Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy originating from mesothelial cells of the pleura, primarily associated with asbestos exposure, and is often characterized by poor prognosis. Due to the lack of specific clinical manifestations in the early stages, the diagnosis of MPM presents a significant challenge, leading to most patients being diagnosed at an advanced stage, which limits the effectiveness of surgical treatment. Consequently, systemic therapies are commonly required. Although Pemetrexed in combination with Platinum-based chemotherapy remains the first-line standard treatment for unresectable MPM, its therapeutic efficacy is limited, and more effective treatment strategies are urgently needed. In recent years, immune checkpoint inhibitors have made significant progress in the treatment of MPM, markedly improving patient survival outcomes. With the increasing depth of molecular biological research on MPM, targeted therapies offer promising personalized treatment options. Additionally, the therapeutic potential of novel strategies such as cell therapy and oncolytic virus therapy is beginning to emerge. This review summarizes the latest advancements in the medical treatment of MPM and looks forward to future therapeutic directions, aiming to provide insights for clinical practice.
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Humans ; Mesothelioma, Malignant ; Pleural Neoplasms/drug therapy* ; Lung Neoplasms/drug therapy*

Malignant pleural effusion (MPE) refers to the accumulation of pleural fluid caused by metastasis from primary pleural malignancies or tumors originating elsewhere. It is associated with a poor prognosis. Current treatment strategies primarily include systemic anti-tumor therapy and local management of MPE based on the primary tumor. Numerous studies have documented diverse approaches for the local control of MPE. This review summarizes recent advances in local treatment strategies for primary tumor-related MPE, highlighting emerging pharmacological agents and innovative techniques.
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Humans ; Pleural Effusion, Malignant/drug therapy*

BACKGROUND: A prognostic nutritional index (PNI) developed by nutritional status and inflammation are closely associated with poor prognosis in malignant tumors. However, the predictive impact of PNI in patients with malignant pleural effusion (MPE) remains inconclusive. The study aimed to determine the predictive value of PNI in prognosis and spontaneous pleurodesis among patients with MPE. METHODS: The patients diagnosed with advanced non-small cell lung cancer (NSCLC) with MPE in West China Hospital between January 2015 and December 2022 were reviewed and allocated randomly to development set(60%) and validation set(40%). After collecting clinical data, peripheral blood inflammation indices and calculating systemic inflammation indices, the effects of PNI on prognosis and spontaneous pleurodesis have been evaluated by Cox proportional hazards models, Kaplan-Meier method and Nelson-Aalen cumulative risk curve. RESULTS: In total, 261 patients diagnosed NSCLC with MPE were selected (development set: n=157; validation set: n=104), of whom 58.2% were aged <65 years, 53.6% were male and 95.8% were diagnosed with adenocarcinoma. The dichotomous cut-off value for PNI was 44.1, respectively. Compared with lower PNI (PNI<44.1) cases, patients with higher PNI (PNI≥44.1) showed significantly longer overall survival (36.5 vs 24.3 mon, P=0.02) and higher incidence of spontaneous pleurodesis (P=0.009). According to the multivariate Cox analysis, higher PNI was associated with good prognosis and successful spontaneous pleurodesis (P<0.05). According to the results of Cox regression analysis, the PNI-prognosis and PNI-spontaneous pleurodesis models are determined, the receiver operating characteristic (ROC) curves are drawn, and the area under the curves (AUC) value of development set are 0.694 (95%CI: 0.620-0.776) and 0.673 (95%CI: 0.590-0.737). CONCLUSIONS PNI is a reliable biomarker of prognosis and spontaneous pleurodesis in patients with MPE. Attention to the patient's nutritional status and inflammation may improve the prognosis and efficacy of pleural effusion.
Humans ; Male ; Female ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/mortality* ; Lung Neoplasms/mortality* ; Aged ; Prognosis ; Pleurodesis ; Pleural Effusion, Malignant/mortality* ; Nutrition Assessment ; Adult ; Nutritional Status

Humans ; Mesothelioma, Malignant/diagnosis* ; Diagnosis, Differential ; Adenocarcinoma/pathology* ; Mesothelioma/pathology* ; Lung Neoplasms/pathology* ; Biomarkers, Tumor ; Pleural Neoplasms/diagnosis* ; Extracellular Matrix Proteins

Humans ; Pleura/pathology* ; Solitary Fibrous Tumor, Pleural/pathology* ; Adenocarcinoma of Lung ; Lung Neoplasms ; Pleural Neoplasms/pathology*

Humans ; Mesothelioma/pathology* ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis* ; Pleural Effusion, Malignant ; Pleural Effusion/pathology*

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.
Humans ; Mesothelioma, Malignant/drug therapy* ; Mesothelioma/diagnosis* ; Pemetrexed/therapeutic use* ; Cisplatin/therapeutic use* ; Peritoneal Neoplasms/diagnosis* ; Pleural Neoplasms ; Lung Neoplasms/drug therapy*

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.
Humans ; Mesothelioma, Malignant ; Mesothelioma/diagnosis* ; Lung Neoplasms/genetics* ; Pleural Neoplasms/diagnosis* ; Prognosis ; Biomarkers, Tumor/analysis* ; Extracellular Matrix Proteins ; CD24 Antigen/genetics*

BACKGROUND: Thyroid function abnormality (TFA) is one of the common adverse reactions in patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy, but the risk factors of TFA and its relationship with efficacy are not completely clear. The purpose of this study was to explore the risk factors of TFA and its relationship with efficacy in patients with advanced NSCLC after immunotherapy. METHODS: The general clinical data of 200 patients with advanced NSCLC in The First Affiliated Hospital of Zhengzhou University from July 1, 2019 to June 31, 2021 were collected and analyzed retrospectively. χ² test and multivariate Logistic regression were used to explore the risk factors of TFA. Kaplan-Meier curve was drawn and Log-rank test was used for comparison between groups. Univariate and multivariate Cox analysis was used to explore the efficacy factors. RESULTS: A total of 86 (43.0%) patients developed TFA. Logistic regression analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS), pleural effusion and lactic dehydrogenase (LDH) were factors influencing TFA (P<0.05). Compared with normal thyroid function group, the median progression-free survival (PFS) of patients in the TFA group was significantly longer (19.0 months vs 6.3 months, P<0.001), and the objective response rate (ORR) (65.1% vs 28.9%, P=0.020) and disease control rate (DCR) (100.0% vs 92.1%, P=0.020) of the TFA group were better than those of the normal thyroid function group. Cox regression analysis showed that ECOG PS, LDH, cytokeratin 19 fragment (CYFRA21-1) and TFA were factors influencing prognosis (P<0.05). CONCLUSIONS ECOG PS, pleural effusion and LDH may be risk factors affecting the occurrence of TFA and TFA may be a predictor of the efficacy of immunotherapy. Patients with advanced NSCLC who have TFA after immunotherapy may obtain better efficacy.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Retrospective Studies ; Thyroid Gland ; Lung Neoplasms/therapy* ; Immunotherapy/adverse effects* ; Pleural Effusion

Background: The etiology of pleural effusion remains unclear in nearly 20% of cases. One way to diagnose malignancy is by doing pleural fluid cytology. There are factors that influence the yield of pleural fluid cytology and one of them is appropriate and timely fixation of samples. Currently, there is no local consensus regarding the timing with which the specimen should be fixed. Objective: The study aims to compare the yield of malignancy between early fixation versus usual fixation of pleural fluid samples, meaning there is no set time for fixation to be done. Methodology: The study employed a prospective cross-sectional research design. All patients with pleural effusion who fulfilled the criteria set by the study were included. Two sets of pleural fluid samples were collected amounting to 20cc each. First sample was assigned as Bottle #1 and placed immediately with fixative while the second sample was assigned as Bottle #2. Bottle #2 underwent routine fixation which follows no fixed or standard time of fixation. The time difference between the fixation of two sample groups greatly varied with Bottle #1 fixed immediately right after collection while Bottle#2 depends on the time it will be processed by the laboratory personnel. Both samples were submitted for cell block and cell cytology reading. Results: Characteristics of the 55 patients included in the study showed age group range from 41 to 65 years of age, with 27 male and 28 female patients. Only one third had history of smoking. There were 21.82% who had family history of cancer and with and suspicious mass on chest radiograph. Out of 55 patients, 29 patients had history of previous diagnosis of cancer, 23 had recurrent pleural effusion, and 28 had chest radiograph with suspicious nodules. Based on gross appearance, there were 20 serous and 21 sanguineous pleural fluid noted. Mean cell count was high (1,115.50 ± 741.02) with lymphocytic predominance (82.56 ± 24.46). Elevated protein concentration (5,388.25 ± 8,230.46) and LDH (484.17 ± 248.72) were noted. Glucose (8.78 ± 6.68 mmol/L) was low. There were 21 patients who had high WBC, 24 with high protein and 16 with elevated LDH. There were 3 patients who were positive for AFB and none for KOH. Comparative analysis showed that the pleural fluid samples assigned to the routinely fixed group which were handed to the nurse after thoracentesis, then forwarded to the laboratory through a ward laboratory aide or patient watcherfor fixation with with 95% alcoholby thelaboratory personnel significantly had a longer duration of 406.62 minutes as compared to immediately fixed at 12.27 minutes (P<0.01). For diagnosis of malignancy, significantly more cases were diagnosed in the immediately fixed group with 36.36% cases versus 18.18% (p=0.016). Conclusion Among patients with suspected malignant pleural effusions, early fixation of pleural fluid samples resulted in higher histopathology yields as compared to those fixed after going through the routine fixation.
Pleural Effusion, Malignant