thoracic diseases.In pleural diseases, TU has been a real revolution. It helps to differentiate between different types of pleural effusions, guides the performance of pleural biopsies when necessary and is more cost-effective under these conditions, and assists in the decision to remove thoracic drainage after talc pleurodesis.With the advent of COVID19, the use of TU has increased for the study of lung involvement. Nowadays it helps in the diagnosis of pneumonias, tumours and interstitial diseases, and its use is becoming more and more widespread in the Pneumology ward.In recent years, TU guided biopsies have been shown to be highly cost-effective, with other advantages such as the absence of radiation and the possibility of being performed at bedside. The use of contrast in ultrasound to increase the cost-effectiveness of these biopsies is very promising.In the study of the mediastinum and peripheral pulmonary nodules, the introduction of echobronchoscopy has brought about a radical change. It is a fully established technique in the study of lung cancer patients. The introduction of elastography may help to further improve its cost-effectiveness.In critically-ill patients, diaphragmatic ultrasound helps in the assessment of withdrawal of mechanical ventilation, and is now an indispensable tool in the management of these patients. (AU)

[Expert consensus on diagnosis and treatment of malignant pleural effusion caused by lung cancer].

Malignant pleural effusion (MPE) can occur in nearly all types of malignant tumors, with lung cancer being the most prevalent cause. The presence of MPE indicates an advanced stage or distant spread of the tumor, significantly reducing the patient's life expectancy. Particularly, a substantial amount of pleural effusion can impede heart and lung function, impair blood oxygen perfusion levels in the body, and greatly diminish patients' quality of life. Even when systemic treatment has alleviated the primary lung tumor in some patients, effective control over MPE remains challenging and impacts clinical outcomes. Therefore, it is crucial to implement measures for reducing or managing MPE while ensuring standardized treatment for lung cancer. In recent years, significant advancements have been made in diagnosing and treating lung cancer complicated by MPE through extensive basic and clinical research. Based on existing evidence and China's clinical practice experience, relevant experts from the China Association of Health Promotion and Education and Cancer Rehabilitation and Palliative Treatment Professional Committee of China Anti-Cancer Association (CRPC) have summarized key aspects related to diagnosis and treatment consensus opinions for lung cancer complicated by MPE. This aims to establish standardized procedures that will serve as a reference for doctors' clinical practice.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.