Malignant pleural mesothelioma:The disdained member of thoracic oncology!

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure.The ban on asbestos has helped to lower the incidence,but in developing countries like India,it is expected to rise.It has an extended latency period usually progressing over decades and presents with nonspecific symptoms.It has a median survival ranging between 10-22 months.The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography(CT),magnetic resonance imaging,or positron emission tomography-CT,with the last two predicting the resectability of the tumor better than CT alone.A pleural biopsy along with an array of immunohistochemical markers,such as p16,BRCA1 associated protein 1,and claudin-4,are required for a definitive diagnosis.Several genetic alterations have prognostic significance as well.The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored.The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes.However,the latter continues to be a robust treatment option for patients with the epithelioid subtype.Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant,adjuvant,and palliative settings along with systemic treatment.This review article provides an overview of epidemiology,etiology,clinical manifestations,diagnostic approaches(including immunohistochemical and genetic markers),staging,and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery,chemotherapy,immunotherapy,and radiotherapy.It also sheds light on some recent studies(EMPHACIS,CALGB30901,Checkmate-743,etc.)that have led to significant developments in recent years with clinically meaningful results.

Effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion

Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural effusion treated in our hospital between April 2013 and December 2015 were selected and randomly divided into two groups, the observation group received intrapleural endostatin and mannatide infusion treatment and control group accepted routine intrapleural infusion treatment. 4 weeks after treatment, the pleural fluid samples were collected to determine the levels of tumor markers, invasion-related molecules, VEGF-related molecules and anti-tumor cytokines.Results:4 weeks after treatment, CEA, CYFRA21-1, NSE, SCC-Ag, CXCL12, CXCR4, MMP2, MMP9, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 levels in pleural fluid of observation group were significantly lower than those of control group while LASS2/TMSG-1, IFN-γ, IL-2, TNF-α, IL-17 and IL-23 levels were significantly higher than those of control group.Conclusion:Intrapleural endostatin and mannatide infusion treatment of malignant pleural effusion can more effectively kill cancer cells, inhibit cell invasion, angiogenesis and lymphangiogenesis, and enhance antitumor immune response.

Pleural Fluid Alkaline Phosphate Levels to Differentiate between Tuberculosis and Malignant Pleural Effusion a Tertiary Care Experience

Introduction: Pleural effusion (PF) is a common clinical presentation in several diseases. Tuberculosis is one of the most frequent causes of exudative pleural effusions in immunocompetent patients. Tuberculosis is the leading cause of morbidity and mortality from an infectious disease in developing countries. Pakistan is ranked fifth in the world in terms of tuberculosis high-burden countries. Various pleural fluid parameters have been used to identify the cause of pleural effusion. It has been discovered that tuberculous pleural effusions had a greater alkaline phosphatase (ALP) concentration than transudative effusions. This study used pleural fluid alkaline phosphatase levels to distinguish between tuberculous pleural effusion and malignant pleural effusion because there is little information from tuberculosis-high burden nations like Pakistan. Study Design: A descriptive cross-sectional study conducted at the Jinnah Postgraduate Medical Center in Karachi between October 2016 and October 2017. Material and Methods: The study comprised all patients who were admitted to the department of chest medicine at Jinnah post graduate medical centre (JPMC) of either gender between the ages of 18 and 70 who had exudative lymphocytic pleural effusions lasting two weeks or more included in the study. Non probability consecutive sampling was used to collect data. Patients who have tonsillitis, pharyngitis, pneumonia, asthma, Chronic obstructive pulmonary disease (COPD), or a history of hemoptysis, Bleeding disorders like, platelet function disorder, thrombocytopenia, Liver cirrhosis and Pregnant women were excluded. Parents’ informed consent was obtained after being informed of the study’s protocol, hazards, and advantages. Each patient had their level of pleural fluid alkaline phosphate (PALP) assessed. In order to evaluate the patient’s pleural effusion, a pre-made questionnaire was used. All the collected data were entered into the SPSS 20. An independent sample t-test was used to recognize alkaline phosphate levels association with pleural fluid secondary to tuberculosis or malignancy. Results: In this Descriptive Cross-Sectional Study, the total of 156 patients with age Mean ± SD of was 41.96 ± 17.05 years. The majority of patients 110 (70.5%) were male and 46 (29.5%) were female. Advanced age was associated with raised pleural fluid alkaline phosphatase. The difference of pleural fluid alkaline phosphate level between tuberculous v/s malignant group was found to be (38.03 ± 45.97) v/s (82.77 ± 61.80) respectively with P-value (P = 0.0001). Conclusion: Malignant pleural effusions had elevated PALP when compared to tuberculous pleural effusions in exudative lymphocytic pleural effusions;better differences are seen in older ages and shorter disease durations.

Malignant pleural mesothelioma mimics thoracic empyema: A case report

BACKGROUND Thoracic empyema and malignant pleural mesothelioma(MPM)are distinct medical conditions with similar symptoms,including cough,chest pain,and breathing difficulty.We present a rare MPM case mimicking thoracic empyema.Physicians must consider MPM risks for patients exposed to building material who exhibit lobulated pleural effusions,indicating thoracic empyema.CASE SUMMARY A 68-year-old retired male construction worker suffered from shortness of breath and chest tightness over 10 d,particularly during physical activity.A poor appetite and 4 kg weight loss over the past 3 wk were also reported.Chest images and laboratory data concluded a tentative impression of empyema thoracis(right).Video-assisted thoracic surgery with decortication and delobulation(right)was conducted.The pathological report yielded an MPM diagnosis.Refractory pleural bilateral effusions and respiratory failure developed postoperatively,and the patient died three weeks after the operation.CONCLUSION Thoracic empyema and MPM are distinct medical conditions that can present similar symptoms,and video-assisted thoracic surgery facilitates an accurate diagnosis.Empyema-mimicking presentations and postoperative refractory pleural effusion may indicate a poor MPM outcome.

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.

Management of recurrent malignant pleural effusions with a tunneled indwelling pleural catheter

In this review, we report on the use of indwelling pleural catheters in the treatment of malignant pleural effusions. We describe the most commonly used catheter. Also, treatment with indwelling pleuralcatheters as compared to talc pleurodesis is reviewed. A comparison of efficacy, costs, effects on quality of life, and complications is made. Only one randomized controlled trial comparing the two is available up to date, but several are underway. We conclude that treatment for malignant pleural effusions with indwelling pleural catheters is a save, cost-effective, and patientfriendly method, with low complication rates.

The diagnostic significance and the assessment of the value of vascular endothelial growth factor as a marker for success of chemical pleurodesis in malignant pleural effusion

Differential diagnosis of pleural effusion is an important issue, since the treatment modalities and prognosis strictly depend on early and correct diagnosis of the underlying etiology. We assessed the efficacy of vascular endothelial growth factor (VEGF) in the differential diagnosis of patients with malignant and non-malignant pleural diseases. And also is assessed of the VEGF as a marker for success of chemical pleurodesis in malignant pleural effusion. Pleural effusions of 40 patients with a mean age of 55 (range, 26 to 78 years) were examined. A total of 20 patients had malignant pleural effusion;malignant mesothelioma (n=7), lung cancer (n=5) and metastatic malignancies (n=8). Twenty patients had benign pleural effusion;fibrinous pleuritis (n=6), tuberculosis (n=3) empyema (n=5), congestive heart failure (n=3), and acute pancreatitis (n=3). Definitive diagnosis was obtained in all cases with blind or open pleural biopsy, and cytological examination. VEGF levels were determined by enzyme-linked immunosorbent assay. The VEGF level of pleural effusion was comparably higher in the malignant group. The mean level of VEGF in patients with malignant pleural effusions (21.7 ± 1.8 ng/ml) was significantly (P <0.001) higher than that of (13.2 ± 1.5 ng/ml) non-malignant effusions. No significant difference was found regarding the VEGF levels and histological types in malignant pleural effusions. Negative correlation was observed between success rate of pleurodesis and VEGF level of pleural effusion (p= 0.015). The measurement of VEGF levels in pleural effusion may be useful to differentiate malignant from nonmalignant pleural effusions. VEGF level may also be an important prognostic marker for effective treatment of the patients who had malignant pleural effusions with pleurodesis. It is important issue in here whether VEGF could be useful in prognostication of outcome of chemical pleurodesis or not.

GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma

Malignant pleural mesothelioma(MPM)is a rare tumor with poor prognosis and rising incidence.Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement.Numerous therapeutic advances have been made in recent years,including the use of less aggressive surgical techniques associated with lower morbidity and mortality(e.g.,pleurectomy/decortication),technological advancements in the field of radiotherapy(intensity-modulated radiotherapy,image-guided radiotherapy,stereotactic body radiotherapy,proton therapy),and developments in systemic therapies(chemotherapy and immunotherapy).These improvements have had as yet only a modest effect on local control and survival.Advances in the management of MPM and standardization of care are hampered by the evidence to date,limited by high heterogeneity among studies and small sample sizes.In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology,we review clinical,histologic,and therapeutic aspects of MPM,with a particular focus on all aspects relating to radiotherapy,including the current evidence base,associations with chemotherapy and surgery,treatment volumes and planning,technological advances,and reradiation.

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.

Comparison of intra-pleural injection efficacy between Endostar and Bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor-/anaplastic lymphoma kinase-lung adenocarci

Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.

Multiple bowel intussusceptions from metastatic localized malignant pleural mesothelioma:A case report

Localized malignant pleural mesothelioma (LMPM) is a rare occurrence, and gastrointestinal intra-luminal metastases have not previously been reported. Herein, we report a patient with LMPM who presented with a local recurrence 10 mo after initial en bloc surgical resection. Abdominal computed tomography was performed for intractable, vague abdominal pain with episodic vomiting, which showed a "target sign" over the left lower quadrant. Laparotomy revealed several intra-luminal metastatic tumors in the small intestine and colon and a segmental resection of metastatic lesions was performed. Unfortunately, the patient died of sepsis despite successful surgical intervention. Though local recurrence is more frequent in LMPM, the possibility of distant metastasis should not be ignored in patients with non-specifi c abdominal pain.

Malignant Pleural Mesothelioma in Young People

Background: malignant pleural mesothelioma (MPM) is characterized by long latency period between exposure to asbestos and development of the disease so we hypothesize that MPM in the young has different characteristics. Patients and Methods: This is a retrospective study including all eligible patients with malignant pleural mesothelioma presenting to National Cancer Institute, Cairo University during the period from 2008 to 2013. Patients were divided into two groups: Group 1: patients aged ≤45 years. Group 2: Patients aged >45 years. Both groups were assessed regarding different clinicpathological features. Primary Objectives: comparison of different epidemiological features of both groups. Secondary Objectives: assessment of clinical response (CR), progression free survival (PFS) and overall survival (OS) in both groups. Results: 102 Patients were included with median follow up of 14.4 months. Group (1) included 35 patients with mean age 40 ± 3.65 years (31 to 45 years). Group (2) included 67 patients with mean age of 58.6 ± 8.5 years (46 to 87 years). 68% of group (1) came from endemic areas which is significantly higher than group (2): (35.8%), p = 0.02. History of Asbestos exposure was highly significantly different between the 2 groups, 77.1% in group (1) versus 38.8% in group (2), p < 0.001. Other factors showed no significant differences between the two groups. Overall clinical response (CR + PR) was 20% in group (1) versus 17.9% in group (2). P = 0.7. There was a trend towards longer median PFS in young patients, (19.8 ± 8.4 versus 6.9 ± 1.4 months). p = 0.09. The median OS of young patients is significantly longer (20.6 ± 6.3 months) than older patients (11.4 ± 3.6). p = 0.05. Conclusions: Mesothelioma in the young is more sensitive to asbestos exposure, has better OS and likely a different disease entity which needs further studies to understand its underlying biological features.

The Role of Thymidylate Synthase in Pemetrexed-Resistant Malignant Pleural Mesothelioma Cells

We established new pemetrexed-resistant cells originating from malignant pleural mesothelioma MSTO-211H cells to clarify the mechanism involved in pemetrexed resistance in malignant pleural mesothelioma. In the pemetrexed-resistant cells, only thymidylate synthase (TYMS) mRNA was overexpressed among other well-known molecular targets and chemosensitivity determinants of pemetrexed, and the role of the TYMS gene was ascertained by artificial regulation induced by specific siRNA. Silencing the TYMS expression partially restored the cytotoxicity of pemetrexed. The resistant cells did not display other gene alterations related to folate metabolism. We conclude that the primary mechanism imparting resistance to these cells is specific up-regulation of TYMS function. Further, the TYMS gene may serve as a useful biomarker for the prediction of pemetrexed chemosensitivity in patients with malignant pleural mesothelioma. We also investigated the efficacy of 1-(3-C-ethynyl-β-D-ribo-pento furanosyl)cytosine (ECyd) in overcoming pemetrexed resistance;this compound is presently undergoing clinical trials in the USA as TAS-106. ECyd had a similar antitumor effect on the resistant cells as that on the parental cells. In the clinical treatment of malignant pleural mesothelioma, ECyd promises to emerge as a novel drug.

Complex Target Volume Delineation and Treatment Planning in Radiotherapy for Malignant Pleural Mesothelioma (MPM)

Introduction: Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. Materials and Methods: CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178° - 182°, the collimator angles of each arc were set to 90°, Octavius® 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. Results: A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. Conclusion: Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.

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.

Results of flexible 3D-conformal radiotherapy for patients with diffuse malignant pleural mesothelioma and comparative study of this technique with conventional radiotherapy

Objective： To observe the effects of the new technique of flexible 3D-conformal radiotherapy with combination of photon and electron （3DCRT） in the treatment of the patients with diffuse malignant pleural mesothelioma （MPM）, and carry out the comparative study between flexible 3DCRT and hemithoracic conventional radiotherapy （CRT）. Methods： From January 2004 to October 2007, 8 patients with MPM were treated with flexible 3DCRT. 5 patients had received cycles of chemotherapy before radiation. New technique of flexible 3DCRT with combination of photon and electron was used in our study, and DT 32.2-64 Gy with conventional split were delivered. CRT technique was mimicked to compare with 3DCRT technique to predict the possibility of lung damage in two methods. Results： One patient reached CR and other 7 patients got PR after radiation. Two patients died during the follow-up. The median survival time （MST） was 15.4 months and it was 18.8 months for sequential chemotherapy and radiotherapy group and 9.7 months for radiotherapy alone group. The V20, V30, and ipsilateral and contralateral median lung dosage （MLD） were 20.5%, 15.6%, 18.8 Gy and 2.2 Gy respectively when the flexible 3DCRT technique was used, whereas they were 36.8%, 27.9%, 31.1 Gy and 1.2 Gy respectively when the CRT technique was used. They were statistically different for the lung V20, V30 and ipsilateral MLD between the two techniques （P 〈 0.01）, whereas there was no different for the contralateral MLD （P = 0.08）. All patients received radiation were found to have lung fibrosis and classified as grades 1-2 radiation pneumonitis. The quality of life was increased from score 2.83 to 3.76 and it was significantly different （P 〈 0.01）. Conclusion： MPM is moderately sensitive to radiation. The flexible 3DCRT technique is feasible in the treatment of MPM and lung damage is reduced apparently comparing with the CRT technique. The quality of life of patients with MPM is improved after irradiation.

Intrathoracic latissimus dorsi muscle transposition: a reliable technique for prevention of bronchopleural fistula developing after extrapleural pneumonectomy and external beam radiotherapy in malignant pleural mesothelioma

Objective: Bronchopleural fistula (BPF) is a life threatening complication after pneumonectomy. Extra thoracic skeletal muscle transposition especially latissimus dorsi muscle flap (LDMF) had been used to prevent this complication. The aim of this study was to assess the effectiveness of LDMF in preventing BPF developing after extrapleural pneumonectomy (EPP) and external radiation therapy in malignant pleural mesothelioma (MPM). Methods: Between May 1999 and Dec. 2008, 37 patients with MPM were operated upon by EPP using LDMF prophylactically to reinforce the bronchial stump, and then received external radiation therapy with or without postoperative chemotherapy. Results: The mean age of all patients was 46.7 (range 26-57) years. Twenty five patients were males and 12 patients were females. Twenty three patients had MPM of the right side and 14 patients had MPM of the left side. The peri-operative mortality was 2.7% and only few flap related postoperative morbidity were reported in the form of minor seroma and subcutaneous surgical emphysema. The median follow up was 17 (range 9-43) months. All cases completed their postoperative external radiation therapy with no reported cases of early or late BPF. Conclusion: Intrathoracic pedicled LDMF transposition is proved to be effective in prevention of BPF developing after EPP and external radiation therapy in MPM and it is advised to be a routine step in EPP in these cases and to use more sophisticated technique of postoperative external beam radiotherapy (3D conformal or IMRT) to minimize this complication.

Extra-pleural pneumonectomy in the setting of tri-modality therapy for patients with malignant pleural mesothelioma

Although declining in the US due to restrictions of asbestos exposure, malignant pleura/mesothelioma （MPP） remains a very serious thoracic malignancy that is rising in incidence worldwide （1）. Trirnodality therapy with chemotherapy and radiotherapy combined with extrapleural pneumonectomy （EPP） has gained acceptance given the acceptable mortality rate （〈5%） and long term survival reported in patients with epithelial histology, negative margins, and no extrapleural lymph node involvement after trimodalitv treatment （2）.

Correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion

Objective: To investigate the correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion. Methods: A total of 187 patients with primary non-small cell lung cancer complicated by malignant pleural effusion were selected as malignant pleural effusion group and 56 patients with tuberculous pleural effusion were selected as tuberculous pleural effusion group. The expression of RCAS1 and Claudin-18 gene as well as proliferation and invasion-related genes in the pleural effusion were compared between the two groups, and Pearson test was used to evaluate the correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion. Results: RCAS1 and Claudin-18 mRNA expression in pleural effusion of malignant pleural effusion group were greatly higher than those of tuberculous pleural effusion group. Proliferation genes LRRC3B and TCF21 mRNA expression in pleural effusion of malignant pleural effusion group were lower than those of tuberculous pleural effusion group whereas SIRT1 and EZH2 mRNA expression were higher than those of tuberculous pleural effusion group;invasion genes DDX17, Nectin4, Vav3, NGAL and Snail mRNA expression were higher than those of tuberculous pleural effusion group whereas EFEMP1 and MCPH1 mRNA expression were lower than those of tuberculous pleural effusion group. The Pearson test showed that the RCAS1 and Claudin-18 expression in malignant pleural effusion were directly correlated with the expression of proliferation-related genes and invasion-related genes. Conclusion: RCAS1 and Claudin-18 expression increase abnormally in malignant pleural effusion, the specific expression is directly correlated with tumor cell proliferation and invasion activity, and they can be used as the reliable indicators for the identification of benign or malignant pleural effusion.

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.