Clinical Value of Vascular Endothelial Growth Factor Combined with Interferon-γ in Diagnosing Malignant Pleural Effusion and Tuberculous Pleural Effusion

In order to investigate the clinical value of vascular endothelial growth factor （VEGF） combined with interferon-γ （IFN-γ） in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen （CEA）, VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase （ADA） activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve （AUCR^ROC） of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve （ROC）, The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group （P〈0,01）, The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio （88,7%, 99,8%, 94,4%, 0.96 respectively） were higher than those of CEA （67.8%, 96.1%, 82,4%, 0.78 respectively） and VEGF （81,5%, 84,3%, 82.9%, 0.79 respectively）. The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ （85.7%, 96,4%, 90.9%, 0.94 respectively） were higher than those of ADA （80,2%, 87,6%, 83.8%, 0,81 respectively）. It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.

Th17/Treg Imbalance in Malignant Pleural Effusion

Both T helper IL-17-producing cells （Thl7 cells） and regulatory T cells （Tregs） have been found to be increased in malignant pleural effusion （MPE）. However, the possible imbalance between Thl7 cells and Tregs, as well as the association of.Thl7/Treg and Thl/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th 17 cells in relation to Tregs, as well as Thl/Th2 balance in MPE. The number ofThl7, Tregs, Thl, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Thl7, Tregs, Thl, and Th2 cells was explored. It was found that the number of Thl7, Tregs, Thl, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Thl7 cells was correlated negatively with Tregs in MPE, but not in blood. Thl7 cells and Thl7/Treg ratio were positively, and Tregs were negatively, correlated with Thl cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Thl7 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Thl7/Treg imbalance exists in MPE.

Regional hyperthermia combined with intrapleural chemotherapy in patients with malignant pleural effusion

Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P < 0.01), 86.7% vs 56.3% (P > 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.

Study on the Correlation between Syndrome Differentiation of Malignant Pleural Effusion Treated by External Treatment of Traditional Chinese Medicine and Immunohistochemistry of Biopsy Tissue Based on Medical Video-assisted Thoracoscope

Objective:Guided by the theory of syndrome differentiation of yin and yang in traditional Chinese medicine surgery,through visual observation of internal medicine thoracoscope,comprehensive observation of pleural cavity and immunohistochemistry of biopsy tissue,to classify malignant pleural effusion according to syndrome differentiation,and to explore the scientific nature of its theory.Methods:From March 1,2014 to February 28,2015,40 cases of malignant pleural effusion were treated in Beijing Chaoyang Hospital affiliated to Capital Medical University.According to the proposed TCM diagnostic criteria for yin and yang syndrome differentiation,and collect age,gender,course of disease,clinical symptoms,tumor primary focus,histomorphological manifestations and immunohistochemical results and other related information,and carry out statistical data processing.Results:The positive syndrome was mainly metastatic lung adenocarcinoma,which accounted for the majority of all MPE cases,up to 75%.The immunohistochemical results of biopsy tissues were mainly CEA and TTF-1 positive;While pleural effusion caused by pleural mesothelioma was the main type of yin syndrome,and the results of immunohistochemistry combined with biopsy were mainly positive for D2-40,Calretinin,WT-1 and CK5/6.Conclusion:TCM syndrome differentiation of MPE based on internal thoracoscopy combined with biopsy immunohistochemical results has sufficient theoretical basis and certain scientific nature,and further clinical research is needed to verify its effectiveness and practicability in the future.

Observation of the curative effect between Nocardia rubra cell wall skeleton-injection combined with the intrapleural chemotherapy and following the intrapleural chemotherapy

Objective:To observe and compare the curative effect between the intrapleural-chemotherapy combined Nocardia rubra cell wall skeleton-injection and the Nocardia rubra cell wall skeleton-injection after control of the malignant pleural effusion by chemotherapy.Methods:Every time after elimination of pleural effusion,we injected DDP and Nocardia rubra cell wall skeleton at the same time into pleural cavity;or after we emplaced an improved central vena catheter into pleural cavity then took out closed-drainage or eliminated the pleural effusion every day,then injected 5-FU 0.5 qd intrapleural-space.After the malignant pleural effusion had being controlled,800μg Nocardia rubra cell wall skeleton was injected intrapleural-space. (We call it as"improved following-therapy").Results:Using the improved following-therapy,the control rate of malignant pleural effusion increased:CR+PR,79.07%>65.79%(P<0.05),and the incidence rate of the encapsulated pleural effusion that would impact on patient’s respiratory faction decreased.Conclusion:Giving chemotherapy after closed-drainage or immediately after taking out pleural effusion everyday,then giving biotherapy after pleural effusion had been controlled,the curative effect would be enhanced and the side-reaction would be reduced.

Immune Regulation of Interleukin-27 in Malignant Pleural Effusion

Background： lnterlcukin （IL）-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion （MPE） remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon （IFN）-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods： The distribution ofl L-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions otcytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription （STAT） signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results： The expression of IL-27 was increased in M PE when compared with blood （ 147.3 ± 25. 1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04）. IL-27 was noted to suppress both proliferation （18.33 ±0.21 vs. 27.77 ±0.88, P = 0.0005） and migration （1.82 ±0.44 vs. 3.13 ±0.07, P = 0.04） of A549 cells, but obviously prornoted apoptosis of A549 cells （9.47 ±1.14 vs. 4.96 ±0.17, P = 0.02） by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities ofA549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conelusions： IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9-dependent mechanism.

Clinical Observation on the Efficacy of Xiaoshui Decoction (消水方) Combined with Intrapleural Perfusion of Cisplatin in Treating Malignant Pleural Effusion

Objective： To observe the clinical efficacy of Xiaoshui decoction （XSD,消水方） combined with intrapleural perfusion of cisplatin in the treatment of malignant pleural effusion. Methods： Fifty-one patients with malignant pleural effusion were randomly assigned to two groups. The treated group patients） received oral administration of XSD combined with intrapleural perfusion of cisplatin, and control group （25 patients） was only treated with intrapleural perfusion of cisplatin. The effects of 26 he he short-term efficacy, quality of life scores and clinical symptom scores of malignant pleural effusion were evaluated. Results： The short-term efficacy in the treated group and the control group was 72.0% and 58.3%, respectively, and no significant difference was found （P〉0.05）. In contrast, the quality of life in the treated group was significantly improved compared to that of the control group （P〈0.05）, and so was the symptom remission （P〈0.05）. Conclusions： The combined therapy of XSD and intrapleural perfusion of cisplatin did not show obvious improvement in short-term efficacy, but the therapy remarkably alleviated the symptoms and improved the quality of life of patients.

Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung cancer:A potential marker of prognosis

Objective: Soluble CD40 (sCD40) is a potential modulator for both antitumor responses and CD40-based immunotherapy;however the levels and significance of sCD40 in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion are unknown. Methods: Forty-eight patients with lung cancer were treated in our institutions from January 2008 to January 2010. Peripheral blood and pleural effusion samples were collected from each subject. sCD40 levels in plasma and malignant pleural effusions supernatant were measured. The CD40L expression on CD3t T-cells was confirmed by flow cytometric direct immunofluorescence analysis. All patients were followed up after the study ended on January 1, 2010. Results: Patients with malignant pleural effusion of NSCLC had elevated circulating and pleural effusion levels of sCD40, and these elevated sCD40 levels were associated with advanced diseases and a poor prognosis. Conclusions: These findings indicate that elevated sCD40 may have a role in modulating antitumor responses and may also be a useful prognostic marker. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A STUDY OF THE CYTOTOXICITY OF MALIGNANT PLEURAL EFFUSION LYMPHOCYTES AND LAK CELLS AGAINST AUTOLOGOUS TUMOR CELLS

The cytotoxicity of malignant pleural effusion lymphocytes (MPEL) against autologous tumor cells (ATC) were compared with that of peripheral blood lymphocytes (PBL). It was demonstracted that the cytotoxicity of PBL was higher than that of MPEL (P< 0.001), but the cytotoxicity and expansion of MPEL-activated by rIL-2 was much higher than that of PBL activated by rIL-2 (LAK cells) (P< 0.001). This shows that local immune reaction of the pleural cavity of patients with malignant pleural effusion was in the state of suppression. MPEL activated are better effector cells than LAK cells in tumor adoptive immunotherapy.

Meta Analysis of Lentinan Injection plus Cisplatin in Treatment of Malignant Pleural Effusion

Objective To evaluate the efficacy and safety of lentinan injection plus cisplatin(LIC)in the treatment of malignant pleural effusion(MPE).Methods We searched the database of Cochrane Library,PubMed,EMBASE, ISI Web of Knowledge,Chinese Biomedical Literature Database,Chinese Scientific Journals Full-text Database, Chinese Journal Full-text,and Google Scholar,etc.,up to February 28th,2011 to identify randomized controlled trials(RCTs)about lentinan injection(LI)for MPE,evaluate the quality of the included studies,and analyze the data by Cochrane Collaboration’s RevMan5.0 software.Results Twenty-nine RCTs involving 1831 patients were included.Meta analysis results suggested that there were some differences when comparing LIC with control groups suffering from MPE,for LIC could improve the near-term curative effect and the quality of life to some extent. Besides,compared with chemotherapy alone,LI plus chemotherapy had an advantage in relieving adverse reactions, such as gastrointestinal reactions,myelosuppression,chest pain,and general malaise.Conclusion The current evidence indicates that LI may have adjuvant therapeutic effects for MPE.

Clinical Value of Tumor Markers for Determining Cause of Pleural Effusion

Background： It is often challenging to distinguish tuberculous pleural effusion （TPE） from malignant pleural effusion （MPE）;thoracoscopy is among the techniques with the highest diagnostic ability in this regard.However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition.The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 （CA 125）, carbohydrate antigen 199 （CA 199）, carcinoembryonic antigen （CEA）, neuron-specific enolase （NS E）, and squamous cell carcinoma （SCC） associated antigen in patients with TPE and MPE.Methods： Using electrochemiluminescence, we measured the concentration of tumor markers （TMs） in the pleural effusion and serum of patients with TPE （n =35） and MPE （n =95）.We used receiver operating characteristic （ROC） curve analysis to evaluate the TMs and differentiate between TPE and MPE.Results： The cut-offvalues for each TM in serum were： CA125, 151.55 U/ml;CA199, 9.88 U/ml;CEA, 3.50 ng/ml;NSE, 13.27 ng/ml;and SCC, 0.85 ng/ml.Those in pleural fluid were： CA125, 644.30 U/ml;CA199, 12.08 U/ml;CEA, 3.35 ng/ml;NSE, 9.71 ng/ml;and SCC, 1.35 ng/ml.The cut-offvalues for the ratio ofpleural fluid concentration to serum concentration （P/S ratio） of each TM were： CA125, 5.93;CA199, 0.80;CEA, 1.47;NSE, 0.76;and SCC, 0.90.The P/S ratio showed the highest specificity in the case of CEA （97.14%）.ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid （0.95） was significantly different from that in serum （0.85;P 〈 0.001）.Conclusions： TMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid.The combined detection of TMs can improve diagnostic sensitivity.

Renal cell carcinoma presents as pleural metastasis without pulmonary involvement

Although lung metastasis is common in renal cell carcinoma （RCC）, only a few cases of pleural metastasis without lung involvement have been reported. We present here not only a special case of pleural metastases from RCC without lung involvement, but also discussion about the specific metastatic pathway and the treatment of sole pleural metastasis.