Galbis JM, Mata M, Guijarro R, Esturi R, Figueroa S, Arnau A.

Thoracic Surgery Service, General University Hospital of Valencia, Valencia, Spain.

Abstract

Introduction: The aim of this study was to investigate the effectiveness of thoracoscopy in the diagnosis of non-affiliated pleural effusions (PE).

Material and methods: A five-year prospective study including data from 110 patients that were clinically diagnosed as benign (14.5%), malign (34.5%) and non-affiliated (50.9%). PE in patents without oncology disease and negative biopsy or cytology were considered as benign. Malignant diagnosis was established according to a pleural biopsy, compatible cytology and/or clinical features. Remaining cases were considered as non-affiliated. Thoracoscopy was done under local anaesthesia and sedation.

Results: Thoracoscopy confirmed previous clinical diagnosis of benignity and malignity. Regarding non-affiliated patients, 30.35% were diagnosed after thoracoscopy as unspecific pleuritis, 17.86% mesothelioma and 1.79% pleural tuberculosis (TBC). The other 48.21% of patients reported as non-affiliated were diagnosed with pleural carcinoma. Statistical analysis did not reveal differences between frequencies analysed.

Conclusions: Our results indicate that thoracoscopy is a cost-effective and reliable technique for obtaining histological diagnosis in PE and also allows a directed pleurodesis if indicated.

Goyal M, Kodandapani S, Sharanabasappa SN, Palanki SD.

Department of Laboratory Medicine, Indo-American Cancer Institute and Research Centre, Hyderabad, India.

Abstract

Mesothelial cell inclusions in lymph nodes are of rare occurrence and can be mistaken as metastatic adenocarcinomas, mesothelioma or sinus histiocytosis. These are usually found in mediastinal and abdominal lymph nodes and are associated with effusions. We report a case of benign mesothelial cell inclusions in cervical lymph nodes, which was associated with chylous effusion, and immunohistochemistry revealed unusual weak cytoplasmic epithelial membrane antigen positivity in the cells.

Keywords: Adenocarcinoma, chylous effusion, epithelial membrane antigen, mesothelial cell inclusions

Sato A, Torii I, Tao LH, Song M, Kondo N, Yoshikawa Y, Hashimoto-Tamaoki T, Hasegawa S, Nakano T, Tsujimura T.

Department of Pathology Department of General Thoracic Surgery Department of Genetics Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

Abstract

Malignant pleural mesothelioma is a refractory tumor with an increasing incidence. In this study, we established six mesothelioma cell lines possessing two allele deletion of the p16(INK4A) gene and one allele deletion of the neurofibromatosis type 2 gene, MM16, MM21, MM26, MM35, MM46, and MM56, from pleural effusion fluids or surgically resected tumors of Japanese patients. MM21, MM26, and MM46 cells failed to develop tumors in BALB/c-nude mice following subcutaneous inoculation. MM16 and MM35 cells slowly generated tumors at the site of subcutaneous inoculation in BALB/c-nude mice, but lost the expression of mesothelioma-related markers, such as calretinin, D2-40, and Wilms’ tumor 1, in the subcutaneous tumors. On the other hand, MM56 cells rapidly generated tumors with the expression of calretinin and D2-40 in BALB/c-nude mice following subcutaneous inoculation. In addition, orthotopic implantation of MM56 cells into BALB/c-nude mice developed diffusely growing thoracic tumors by 3 weeks after implantation. Pleural effusions were observed in these mice 4 weeks after implantation. Thoracic tumors invaded aggressively into the chest wall 5 weeks after implantation and often metastasized into the lung, rib, peritoneum, and pericardial cavity. On the pleural surface, MM56 cells were growing as single or multiple cell layers with reactive mesothelium of recipient mice. These results indicate that MM56 cells can behave in a manner characteristic of human malignant pleural mesothelioma in the thoracic cavity of BALB/c-nude mice. The in vivo model using MM56 cells may be useful to study the biological behavior of malignant pleural mesothelioma and develop its diagnostic and therapeutic strategies.

Hansson M, Zendehrokh N, Ohyashiki J, Ohyashiki K, Westman UB, Roos G, Dejmek A.

Department of Laboratory Medicine, Lund University, Malmö, Sweden.

Abstract

Context: We previously found telomere repeat amplification protocol (TRAP) in situ helpful in the diagnosis of malignancy in effusions, whereas varying sensitivities and specificities for malignancy were reported by investigators using extract-based TRAP.

Objective: To compare the 2 methods and to elucidate the discrepancies between them.

Design: Twenty-three effusions were analyzed. Telomerase activity of whole cell lysate was measured with a Telo TAGGG telomerase polymerase chain reaction ELISA PLUS kit with modifications to exclude polymerase chain reaction inhibitors. TRAP in situ was performed on cytospins. An estimate of total TRAP activity in the specimen was made based on the amount of positive cells, their fluorescence intensity, and the proportion of different cell types in the specimen. The estimate was compared with the level of telomerase activity in cell lysate–based TRAP.

Results: TRAP in situ: Thirteen of 14 malignant cases and 2 of 2 equivocal cases showed moderate/strong reactivity. Five of 7 benign effusions were negative; in 2 of 7, mesothelial cells showed weak reactivity. Cell lysate–based TRAP assay: In 4 cases no internal standard was detected, indicating the presence of polymerase chain reaction inhibitors. The relative telomerase activities were 33.1 to 72.7 with a considerable overlap between malignant (48 ± 9, mean ± SD) and benign (43 ± 9) cases.

Conclusions: The TRAP in situ results correlated to final diagnoses, whereas the cell lysate–based TRAP assay did not differentiate between malignant and benign cases. The varying proportions of positive cells and the variation in fluorescence intensity in the TRAP in situ slides explained some of the discrepancies. The problems encountered with TRAP performed on cell lysates are partly overcome using TRAP in situ.

Cellerin L, Marcq M, Sagan C, Chailleux E.

Service de Pneumologie, Hôpital G. & R. Laennec, CHU de Nantes, France. laurent.cellerin@chu-nantes.fr

Abstract

Introduction: Few studies have focused on malignant pleural effusions as the presenting site of cancer. The aim of our study is to evaluate their proportion in the total number of malignant pleural effusions, to identify their causes and determine their prognosis.

Patients and Methods: Patients were selected retrospectively from the database of the Pathology Department of the University Hospital of Nantes (France), which contained only the patients in whom a diagnosis of malignant effusion was made as the result of cytology of pleural fluid or pleural biopsy, between January 1999 and December 2001. Pleural effusions as the presenting site of cancer (R group) and those metastatic from known cancer (C group) were identified by study of the clinical data.

Results: Of 209 cases, the malignant effusion was presenting site of cancer in 85 patients. In this group (R), a male predominance was identified (sex-ratio 1.36 vs. 0.42 in group C, p<0.01). In order of frequency the causes were: lung cancer (31 cases), mesothelioma (18 cases), primary cancer unknown (15 cases), ovarian carcinoma (10 cases), lymphoma (5 cases) and other carcinoma (2 cases). In men lung cancer was the leading cause (42.8%); and in women its frequency was the same as ovarian carcinoma (27.7%). The median survival of these patients was 6.5 months.

Conclusion: Pleural effusions as the presenting site of cancer account for 41% of all malignant pleural effusions. Their causes are mainly lung cancer in men and lung and ovarian cancers in women.

Moore AJ, Parker RJ, Wiggins J.

Department of Respiratory Medicine, Wexham Park Hospital, Wexham, Slough, Berkshire, UK. a.moore@ic.ac.uk

Abstract

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational “environmental” exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Zhang W, Wang GF, Zhang H, Mu XD, Jin Z.

Department of Respiratory Medicine, Peking University First Hospital, Beijing, China.

Abstract

Objective: To evaluate the efficacy and safety of talc poudrage pleurodesis via semi-rigid medical thoracoscopy in the treatment of malignant pleural effusions, as well as the factors that may influence the outcomes.

Methods: A series of 27 patients with malignant pleural effusion underwent medical thoracoscopic talc poudrage pleurodesis between July 2005 and September 2007 in Peking University First Hospital.

Results: There were 16 male and 11 female patients in the series, the average age being 65.2 years. All the patients had documented malignant pleural effusions, including 16 cases of adenocarcinoma, 6 of malignant mesothelioma, 2 of squamous cell carcinoma, 1 of lymphoepithelioma-like carcinoma, 1 of small cell carcinoma and 1 of undifferentiated lung cancer. Thirty days after the procedures, complete successful pleurodesis was achieved in 22 cases, and partial successful in 4 cases. Pleurodesis was not successful in one case. Overall successful rate was 96.3% (26/27). The average duration of thoracic tubing was 6.85 days. Chest pain, fever and an increase in peripheral WBC after the procedure occurred in 19(70.4%, 19/27), 21(77.8%, 21/27), and 12(44.4%, 12/27) cases respectively. No respiratory failure occurred.

Conclusion: Medical thoracoscopic talc poudrage pleurodesis is a safe and effective method for the treatment of malignant pleural effusion.

Greillier L, Baas P, Welch JJ, Hasan B, Passioukov A.

European Organisation for Research and Treatment of Cancer (EORTC), Headquarters, Brussels, Belgium. laurent.greillier@mail.ap-hm.fr

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose main etiology is exposure to asbestos fibers. The incidence of MPM is anticipated to increase worldwide during the first half of this century. For various reasons, MPM is difficult to diagnose and is notoriously refractory to most treatments. However, recently two active chemotherapy regimens have been demonstrated to significantly increase survival in patients with MPM, and several therapeutic agents and strategies are currently under evaluation.

Researchers have actively sought MPM biomarkers for more than 20 years. Biomarkers would be helpful in managing three clinical aspects of MPM: early diagnosis, prognosis, and treatment outcome prediction. The aims of the present review are to summarize the published and recently presented data on MPM biomarkers and to identify the prospects for future translational research projects.

Among the ‘classical’ diagnostic biomarkers measured in biological fluids, such as cytokeratins and cell surface antigens, none discriminate patients with MPM from those with other malignancies and nonmalignant diseases. Osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF) appear to be the most promising of the recent biomarkers, but are still subject to some limitations. Osteopontin lacks specificity for mesothelioma, while both soluble mesothelin and MPF lack sensitivity for detecting non-epithelial subtypes. Panels consisting of a small set of biomarkers do not improve the diagnostic yield, and results from molecular profiling are too preliminary to be brought into daily clinical practice. While a large number of biomarkers have been assessed in biological fluids and tumor tissue for their prognostic value, none have had a widespread impact on clinical practice. In contrast, data concerning predictive biomarkers are very limited, even though they are most interesting from the perspective of clinicians.

Additional prospective studies, in large and independent samples of patients, with rigorous statistical methodology and standardized laboratory techniques are now warranted to validate and define the precise value of diagnostic and prognostic MPM biomarkers. Future research efforts should focus on biomarkers predictive of the efficacy and toxicity of standard chemotherapy. Translational research should be systematically incorporated into the design of clinical trials assessing new targeted agents in MPM.

Wörnle M, Sauter M, Kastenmüller K, Ribeiro A, Roeder M, Mussack T, Ladurner R, Sitter T.

Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany. markus.woernle@med.uni-muenchen.de

Abstract

Vascular endothelial growth factor (VEGF) plays a key role in formation of pleural effusions and in tumorigenesis and progression of malignant mesothelioma. Mesothelial cells (MC) express the viral receptors Toll-like receptor 3 (TLR3), RIG-I and MDA5. Activation of these receptors by viral RNA exemplified by poly(I:C) RNA leads to a time- and dose-dependent increase of mesothelial VEGF synthesis. To show the specific effect of viral receptors knockdown experiments with siRNA for TLR3, RIG-I and MDA5 were performed. This finding of viral induced mesothelial VEGF synthesis may indicate a novel link between viral infections and formation of pleural effusions and progression of malignant mesothelioma.

Keywords: Malignant mesothelioma; MDA5; RIG-I; Toll-like receptor 3; VEGF

Gonlugur TE, Gonlugur U.

Canakkale State Hospital, Department of Chest Diseases, Canakkale, Turkey. tefeoglu@gmail.com

Abstract

Introduction: The aims of this study were to determine the distribution of transudates and exudates among pathologically proven malignant pleural effusions, and to demonstrate the
necessity for cytologic studies in patients with a transudative effusion.

Materials and Methods: This study is a retrospective review of all subjects diagnosed with malignant or paramalignant pleural effusion over a 10-year period at a tertiary hospital. The study included 67 subjects with malignant mesothelioma, 45 subjects with metastatic disease, and 36 subjects with paramalignant effusions.

Results: There were 55 female and 93 male subjects; the mean age of the sample was 62 years. Malignant pleural effusions were transudative in 1.5% of malignant mesotheliomas, 6.8% of metastatic diseases, and 11.1% of paramalignant effusions.

Conclusions: Cytological examination of pleural fluid in patients with unexplained transudative effusion is essential to rule out malignant processes.

Keywords: Biochemical criteria, Pleural malignancy, Pleural neoplasms