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The Patient-Derived Organoids (PDOs) has demonstrated significant potential in personalized medicine. However, the initial establishment of lung cancer organoids (LCOs), and timely therapeutic recommendations face several challenges. Particularly, the current culture systems have not yet achieved the capability to long-term cultivation of all lung tumor sample sources, including malignant pleural effusion (MPE), which poses significant barriers to the rapid clinical translation of PDOs. Here, we established a LCOs biobank derived from various tumor cell origins and investigated the impact of supplementing culture media with MPE supernatant on organoid formation, culture duration, and drug sensitivity. Our findings indicate that MPE can enhance the successful rate of LCOs by extending the passage number and promoting the initial formation of difficult-to-culture samples, such as those derived from MPE or cell lines that were previously unsuccessful in Airway Organoid (AO) medium. MPE also facilitates the rapid proliferation of LCOs, reducing the culture duration by over 50%. Additionally, LCOs exhibit increased chemoresistance in the presence of MPE, which modifies stem cell distribution and reshapes the internal structure of the organoids. Overall, this study highlights the significance of MPE in facilitating the establishment and maintenance of LCOs, and its potential for translational applications in lung cancer research and personalized. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion is the presence of malignant cells within the pleural fluid, representing the second most common cause of pleural exudate. Although diagnostic methods and management techniques for malignant pleural effusion have dramatically improved over the decades, the current treatment is still palliative, aiming to remove pleural fluid, possibly prevent its recurrence, and alleviate symptoms through a wide range of available procedures. Treatment should be tailored to the individual patient, considering comorbidities, size of the effusion, rate of fluid accumulation, underlying cardiac or respiratory conditions, rate of recurrence, presence of loculations or trapped lung, tumor characteristics, cancer type, and patient preferences. This manuscript aims to review the available literature and to present the latest evidence on malignant pleural effusion management in order to provide an updated perspective on its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: There are guidelines recommending the use of Indwelling pleural catheter (IPC), but there is no established consensus or guidelines regarding the modality of drainage post-IPC insertion. We have devised a novel drainage technique that combines the advantages of both aggressive and symptom-guided drainage. Method: This was a prospective intervention trial in which patients with malignant pleural effusion, drained with IPC, were initially given one week of 'high-intensity' drainage on an outpatient basis using a low-pressure suction pump, followed by symptom-based home drainage using vacuum bottles. Patients were assessed for improvement in breathlessness, the number of autos pleurodesis, and the number of vacuum bottles consumed. Results: A total of 25 patients with malignant pleural effusion who satisfied the inclusion criteria were selected. The mean breathlessness as per the visual analogue scale (VAS) was 87 before the insertion of IPC, which decreased to 48.2 immediately after IPC insertion and drainage. The 'high-intensity' drainage was able to maintain this fall in VAS. Thirteen patients (52%) achieved pleurodesis, of which 10 achieved pleurodesis after 5 weeks of IPC insertion, and 3 achieved pleurodesis after 7 weeks of IPC insertion. Eleven patients (44%) had the IPC in situ until death. One patient had the IPC removed due to empyema. None of the 10 patients who achieved pleurodesis within 5 weeks of IPC insertion had to use vacuum bottles at home for 'symptom-guided' fluid drainage. Conclusion: This novel method of draining malignant pleural effusion brought about symptomatic improvement, increase auto-pleurodesis, and thereby reduce the number of vacuum bottles consumed in the study population. [ABSTRACT FROM AUTHOR]

Background and Objectives: The diversity of patients with malignant pleural effusion (MPE) due to non-small cell lung cancer (NSCLC) as well as the variability in mutations makes it essential to improve molecular characterization. Objective: Describe clinical, pathological, and molecular characteristics MPE in a Caucasian population. Materials and Methods: Retrospective study of patients with NSCLC diagnosis who had undergone a molecular study from 1 January 2018–31 December 2022. Univariate analysis was performed to compare patient characteristics between the group with and without MPE and molecular biomarkers. Results: A total of 400 patients were included; 53% presented any biomarker and 29% had MPE.PDL1, which was the most frequent. EGFR mutation was associated with women (OR:3.873) and lack of smoking (OR:5.105), but not with MPE. Patients with pleural effusion were older and had lower ECOG. There was no significant difference in the presence of any biomarker. We also did not find an association between the presence of specific mutations and MPE (22.4% vs. 18%, p = 0.2), or PDL1 expression (31.9% vs. 35.9%, p = 0.3). Being younger constituted a protective factor for the presence of MPE (OR:0.962; 95% CI 0.939–0.985, p = 0.002), as well as ECOG ≤ 1 (OR:0.539; 95% CI 0.322–0.902, p = 0.01). Conclusions: This is the first study that describes the clinical, pathological, and molecular characteristics of MPE patients due to NSCLC in a Caucasian population. Although overall we did not find significant differences in the molecular profile between patients with MPE and without effusion, EGFR mutation was associated with a tendency towards pleural progression. [ABSTRACT FROM AUTHOR]

Background: Though the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE. Methods: We retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups. Results: The mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age < 50 years patients, the shorter the overall survival, while age > 50 years patients was not. (P < 0.05). Conclusions: There was no difference in the overall survival between luminal B-BC patients with MPE and those without. Clinical stages at initial diagnosis were an independent prognostic factor for age < 50 years luminal B BC with MPE overall survival. Our results may help clinicians make positive decisions regarding personalized treatment of luminal B-BC with MPE. [ABSTRACT FROM AUTHOR]

Background: There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy. Methods: A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort. Results: The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort. Conclusion: We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy. [ABSTRACT FROM AUTHOR]

RET fusions were discovered in non-small cell lung cancer (NSCLC), and the efficacy of RET-targeted treatment in these patients has been previously established. However, patients with required resistance to RET-TKIs have limited treatment options. Herein, we describe a case of critical and advanced lung adenocarcinoma harboring RET fusion. Despite a significant response to Prasetinib previously, the patient developed refractory malignant pleural effusion after 24 months of treatment. He was treated simultaneously with intrapleural plus systemic Tislelizumab injection combined chemotherapy, thereby achieving an excellent clinical benefit maintaining control of pleural effusion for over 6 months. Hence, we would like to discuss intrapleural immunotherapy as an additional treatment method in refractory malignant pleural effusion while demonstrating good treatment tolerance. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) is one of the most common complications of advanced malignant diseases. The patients with MPE have a short survival time and poor prognosis. Clinical therapeutic measures have greatly improved with the deepened exploration of the mechanisms of MPE. Diagnosis hinges on cytology, which is typically based on pleural fluid aspiration or pleural biopsy. Although numerous interventions exist, local palliative treatment is favored for the treatment of MPE. Such treatment aims to alleviate symptoms, such as aggravated dyspnea, and prolong survival time. As molecular targeted therapies and immunotherapies have developed, new diagnostic procedures and treatments have become available for patients with MPE. The recent discovery of the progrowth property of pleural fluid which may be an active promoter of cancer progression suggests that early intervention for the management of MPE may have a positive effect on inhibiting cancer progression and improving prognosis. In coming years, considerable effort should be directed at sophisticated biomarker analysis to select appropriate treatment strategies for the management of MPE. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) is a common cancer complication. Clinical and economic implications of different recurrent MPE treatment pathways have not been evaluated fully. What clinical outcomes, complications, health care resource use, and costs are associated with various rapidly recurrent MPE treatment pathways? This retrospective cohort study using Surveillance, Epidemiology and End Results Medicare data (2011-2015) included patients 66 to 90 years of age with rapidly recurrent MPE. Rapid recurrence was defined as receipt of a second pleural procedure within 14 days of the first thoracentesis, including nondefinitive repeated thoracentesis or a definitive treatment option including chest tube, indwelling pleural catheter (IPC), or thoracoscopy. Among 8,378 patients with MPE, 3,090 patients (36.9%) had rapidly recurrent MPE (mean ± SD age, 75.9 ± 6.6 years; 45.6% male; primary cancer, 62.9% lung and 37.1% other). Second pleural procedures were nondefinitive thoracentesis (62.3%), chest tube (17.1%), IPC (13.2%), or thoracoscopy (7.4%). A third pleural procedure was required more frequently if the second pleural procedure was nondefinitive thoracentesis vs chest tube placement, IPC placement, or thoracoscopy (70.3% vs 44.1% vs 17.9% vs 14.4%, respectively). The mean number of subsequent pleural procedures over the patient's lifetime varied significantly among the procedures (1.74, 0.82, 0.31, and 0.22 procedures for patients receiving thoracentesis, chest tube, IPC, and thoracoscopy, respectively; P <. 05). Average total costs after the second pleural procedure to death adjusted for age at primary cancer diagnosis, race, year of second pleural procedure, Charlson comorbidity index, cancer stage at primary diagnosis, and time from primary cancer diagnosis to diagnostic thoracentesis were lower with IPC ($37,443; P <.0001) or chest tube placement ($40,627; P =.004) vs thoracentesis ($47,711). Patients receiving thoracoscopy ($45,386; P =.5) incurred similar costs as patients receiving thoracentesis. Early definitive treatment was associated with fewer subsequent procedures and lower costs in patients with rapidly recurrent MPE. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer in women. Progression-free survival for hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer treated with endocrine therapy in combination with cyclin4/6-dependent kinase is approximately 25 months. This case represents metastatic breast cancer treated with endocrine therapy, leading to long-term survival. Case presentation: A 40-year-old Syrian woman diagnosed with hormone receptor-negative breast cancer was treated surgically with adjuvant chemotherapy and radiotherapy. She developed local and nodal recurrences that were hormone receptor-positive, followed by a recurrence of malignant pleural effusion. She was initially treated with chemotherapy and then placed on endocrine therapy with a complete response from 2014 until now. The patient also suffered from adverse events of medications, such as heart failure and osteoporosis, which were treated appropriately. Conclusion: This case demonstrates a long-lasting complete response to metastatic breast cancer with malignant pleural effusion. This shows the validity of endocrine therapy in recurrent hormone receptor-positive breast cancer, especially in countries that cannot afford targeted therapies or genetic tests. It also highlights the necessity for a better understanding of the prognostic and predictive factors. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion is the presence of malignant cells within the pleural fluid, representing the second most common cause of pleural exudate. Although diagnostic methods and management techniques for malignant pleural effusion have dramatically improved over the decades, the current treatment is still palliative, aiming to remove pleural fluid, possibly prevent its recurrence, and alleviate symptoms through a wide range of available procedures. Treatment should be tailored to the individual patient, considering comorbidities, size of the effusion, rate of fluid accumulation, underlying cardiac or respiratory conditions, rate of recurrence, presence of loculations or trapped lung, tumor characteristics, cancer type, and patient preferences. This manuscript aims to review the available literature and to present the latest evidence on malignant pleural effusion management in order to provide an updated perspective on its diagnosis and treatment.

Abstract The Patient-Derived Organoids (PDOs) has demonstrated significant potential in personalized medicine. However, the initial establishment of lung cancer organoids (LCOs), and timely therapeutic recommendations face several challenges. Particularly, the current culture systems have not yet achieved the capability to long-term cultivation of all lung tumor sample sources, including malignant pleural effusion (MPE), which poses significant barriers to the rapid clinical translation of PDOs. Here, we established a LCOs biobank derived from various tumor cell origins and investigated the impact of supplementing culture media with MPE supernatant on organoid formation, culture duration, and drug sensitivity. Our findings indicate that MPE can enhance the successful rate of LCOs by extending the passage number and promoting the initial formation of difficult-to-culture samples, such as those derived from MPE or cell lines that were previously unsuccessful in Airway Organoid (AO) medium. MPE also facilitates the rapid proliferation of LCOs, reducing the culture duration by over 50%. Additionally, LCOs exhibit increased chemoresistance in the presence of MPE, which modifies stem cell distribution and reshapes the internal structure of the organoids. Overall, this study highlights the significance of MPE in facilitating the establishment and maintenance of LCOs, and its potential for translational applications in lung cancer research and personalized.

Abstract Background Though the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE. Methods We retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups. Results The mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age 50 years patients was not. (P

Malignant pleural effusion (MPE) is one of the most common complications of advanced malignant diseases. The patients with MPE have a short survival time and poor prognosis. Clinical therapeutic measures have greatly improved with the deepened exploration of the mechanisms of MPE. Diagnosis hinges on cytology, which is typically based on pleural fluid aspiration or pleural biopsy. Although numerous interventions exist, local palliative treatment is favored for the treatment of MPE. Such treatment aims to alleviate symptoms, such as aggravated dyspnea, and prolong survival time. As molecular targeted therapies and immunotherapies have developed, new diagnostic procedures and treatments have become available for patients with MPE. The recent discovery of the progrowth property of pleural fluid which may be an active promoter of cancer progression suggests that early intervention for the management of MPE may have a positive effect on inhibiting cancer progression and improving prognosis. In coming years, considerable effort should be directed at sophisticated biomarker analysis to select appropriate treatment strategies for the management of MPE.

Abstract Background There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy. Methods A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort. Results The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P

Abstract Background Breast cancer is the most common cancer in women. Progression-free survival for hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer treated with endocrine therapy in combination with cyclin4/6-dependent kinase is approximately 25 months. This case represents metastatic breast cancer treated with endocrine therapy, leading to long-term survival. Case presentation A 40-year-old Syrian woman diagnosed with hormone receptor-negative breast cancer was treated surgically with adjuvant chemotherapy and radiotherapy. She developed local and nodal recurrences that were hormone receptor-positive, followed by a recurrence of malignant pleural effusion. She was initially treated with chemotherapy and then placed on endocrine therapy with a complete response from 2014 until now. The patient also suffered from adverse events of medications, such as heart failure and osteoporosis, which were treated appropriately. Conclusion This case demonstrates a long-lasting complete response to metastatic breast cancer with malignant pleural effusion. This shows the validity of endocrine therapy in recurrent hormone receptor-positive breast cancer, especially in countries that cannot afford targeted therapies or genetic tests. It also highlights the necessity for a better understanding of the prognostic and predictive factors.

Abstract Background Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology. Methods The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry. Results FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA. Conclusions FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion.

Serum and pleural fluid tumor markers are well-recognized auxiliary diagnostic tools for malignant pleural effusion (MPE). Here, we discuss some pearls and pitfalls regarding the role of tumor markers in MPE management. The following issues are discussed in this article: What is the appropriate clinical scenario for evaluating pleural tumor markers? Which tumor markers should be advocated for diagnosing MPE? Can extremely high levels of tumor markers be employed to establish a diagnosis of MPE? Does the serum-to-pleural fluid ratio of a tumor marker have the same diagnostic efficacy as the measurement of that marker alone in the pleural fluid? Can tumor markers be used to estimate the risk of specific cancers? What should be considered when interpreting the diagnostic accuracy of tumor markers? How should tumor marker studies be performed? We addressed these issues with published works, particularly systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]

Background: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy. Method: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology. Results: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor. Conclusion: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) poses a significant challenge in local treatment, primarily attributed to its intricate tumor immune microenvironment. The immunosuppression of natural killer (NK) cells within the microenvironment, exacerbated by selenium (Se) deficiency, constitutes a pivotal treatment bottleneck. Building upon prior investigations, this study delves into the impact and mechanisms of functionalized lentinan selenium nanoparticles (LET‐SeNPs) on NK cells in MPE, presenting a novel local treatment strategy for lung adenocarcinoma with malignant pleural effusion (MPE‐LA). The synergistic application of LET‐SeNPs serves to replenish Se levels in MPE, modulate NK cells, augment their quantity, restore and enhance their functionality. Additionally, LET‐SeNPs facilitate NK cells activation through the TrxR1‐IL18RAP‐pSTAT3 pathway, resulting in effective lung cancer cell eradication and reduced pleural effusion production. Furthermore, pre‐stimulation of NK cells by LET‐SeNPs, combined with CAR‐NK cell therapy, harnesses the innate immune system, exhibiting a potent anti‐tumor effect. This research introduces a compelling strategy to advance the clinical implementation of targeted nanomaterials or lead compounds with explicit targets and mechanisms, thereby enhancing NK cell therapy for comprehensive diagnosis and treatment of MPE. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing—NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE. Methods: From July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram's performance, including calibration, discrimination, and clinical applicability. Results: Seven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients. Conclusion: This study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology. Methods: The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry. Results: FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA. Conclusions: FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural effusion (MPE) affects up to 15% of patients with malignancy, and the prevalence is increasing. Non-expandable lung (NEL) complicates MPE in up to 30% of cases. However, it is not known if patients with malignant pleural effusion and NEL are more symptomatic in activities of daily living compared to patients with MPE with expandable lung. Methods: This was an observational study on consecutively recruited patients with MPE from our pleural clinic. Before thoracentesis, patients completed patient-reported outcomes on cancer symptoms (ESAS), health-related quality of life (5Q-5D-5L), and dyspnoea scores. Following thoracentesis, patients scored dyspnoea relief and symptoms during thoracentesis. Data on focused lung ultrasound and pleural effusion biochemistry were collected. The non-expandable lung diagnosis was made by pleural experts based on radiological and clinical information. Results: We recruited 43 patients, including 12 with NEL (28%). The NEL cohort resembled those from previous studies concerning ultrasonography, pleural fluid biochemistry, and fewer cases with high volume thoracentesis. Patients with and without NEL were comparable concerning baseline demography. The 5Q-5D-5L utility scores were 0.836 (0.691–0.906) and 0.806 (0.409–0.866), respectively, for patients with and without NEL. We observed no between-group differences in symptom burden or health-related quality of life. Conclusion: While the presence of NEL affects the clinical management of recurrent MPE, the presence of NEL seems not to affect patients' overall symptom burden in patients with MPE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chemical pleurodesis using tetracycline is an acceptable and commonly employed palliation for malignant pleural effusion. Rotation of patient during pleurodesis using the powder from tetracycline capsule is still practised in some centres and is undoubtedly associated with additional stress on the patients. The practice of rotation can only be eliminated after a properly designed study on the outcome of pleurodesis with rotation and non-rotation would fail to show benefit of rotation. Objective: To determine the association between patients positioning and the outcome of tetracycline pleurodesis in patients with malignant pleural effusion. Patients and methods: It is a prospective randomized study involving adults patients with cytologically proven malignant pleural effusion. Patients were randomized into 2 groups (rotation and supine) using alternate sampling technique. Tube thoracostomy was done and tetracycline pleurodesis using 2g of powder from tetracycline capsule via slurry instillation method was carried out. The outcome of the pleurodesis was assessed with a chest radiograph on the 30th day after removal of chest tube. Results: There were 51 patients studied with malignant pleural effusion. These consisted of 12 males (23.5%) and 39 females (76.5%). Twenty-five patients (49.0%) were rotated in the study while 26 patients (51.0%) were on supine position. A total of 30 patients (58.8%) achieved complete response, 16 patients (31.4%) achieved partial response while 5 patients (9.8%) had failed response. The study also showed that in the rotated group, 23 patients (92%) had successful response and 23 patients (88.5%) in the supine group also achieved successful response (P = 0.175); there was no significant difference between the two groups. Conclusion: This study showed that, though the powder from tetracycline capsule is only slightly soluble in water, it gives a good and similar successful outcome in both arms of the study. This implies that positioning of patient during pleurodesis plays no significant role in the outcome of tetracycline pleurodesis using the powder from tetracycline capsule.

Background: Although pleural fluid adenosine deaminase (ADA) level >70 U/L suggestive tuberculous pleural effusion (TPE). High ADA levels can also be seen in pneumonia, empyema, lymphoma, malignancy, and rheumatoid pleuritis. Elevated pleural fluid lactate dehydrogenase (LDH) is seen in tubercular pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). Therefore, it is challenging distinguish between TPE, PPE, and MPE based on elevated pleural fluid ADA and LDH levels. In this study, we evaluated the use of pleural fluid LDH/ADA ratio as a new parameter for etiological differentiation of exudative pleural effusions. Materials and Methods: A retrospective hospital-based observational study conducted in GHCCD, Visakhapatnam. A total of 52 patients (TPE – 19, PPE – 16, and MPE – 17) with exudative pleural effusion who fulfilled inclusion criteria were taken into study. Qualitative variables have been described in the form of frequency and percentages. Median and interquartile ranges were used for nonnormal distribution values. Receiver operating curve (ROC) curves with area under the curve (AUC) were calculated. P ≤ 0.05 was considered statistically significant. Results: The mean ADA value for TPE was 75.4 U/L (25–195 U/L), PPE was 59.1 U/L (13–180 U/L), and for MPE was 35.52 U/L (10–75 U/L). The mean LDH value for TPE was 887.8 U/L (139–2213 U/L), PPE was 1128 U/L (334–3110 U/L), and for MPE was 1470 U/L (234–4285 U/L). On ROC analysis, pleural LDH/ADA ratio ≤20.81 diagnose TPE with (sensitivity – 84.2%, specificity – 63.6%) with AUC of 0.758 (95% confidence interval [CI]: 0.619–0.866) (P = 0.0001) whereas LDH/ADA ratio in the diagnosis of PPE was found to be >23.39 (sensitivity – 50%, specificity – 66.7%) with AUC of 0.535 (95% CI: 0.391–0.674) (P = 0.689) and the cutoff LDH/ADA ratio in the diagnosis of MPE was found to be >20.86 (sensitivity – 70.6%, specificity – 68.6%) with AUC of 0.724 (95% CI: 0.583–0.839) (P = 0.007). The cutoff value of the LDH/ADA ratio in PPE does not reach the statistical significant value. Conclusion: Pleural fluid LDH/ADA ratio ≤20.81 U/L is predictive of TPE, and >20.86 U/L is predictive of MPE and the cutoff value of 20.8 U/L can be used for etiological differentiation of pleural effusion.

Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space.

Abstract 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

Abstract Objective To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). Methods PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. Results Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P

Background Pleural effusion may be malignant or nonmalignant, Cytology has been used in malignant pleural effusion (MPE) diagnosis due to its high specificity. Its sensitivity is about 0.6. Cancer ratio (CR) and carcinoembryonic antigen (CEA) may be used in MPE diagnosis. Aim Evaluate the role of CR and CEA as diagnostic markers of MPE and their role in differentiating different types of MPE. Patients and methods This cross-sectional study included 70 patients with pleural effusion admitted to Chest Department, Kasr Alainy Faculty of Medicine, Cairo University. Thirty-five patients had benign pleural effusions and 35 patients had MPE. Pleural fluid sample obtained from each patient for ADA, CEA, and serum LDH. CR and pleural fluid CEA were compared between patients with MPE and those with benign effusion. Results CR was statistically significantly higher in the malignant group (mean 23.66 ± 7.75) compared with benign group (mean 14.47 ± 11.42) with P value less than 0.001. CR cut-off value was 19.79, the sensitivity and specificity were 74.3 and 82.9%, respectively. Pleural fluid CEA had higher levels in malignant group (mean 104.78 ± 262.7) compared with benign group (mean 2.08 ± 2.49) with P value less than 0.001. The cut-off value of CEA was 3.4 U/l with sensitivity 74.3% and specificity 94.3%. Pleural fluid CEA was significantly higher in metastatic adenocarcinoma (mean 154.58 ± 314.53) compared with other types of malignancy (mean 9.34 ± 17.98) with P value less than 0.001. Conclusion CR and CEA could be used together as simple screening tests in cytology negative MPE with high specificity and sensitivity. CEA was significantly higher in metastatic adenocarcinoma compared with other types of malignancy and could be used to differentiate different types of MPE.

Abstract 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.

Abstract Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of 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.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients’ prognosis. (233 words)

Malignant pleural effusion (MPE) is a manifestation of advanced cancer that requires a prompt and accurate diagnosis. Ultrasonography (US) and computed tomography (CT) are valuable imaging techniques for evaluating pleural effusions; however, their relative predictive ability for a malignant origin remains debatable. This prospective study aimed to compare chest US with CT findings as predictors of malignancy in patients with undiagnosed exudative pleural effusion. Fifty-four adults with undiagnosed exudative pleural effusions underwent comprehensive clinical evaluation including chest US, CT, and histopathologic biopsy. Blinded radiologists evaluated the US and CT images for features suggestive of malignancy, based on predefined criteria. Diagnostic performance measures were calculated using histopathology as a reference standard. Of the 54 patients, 33 (61.1%) had MPEs confirmed on biopsy. No significant differences between US and CT were found in detecting parietal pleural abnormalities, lung lesions, chest wall invasion, or liver metastasis. US outperformed CT in identifying diaphragmatic pleural thickening ≥10 mm (33.3% vs. 6.1%, p < 0.001) and nodularity (45.5% vs. 3%, p < 0.001), whereas CT was superior for mediastinal thickening (48.5% vs. 15.2%, p = 0.002). For diagnosing MPE, diaphragmatic nodularity detected by US had 45.5% sensitivity and 100% specificity, whereas CT mediastinal thickening had 48.5% sensitivity and 90.5% specificity. Both US and CT demonstrate reasonable diagnostic performance for detecting MPE, with particular imaging findings favoring a malignant origin. US may be advantageous for evaluating diaphragmatic pleural involvement, whereas CT is more sensitive to mediastinal abnormalities. [ABSTRACT FROM AUTHOR]

Background: Spheroids generated by tumor cells collected from malignant pleural effusion (MPE) were shown to retain the characteristics of the original tumors. This ex vivo model might be used to predict the response of non-small cell lung cancer (NSCLC) to anticancer treatments. Methods: The characteristics, epidermal growth factor receptor (EGFR) mutation status, and clinical response to EGFR-TKIs treatment of enrolled patients were recorded. The viability of the spheroids generated from MPE of enrolled patients were evaluated by visualization of the formazan product of the MTT assay. Results: Spheroids were generated from 14 patients with NSCLC-related MPE. Patients with EGFR L861Q, L858R, or Exon 19 deletion all received EGFR-TKIs, and five of these seven patients responded to treatment. The viability of the spheroids generated from MPE of these five patients who responded to EGFR-TKIs treatment was significantly reduced after gefitinib treatment. On the other hand, gefitinib treatment did not reduce the viability of the spheroids generated from MPE of patients with EGFR wild type, Exon 20 insertion, or patients with sensitive EGFR mutation but did not respond to EGFR-TKIs treatment. Conclusion: Multicellular spheroids generated from NSCLC-related MPE might be used to predict the response of NSCLC to treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). Methods: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. Results: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. Conclusion: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion. Methods: This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed. Results: The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05). Conclusion: The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes. [ABSTRACT FROM AUTHOR]

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%. Conclusion 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. [ABSTRACT FROM AUTHOR]

Objective: To study Diagnostic value of Cytokeratin 19 fragment (CYFRA21-1), matrix metalloproteinase-3 (MMP-3) and carcinoembryonic antigen (CEA) combined with cytology in malignant pleural effusion. Methods: 100 patients with pleural effusion admitted to our hospital from January 2020 to January 2023 were selected for study, and were divided into experimental group (47 cases with malignant pathological examination results) and control group (53 cases with benign pathological examination results) according to pathological findings. The changes of serum CYFRA21-1, MMP-3, CEA and cytology levels and their diagnostic value were analyzed. Results: The serum levels of CYFRA21-1, MMP-3 and CEA in experimental group were significantly higher than those in control group (P<0.05). The positive rates of CYFRA21-1, MMP-3, CEA and cytology in experimental group were significantly higher than those in control group (P<0.05). The AUC of CYFRA21-1 in the diagnosis of malignant pleural effusion was 0.989, 95%CI was 0.977~1.000. The AUC and 95%CI of MMP-3 in the diagnosis of malignant pleural effusion were 0.979 and 0.964-0.994. The AUC for CEA diagnosis of malignant pleural effusion was 0.982, 95%CI was 0.967~0.997. The AUC and 95%CI for the diagnosis of malignant pleural effusion were 0.823, 0.766~0.879, and the AUC and 95%CI for combined detection were 0.995 and 0.990~1.000, which were significantly different from the area under the curve for single detection. The specificity and accuracy are higher than that of single detection. Conclusion: CYFRA21-1, MMP-3 and CEA combined with cytology can effectively improve the accuracy of diagnosis of malignant pleural effusion, and have high clinical application value. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) is one of the common complications of lung cancer. The quality of life and prognoses for MPE patients are significantly compromised. Controlling the production of MPE can relieve patients' symptoms, improve their quality of life, and prolong their survival. This article presents a case of advanced non-small cell lung cancer (NSCLC) with MPE and negative driver genes. The patient received envafolimab and Endostar in combination, resulting in a complete reduction of MPE and durable clinical benefits. The exploratory use of this treatment method improved the quality of life of this patient and has the potential to prolong the survival of this patient. [ABSTRACT FROM AUTHOR]

Background Pleural effusion may be malignant or nonmalignant, Cytology has been used in malignant pleural effusion (MPE) diagnosis due to its high specificity. Its sensitivity is about 0.6. Cancer ratio (CR) and carcinoembryonic antigen (CEA) may be used in MPE diagnosis. Aim Evaluate the role of CR and CEA as diagnostic markers of MPE and their role in differentiating different types of MPE. Patients and methods This cross-sectional study included 70 patients with pleural effusion admitted to Chest Department, Kasr Alainy Faculty of Medicine, Cairo University. Thirtyfive patients had benign pleural effusions and 35 patients had MPE. Pleural fluid sample obtained from each patient for ADA, CEA, and serum LDH. CR and pleural fluid CEA were compared between patients with MPE and those with benign effusion. Results CR was statistically significantly higher in the malignant group (mean 23.66±7.75) compared with benign group (mean 14.47±11.42) with P value less than 0.001. CR cut-off value was 19.79, the sensitivity and specificity were 74.3 and 82.9%, respectively. Pleural fluid CEA had higher levels in malignant group (mean 104.78±262.7) compared with benign group (mean 2.08±2.49) with P value less than 0.001. The cut-off value of CEA was 3.4 U/l with sensitivity 74.3% and specificity 94.3%. Pleural fluid CEA was significantly higher in metastatic adenocarcinoma (mean 154.58±314.53) compared with other types of malignancy (mean 9.34±17.98) with P value less than 0.001. Conclusion CR and CEA could be used together as simple screening tests in cytology negative MPE with high specificity and sensitivity. CEA was significantly higher in metastatic adenocarcinoma compared with other types of malignancy and could be used to differentiate different types of MPE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of malignant pleural effusion. [ABSTRACT FROM AUTHOR]

Objective: Pleural procedure-related tumor seeding detected by computed tomography (CT) is common in lung cancer patients with malignant pleural effusion. This study aimed to identify the incidence of tumor seeding and the associated factors among lung cancer patients with malignant pleural effusions. Material and Methods: This retrospective cohort study was conducted on 146 lung cancer patients with malignant pleural effusions, diagnosed between 2010 and 2017, who underwent at least 1 pleural procedure and had at least 2 series of CT images. The potential factors were categorized into clinical characteristics, pleural characteristics, treatment factors, and pleural procedures. Incidence rate ratios (IRR) were analyzed by Poisson regression to identify factors that were independently associated with tumor seeding. Results: The incidence of procedure-related tumor seeding was 26%. Significantly increased IRRs of tumor seeding were found in relation to 1 time (IRR 5.653, 95% confidence interval [CI] 2.549 to 12.538) and ≥2 times of conventional intercostal chest drainage (ICD) insertion (IRR 5.837, 95% CI 1.768 to 19.266), 1 time (IRR 8.924, 95% CI 3.181 to 25.033) and ≥2 times of pleural biopsy (IRR 6.485, 95% CI 1.372 to 30.660), adenocarcinoma (IRR 8.329, 95% CI 2.804 to 24.747), and pleural thickening (IRR 12.458, 95% CI 1.360 to 114.152). Conclusion: Patients who had at least one pleural biopsy or ICD insertion, pleural fluid cytology positive or suspicious for malignancy, adenocarcinoma, or pleural thickening were found to be significantly at risk for tumor seeding.

BackgroundMany cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.MethodWe measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.ResultsEleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.ConclusionThe data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.