[Management of Malignant Pleural Effusion]. / Management des malignen Pleuraergusses.

Malignant pleural effusion is a common diagnosis in metastasized cancers. It is always of palliative character. Main symptoms are dyspnoea and reduced quality of life. Diagnosis is made by ultrasound-guided puncture of the pleural effusion (cytology) and often video-assisted thoracic surgery with biopsy of the pleural surface (histology). The goal of treatment is a fast, sustainable, minimally invasive, patient-centred therapy that increases quality of life. Besides systemic therapy and best supportive care the patient can be treated with local therapy including either pleurodesis (via drainage or VATS) or an indwelling-pleural catheter (IPC). Decision for one of these procedures is made upon performance index (ECOG), expandability of the lung, prognosis and the patient's wish. For the first technique, the lung must be expandable. The latter one (IPC) can be implanted both with expandable and trapped lung. Both are similarly effective in symptom control.

Needle Biopsy of Pleura in the Aetiological Diagnosis of Pleural Effusion.

Exudative pleural effusion appears as manifestation of underlying specific disease process and pleural biopsy is usually enough to find out the underlying causative disease. The aim of the study was to find out the efficacy of needle biopsy of pleura in the aetiological diagnosis of pleural effusion. This cross-sectional study was conducted for a period of one year from January 2008 to December 2008 in the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh enrolling 50 subjects with exudative pleural effusion. The cases with transudative pleural effusion were not included. Needle biopsy was done in all the cases. Histopathological reports of pleural biopsy specimen were correlated with other data and analyzed to detect the causes of effusion. Major incidence of malignant effusion occurred between 41 to 70 years of age. No malignant effusion was found before 30 years of age. Incidence of tuberculous and malignant pleural effusion was much more common in males than in females. Sensitivity and specificity of combined pleural biopsy and pleural fluid analysis in the diagnosis of pleural effusion was 97.06% and 100.% for tuberculosis and 81.82% and 100.0% for malignancy. The present study reveals that pleural biopsy was very effective method in the diagnosis of cause of pleural effusion.

Identification of Potential Biomarkers of EGFR Mutation in Pleural Effusion of Non-Small Cell Lung Cancer Patients Based on Metabolomics.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of non-small cell lung cancer (NSCLC). Patients with NSCLC exhibit a high rate of epidermal growth factor receptor (EGFR) mutations. The detection of EGFR mutations is usually time-consuming and costly. This study aimed at identifying potential biomarkers of EGFR mutations in MPE of NSCLC patients by metabolomics. METHODS: In total, 58 MPE samples from 30 EGFR mutant and from 28 wild-type NSCLC patients were collected and analyzed by using hydrogen nuclear magnetic resonance (1H NMR) based metabolomics and UPLC-MS/MS based amino acid analysis. RESULTS: Our 1H NMR study showed a significant increase in the lysine levels but a significant decrease in the alanine levels in MPE of NSCLC patients with EGFR-mutant. Twelve amino acids in MPE were further determined by UPLC-MS/MS. It showed that alanine in MPE (6.34 ± 1.88 vs. 8.73 ± 3.68) were significantly decreased and leucine (3.13 ± 0.57 vs. 2.22 ± 0.13), lysine (2.19 ± 0.50 vs. 1.53 ± 0.40), and tyrosine (2.69 ± 0.71 vs. 1.89 ± 0.46) were increased in the EGFR mutation group; leucine (2.19 ± 0.50 vs. 1.53 ± 0.40), methionine (2.19 ± 0.50 vs. 1.53 ± 0.40), and threonine (2.19 ± 0.50 vs. 1.53 ± 0.40) in MPE were significantly lower in the EGRF 19 mutation compared with 21 mutation patients. The area under the receiver operating characteristic curve of 0.851 and 0.931 would be achieved by the logistic model for classification of EGFR-mutant patients from the wild-type controls or the exon 19 from exon 21 mutant patients. CONCLUSIONS: Amino acids in MPE are significantly altered and helpful in the diagnosis of EGFR-mutant patients from the wild-type controls or the exon 19 from exon 21 mutant patients with high accuracy, which is worthy of further study.

Bilateral myelomatous pleural effusions: an unusual presentation in newly diagnosed multiple myeloma.

Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.

Quantitative proteomics revealed protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion.

To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000，with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.

Pleural effusion supernatant: a reliable resource for cell-free DNA in molecular testing of lung cancer.

INTRODUCTION: DNA extracted from malignant pleural effusion (PE) sediments is the traditional source of tumor DNA for predictive biomarker molecular testing (MT). Few recent studies have proposed the utility of cell-free DNA (cfDNA) extracted from effusion cytology centrifuged supernatants (CCS) in MT. The aim of this study was to assess the feasibility and utility of molecular testing on cfDNA extracted from PE CCS in lung cancer patients. MATERIALS AND METHODS: The study was of prospective design. All PE CCS were collected and stored. Subsequently, in patients confirmed as primary lung adenocarcinoma (LUAD) and where patient matched effusion sediment/tissue biopsy/plasma was being tested for EGFR mutations, cfDNA extraction and EGFR MT by real-time polymerase chain reaction (qPCR) were performed. Custom panel targeted next-generation sequencing (NGS) (Ion Torrent; Thermo Fisher, Carlsbad, CA) was also performed wherever feasible. RESULTS: Out of 299 PE CCS collected, 20 CCS samples were included in the study. Concordant EGFR mutations were detected in pleural effusion CCS of 10 of 11 (91%) EGFR mutant cases as per qPCR performed on the matched sediment DNA (n = 8), lung biopsy (n = 2), and plasma (n = 1) samples. In 1 positive sample, CCS detected additional EGFR T790M mutation. Among 10 CCS samples also tested by NGS, additional EGFR mutations missed by qPCR were picked up in 2 (2 of 10). Success of mutation detection in CCS cfDNA did not correlate with cfDNA quantity or tumor fraction in sediment. CONCLUSIONS: cfDNA from effusion CCS is a reliable and independent source of tumor DNA highly amenable for MT and complement results from other tumor DNA sources for comprehensive mutation profiling in LUAD patients.

Clinical significance of pleural fluid lactate dehydrogenase/adenosine deaminase ratio in the diagnosis of tuberculous pleural effusion.

BACKGROUND: Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE. METHODS: The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE. RESULTS: The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P < 0.01) and MPE group (10 U/L, P < 0.001). The median pfADA level in the TPE group was 41 (32, 52) U/L; it was lowest in the MPE group at 9 (7, 12) U/L and highest in the PPE group at 43 (23, 145) U/L. The pfLDH level in the PPE group was 2542 (1109, 6219) U/L, which was significantly higher than that in the TPE group 449 (293, 664) U/L. In the differential diagnosis between TPE and non-TPE, the AUC of pfLDH/pfADA for diagnosing TPE was the highest at 0.946 (0.925, 0.966), with an optimal cutoff value of 23.20, sensitivity of 93.9%, specificity of 87.0%, and Youden index of 0.809. In the differential diagnosis of TPE and PPE, the AUC of pfLDH/pfADA was the highest at 0.964 (0.939, 0.989), with an optimal cutoff value of 24.32, sensitivity of 94.6%, and specificity of 94.4%; this indicated significantly better diagnostic efficacy than that of the single index of pfLDH. In the differential diagnosis between TPE and MPE, the AUC of pfLDH/pfADA was 0.926 (0.896, 0.956), with a sensitivity of 93.4% and specificity of 80.0%; this was not significantly different from the diagnostic efficacy of pfADA. CONCLUSIONS: Compared with single biomarkers, pfLDH/pfADA has higher diagnostic value for TPE and can identify patients with TPE early, easily, and economically.

Differences in 1HNMR Based Metabolomic Patterns of Malignant and Benign Pleural Effusions.

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.

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.

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.

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.

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.

Reliably making the primary diagnosis of mesothelioma utilizing serous fluid cytology specimens: an institutional experience.

INTRODUCTION: The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy. MATERIALS AND METHODS: SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered. RESULTS: One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis. CONCLUSIONS: The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.

Detection of effusion tumor cells under different storage and processing conditions.

BACKGROUND: Circulating tumor cells (CTCs) shed into blood provide prognostic and/or predictive information. Previously, the authors established an assay to detect carcinoma cells from pleural fluid, termed effusion tumor cells (ETCs), by employing an immunofluorescence-based CTC-identification platform (RareCyte) on air-dried unstained ThinPrep (TP) slides. To facilitate clinical integration, they evaluated different slide processing and storage conditions, hypothesizing that alternative comparable conditions for ETC detection exist. METHODS: The authors enumerated ETCs on RareCyte, using morphology and mean fluorescence intensity (MFI) cutoffs of >100 arbitrary units (a.u.) for epithelial cellular adhesion molecule (EpCAM) and <100 a.u. for CD45. They analyzed malignant pleural fluid from three patients under seven processing and/or staining conditions, three patients after short-term storage under three conditions, and seven samples following long-term storage at -80°C. MFI values of 4',6-diamidino-2-phenylindol, cytokeratin, CD45, and EpCAM were compared. RESULTS: ETCs were detected in all conditions. Among the different processing conditions tested, the ethanol-fixed, unstained TP was most similar to the previously established air-dried, unstained TP protocol. All smears and Pap-stained TPs had significantly different marker MFIs from the established condition. After short-term storage, the established condition showed comparable results, but ethanol-fixed and Pap-stained slides showed significant differences. ETCs were detectable after long-term storage at -80°C in comparable numbers to freshly prepared slides, but most marker MFIs were significantly different. CONCLUSIONS: It is possible to detect ETCs under different processing and storage conditions, lending promise to the application of this method in broader settings. Because of decreased immunofluorescence-signature distinctions between cells, morphology may need to play a larger role.

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.

[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.

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase.

BACKGROUND: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L. METHODS: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively. RESULTS: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP. CONCLUSION: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

IR808@MnO nano-near infrared fluorescent dye's diagnostic value for malignant pleural effusion.

BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.