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Sample records for experimental malignant pleural

  1. Pleural malignancies.

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    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Malignant pleural effusion

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    Teixeira, Lisete Ribeiro; Pinto, José Antonio de Figueiredo; Marchi, Evaldo

    2006-01-01

    O derrame pleural neoplásico é uma complicação freqüente nos pacientes portadores de tumores avançados. A presença de células malignas no líquido pleural ou na biópsia da pleura é indicativa de disseminação da doença primária, com conseqüente redução da expectativa de vida. O diagnóstico e tratamento precoce do derrame pleural maligno são fundamentais para promover uma melhor qualidade de vida aos pacientes portadores de câncer avançado.The malignant pleural effusion is a frequent complicatio...

  3. Management of malignant pleural effusions.

    LENUS (Irish Health Repository)

    Uzbeck, Mateen H

    2010-06-01

    Malignant pleural effusions are a common clinical problem in patients with primary thoracic malignancy and metastatic malignancy to the thorax. Symptoms can be debilitating and can impair tolerance of anticancer therapy. This article presents a comprehensive review of pharmaceutical and nonpharmaceutical approaches to the management of malignant pleural effusion, and a novel algorithm for management based on patients\\' performance status.

  4. Management of malignant pleural effusion

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    Boshuizen, R.C.

    2017-01-01

    The first part of this thesis focuses on IPCs (indwelling pleural catheters) in malignant pleural effusion (MPE) management. In an invited review, the (dis)advantages and prejudices of IPCs are described (Chapter1.1). Since costs and reimbursement issues are the main reasons in the Netherlands to

  5. Beneficial impact of CCL2 and CCL12 neutralization on experimental malignant pleural effusion.

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    Antonia Marazioti

    Full Text Available Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2 promotes malignant pleural effusion (MPE formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC or colon (MC38 adenocarcinoma cells. Human lung adenocarcinoma cells (A549 were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.

  6. Hedgehog Signaling in Malignant Pleural Mesothelioma

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    Emanuela Felley-Bosco

    2015-07-01

    Full Text Available Malignant pleural mesothelioma (MPM is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo or glioma-associated protein transcription factors (Gli have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition.

  7. Derrame pleural neoplásico Malignant pleural effusion

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    Lisete Ribeiro Teixeira

    2006-08-01

    Full Text Available O derrame pleural neoplásico é uma complicação freqüente nos pacientes portadores de tumores avançados. A presença de células malignas no líquido pleural ou na biópsia da pleura é indicativa de disseminação da doença primária, com conseqüente redução da expectativa de vida. O diagnóstico e tratamento precoce do derrame pleural maligno são fundamentais para promover uma melhor qualidade de vida aos pacientes portadores de câncer avançado.The malignant pleural effusion is a frequent complication in patients with of advanced tumors. The presence of malignant cells in the pleural fluid or in the pleural biopsy is indicative of dissemination of the primary disease, with consequent reduction of life expectancy. The early diagnosis and treatment of the malignant effusion is pivotal in promoting a better quality of life to patients with advanced cancer.

  8. Role of Bronchoscopy in Malignant Pleural effusion

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    Gomathi. R. G.

    2016-04-01

    Full Text Available The aim of this study was to assess the role of Bronchoscopy in plural effusion in cancer condition. Pleural effusion is one of the commonest problems with which patients present to the hospital. Around a million patients worldwide develop pleural effusion each year. This is a Prospective and Observational Study. All patients diagnosed to have pleural effusion by xray, clinical examination and ultrasound examination of pleura if needed will undergo informed. All 32 patients underwent bronchoscopy procedure, 30 patients had endobronchial mass and biopsy was done which was positive for malignancy and 2 patients had bronchial wash cytology positive for malignancy We conclude that bronchoscopy has a definite role in the etiological diagnosis of pleural effusion.

  9. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

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    Rosenzweig, Kenneth E., E-mail: ken.rosenzweig@mountsinai.org [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Zauderer, Marjorie G. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Laser, Benjamin [Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI (United States); Krug, Lee M. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Yorke, Ellen [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Sima, Camelia S. [Department of Epidemiology/Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Flores, Raja [Department of Surgery, Mount Sinai Medical Center, New York, NY (United States); Rusch, Valerie [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-07-15

    Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy

  10. Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment

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    Anna C. Bibby

    2016-12-01

    Full Text Available Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years. This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.

  11. Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.

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    Bibby, Anna C; Tsim, Selina; Kanellakis, Nikolaos; Ball, Hannah; Talbot, Denis C; Blyth, Kevin G; Maskell, Nick A; Psallidas, Ioannis

    2016-12-01

    Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised. Copyright ©ERS 2016.

  12. Palliative Treatment of Malignant Pleural Effusion

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    Chenyang Liu

    2015-01-01

    Full Text Available Malignant pleural effusion (MPE is a common clinical problem caused by cancers. Pleural effusion can be the first sign of cancer in more than 25% of patients. Lung cancer and breast cancer are the most common cancers that metastasize to the pleura in men and women, respectively. Other cancers, including, but not limited to, lymphomas, ovarian cancer, stomach cancer, and several unknown primary cancers can also lead to MPE. Dyspnea and chest pain are the most common symptoms of MPE along with other symptoms such as a cough, weight loss, anorexia, fatigue, and weakness. Aggravation of these symptoms is closely related to the rate of accumulation of pleural effusion. Treatment options to MPE are determined by the type and extent of the underlying malignancy. The major goals of the treatment are to relieve symptoms, restore functions, improve the quality of life, and minimize the duration of hospital stay and costs. Although some patients can be treated with systemic therapies, most of these treatments are temporary, and MPE would recur soon. Hence, further palliative treatments to effectively control pleural effusions and relieve symptoms are necessary. This review addresses the pathophysiology of MPE and the treatment options for patients with MPE.

  13. Closed pleural biopsy is still useful in the evaluation of malignant pleural effusion

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    Somnath Bhattacharya

    2012-01-01

    Full Text Available Background: Pleural fluid cytology for malignant cells is the easiest way to diagnose malignant pleural effusion with good sensitivity and specificity. With the introduction of medical thoracoscopy, the use of closed pleural biopsy for the diagnosis of cytology negative malignant pleural effusion is gradually decreasing. However use of thoracoscopy is limited due to its high cost and procedure related complications. Aims: The aim was to assess the usefulness of closed pleural biopsy in the diagnosis of malignant pleural effusion. Materials and Methods: Sixty-six patients of pleural effusion associated with malignancy were selected from the patients admitted in the chest ward of a tertiary care hospital over a period of 1 year. Pleural fluid aspiration for cytology and closed pleural biopsy were done in all the patients. Results: Out of 66 patients, 46 (69% patients showed malignant cells in pleural fluid cytology examination. Cytology was positive in 35 (52%, 10 (15%, and 1 (1.5% patients in the first, second, and third samples respectively. Closed pleural biopsy was positive in 32 (48% patients. Among them, 22 also had positive cytology. Additional 10 cytology negative patients were diagnosed by pleural biopsy. Cytology-histology concordance was seen in 12 patients. Definite histological diagnosis could be achieved in five patients with indeterminate cytology. Pleural biopsy was not associated with any major postoperative complication. Conclusion: Closed pleural biopsy can improve the diagnostic ability in cytology negative malignant pleural effusion. Closed pleural biopsy has still a place in evaluation of malignant pleural effusion especially in a resource-limited country like India.

  14. Diagnosis and treatment of malignant pleural mesothelioma.

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    Rodríguez Panadero, Francisco

    2015-04-01

    There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  15. Duodenal Metastasis of Malignant Pleural Mesothelioma

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    Huang-Chi Chen

    2008-12-01

    Full Text Available Metastatic malignant mesothelioma of the pleura is uncommon at the time of initial diagnosis. The gastrointestinal lumen is rarely found at autopsy in patients with widespread disease. Here, we describe an extremely rare case of isolated duodenal metastasis of sarcomatoid mesothelioma of the pleura in a 73-year-old man, without memory of any direct exposure to asbestos. The possibility of gastrointestinal tract metastasis should be considered in the presence of anemia or positive occult blood test in patients with malignant pleural mesothelioma.

  16. Malignant pleural mesothelioma in a child

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    Jed Brendan Scharf

    2015-10-01

    Full Text Available Malignant pleural mesothelioma (MPM is an aggressive malignancy that occurs extremely rarely in the pediatric population. It carries a dismal prognosis. Adult studies are often used to guide therapy in the pediatric population, as a limited number of case reports form the body of pediatric literature. Herein, we document the course and treatment of an 8-year old male diagnosed with MPM. The diagnosis came after he presented to his family physician with dyspnea and was found to have a large right-sided chest mass on subsequent imaging. Through an initial right pneumonectomy and subsequent chest wall excision, followed by chemotherapy with Pemetrexed and Cisplatin he remains virtually disease free today, almost 2 years following surgery.

  17. A catalogue of treatment and technologies for malignant pleural mesothelioma.

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    Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Neefjes, Jacques J C; Baas, Paul

    2016-01-01

    Malignant pleural mesothelioma is an aggressive fatal malignancy with a prognosis that has not significantly improved in the last decades. This review summarizes the current state of treatment and the various attempts that are made to improve overall survival for patients with malignant pleural mesothelioma. It also discusses technologies and protocols to test new and hopefully more effective compounds in a more individualized manner. These developments are expected to improve the prognosis for this group of patients.

  18. Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma

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    de Bree, Eelco; van Ruth, Serge; Baas, Paul; Rutgers, Emiel J. Th; van Zandwijk, Nico; Witkamp, Arjen J.; Zoetmulder, Frans A. N.

    2002-01-01

    STUDY OBJECTIVES: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We

  19. The role of tumor necrosis factor alpha in differentiation between malignant and non malignant pleural effusion

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    Heba M. Atef

    2016-07-01

    Conclusion: Pleural fluid level of TNF-α can be used in differentiating malignant from non malignant effusion. Also levels of TNF-α in the serum and pleural fluid could be useful as a complementary marker in the differential diagnosis of two most common types of exudates (tuberculous and malignant.

  20. Radical multimodality therapy for malignant pleural mesothelioma.

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    Abdel-Rahman, Omar; Elsayed, Zeinab; Mohamed, Hadeer; Eltobgy, Mostafa

    2018-01-08

    Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness. To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma. We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017. We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status. Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE. We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated

  1. Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea

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    Kim, Yoon Kyung [Department of Radiology, Gachon University Gil Medical Center, Incheon 21565 (Korea, Republic of); Kim, Jeung Sook [Department of Radiology, Dongguk University Ilsan Hospital, Goyang 10326 (Korea, Republic of); Lee, Kyung Won [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Yi, Chin A [Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Koo, Jin Mo [Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Jung, Soon-Hee [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426 (Korea, Republic of)

    2016-11-01

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  2. Multidetector CT findings and differential diagnoses of malignant pleural mesothelioma and metastatic pleural diseases in Korea

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    Kim, Yoon Kyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of); Kim, Jeung Sook [Dept. of Radiology, Dongguk University Ilsan Hospital, Goyang (Korea, Republic of); Lee, Kyung Won [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yi, Chin A [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Koo, Jin Mo [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Soon Hee [Dept. of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2016-07-15

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  3. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

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    James Benjamin Gleason

    2016-01-01

    Full Text Available Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma, with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid, supporting the diagnosis of biphasic malignant mesothelioma.

  4. Advance of Therapeutic Methods for Malignant Pleural Effusion

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    Tao-tao XU

    2016-06-01

    Full Text Available Malignant pleural effusion (MPE is a condition caused by primary malignant tumors in the pleura or other malignant tumors metastasis to the pleura. It is also one of common serious complications of middle-late malignant tumor, which has severe impact on the quality of life, even threatening the life of the patients. The selection of treatments for MPE depends on many factors, including the symptoms, performance status, primary tumor types, response to systemic therapy, and degree of lung recruitment maneuvers (LRM after drainage of pleural effusion. Generally, the treatment methods include thoracentesis, indwelling pleural catheter, pleurodesis, intrapleural injection of drugs, chemotherapy, radiotherapy, anti-angiogenesis therapy, surgery, and thermotherapy. With the in-depth study on pathogenesis of MPE, the treatments of MPE have continuous improvements. This study mainly reviewed the treatment methods for MPE so as to provide the basis for clinical practice in the future.

  5. Multimodal treatment for resectable epithelial type malignant pleural mesothelioma

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    Fukuyama Yasuro

    2004-05-01

    Full Text Available Abstract Background Malignant pleural mesothelioma is a rare malignancy. The outcome remains poor despite complete surgical resection. Patients and methods Eleven patients with histologicaly proven epithelial type malignant pleural mesothelioma undergoing extrapleural pneumonectomy with systemic chemotherapy and/or radiotherapy before and after surgical resection were retrospectively reviewed. Results Ten out of 11 patients underwent complete surgical resection, of these 7 patients had stage I disease. Of these 7 patients, 5 are alive without any recurrence, a 2-year survival rate of 80% was observed in this group. There was no operative mortality or morbidity. Conclusion Extrapleural pneumonectomy with perioperative adjuvant treatment is safe and effective procedure for epithelial type malignant pleural mesothelioma.

  6. Lymphangitic Carcinomatosis as a Cause of Malignant Transient Pleural Transudate

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    Raquel Garcia Sevila

    2009-01-01

    Full Text Available Although it is generally accepted that a malignant transient pleural transudate may appear during the early stages of lymphatic obstruction, cases demonstrating such probability are rare in literature. A 67-year-old woman was admitted to hospital because a lymphangitic carcinomatosis and a transudative infrapulmonary pleural effusion with a cytology positive for adenocarcinoma. One month later the effusion keeps being positive for adenocarcinoma but exudative in character. Lymphatic obstruction appears as the cause of the initial transudative characteristics of the pleural effusion.

  7. Management of malignant pleural effusion: challenges and solutions

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    Penz E

    2017-06-01

    Full Text Available Erika Penz,1 Kristina N Watt,1 Christopher A Hergott,2 Najib M Rahman,3 Ioannis Psallidas3 1Division of Respirology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, 2Division of Respirology, Department of Medicine, University of Calgary, Calgary, AB, Canada; 3Oxford Centre for Respiratory Medicine, Respiratory Trials Unit, Oxford University, Oxford, UK Abstract: Malignant pleural effusion (MPE is a sign of advanced cancer and is associated with significant symptom burden and mortality. To date, management has been palliative in nature with a focus on draining the pleural space, with therapies aimed at preventing recurrence or providing intermittent drainage through indwelling catheters. Given that patients with MPEs are heterogeneous with respect to their cancer type and response to systemic therapy, functional status, and pleural milieu, response to MPE therapy is also heterogeneous and difficult to predict. Furthermore, the impact of therapies on important patient outcomes has only recently been evaluated consistently in clinical trials and cohort studies. In this review, we examine patient outcomes that have been studied to date, address the question of which are most important for managing patients, and review the literature related to the expected value for money (cost-effectiveness of indwelling pleural catheters relative to traditionally recommended approaches. Keywords: malignant pleural effusion, therapeutics, cost-effectiveness, quality of life 

  8. Diagnosing malignant pleural effusions: how do we compare?

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    Lim, Ming Han; Garrettc, Jeffrey; Mowlem, Lydia; Yap, Elaine

    2013-08-30

    Accurate and prompt diagnosis of malignant pleural effusion (MPE) is important as patients with suspected MPE often wait for many days before the diagnosis is secure. (1) To evaluate the diagnostic yield of pleural fluid cytology for patients admitted to Middlemore Hospital (MMH) in Auckland, New Zealand with MPE between 31 May 2010-1 June 2011. (2) To document the waiting time for cytology results to be made available and whether this contributed to length of stay. (3) To evaluate whether the volume of pleural fluid analysed contributed to diagnostic yield. A retrospective audit of pleural fluid cytology results on 36 consecutive patients admitted to MMH with a pleural effusion which was subsequently proven to be due to malignancy. Data was obtained from hospital medical records and Web Eclair databases. 54.8% (17/31) of patients had positive pleural fluid cytology. Initial pleural fluid cytology was positive in 16 (51.6%). Only 4/15 patients with negative pleural fluid cytology had a repeat aspiration (1 was positive). Median cytology turnaround time was 6.72 days, range 2.23-43.06 days. Average length of stay (ALOS) was 7.78 days, range 1.11-20.8 days. Cytology turnaround times seem shorter for inpatients and when a diagnosis of cancer is unknown but the ALOS is longer if patients have negative initial cytology and when a diagnosis of cancer is uncertain. Samples >50mL appear to have a higher diagnostic yield compared to samples less than and equal to 50mL but this was not statistically significant (77.8% to 41.2%, p=0.08). Diagnostic yield from pleural fluid cytology at our hospital is comparable with other documented studies. ALOS appears to be influenced by a negative initial pleural fluid cytology and the uncertainty of diagnosis of cancer, not cytology turnaround time. The results suggest a more efficient diagnostic and treatment algorithm could be considered with emphasis on Day Stay investigation and treatment.

  9. Diagnosis and management options in malignant pleural effusions

    Directory of Open Access Journals (Sweden)

    Ramakant Dixit

    2017-01-01

    Full Text Available Malignant pleural effusion (MPE denotes an advanced malignant disease process. Most of the MPE are metastatic involvement of the pleura from primary malignancy at lung, breast, and other body sites apart from lymphomas. The diagnosis of MPE has been traditionally made on cytological examination of pleural fluid and/or histological examination of pleural biopsy tissue that still remains the initial approach in these cases. There has been tremendous advancement in the diagnosis of MPE now a day with techniques i.e. characteristic Ultrasound and computed tomography features, image guided biopsies, fluorodeoxyglucose-positron emission tomography imaging, thoracoscopy with direct biopsy under vision, tumor marker studies and immunocytochemical analysis etc., that have made possible an early diagnosis of MPE. The management of MPE still remains a challenge to pulmonologist and oncologist. Despite having various modalities with better tolerance such as pleurodesis and indwelling pleural catheters etc., for long-term control, all the management approaches remain palliative to improve the quality of life and reduce symptoms. While choosing an appropriate management intervention, one should consider the clinical status of the patient, life expectancy, overall cost, availability and comparative institutional outcomes, etc.

  10. Role of DR-70 immunoassay in suspected malignant pleural effusion

    Science.gov (United States)

    Sengupta, Amitabha; Saha, Kaushik; Jash, Debraj; Banerjee, Sourindra Nath; Biswas, Nirendra Mohan; Dey, Atin

    2013-01-01

    Context: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow-up. Aims: The aims of this study were to evaluate the role of DR-70 immunoassay in suspected malignant PE. Settings and Design: We conducted a cross-sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control. Materials and Methods: Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase less than 30 U/L were taken as cases. We had selected NSs among relatives of patients having normal blood chemistry and radiological investigations. Sensitivity and specificity of the test to differentiate malignant and non-malignant PE and also to identify PE with underlying malignancy was analyzed. Results: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut-off value of 2 mg/L. Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (P = 0.08). Conclusions: DR-70 assay has high sensitivity in detecting underlying lung cancer, but has no role in differentiating malignant PE from non-malignant PE. PMID:24339491

  11. Advances in diagnosis and treatment of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Giorgio Vittorio Scagliotti

    2011-12-01

    Full Text Available Malignant pleural mesothelioma (MPM is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease.The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

  12. Morphologic and functional imaging of malignant pleural mesothelioma

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    Yamamuro, Masaki; Gerbaudo, Victor H.; Gill, Ritu R.; Jacobson, Francine L.; Sugarbaker, David J. [Department of Radiology and Surgery, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Hatabu, Hiroto [Department of Radiology and Surgery, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States)], E-mail: hhatabu@partners.org

    2007-12-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumor that arises from the pleura and frequently extends to adjacent structures. MPM cells produce and respond to many angiogenic factors, such as vascular endothelial growth factor (VEGF). VEGF expression in MPM is correlated with microvascular density, which is associated with poor survival. CT has been widely used as the primary imaging modality for the clinical evaluation of MPM. Major findings include nodular pleural thickening, unilateral pleural effusion, and tumor invasion of adjacent structures. CT tends to underestimate early chest wall invasion and peritoneal involvement and has well-known limitations in the evaluation of lymph node metastases. Perfusion CT can evaluate the microvasculature of tumors, while its disadvantages, such as high radiation exposure or side effects from iodinated contrast, limit its use in both research and clinical settings. MRI can provide additional information to CT. Because of its excellent contrast resolution, MRI is superior to CT, both in the differentiation of malignant from benign pleural disease, and in the assessment of chest wall and diaphragmatic involvement. Perfusion MRI is the most promising technique for the assessment of the tumor microvasculature. In MPM, therapeutic effects of chemotherapy can be monitored with perfusion MRI. It has been shown that FDG-PET is useful for the differentiation of benign from malignant lesions, for staging and monitoring metabolic response to therapy against MPM, and that it has prognostic value. An initial report on PET/CT imaging of MPM has shown increased accuracy of overall staging, improving the assessment of tumor resectability. PET/CT seems to be superior to other imaging modalities in detecting more extensive disease involvement, and identifying unsuspected occult distant metastases.

  13. Histopathologic features predict survival in diffuse pleural malignant mesothelioma on pleural biopsies.

    Science.gov (United States)

    Habougit, Cyril; Trombert-Paviot, Béatrice; Karpathiou, Georgia; Casteillo, François; Bayle-Bleuez, Sophie; Fournel, Pierre; Vergnon, Jean-Michel; Tiffet, Olivier; Péoc'h, Michel; Forest, Fabien

    2017-06-01

    Malignant pleural mesothelioma is a rare tumor with a poor prognosis. The only universally recognized pathological prognostic factor is histopathological subtype with a shorter survival in non-epithelioid subtypes. Recently, a grading of epithelioid mesothelioma on surgical resection has been proposed. The aim of our work is to assess the prognostic role of several histopathological factors on a retrospective cohort of 116 patients diagnosed as a pleural mesothelioma for more than 95% of patients on pleural biopsy. Our work shows that mitotic count mesothelioma. The presence of atypical mitoses was found to be related to a worse median survival in non-epithelioid mesothelioma. Mitotic count, necrosis, nuclear atypia, and nucleoli size are not associated with overall survival in non-epithelioid mesothelioma. Our work highlights that histopathological prognostic factors can be assessed on pleural biopsies and can predict reliably median overall survival. This is of interest in order to define subgroups of patients who could benefit of different therapies and select patients who could benefit of surgical excision.

  14. Detection, modeling and matching of pleural thickenings from CT data towards an early diagnosis of malignant pleural mesothelioma

    Science.gov (United States)

    Chaisaowong, Kraisorn; Kraus, Thomas

    2014-03-01

    Pleural thickenings can be caused by asbestos exposure and may evolve into malignant pleural mesothelioma. While an early diagnosis plays the key role to an early treatment, and therefore helping to reduce morbidity, the growth rate of a pleural thickening can be in turn essential evidence to an early diagnosis of the pleural mesothelioma. The detection of pleural thickenings is today done by a visual inspection of CT data, which is time-consuming and underlies the physician's subjective judgment. Computer-assisted diagnosis systems to automatically assess pleural mesothelioma have been reported worldwide. But in this paper, an image analysis pipeline to automatically detect pleural thickenings and measure their volume is described. We first delineate automatically the pleural contour in the CT images. An adaptive surface-base smoothing technique is then applied to the pleural contours to identify all potential thickenings. A following tissue-specific topology-oriented detection based on a probabilistic Hounsfield Unit model of pleural plaques specify then the genuine pleural thickenings among them. The assessment of the detected pleural thickenings is based on the volumetry of the 3D model, created by mesh construction algorithm followed by Laplace-Beltrami eigenfunction expansion surface smoothing technique. Finally, the spatiotemporal matching of pleural thickenings from consecutive CT data is carried out based on the semi-automatic lung registration towards the assessment of its growth rate. With these methods, a new computer-assisted diagnosis system is presented in order to assure a precise and reproducible assessment of pleural thickenings towards the diagnosis of the pleural mesothelioma in its early stage.

  15. Malignant pleural mesothelioma: an update on diagnosis and treatment options.

    Science.gov (United States)

    Kondola, Sanjana; Manners, David; Nowak, Anna K

    2016-06-01

    Malignant pleural mesothelioma (MPM) represents a significant diagnostic and therapeutic challenge and is almost always a fatal disease. Imaging abnormalities are common, but have a limited role in distinguishing mesothelioma from metastatic pleural disease. Similarly, minimally invasive biomarkers have shown promise but also have limitations in the diagnosis of mesothelioma. In experienced centers, cytology and immunohistochemistry are now sufficient to diagnose the epithelioid subtype of mesothelioma, which can reduce the need for more invasive diagnostic investigations. Prognosis of MPM is modestly impacted by oncological treatments. Chemotherapy with cisplatin and pemetrexed is considered the standard of care, though the addition of bevacizumab to the platinum doublet may be the new standard of care. New targeted therapies have demonstrated some promise and are being addressed in clinical trials. This review focuses on the current data on the diagnostic and therapeutic issues of MPM. © The Author(s), 2016.

  16. Pleural changes after talc pleurodesis in patients with underlying malignancy: Comparison with recurrent malignant pleural lesions on CT and fluorodeoxyglucose-positron emission tomography/CT

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    Kim, Beom Soo; Kang, Hee; Park, Jung Gu [Dept. of Radiology, Kosin University Gospel Hospital, Busan (Korea, Republic of)

    2014-01-15

    To compare computed tomography (CT) and fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) findings of benign pleural changes with those of recurrent malignant pleural lesions in patients with a history of underlying malignancy after talc pleurodesis. Of 194 patients who underwent talc pleurodesis, we retrospectively reviewed 16 patients for whom both follow-up CT and FDG-PET/CT were performed. The morphologic CT findings and maximum standard uptake values (SUVmax) were evaluated and compared between benign pleural changes and recurrent malignant pleural lesions. Twenty-two lesions were found in 16 patients; six patients had no evidence of active pleural disease (group 1) and 10 patients had recurrent malignant pleural lesions on radiological or clinical follow-up (group 2). Characteristic high-density pleural deposits [mean, 131 Hounsfield unit (HU); range, 28-251 HU] were seen along the pleural thickenings (mean, 13.4 mm; range, 4.9-62.3 mm) in 15 patients. The shape and thickness on CT and the SUVmax on FDG-PET/CT showed no significant differences between the two groups. On CT, the pre-contrast attenuation was higher in group 1 than group 2 (165 HU vs. 101 HU, respectively, p = 0.030), and the degree of enhancement was higher in group 2 than that in group 1 (29 HU vs. 48 HU, respectively, p = 0.048). Pleural effusions (n = 5) and other pleural thickening without high-density foci (n = 4) were observed only in group 2; however, no statistical significance was observed between the two groups. Malignant pleural lesions can be characterized by lower pre-contrast attenuation and higher contrast enhancement, whereas benign pleural changes after talc pleurodesis are characterized by higher pre-contrast attenuation and lower contrast enhancement on CT.

  17. Non-coding RNA repertoires in malignant pleural mesothelioma.

    Science.gov (United States)

    Quinn, Leah; Finn, Stephen P; Cuffe, Sinead; Gray, Steven G

    2015-12-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. There are limited treatment options, with no second line standard of care for those who fail first line chemotherapy. Recent advances have been made to characterise the underlying molecular mechanisms of mesothelioma, in the hope of providing new targets for therapy. With the discovery that non-coding regions of our DNA are more than mere junk, the field of research into non-coding RNAs (ncRNAs) has exploded in recent years. Non-coding RNAs have diverse and important roles in a variety of cellular processes, but are also implicated in malignancy. In the following review, we discuss two types of non-coding RNAs, long non-coding RNAs and microRNAs, in terms of their role in the pathogenesis of MPM and their potential as both biomarkers and as therapeutic targets in this disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Oral cyclophosphamide and etoposide in treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Gunduz, Seyda; Mutlu, Hasan; Goksu, Sema Sezgin; Arslan, Deniz; Tatli, Ali Murat; Uysal, Mukremin; Coskun, Hasan Senol; Bozcuk, Hakan; Ozdogan, Mustafa; Savas, Burhan

    2014-01-01

    Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression- free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

  19. Photodynamic therapy for lung cancer and malignant pleural mesothelioma.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-12-01

    Photodynamic therapy (PDT) is a form of non-ionizing radiation therapy that uses a drug, called a photosensitizer, combined with light to produce singlet oxygen ((1)O2) that can exert anti-cancer activity through apoptotic, necrotic, or autophagic tumor cell death. PDT is increasingly being used to treat thoracic malignancies. For early-stage non-small cell lung cancer (NSCLC), PDT is primarily employed as an endobronchial therapy to definitively treat endobronchial or roentgenographically occult tumors. Similarly, patients with multiple primary lung cancers may be definitively treated with PDT. For advanced or metastatic NSCLC and small cell lung cancer (SCLC), PDT is primarily employed to palliate symptoms from obstructing endobronchial lesions causing airway compromise or hemoptysis. PDT can be used in advanced NSCLC to attempt to increase operability or to reduce the extent of operation intervention required, and selectively to treat pleural dissemination intraoperatively following macroscopically complete surgical resection. Intraoperative PDT can be safely combined with macroscopically complete surgical resection and other treatment modalities for malignant pleural mesothelioma (MPM) to improve local control and prolong survival. This report reviews the mechanism of and rationale for using PDT to treat thoracic malignancies, details prospective and major retrospectives studies of PDT to treat NSCLC, SCLC, and MPM, and describes improvements in and future roles and directions of PDT. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Retroperitoneal extension via the retrocrural space of malignant thymoma and malignant pleural mesothelioma. Retrospective evaluation by CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1995-01-01

    We reviewed CT findings of 31 patients with malignant thymoma and one patient with malignant pleural mesothelioma in our institution. Transdiaphragmatic extension into the retroperitoneum via the retrocrural space was observed in 10% of malignant thymomas. In the same way, this spread from chest to abdomen was demonstrated in the case of malignant pleural mesothelioma. CT is especially useful in assessing extent of these tumors and determining the optimal treatment plan. (author).

  1. The role of epigenetics in malignant pleural mesothelioma.

    Science.gov (United States)

    Vandermeers, Fabian; Neelature Sriramareddy, Sathya; Costa, Chrisostome; Hubaux, Roland; Cosse, Jean-Philippe; Willems, Luc

    2013-09-01

    Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic errors leading to inadequate gene expression in tumor cells. The availability of compounds that modulate epigenetic modifications, such as histone acetylation or DNA methylation, offers new prospects for treatment of MPM. Here, we review latest findings on epigenetics in mesothelioma and present novel strategies for promising epigenetic therapies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Malignant pleural mesothelioma - Pleural cavity irradiation after decortication with helical tomotherapy.

    Science.gov (United States)

    Harrabi, Semi B; Koerber, Stefan A; Adeberg, Sebastian; Katayama, Sonja; Herfarth, Klaus; Debus, Juergen; Sterzing, Florian

    2017-01-01

    Malignant pleural mesothelioma (MPM) is a rare and aggressive disease that poses a treatment challenge in spite of recent technical developments. The aim of this retrospective analysis is to assess the feasibility of administering intensity-modulated radiotherapy (IMRT) to the pleural cavity using helical tomotherapy in patients who had undergone pleurectomy/decortication (P/D) and also the resulting toxicity levels. Ten patients who had MPM and had undergone P/D were treated with pleural cavity irradiation that included a median dose of 52.2 Gy using helical tomotherapy. The median age of the patients was 53 years (31-74). In addition to clinical and diagnostic findings from regular follow-up examinations, we evaluated the dose distribution for other organs at risk to assess treatment in relation to toxicity, with special regard for the underlying intact lung. The mean lung dose on the treatment site was 32.8 Gy (±6.8). The V20 Gy was 71.7% (±17.2). No treatment-related toxicity that exceeded grade III according to common toxicity criteria (CTC) was observed. Median progression-free survival (PFS) was 13 months with a median overall survival (OAS) of 19 months. The findings of this analysis provide data indicating that sparing the underlying lung in patients with MPM after P/D is not only feasible with helical tomotherapy, but that this treatment also causes reasonably few side effects.

  3. Use of indwelling pleural catheters for the definitive treatment of malignant pleural effusion

    Directory of Open Access Journals (Sweden)

    Fernando Conrado Abrão

    Full Text Available ABSTRACT Objective: To evaluate the safety and feasibility of the use of indwelling pleural catheters (IPCs in patients with malignant pleural effusion (MPE. Methods: We prospectively collected data from patients with MPE undergoing IPC placement between January of 2014 and July of 2015. All patients submitted to IPC placement had a life expectancy > 30 days, in accordance with the MPE treatment guidelines established by the British Thoracic Society. The data collected included gender, age, body mass index, primary cancer site, duration of IPC drainage, IPC-related complications, length of hospital stay, pleural effusion recurrence, and occurrence of spontaneous pleurodesis. Results: A total of 19 patients underwent IPC placement during the study period. Median overall survival after IPC insertion was 145 days. The median follow-up among the surviving patients was 125 days (range, 53-485 days, and the median time between catheter insertion and removal was 31 days (range, 2-126 days. There were IPC-related complications in 5 patients (26.2%, and spontaneous pleurodesis was achieved in 8 (42.0%. Among those 8 patients, the IPC was removed between days 30 and 126 in 4, and spontaneous pleurodesis occurred within the first 30 days in 4. Conclusions: The use of IPCs seems to be feasible and safe in patients with MPE.

  4. Failure Patterns After Hemithoracic Pleural Intensity Modulated Radiation Therapy for Malignant Pleural Mesothelioma

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    Rimner, Andreas, E-mail: rimnera@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Spratt, Daniel E. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zauderer, Marjorie G. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York (United States); Rosenzweig, Kenneth E. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York (United States); Wu, Abraham J.; Foster, Amanda [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yorke, Ellen D. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Adusumilli, Prasad; Rusch, Valerie W. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Krug, Lee M. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York (United States)

    2014-10-01

    Purpose: We previously reported our technique for delivering intensity modulated radiation therapy (IMRT) to the entire pleura while attempting to spare the lung in patients with malignant pleural mesothelioma (MPM). Herein, we report a detailed pattern-of-failure analysis in patients with MPM who were unresectable or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic pleural IMRT. Methods and Materials: Sixty-seven patients with MPM were treated with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were retrospectively reviewed to determine failure location(s). Failures were categorized as in-field (within the 90% isodose line), marginal (<90% and ≥50% isodose lines), out-of-field (outside the 50% isodose line), or distant. Results: The median follow-up was 24 months from diagnosis and the median time to in-field local failure from the end of RT was 10 months. Forty-three in-field local failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and 74%, respectively. For patients who underwent P/D versus those who received a partial pleurectomy or were deemed unresectable, the median time to in-field local failure was 14 months versus 6 months, respectively, with 1- and 2-year actuarial in-field local failure rates of 43% and 60% versus 66% and 83%, respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal failures (38%) were located within the costomediastinal recess. Marginal failures decreased with increasing institutional experience (P=.04). Twenty-five patients (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%). Conclusions: After hemithoracic pleural IMRT, local failure remains the dominant form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT after P/D experience a significantly longer time to local and distant failure than

  5. Failure patterns after hemithoracic pleural intensity modulated radiation therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Rimner, Andreas; Spratt, Daniel E; Zauderer, Marjorie G; Rosenzweig, Kenneth E; Wu, Abraham J; Foster, Amanda; Yorke, Ellen D; Adusumilli, Prasad; Rusch, Valerie W; Krug, Lee M

    2014-10-01

    We previously reported our technique for delivering intensity modulated radiation therapy (IMRT) to the entire pleura while attempting to spare the lung in patients with malignant pleural mesothelioma (MPM). Herein, we report a detailed pattern-of-failure analysis in patients with MPM who were unresectable or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic pleural IMRT. Sixty-seven patients with MPM were treated with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were retrospectively reviewed to determine failure location(s). Failures were categorized as in-field (within the 90% isodose line), marginal (<90% and ≥50% isodose lines), out-of-field (outside the 50% isodose line), or distant. The median follow-up was 24 months from diagnosis and the median time to in-field local failure from the end of RT was 10 months. Forty-three in-field local failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and 74%, respectively. For patients who underwent P/D versus those who received a partial pleurectomy or were deemed unresectable, the median time to in-field local failure was 14 months versus 6 months, respectively, with 1- and 2-year actuarial in-field local failure rates of 43% and 60% versus 66% and 83%, respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal failures (38%) were located within the costomediastinal recess. Marginal failures decreased with increasing institutional experience (P=.04). Twenty-five patients (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%). After hemithoracic pleural IMRT, local failure remains the dominant form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT after P/D experience a significantly longer time to local and distant failure than patients treated with definitive pleural IMRT. Increasing

  6. Malignant pleural mesothelioma: Computed tomography and correlation with histology

    Energy Technology Data Exchange (ETDEWEB)

    Seely, Jean M. [Department of Diagnostic Imaging, Ottawa Hospital, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9 (Canada)], E-mail: jeseely@ottawahospital.on.ca; Nguyen, Elsie T., E-mail: nguyen_elsie@hotmail.com; Churg, Andrew M. [University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 1W5 (Canada)], E-mail: achurg@interchange.ubc.ca; Mueller, Nestor L. [University of British Columbia, Vancouver Hospital and Health Sciences Centre, 855 West 12th Avenue, Vancouver, BC V5Z 1M9 (Canada)], E-mail: nmuller@vanhosp.bc.ca

    2009-06-15

    Objective: To review the computed tomography (CT) imaging findings of pleural mesothelioma at presentation and to correlate the CT with the histological subtype. Materials and methods: Pathology reports from 1997 to 2006 were reviewed at two academic institutions to identify patients with proven pleural mesothelioma. Diagnosis was based on histologic findings in specimens obtained by transthoracic needle biopsy, surgical biopsy or resection. All histology slides were reviewed by a lung pathologist. CT scans, available in 92 patients, were reviewed blindly and in random order by two independent radiologists. Kappa analysis was completed to assess inter-observer agreement. Eighty patients in whom there was no significant delay between CT imaging and histological diagnosis were assessed by logistic regression analysis to correlate CT and histologic findings. Results: Seventy-two of the 92 mesotheliomas were epithelial, 15 sarcomatous, and 5 of mixed histology. All patients (77 male, 15 female, mean age 68 years) had pleural thickening on CT; the thickening was nodular in 79 patients (86%) and mediastinal in 87 (95%). Ipsilateral volume loss was seen in 42 patients (46%). Pleural effusions were present in 80 patients (87%), being large (>2/3 hemithorax) in 19 patients (21%). Atypical features at presentation included bilateral disease in three patients (3%), and spontaneous pneumothoraces in nine patients (10%). Internal mammary lymphadenopathy was observed in 48 patients (52%) and cardiophrenic lymphadenopathy in 42 (46%). Inter-observer agreement was excellent (average kappa = 0.89). Ipsilateral volume loss was associated with sarcomatous or mixed mesothelioma (p = 0.004). Using logistic regression analysis, other CT findings did not correlate with histological subtype. Conclusions: Ipsilateral volume loss is most frequently associated with sarcomatous or mixed mesothelioma. The remaining imaging findings are not helpful in predicting the histological subtype of

  7. Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation. A planning study

    Energy Technology Data Exchange (ETDEWEB)

    Botticella, A.; Defraene, G. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Nackaerts, K. [KU Leuven - University of Leuven, University Hospitals Leuven, Department of Respiratory Medicine, Leuven (Belgium); Deroose, C. [KU Leuven - University of Leuven, University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); Coolen, J. [KU Leuven - University of Leuven, University Hospitals Leuven, Radiology Department, Leuven (Belgium); Nafteux, P. [University Hospitals Leuven, Department of Thoracic Surgery, Leuven (Belgium); Vanstraelen, B. [University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Joosten, S.; Michiels, L.A.W. [Fontys University of Applied Science, Institute Paramedical Studies, Medical Imaging and Radiotherapeutic Techniques, Eindhoven (Netherlands); Peeters, S. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Ruysscher, D. de [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Department of Radiation Oncology (MAASTRO Clinic), Maastricht (Netherlands)

    2017-04-15

    After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a ''selective'' PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an ''elective'' PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a ''selective'' pleural irradiation plan (SPI plan) and an ''elective'' pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). In the SPI plans, the average median dose to the S-PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S-PTV to >58 Gy. In the EPI plans, the average median doses to the E-PTV and to the S-PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM. (orig.) [German] Beim malignen Pleuramesotheliom (MPM) ist nach lungenschonender Radiotherapie das lokale Scheitern an Stellen eines frueheren, sichtbaren Tumors die dominierende Form des Scheiterns. Unser Ziel ist es, zu untersuchen, ob die selektive

  8. Pleural malignant mesothelioma in dental laboratory technicians: A case series.

    Science.gov (United States)

    Mensi, Carolina; Ciullo, Francesco; Barbieri, Gino Pietro; Riboldi, Luciano; Somigliana, Anna; Rasperini, Giulio; Pesatori, Angela Cecilia; Consonni, Dario

    2017-05-01

    Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure. © 2017 Wiley Periodicals, Inc.

  9. Surgery as part of radical treatment for malignant pleural mesothelioma.

    Science.gov (United States)

    Waller, David A; Tenconi, Sara

    2017-07-01

    To review the latest developments in surgery for malignant pleural mesothelioma both in patient selection, surgical technique, and strategy. The International Association for the Study of Lung Cancer mesothelioma staging project has produced data to inform the 8th tumour node metastasis revision. The difficulty in clinical N staging and clinical T staging are highlighted and the importance of tumour volume is recognized. New imaging techniques can be utilized to assess tumour volume. The transition from extrapleural pneumonectomy to lung-sparing pleurectomy/decortication has extended the role of cancer-directed surgery into a more elderly population. More aggressive multimodality regimes, including induction radiotherapy are available to a selected population and adjuvant radiotherapy and chemotherapy are feasible in the elderly majority. Additional chemotherapy should not be delayed in those with poorer prognosis node positive, nonepithelioid disease. Radical surgery for malignant pleural mesothelioma can achieve significant survival when targeted in those with the best prognosis by careful staging. It can be made more accessible by lung preservation without compromising outcome. It should be part of multimodality therapy.

  10. Intercellular Communication in Malignant Pleural Mesothelioma: Properties of Tunneling Nanotubes

    Directory of Open Access Journals (Sweden)

    Justin William Ady

    2014-10-01

    Full Text Available Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs. TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined TnT length among adherent cells and cells in suspension. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo.

  11. Malignant pleural mesothelioma risk among nuclear workers: a review

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, C; Guseva Canu, I; Laurier, D, E-mail: camille.metz@irsn.fr [Laboratory of Epidemiology, Institute of Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses (France)

    2011-03-01

    Exposure to ionising radiation has been suggested as a causal risk factor for malignant pleural mesothelioma (MPM). Studies of patients treated by radiotherapy for primary cancers have suggested that radiation contributes to the development of secondary MPM. Here we examined the risk to nuclear workers of MPM related to exposure to low doses of occupational radiation at low dose rates. All results concerning MPM risk in published studies of nuclear workers were examined for their association with radiation exposure and potential confounders. We found 19 relevant studies. Elevated risks of pleural cancer were reported in most (15/17) of these studies. Eight reported risks higher for radiation monitored workers than for other workers. However, of 12 studies that looked at associations with ionising radiation, only one reported a significant dose-risk association. Asbestos was an important confounder in most studies. We conclude that studies of nuclear workers have not detected an association between ionising radiation exposure and MPM. Further investigations should improve the consideration of asbestos exposure at the same time as they address the risk of MPM related to occupational exposure of nuclear workers to low doses of ionising radiation at low dose rates. (review)

  12. [Malignant pleural mesothelioma in housewives in the province of Catania].

    Science.gov (United States)

    Proietti, Lidia; Migliore, Marcello; Polosa, Riccardo; Comba, Pietro; Circo, Cristina; Di Maria, Giuseppe U

    2004-01-01

    Our study reports pleural malignant mesothelioma (PMM) in seven female patients. All patients were resident in Catania area (Sicily), the median age was 69.2 years and ranged from 59 to 81 years. They were housewife. Their anamnesis was negative for both direct and indirect previous exposure to asbestos; the partners of all patients were also not exposed to asbestos. The exposure to X-rays was also excluded for these patients. Different pathogenetic mechanisms for the appearance of PMM in these patients can be hypothesized, for example, SV40 infection and genetic susceptibility; a minimal domestic exposure to asbestos can be not excluded. Therefore, further studies in a more large number of subjects are necessary to determine whether one or all of these hypothetic pathogenetic mechanisms are more significant for the develop of PMM.

  13. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis.

    Science.gov (United States)

    Tian, Long; Zeng, Rujun; Wang, Xin; Shen, Cheng; Lai, Yutian; Wang, Mingming; Che, Guowei

    2017-07-11

    Soluble mesothelin is beneficial to detect the progression and the treatment response of malignant pleural mesothelioma. However, the prognostic value of soluble mesothelin in malignant pleural mesothelioma remains unclear. Hazard ratio with 95% CI was used to evaluate the prognostic value of soluble mesothelin and the effect of clinicopathological characteristics on the survival of malignant pleural mesothelioma. Eight eligible studies involving 579 patients were selected for this meta-analysis. The results showed that soluble mesothelin level was significantly correlated with the survival of malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000; heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant pleural mesothelioma was significantly correlated with some clinicopathological characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95% CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966). The survival of malignant pleural mesothelioma is significantly correlated with tumor histology and tumor stage. Furthermore, high soluble mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma patients.

  14. Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Aigner KR

    2017-06-01

    Full Text Available Karl Reinhard Aigner, Emir Selak, Sabine Gailhofer Department of Surgical Oncology, Medias Klinikum, Burghausen, Germany Introduction: Therapy of malignant pleural mesothelioma and especially the adequate role of surgery in this context remain the subject of controversial discussions. Radical surgery in particular, which is associated with substantial morbidity, failed to translate into a definite survival advantage. We report on interim results of an ongoing Phase II study of regional chemotherapy in terms of isolated thoracic perfusion with chemofiltration (ITP-F.Patients and methods: Twenty-eight patients (25 male, 3 female, mean age 63.4 years with advanced pleural mesothelioma were included in this study. Isolation of the chest was achieved by insertion of a venous and arterial stop-flow balloon catheter via a femoral access. The aorta and inferior vena cava were blocked at the level of the diaphragm and the upper arms were blocked by pneumatic cuffs. Chemotherapy, consisting of 60 mg/m² cisplatin and 15 mg/m² mitoxantrone, was administered directly into the aorta. The isolated circuit was maintained for 15 minutes followed by ~45 minutes of chemofiltration with a hemoprocessor until 5 L of filtrate were reached. The endpoints of the study were overall survival and quality of life (QoL.Results: Out of 28 patients enrolled in the study, 5 had prior surgeries, 10 patients had systemic chemotherapy, and 5 patients additional irradiation. In all patients in restaging, clinical progress was noted. In all, 162 cycles were administered. Due to chemofiltration, toxicity was within tolerable limits, revealing World Health Organization grade I leucopenia and thrombocytopenia in 9 patients and mucositis grade I in 6 patients. The major surgical complication was inguinal lymphatic fistula in 40% of the cases. Gastrointestinal toxicity and/or neurotoxicity were never observed. One-year survival was 49%, 2-year and 3-year survival was 31%, and 5

  15. Use of indwelling pleural catheters for the definitive treatment of malignant pleural effusion.

    Science.gov (United States)

    Abrão, Fernando Conrado; Abreu, Igor Renato Louro Bruno de; Cavalcanti, Maria Gabriela; Pompa-Filho, José Franklin Soares

    2017-01-01

    To evaluate the safety and feasibility of the use of indwelling pleural catheters (IPCs) in patients with malignant pleural effusion (MPE). We prospectively collected data from patients with MPE undergoing IPC placement between January of 2014 and July of 2015. All patients submitted to IPC placement had a life expectancy > 30 days, in accordance with the MPE treatment guidelines established by the British Thoracic Society. The data collected included gender, age, body mass index, primary cancer site, duration of IPC drainage, IPC-related complications, length of hospital stay, pleural effusion recurrence, and occurrence of spontaneous pleurodesis. A total of 19 patients underwent IPC placement during the study period. Median overall survival after IPC insertion was 145 days. The median follow-up among the surviving patients was 125 days (range, 53-485 days), and the median time between catheter insertion and removal was 31 days (range, 2-126 days). There were IPC-related complications in 5 patients (26.2%), and spontaneous pleurodesis was achieved in 8 (42.0%). Among those 8 patients, the IPC was removed between days 30 and 126 in 4, and spontaneous pleurodesis occurred within the first 30 days in 4. The use of IPCs seems to be feasible and safe in patients with MPE. Avaliar a segurança e a viabilidade do uso de cateter pleural de longa permanência (CPLP) em pacientes com derrame pleural neoplásico (DPN). Dados referentes a pacientes com DPN que receberam CPLP entre janeiro de 2014 e julho de 2015 foram colhidos prospectivamente. Todos os pacientes que receberam CPLP tinham expectativa de vida > 30 dias, em conformidade com as diretrizes de tratamento de DPN da Sociedade Torácica Britânica. Foram colhidos dados sobre sexo, idade, índice de massa corporal, local do câncer primário, tempo de drenagem com o CPLP, complicações relacionadas com o CPLP, tempo de internação hospitalar, recidiva do derrame pleural e ocorrência de pleurodese espont

  16. Metastatic thyroid carcinoma presenting as malignant pleural effusion: A cytologic review of 5 cases.

    Science.gov (United States)

    Vyas, Monika; Harigopal, Malini

    2016-12-01

    Malignant pleural effusion can be a manifestation of many malignancies. Involvement of pleural fluid by metatstatic thyroid carcinoma, though reported, is relatively rare. We present 5 cases of metastatic thyroid carcinoma involving the pleural fluid. The diagnosis of thyroid carcinoma in pleural fluid can be particularly challenging as thyroid transcription factor -1 (TTF-1) which is a marker for carcinoma of thyroid origin is also positive in lung adenocarcinomas (which are more frequently associated with pleural effusions) and thyroglobulin (TG) can often be negative in poorly differentiated/analplastic thyroid carcinomas. In our experience, PAX8 is a particularly useful marker in making the distinction. The diagnosis of metastatic thyroid carcinoma in pleural fluid can be challenging and knowledge of the clinical context and supporting immunohistochemical stains is essential for making the right diagnosis. Diagn. Cytopathol. 2016;44:1085-1089. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Potential role of cholesterol in distinguishing malignant from benign pleural effusion

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2004-01-01

    Full Text Available Cholesterol and carcinoembryonic antigen (CEA levels in pleural effusion and sera, were measured in 199 patients with pleural effusions of various origins. Malignant cause was found in 93, and nonmalignant in 106 patients. Mean cholesterol level in sera of patient with malignant disease was 5.0 ± 0.93mmol/L, and in nonmalignant group 4.34 ± 1.32 mmol/L. The difference was not statistically significant. Mean cholesterol level in nonmalignant pleural effusions was higher thAn those in malignant (2.51 ± 1.23 mmol/L; and 2.28 ± 1.06 mmol/L, but the difference was also not significant. Average pleural fluid/serum cholesterol ratio (HolI/S in nonmalignant group was 0.61 ± 0.32 and in malignant group 0.46 ± 0.22. The difference between those mean values was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106 and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%, positive predictive value 76%, negative predictive value 65% and accuracy 69%. Significant negative correlation between Holi/S and pleural fluid CEA was found (p<0.05. It was assumed that pleural fluid/serum cholesterol ratio lower than 0,5 could be of great benefit, as an additional test in the differentiation of malignant from benign pleural effusion.

  18. [Potential role of cholesterol in distinguishing malignant from benign pleural effusion].

    Science.gov (United States)

    Plavec, Goran; Tomić, Ilija; Nidzović, Natasa; Radojcić, Branko; Aćimović, Slobodan; Bokun, Radojka

    2004-01-01

    Cholesterol and carcinoembryonic antigen (CEA) levels in pleural effusion and sera, were measured in 199 patients with pleural effusions of various origins. Malignant cause was found in 93, and nonmalignant in 106 patients. Mean cholesterol level in sera of patient with malignant disease was 5.0 +/- 0.93 mmol/L, and in nonmalignant group 4.34 +/- 1.32 mmol/L. The difference was not statistically significant. Mean cholesterol level in nonmalignant pleural effusions was higher thAn those in malignant (2.51 +/- 1.23 mmol/L; and 2.28 +/- 1.06 mmol/L), but the difference was also not significant. Average pleural fluid/serum cholesterol ratio (Holl/S) in nonmalignant group was 0.61 +/- 0.32 and in malignant group 0.46 +/- 0.22. The difference between those mean values was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106 and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%, positive predictive value 76%, negative predictive value 65% and accuracy 69%. Significant negative correlation between Holi/S and pleural fluid CEA was found (p < 0.05). It was assumed that pleural fluid/serum cholesterol ratio lower than 0.5 could be of great benefit, as an additional test in the differentiation of malignant from benign pleural effusion.

  19. Combined blood and pleural levels of mesothelin and osteopontin for the diagnosis of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Wafaa M. Ashour

    2012-07-01

    Conclusion: The performance of serum and pleural mesothelin in diagnosing MPM was improved when combined with plasma and pleural osteopontin (respectively through logistic regression analysis model. This will be a great advance in screening and management of MPM.

  20. Immunotherapy and radiation therapy for malignant pleural mesothelioma

    Science.gov (United States)

    Katz, Sharyn I.; Cengel, Keith A.; Simone, Charles B.

    2017-01-01

    Malignant pleural mesothelioma (MPM) is a particularly aggressive thoracic malignancy with limited survival following combination chemotherapy. As a result, there has been increased interested in immunotherapy for mesothelioma, both in the first-line and salvage settings. Early investigations of interleukin-2 (IL-2) and interferon alfa-2a/b have been limited by modest response rates and toxicity, whereas cytokine gene therapy is currently being investigated and shows early promise. The most prominent class of immunotherapies to be trialed with mesothelioma in the past half-decade has been immune checkpoint inhibitors (CPI). Early results are encouraging, particularly for agents targeting the PD-1/PD-L1 pathways. With the increasing recognition of the immune potential of mesothelioma, interest in the immunomodulatory properties of radiation therapy has emerged. The combination of immunotherapy and radiation therapy may allow for complimentary immunologic effects that can enhance antitumor response. This article reviews the existing literature on the efficacy of immunotherapy for MPM, describes the rationale for combining immunotherapy with radiation therapy, and discusses early literature on this treatment combination. PMID:28529903

  1. Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Kristensen, C.A.; Nottrup, T.J.; Berthelsen, A.K.

    2009-01-01

    BACKGROUND AND PURPOSE: The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses...

  2. Pelvic and lumbar metastasis detected by bone scintigraphy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C. [Hospital Clinic Universitari de Valencia (Spain). Servei de Medicina Nuclear; Garcia Garc`ia, T.; Azagra Ros, P. [Hospital Clinic Universitari de Valencia (Spain). Servei d`Oncologia; Maruenda Paulino, J.I. [Hospital Clinic Universitari de Valencia (Spain). Servei Traumatologia; Ferrer Albiach, C. [Hospital Clinic Universitari de Valencia (Spain). Servei Radioterapia

    1999-05-01

    A case of a 43-year-old man suffering from pleural mesothelioma with distant bone metastasis is reported. The results of bone scintigraphy and NMR findings allowed the diagnosis. The current case describes a hematogenous metastasis to the pelvis and vertebral column from a malignant pleural mesothelioma that was detected initally by bone scintigraphy. (orig.) [Deutsch] Fallbericht ueber einen 43jaehrigen Mann mit Pleural-Mesotheliom und Knochenmetastasen. Die Diagnose wurde durch Knochenszintigraphie und NMR gestellt. Der vorliegende Fall beschreibt die haematogene Metastasierung ins Becken und in die Wirbelsaeule, ausgehend von einem malignen Pleural-Mesotheliom, das urspruenglich durch Knochenszintigraphie diagnostiziert wurde. (orig.)

  3. The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Jørgensen, Anne; Santoni-Rugiu, Eric

    2012-01-01

    Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties for pathologists. We assessed whether loss of methylthioadenosine phosphorylase (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate (ATP) often deleted in MPM, could be detected with immunohistoc......  Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties for pathologists. We assessed whether loss of methylthioadenosine phosphorylase (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate (ATP) often deleted in MPM, could be detected...

  4. Efficacy of two fluorescence in situ hybridization (FISH) probes for diagnosing malignant pleural effusions.

    Science.gov (United States)

    Rosolen, Débora C B; Kulikowski, Leslie D; Bottura, Giorgio; Nascimento, Amon M; Acencio, Milena; Teixeira, Lisete; Vargas, Francisco S; Sales, Roberta K; Antonangelo, Leila

    2013-06-01

    It is difficult to differentiate tumor cells in pleural fluid from reactive benign mesothelium. Fluorescence in situ hybridization (FISH) can increase diagnostic accuracy. Two hundred pleural fluid samples were analyzed by using FISH probes for chromosomes 11 and 17. Histological analysis was used to diagnose cancer. Clinical, radiological, and histological data were used to exclude malignancy. Eighty-two pleural effusion samples had positive cytology, 51 were benign, and 67 were atypical, but inconclusive. The 82 positive cases were confirmed to be malignant. Among the 51 negative cytology cases, videothoracoscopy-guided pleural biopsy revealed malignancy in three; aneuploid cells were detected by FISH in all cases. In 43 of the 67 cases with inconclusive cytology, malignancy was confirmed based on histology and fluorescence in situ hybridization. One case of parapneumonic effusion with no evidence of cancer during clinical follow-up had a suspicious cytology and positive fluorescence in situ hybridization result. The remaining 23 cases had no histological, radiological, clinical, or genetic evidence of malignancy. This study demonstrated that cytogenetic analysis of fresh pleural fluid samples using only two FISH probes is a valuable ancillary method for the identification of malignant pleural effusion, particularly in cases in which oncotic cytology is inconclusive. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Malignant pleural effusion in acute myeloid leukemia with hepatitis B virus infection.

    Science.gov (United States)

    Suharti, C; Santosa; Setiawan, Budi

    2015-04-01

    Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML). Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification).

  6. MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Hannah L. Moody

    2017-09-01

    Full Text Available Malignant pleural mesothelioma (MPM is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31 is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. Although miR-31 re-expression increased chemoresistance, paradoxically, a higher relative intracellular accumulation of platinum was detected. This was coupled to a significantly decreased intranuclear concentration of platinum. Linked with a downregulation of OCT1, a bipotential transcriptional regulator with multiple miR-31 target binding sites, we subsequently identified an indirect miR-31-mediated upregulation of ABCB9, a transporter associated with drug accumulation in lysosomes, and increased uptake of platinum to lysosomes. However, when overexpressed directly, ABCB9 promoted cellular chemosensitivity, suggesting that miR-31 promotes chemoresistance largely via an ABCB9-independent mechanism. Overall, our data suggest that miR-31 loss from MPM tumors promotes chemosensitivity and may be prognostically beneficial in the context of therapeutic sensitivity.

  7. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, Andrei; Dell' Oca, Italo; Pasetti, Marcella; Di Muzio, Nadia Gisella [San Raffaele Scientific Institute, Milan (Italy). Dept. of Radiotherapy; Fiorino, Claudio; Broggi, Sara; Cattaneo, Giovanni Mauro; Calandrino, Riccardo [San Raffaele Scientific Institute, Milan (Italy). Medical Physics; Gianolli, Luigi [San Raffaele Scientific Institute, Milan (Italy). Dept. of Nuclear Medicine

    2011-11-15

    To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003). The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. (orig.)

  8. Fast neutron radiotherapy in the treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Patel, Shilpen A; Kusano, Aaron S; Truong, Anh; Stelzer, Keith J; Laramore, George E

    2015-02-01

    Malignant pleural mesothelioma (MPM) is a fatal disease lacking standardized treatment. We describe the use of fast neutron radiation therapy in MPM patients referred to the Department of Radiation Oncology at the University of Washington Medical Center. Retrospective chart review of MPM patients receiving neutron radiotherapy treatment from 1980 to 2012. A total of 30 MPM patients received fast neutron radiotherapy as part of their treatment regimen. Median age at diagnosis was 59.6 years (range, 46.6 to 72.3 y). Eighteen patients received fast neutron radiotherapy as a component of trimodality treatment. Median overall survival was 20.3 months (range, 5.5 to 73.3 mo) with 1 patient censored at 34.8 months and all other patients with confirmed dates of death. One patient receiving radiotherapy alone as a palliative measure died during radiation treatment. One patient was unable to tolerate radiotherapy and stopped before completing prescribed treatment. On univariate analysis, Brigham Stage at presentation was a significant predictor of survival (Ptreatment compared to those who did not. Fast neutron radiotherapy may be utilized in the management of MPM patients. However, treatment with fast neutron radiotherapy did not significantly improvement outcome, even when used in a trimodality regimen.

  9. Prognostic Factors in Patients with Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Vyacheslav P. Kurchin

    2015-03-01

    Full Text Available The aim of the present study was to examine the factors of prognosis in patients with malignant pleural mesothelioma (MPM after combined and multimodality treatment, including the prognostic significance of preoperative intrapleural perfusion hyperthermo-chemotherapy (IPHC. Material and Methods: The study included 20 patients (11 men and 9 women aged from 30 to 70 years (mean age 51.9±8.5 years who underwent surgical treatment for MPM. The diagnosis of MPM was verified by immunohistochemical data. The patients were divided into two groups. Group 1 included 9 patients who underwent combined treatment that included the extrapleural pneumonectomy (EPP and 4 courses of adjuvant chemotherapy. Group 2 included 11 patients who received multimodality treatment (IPHC, EPP, and 4 courses of adjuvant chemotherapy. All patients were followed prospectively at three-monthly intervals for the first year and six-monthly thereafter until the last time of contact or death. Statistical analysis was performed by using Kaplan-Meier method and the log-rank test. Cox-regression model was used for multivariate analysis. Results: Patient’s age over 60 years and the sarcomatoid type of the tumor can be regarded as prognostic factors for poor survival in patients with MPM who underwent EPP. Application of IPHC as a part of a multimodality treatment enhances the survivability of MPM patients.

  10. Current Issues in Malignant Pleural Mesothelioma Evaluation and Management

    Science.gov (United States)

    Ai, Jing

    2014-01-01

    Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer. PMID:25061089

  11. P34. Exploring cell plasticity in malignant pleural mesothelioma

    Science.gov (United States)

    Wagner, Christina; Schelch, Karin; Hoda, Mir Alireza; Klikovits, Thomas; Reid, Glen; Berger, Walter; Hegedus, Balazs; Dome, Balazs; Klepetko, Walter; Grusch, Michael

    2014-01-01

    Background Malignant Pleural Mesothelioma (MPM) is a relatively rare, highly aggressive tumor which originates from pleural mesothelial cells. It has three distinct histological subtypes: the epithelioid, the sarcomatoid (which has a more fibroblast-like morphology than the epithelioid) and the biphasic subtype, the latter being a mixed type of the others. MPM is highly resistant to current chemo- and radiotherapy, resulting in a poor prognosis. Epithelial mesenchymal transition (EMT) is a process best known for its role in development, but it is also known to be involved in the progression of cancer and in chemoresistance. During this process typical epithelial characteristics like cell-polarity and junctions between the cells are lost, and the cells gain migratory and invasive abilities. Understanding of the role of EMT in MPM is currently very limited. Aim of this study was to characterize the influence of growth factors, especially fibroblast growth factor 2 (FGF2), on MPM cell lines regarding EMT-like changes. Methods Changes in the gene and miRNA expression were determined by qPCR and array hybridisation. To characterize the influence of growth factors and/or inhibitors, various treatments (and treatment combinations) were applied to MPM cells in migration and proliferation assays. For analysis of involved downstream signalling pathways immunoblotting was used. Results Treatment with FGF2 or EGF induced a transition to a more fibroblastoid/sarcomatoid morphology in several biphasic MPM cell lines, transmitted by the MAP kinase pathway. Other cytokines like TGF-β, HGF or PDGF did not induce these changes. Additionally also the migration of the FGF2 treated cells increased. Several epithelial markers were down-regulated and mesenchymal markers were up-regulated in the treated cell lines, suggesting not only a switch to a more sarcomatoid morphology but also an underlying EMT in those cells. In addition to the expression-changes of typical EMT-markers some

  12. Gli as a novel therapeutic target in malignant pleural mesothelioma.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available Malignant pleural mesothelioma (MPM is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I. A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.

  13. Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Danijela Štrbac

    2017-01-01

    Full Text Available Background. Malignant pleural mesothelioma (MPM is a rare disease with a relatively short overall survival (OS. Metalloproteinases (MMPs have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of MMP genes could also serve as a prognostic biomarker in MPM. Methods. We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in MMP2; rs17576, rs17577, rs20544, and rs2250889 in MMP9; and rs1042703, rs1042704, and rs743257 in MMP14. We determined the influence on survival using Cox regression. Results. Carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression (TTP (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45–4.14, p=0.001 and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37–4.18, p=0.002. In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38–0.86 p=0.007 and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37–0.85, p=0.007. MMP14 rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06–4.12, p=0.032. Conclusions. Selected MMP SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.

  14. Trimodality Treatment of Malignant Pleural Mesothelioma: An Institutional Review.

    Science.gov (United States)

    Kapeles, Matthew; Gensheimer, Michael F; Mart, Dylan A; Sottero, Theo L; Kusano, Aaron S; Truong, Anh; Farjah, Farhood; Laramore, George E; Stelzer, Keith J; Patel, Shilpen A

    2018-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease with varying treatment options. This study retrospectively describes treatment practices at the University of Washington Medical System from 1980 to 2011, and evaluates the impact of trimodality therapy and radiation (photon and neutron) on survival. A retrospective study was conducted on patients treated for MPM. Univariate and multivariate methods were utilized to evaluate potential factors associated with survival. Treatments received and baseline characteristics were included. Survival analysis of trimodality therapy was performed using a propensity score method to control for baseline characteristics. Among 78 eligible patients, the median age at diagnosis was 59 years and the median survival was 13.7 months. On multivariate analysis, the significant predictors of improved survival were age, smoking history, location, and receipt of radiation therapy or chemotherapy. In the 48 patients receiving radiation therapy, the difference in survival between neutron therapy and non-neutron therapy patients was not statistically significant: hazard ratio, 1.20 (95% confidence interval, 0.68-2.13), P=0.52. Patients receiving trimodality therapy were more likely to have early-stage disease (60% vs. 30%) and epithelioid histology (86% vs. 58%). In a propensity score-weighted Cox proportional hazards model, trimodality therapy patients had improved overall survival, hazard ratio 0.45, P=0.004, median 14.6 versus 8.6 months. Trimodality therapy was significantly associated with prolonged survival in patients with MPM, even when adjusting for baseline patient factors. Radiation therapy was associated with improved survival, but the modality of radiation therapy used was not associated with outcome.

  15. The Role of Trace Elements in the Malignant-Benign Differentation of Pleural Effusions

    Directory of Open Access Journals (Sweden)

    Ozlem Demirpence Demirpence

    2014-12-01

    Full Text Available Aim: It has been speculated that trace elements may play a role in some type of cancers. The aim of the present study was to examine the diagnostic utility of trace elements in pleural fluid with pleural effusions. Material and Method: This study consisted of 38 patients diagnosed with malignant and benign pleural effusions. Chrome, nickel, selenium, copper, lead and zinc concentrations in samples were determined by inductively coupled plasma optical emission spectrometry. Results: No significant difference was found between malignant and benign effusions with respect to Cr, Cu, Ni, Pb, Se and Zn concentrations in samples. Discussion: Trace elements have function as the component of many enzymes and the catalyst of some chemical reactions. There have been studies demonstrating the association of the deficiency or surplus of trace elements (TEs with various type of cancers. In our study, the role of TEs measured in the pleural effusions in the differential diagnosis in the effusion etiology could not be demonstrated.

  16. Unilateral Malignant Pleural Effusion as an Initial Manifestation of Acute Lymphoblastic Leukemia: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Sonia Chabbra

    2015-01-01

    Full Text Available Unilateral malignant pleural effusion as an initial manifestation that leads to the diagnosis of an underlying acute lymphoblastic leukemia is a rare event. Early and accurate diagnosis of this case is important for prompt and adequate therapy. We present the case of an18-year-old male who presented to the emergency department with severe respiratory distress. Chest X-ray revealed a unilateral massive right-sided pleural effusion. Cytological examination of the pleural fluid led to the diagnosis of underlying acute lymphoblastic leukemia. Subsequent hemogram, bone marrow aspirate and flow cytometry analysis confirmed the diagnosis of T-lineage acute lymphoblastic leukemia. The patient underwent induction chemotherapy which led to significant clinical improvement due to resolution of the pleural effusion. The patient is on follow up at present. This case report exemplifies and highlights the importance of cytopathological analysis of body cavity fluids in the diagnosis of underlying unsuspected malignancies.

  17. Efficacy and safety of talc pleurodesis for malignant pleural effusion: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Huan Xia

    Full Text Available BACKGROUND: Talc pleurodesis has been widely used to control malignant pleural effusion; however, it is still not clear whether talc pleurodesis is more effective than other local therapies. We performed a meta-analysis to evaluate the efficacy and safety of talc pleurodesis in the management of malignant pleural effusion. METHODS: PubMed, Embase, and Web of Science were searched for English-language studies of clinical controlled trials comparing talc pleurodesis with control therapies until August 8, 2013. Success rate and incidence of adverse events were evaluated. Relative risks were estimated using random- or fixed- effects model and statistical heterogeneity was assessed using I² test. RESULTS: Twenty trials involving 1,525 patients with malignant pleural effusion were included. The success rate of talc pleurodesis was significantly higher than that of control therapies (relative risk, 1.21; 95% confidence interval, 1.01-1.45; p = 0.035 with similar adverse events. In addition, thoracoscopic talc poudrage was more effective than bedside talc slurry (relative risk, 1.12; 95% confidence interval, 1.01-1.23; p = 0.026. CONCLUSIONS: The current evidences suggested the benefit for talc pleurodesis in the treatment of malignant pleural effusion. Talc pleurodesis, especially thoracoscopic talc poudrage pleurodesis, should be performed in patients with malignant pleural effusion, especially those with life-expectancy longer than one month.

  18. Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis

    OpenAIRE

    Kirschner, Michaela B.; Pulford, Emily; Hoda, Mir Alireza; Rozsas, Anita; Griggs, Kim; Cheng, Yuen Yee; Edelman, J. James B.; Kao, Steven C; Hyland, Rebecca; Dong, Yawen; L?szl?, Viktoria; Klikovits, Thomas; Vallely, Michael P.; Grusch, Michael; Hegedus, Balazs

    2015-01-01

    Background: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. Methods: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics cu...

  19. Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion

    OpenAIRE

    Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Casadei, Luca; Ferraiuolo, Maria; Valerio, Maria Cristina; Santoro, Raffaela; Goeman, Frauke; Maidecchi, Anna; Mattoli, Luisa; Manetti, Cesare; Di Agostino, Silvia; Muti, Paola; Blandino, Giovanni; Strano, Sabrina

    2015-01-01

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors ...

  20. Efficacy and safety of erythromycin as sclerosing agent in patients with recurrent malignant pleural effusion.

    Science.gov (United States)

    Balassoulis, George; Sichletidis, Lazaros; Spyratos, Dionisios; Chloros, Diamantis; Zarogoulidis, Kostas; Kontakiotis, Theodoros; Bagalas, Vassilios; Porpodis, Kostas; Manika, Katerina; Patakas, Dimitrios

    2008-08-01

    The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent. Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded. The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics. This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions.

  1. Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival

    Directory of Open Access Journals (Sweden)

    Zarogoulidis P

    2012-09-01

    Full Text Available Paul Zarogoulidis,1,2 Maria Mavroudi,1 Konstantinos Porpodis,1 Kalliopi Domvri,1 Antonios Sakkas,3 Nikolaos Machairiotis,1 Aikaterini Stylianaki,1 Anastasios Tsiotsios,1 Nikolaos Courcoutsakis,4 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Pulmonary Department-Interventional Unit, Ruhrland Klinik, University of Essen, Essen, Germany; 3Department of Pathology, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Department of Radiology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11–12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient’s follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.Keywords: mesothelioma, asbestos, pegylated liposomal doxorubicin

  2. Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases

    Directory of Open Access Journals (Sweden)

    Reiko Ideguchi

    2017-01-01

    Full Text Available We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.

  3. Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Jelena Kresoja-Rakic

    2017-05-01

    Full Text Available Calretinin (CALB2 is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM. We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide 3′ untranslated region (3′UTR predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3′UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3′UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3′UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3′UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3′UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1 adenine-uridine (AU-binding proteins in calretinin stabilization and (2

  4. A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

    2012-01-01

    Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cispl......Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated...

  5. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma

    DEFF Research Database (Denmark)

    Grosso, Federica; Steele, Nicola; Novello, Silvia

    2017-01-01

    Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unre......Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients...

  6. Diagnostic value of the FHIT and p16 mRNA loss and the K-ras gene mutation in pleural fluids for malignant pleural effusion.

    Science.gov (United States)

    Li, Jian; Bao, Qian-Lei; Wang, Yi; Hu, Yi-Ming; Chen, Ping

    2013-01-01

    Inactivation of the tumor suppressor genes and activation of oncogenes are involved in the development of cancer. The aim of this study was to evaluate the diagnostic value of the fragile histidine triad (FHIT) and p16 mRNA loss and the K-ras gene mutation in distinguishing malignant from benign pleural effusion. A total of 50 patients with malignant pleural effusion and 30 patients with benign pleural effusion were enrolled in this study. All pleural fluid specimens were evaluated in parallel by cytology, reverse transcriptase-PCR for the loss of FHIT and p16 mRNA, and PCR-SSCP (single-stranded conformation polymorphism) for the mutation of K-ras gene. The detection rates of FHIT and p16 mRNA loss were significantly higher in malignant than in benign pleural effusion (P ras mutations were more frequent in malignant than benign pleural effusion (P = 0.006). The sensitivity and specificity were 58% and 93% for FHIT loss, 48% and 90% for p16 loss, and 44% and 87% for the K-ras mutation, respectively. In combined evaluation with both FHIT and p16 loss, the sensitivity was 68%, and specificity was 90%. The combination of the three molecular markers reached 74% sensitivity, whereas the combined use of the cytology and the three markers increased the diagnostic yield of the former by 38%. More than one third of cytology negative malignant pleural effusion could be identified by at least one of the three markers. These results suggest that the detection of FHIT and p16 mRNA loss and the k-ras gene mutation in pleural fluid could be helpful adjunct to cytology in the diagnosis of malignant pleural effusion.

  7. Use of artificial intelligence techniques for diagnosis of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Orhan Er

    2015-03-01

    Full Text Available Objective: Malignant pleural mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. The incidence of malignant mesothelioma is extremely high in some Turkish villages where there is a low-level environmental exposure to erionite, a fibrous zeolite. Therefore epidemiological studies are difficult to perform in Turkey. Methods: In this paper, a study on malignant pleural mesothelioma disease diagnosis was realized by using artificial immune system. Also, the artificial immune system result was compared with the result of the multi-layer neural network focusing on malignant pleural mesothelioma disease diagnosis and using same database. The malignant pleural mesothelioma disease dataset were prepared from a faculty of medicine’s database using patient’s hospital reports. Results: 97.74% accuracy performance is obtained by artificial immune system. The accuracy results of artificial immune system algorithm are much better than the accuracy results of multi-layer neural network algorithm. Conclusion: This system is capable of conducting the classification process with a good performance to help the expert while deciding the healthy and patient subjects. So, this structure can be helpful as learning based decision support system for contributing to the doctors in their diagnosis decisions.

  8. Malignant Pleural Mesothelioma Prognostic Marker: A Review of ...

    African Journals Online (AJOL)

    The first proves the utilization of osteopontin and mesothelin for diagnostic and prognostic assessment of MPM in patients previously exposed to asbestos and those with pleural metastasis. The second proves that immunohistochemical analysis identified osteopontin to have a prognostic role from its expression in MPM.

  9. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy for stage I malignant pleural mesothelioma

    NARCIS (Netherlands)

    van Ruth, S.; Baas, P.; Haas, R. L. M.; Rutgers, E. J. Th; Verwaal, V. J.; Zoetmulder, F. A. N.

    2003-01-01

    BACKGROUND: Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the

  10. Chemotherapy induced pathologic complete response in malignant pleural mesothelioma: a review and case report

    DEFF Research Database (Denmark)

    Bech, Cecilia; Sørensen, Jens Benn

    2010-01-01

    Malignant pleural mesothelioma is a rare aggressive disease with a poor prognosis and usually modest responses to chemotherapy. Complete responses (CRs) to chemotherapy are rare. Evaluation is usually based on radiology, and CR is therefore clinical CR (cCR) and whether this indicates absence...

  11. Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Frank, H.; Palshof, T.; Sørensen, Jens Benn

    2008-01-01

    The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0-2. Treatment was vinorelbine 25 mg m(-2) i.v. weekly and cisplatin 100...

  12. Paclitaxel for malignant pleural mesothelioma : A phase II study of the EORTC Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    vanMeerbeeck, J; Debruyne, C; vanZandwijk, N; Postmus, PE; Pennucci, MC; vanBreukelen, F; Galdermans, D; Groen, H; Pinson, P; vanGlabbeke, M; vanMarck, E; Giaccone, G

    The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m(-2), as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and

  13. Polyneuropathy in a patient with malignant pleural mesothelioma: a paraneoplastic syndrome

    DEFF Research Database (Denmark)

    Bech, C.; Sørensen, Jens Benn

    2008-01-01

    Paraneoplastic syndromes have only been reported in malignant pleural mesothelioma (MPM) in a few cases. In this case, we describe a 57-year-old man with MPM who developed sensory-motor polyneuropathy 18 days after diagnosis. Thorough endocrinological, neurological, and paraclinical examinations...

  14. Etoposide in malignant pleural mesothelioma : Two phase II trials of the EORTC Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    Sahmoud, T; Postmus, PE; van Pottelsberghe, C; Mattson, K; Tammilehto, L; Splinter, TAW; Planting, AST; Sutedja, T; van Pawel, J; van Zandwijk, N; Baas, P; Roozendaal, KJ; Schrijver, M; Kirkpatrick, A; Van Glabbeke, M; Ardizzoni, A; Giaccone, G

    1997-01-01

    Intravenous and oral etoposide (VP 16-213) were tested in two sequential phase II trials in chemotherapy-naive patients with malignant pleural mesothelioma. In the first trial, etoposide was given intravenously (i.v.) at a dose of 150 mg/m(2) on days 1, 3 and 5 every 3 weeks. The second trial

  15. The value of pemetrexed for the treatment of malignant pleural mesothelioma: a comprehensive review.

    NARCIS (Netherlands)

    Boons, C.C.L.M.; Tulder, M.W. van; Burgers, J.A.; Beckeringh, J.J.; Wagner, C.; Hugtenburg, J.G.

    2013-01-01

    This review aims to provide insight into treatment of malignant pleural mesothelioma (MPM) considering effects on survival, quality of life (QoL) and costs, in order to determine the value of pemetrexed in MPM treatment. Cisplatin in combination with pemetrexed or raltitrexed increased survival in

  16. Second line therapy in malignant pleural mesothelioma: A systematic review.

    Science.gov (United States)

    Buikhuisen, Wieneke A; Hiddinga, Birgitta I; Baas, Paul; van Meerbeeck, Jan P

    2015-09-01

    After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Pleural localized malignant mesothelioma mimicking a benign solitary fibrous tumor of the pleura on chest computed tomography: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hwi Ryong; Chong, Se Min; Kim, Mi Kyung [Dept. of Radiology, (Korea, Republic of)

    2017-06-15

    Pleural malignant mesotheliomas arise from mesothelial cells in the pleura. They are characterized as diffuse or localized malignant mesotheliomas (LMM). Diffuse malignant mesotheliomas spread diffusely along pleural surfaces, while LMM are well-circumscribed nodular lesions with no gross or microscopic diffuse pleural spreading. Therefore, LMM can be radiologically confused with solitary fibrous tumors of the pleura (SFTP), which commonly presents as a solitary, well-demarcated peripheral mass abutting the pleural surface upon the completion of a computed tomography (CT). Therefore, this study reports on a 63-year-old female patient with a pathologically-proven LMM of the pleura, mimicking a benign SFTP upon having a chest CT. Although LMM is extremely rare, FDG PET/CT should be recommended for adequate tumor management in order to avoid misdiagnosing the tumor as a benign SFTP when an interfissural or pleural-based mass is seen on the chest CT.

  18. The value of delayed phase enhanced imaging in malignant pleural mesothelioma

    Science.gov (United States)

    Patel, Akash M.; Berger, Ian; Wileyto, E. Paul; Khalid, Urooj; Torigian, Drew A.; Nachiappan, Arun C.; Barbosa, Eduardo M.; Gefter, Warren B.; Galperin-Aizenberg, Maya; Gupta, Narainder K.; Simone, Charles B.; Haas, Andrew R.; Alley, Evan W.; Singhal, Sunil; Cengel, Keith A.

    2017-01-01

    Background Cross-sectional imaging of malignant pleural mesothelioma (MPM) can underestimate the presence of local tumor invasion. Since accurate staging is vital optimal choice of therapy, techniques that optimize pleural imaging are needed. Here we estimate the optimal timing of MPM enhancement on magnetic resonance imaging (MRI). Methods All MPM patients with intravenous (IV) contrast enhanced staging MRI between 2000–2016 at our institution were retrospectively selected for image analysis. Patients with incomplete imaging protocol and maximum pleural tumor thickness 80%, >85%, and >90% peak tumor enhancement. There was a statistically significant correlation between increasing tumor enhancement and subjective lesion conspicuity. Conclusions Optimal MPM enhancement on MRI likely occurs at a time delay between 2.5–5 min following IV contrast administration. Further study of delayed phase enhancement of MPM with dynamic contrast enhanced MRI is warranted. PMID:28932538

  19. Nonselective transarterial chemoperfusion: a palliative treatment for malignant pleural mesothelioma.

    Science.gov (United States)

    Vogl, Thomas J; Lindemayr, Sebastian; Naguib, Nagy N N; Gurung, Jessen; Nour-Eldin, Nour-Eldin A; Zangos, Stephan; Mbalisike, Emmanuel C

    2013-02-01

    To evaluate tumor response by means of volumetric assessment, survival, and changes in patient symptoms after the treatment of unresectable and/or recurrent pleural mesothelioma by using regional nonselective transarterial chemoperfusion as a palliative treatment option. This retrospective study was approved by the hospital ethical committee, and all patients signed an informed consent prior to treatment. Thirty-nine patients (mean age, 64.0 years; 10 women and 29 men) with unresectable pleural mesothelioma were treated with repetitive transarterial chemoperfusion between March 2007 and March 2010, with a mean of 2.9 sessions per patient at 4-week intervals. Transarterial chemoperfusion was performed by using mitomycin C, cisplatin, and gemcitabine. Computed tomography findings and patient symptoms were evaluated. Tumor response was evaluated by using Response Evaluation Criteria in Solid Tumors guidelines, and survival was assessed with the Kaplan-Meier method. The change in volume for the partial-response group was tested by using the Wilcoxon signed-rank test. In 36% of treated tumors (14 of 39), partial response was achieved, and tumor volume decreased from a mean value ± standard deviation of 839.6 mL ± 590.3 (range, 3.9-1972.2 mL) to 137 mL ± 399.8 (range, 0.88-1131.4; P = .00012). In 49% of tumors (19 of 39), stable disease was noted. In 15% of tumors (six of 39), progressive disease was seen. Mean specific growth rate of the tumor was 0.00158% per day. The mean survival time was 14.2 months (range, 2.1-33.1 months) from the start of treatment. For patients with tumors that responded to treatment, mean survival time was 15 months (range, 4.5-33.1 months). Mean time to disease progression was 2.6 months for all tumors, 1.5 months for stable disease, and 1.3 months for progressive disease. Transarterial chemoperfusion may have the potential to yield positive results and response in the treatment of recurrent and/or unresectable pleural mesothelioma. © RSNA

  20. A Systematic Review of Talc Compared with Bleomycin for Patients with Malignant Pleural Effusions

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    Yonggang WEI

    2009-03-01

    Full Text Available Background and objective Malignant pleural effusions are a common complication in advanced malignancy. Talc, bleomycin and the tetracyclines are the three most frequently used sclerosants. The aim of this study is to evaluate the efficacy and adverse effects of patients with malignant pleural effusions treated with talc and bleomycin. Methods We searched PubMed, Embase, the Cochrane Library, Chinese biomedicine literature database (CBM, CNKI, VIP, references of included studies for randomized controlled trials comparing talc with bleomycin for patients with malignant pleural effusions. The quality of included studies was assessed independently by two reviewers, discrepancies were resolved by discussion with the third person. We analyzed the data using Review Manager (version 5.0 software. Results Six studies totaling 224 patients were included. Meta analysis results were as follows: there was significantdifference in treatment success (RR=1.22, 95%CI: 1.05-1.42, recurrence rate (RR=0.31, 95%CI: 0.11-0.87 between talc group and bleomycin group, there was no significant difference between the two groups in case fatality rate (RR=1.39, 95%CI: 0.84-2.30, fever (RR=0.68, 95%CI: 0.24-1.94, pain (RR=0.22, 95%CI: 0.01-4.32. Conclusion Current evidence indicate that talc is super to bleomycin for patients with malignant pleural effusions in terms of improvingtreatment success and reducing recurrence rate, there is no significant difference between the two group with regard to casefatality rate, fever, pain, the results mentioned above still need to be confirmed by high quality, large sample, multicenter randomized controlled trial.

  1. Combined ultrasound-guided cutting-needle biopsy and standard pleural biopsy for diagnosis of malignant pleural effusions.

    Science.gov (United States)

    Wang, Jinlin; Zhou, Xinghua; Xie, Xiaohong; Tang, Qing; Shen, Panxiao; Zeng, Yunxiang

    2016-11-17

    The most efficient approach to diagnose malignant pleural effusions (MPEs) is still controversial and uncertain. This study aimed to evaluate the utility of a combined approach using ultrasound (US)-guided cutting-needle biopsy (CNB) and standard pleural biopsy (SPB) for diagnosing MPE. Pleural effusions were collected from 172 patients for biochemical and microbiological analyses. US-guided CNB and SPB were performed in the same operation sequentially to obtain specimens for histological analysis. US-guided CNB and SPB procedures provided adequate material for histological analysis in 90.7 and 93.0% of cases, respectively, while a combination of the 2 techniques was in 96.5% of cases. The sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV) and diagnostic accuracy of US-guided CNB versus SPB were: 51.2 vs 63.4%, 100 vs 100%, 100 vs 100%, 64.9 vs 72.2% and 74.4 vs 81.3%, respectively. When CNB was combined with SPB, the corresponding values were 88.6, 100, 100, 88.6 and 93.9%, respectively. Whereas sensitivity, NPV and diagnostic accuracy were not significantly different between CNB and SPB, the combination of CNB and SPB significantly improved the sensitivity, NPV and diagnostic accuracy versus each technique alone (p < 0.05). Significant pain (eight patients), moderate haemoptysis (two patients) and chest wall haematomas (two patients) were observed following CNB, while syncope (four patients) and a slight pneumothorax (four patients) were observed following SPB. Use of a combination of US-guided CNB and SPB afforded a high sensitivity to diagnose MPEs, it is a convenient and safe approach.

  2. Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

    Science.gov (United States)

    Tiran, Verena; Stanzer, Stefanie; Heitzer, Ellen; Meilinger, Michael; Rossmann, Christopher; Lax, Sigurd; Tsybrovskyy, Oleksiy; Dandachi, Nadia; Balic, Marija

    2017-01-01

    A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of

  3. Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis.

    Science.gov (United States)

    Kirschner, Michaela B; Pulford, Emily; Hoda, Mir Alireza; Rozsas, Anita; Griggs, Kim; Cheng, Yuen Yee; Edelman, J James B; Kao, Steven C; Hyland, Rebecca; Dong, Yawen; László, Viktoria; Klikovits, Thomas; Vallely, Michael P; Grusch, Michael; Hegedus, Balazs; Dome, Balazs; Klepetko, Walter; van Zandwijk, Nico; Klebe, Sonja; Reid, Glen

    2015-09-15

    Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)). These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients.

  4. Monitoring of impending myocardial damage after pleuropneumonectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma using biochemical markers

    NARCIS (Netherlands)

    Klaase, JM; Swaanenburg, JCJM; Schouwink, H; Sosef, MN; Bonfrer, JMG; Zoetmulder, FAN; Rutgers, EJT; Baas, P

    In five patients who were treated for malignant pleural mesothelioma (MPM) with pleuropneumonectomy and intraoperative photodynamic therapy (IPDT), impending myocardial damage was monitored using EGG, the classical biochemical markers (creatine kinase [CK], total activity; CKMB, mass; and

  5. Talc Pleurodesis Through Very-Small-Bore Catheters in Patients with Recurrent Malignant Pleural Effusion

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    Ali Özgen

    2016-04-01

    Full Text Available Objective: Malignant pleural effusion (MPE is a frequent and disturbing complication of metastatic disease. Talc pleurodesis via percutaneosly placed 12–18F catheters is an effective procedure to treat recurrent MPE. We aimed to determine the efficiency of talc pleurodesis through very-small-bore catheters in the treatment of recurrent malignant pleural effusion. Methods: We performed 13 talc pleurodesis procedures in 10 patients with recurrent MPE via pre-existing 7F (6 patients and 8F (4 patients pig-tail catheters. We analyzed technical and clinical success of the procedure. Results: All procedures were performed successfully. Complete or partial clinical success was achieved in 8 out of 10 patients. No major complication was observed. Conclusion: Talc pleurodesis through 7F or 8F catheters may be performed in selected patients with reduced patient discomfort, and similar success rates that was obtained using higher caliber catheters in the treatment of recurrent MPE.

  6. Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Ranjit K Goudar

    2008-03-01

    Full Text Available Ranjit K GoudarDepartment of Medicine, Division of Hematology, Medical Oncology and Cellular Therapy, Duke University Medical Center, Durham, NC, USAAbstract: Malignant pleural mesothelioma is a resistant form of lung cancer, and its incidence continues to rise in Europe and Australia. Until recently, chemotherapy had not been shown to be effective in the treatment of this slowly progressive disease. In 2004, the combination of pemetrexed and cisplatin was shown to induce high response rates in MPM. This article reviews the published literature describing the development and testing of this therapeutic combination in mesothelioma, and examines in detail the key phase III clinical trial that led to the approval of pemetrexed by the US FDA. Ongoing research will further define the role of pemetrexed plus cisplatin in the treatment of MPM.Keywords: malignant pleural mesothelioma, mesothelioma, pemetrexed, cisplatin

  7. Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study

    DEFF Research Database (Denmark)

    Hillerdal, G.; Sundstrom, S.; Riska, H.

    2008-01-01

    BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. METHODS: From...... January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. RESULTS: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were...

  8. Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion.

    Science.gov (United States)

    Sakaguchi, Hirozo; Ishida, H; Nitanda, H; Yamazaki, N; Kaneko, K; Kobayashi, Kunihiko

    2017-02-01

    Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. Patients with MPE, performance status of 0-1, possibility of good lung expansion and Crcisplatin at a dose of 80mg/m2. Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. Twenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83-100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m2), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  9. Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis.

    Science.gov (United States)

    Cui, Ai; Jin, Xiao-Guang; Zhai, Kan; Tong, Zhao-Hui; Shi, Huan-Zhong

    2014-02-24

    Although the values of soluble mesothelin-related peptides (SMRPs), including mesothelin and megakaryocyte potentiating factor, in serum and/or pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been extensively studied, the exact diagnostic accuracy of these SMRPs remains controversial. The purpose of the present meta-analysis is to update the overall diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic accuracy of SMRPs in pleural fluid for MPM. Systematic review and meta-analysis. A total of 30 articles of diagnostic studies were included in the current meta-analysis. Sensitivity, specificity and other measures of accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was also found that megakaryocyte potentiating factor in serum had a superior diagnostic accuracy compared with mesothelin for MPM. SMRPs in both serum and pleural fluid are helpful markers for diagnosing MPM with similar diagnostic accuracy. The negative results of SMRP determinations are not sufficient to exclude non-MPM, and the positive test results indicate that further invasive diagnostic steps might be necessary for the diagnosis of MPM.

  10. Shoulder ring complaints as a rare first symptom of malignant pleural mesothelioma.

    Science.gov (United States)

    Lorkowski, J; Grzegorowska, O; Kotela, A; Weryński, W; Kotela, I

    2015-01-01

    The prevalence of malignant pleural mesothelioma is often encountered in the areas highly exposed to asbestos. The aim of this paper was a retrospective analysis of shoulder pain as a rare, first symptom of pleural mesothelioma, which constitutes an interdisciplinary diagnostic problem concerning both orthopedics and pulmonology. The research was based on a retrospective review of the patients' medical records. The considered period of time included the years 2006-2012. The study group included a total of 49 patients. Seven patients (14.3%) presented a complain of shoulder pain, as the first symptom of mesothelioma. The remaining 42 mesothelioma patients, without this symptom, constituted a reference group. The intensity of shoulder pain was, on average, 4/10 on an analog scale. A concomitant limitation of mobility was observed in five out of the seven subjects. In one case, limitation of motion and dysfunction of the shoulder joint were at an advanced stage. Neuralgia of upper limbs was found in two cases. We conclude that shoulder pain may be a manifesting symptom of malignant pleural mesothelioma. The neoplasm appears to have a pleiotropic effect on human body, reflected in different ways of its primary manifestation which may also include the motor system.

  11. Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions.

    Science.gov (United States)

    Porcel, J M; Quirós, M; Gatius, S; Bielsa, S

    2017-04-01

    To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  12. Secondary Malignant Peritoneal Mesothelioma of the Greater Omentum after Therapy for Primary Pleural Mesothelioma

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    Andreas Gutzeit

    2013-04-01

    Full Text Available Mesothelioma is the most common malignant primary tumor of the pleura and usually associated with inhalation of asbestos fibers. In contrast, peritoneal mesothelioma is a rare entity whose pathomechanism is not yet fully understood. The coexistence of pleural mesothelioma with secondary involvement of the abdominal cavity has not been addressed in the literature. In this case report, we describe secondary malignant mesothelioma of the greater omentum. A 69-year-old man with histologically proven pleural mesothelioma on the right side and no past medical history of asbestos exposure received palliative treatment consisting of a talc pleurodesis. After a 6-month interval of stable disease, a local progressive tumor of the right pleura was seen on a CT scan. Eleven months later, during follow-up, the patient presented at our emergency department with a sudden onset of diffuse abdominal pain. Abdominal ultrasound revealed a mass within the greater omentum and the coexistence of free fluid. Subsequent abdominal CT scans demonstrated tumor infiltration from the right pleura by a transdiaphragmatic route into the abdomen, where diffuse infiltration of the greater omentum was observed. Aspiration of the ascites and the biopsy of the greater omentum confirmed the diagnosis of secondary malignant mesothelioma of the peritoneum. In conclusion, we present the extremely rare diagnosis of secondary malignant mesothelioma of the abdomen, which arose as a result of local progression from the right pleura into the abdomen.

  13. Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health.

    Science.gov (United States)

    Neumann, Volker; Löseke, Stefan; Nowak, Dennis; Herth, Felix J F; Tannapfel, Andrea

    2013-05-01

    The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come. This article is based on a selective review of the literature, along with data from the German Mesothelioma Register. 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma. The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.

  14. Malignant pleural mesothelioma: initial experience in integrated (18)F-FDG PET/MR imaging.

    Science.gov (United States)

    Schaarschmidt, Benedikt M; Sawicki, Lino M; Gomez, Benedikt; Grueneisen, Johannes; Hoiczyk, Mathias; Heusch, Philipp; Buchbender, Christian

    2016-01-01

    This study aims to compare staging results of (18)F-FDG PET/computed tomography (CT) and integrated PET/magnetic resonance (MR) in malignant pleural mesothelioma (MPM) patients and to investigate a potential apparent diffusion coefficient (ADC)/SUV correlation. Six patients with MPM underwent (18)F-FDG PET/CT and PET/MR including diffusion-weighted imaging. Thoracic TNM staging was performed for both modalities. SUV and ADC were assessed in therapy-naive pleural lesions. In thoracic TNM staging, no differences were found between PET/CT and PET/MR. An inverse correlation was observed between SUVmean and ADCmin (r=-0.63, P=.002). MPM can be staged using PET/MR. The inverse correlation ADC/SUV indicates that future research on multiparametric therapy response evaluation may be warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Ultrasound-guided intrapleural positioning of pleural catheters: influence on immediate lung expansion and pleurodesis in patients with recurrent malignant pleural effusion

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    Pedro Henrique Xavier Nabuco de Araujo

    Full Text Available ABSTRACT Objective: To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE. Methods: This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT and 30 days after pleurodesis (CT30. Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure. Results: Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years. Catheter tip positioning was subpulmonary in 35 patients (41%, anterior in 23 (27%, posterolateral in 17 (20%, and fissural in 10 (12%. No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645, radiological success of pleurodesis (median volume = 33 mL; interquartile range: −225 to 257 mL; p = 0.923, and clinical success of pleurodesis (85.8%; p = 0.676. Conclusions: Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE.

  16. Malignant pleural mesothelioma with heterologous osteoblastic differentiation: case report of the characteristic CT and bone scan findings

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon; Choi, Sang Bong [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2008-06-15

    Malignant pleural mesothelioma is an uncommon neoplasm which is accompanied extremely rarely by osteoblastic heterologous elements. The CT manifestations of this tumor have been reported in several references. And, to our knowledge, only one case report provides a description of the bone scan findings. Here, we report the case of a rapidly progressing malignant pleural mesothelioma with heterologous osteoblastic elements. A CT scan reveals diffuse irregular pleural thickening and very coarse nodular calcifications along the right pleura and major fissure. A bone scan revealed an area of extensive increased radioactivity consistent with the pleural calcifications on the CT scan in the right hemithorax. A follow-up CT scan performed 40 days later suggests the presence of rapidly progressing nodular coarse calcifications.

  17. P36. The prognostic potential of circulating and tissue activin A level in malignant pleural mesothelioma

    Science.gov (United States)

    Dong, Yawen; Hoda, Mir Alireza; Schelch, Karin; Rozsas, Anita; Laszlo, Viktoria; Dome, Balazs; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedus, Balazs

    2014-01-01

    Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by poor outcome and there is a lack of prognostic biomarkers to estimate prognosis. Previously we have shown that suppression of activin A can interfere with MPM tumor growth. In the current study, we compare the circulating and tissue expression level of activin A as a prognostic biomarker in MPM. Methods In a cohort of 53 MPM patients, plasma samples were collected between 2010 and 2014. Controls consisted of age-matched healthy individuals (n=46) and patients with pleuritis or pleural fibrosis (n=16). Circulating activin A was measured by ELISA and correlated to clinicopathological data. Furthermore, activin A expression in the tumor tissue was semiquantitatively measured by immunohistochemistry in 24 patients. Results Plasma activin A level was significantly elevated in MPM patients (n=53, 843±122 pg/mL) when compared to healthy controls (452±144 pg/mL, P=0.0039). Non-malignant pleuritis or pleural fibrosis patients only showed a modest, non-significant increase (625±95 pg/mL, P=0.093). Circulating activin A levels were slightly increased in cases with non-epitheloid morphology (n=16, 1101±183) when compared to epithelioid (n=37, 732±153 pg/mL, P=0.13). MPM patients with below median activin A concentrations had a modestly and non-significantly longer overall survival when compared to the high activin A level patients (469 vs. 271 days, P=0.4751). Interestingly, there was no correlation between circulating and tissue expression level of activin A in 17 patients where both parameters could have been analyzed. Conclusions Our findings suggest that the measurement of circulating activin A may support the diagnosis and prognosis of MPM but additional patient cohorts need to be analyzed to establish the diagnostic and prognostic value of this non-invasive biomarker.

  18. Release of growth factors after mechanical and chemical pleurodesis for treatment of malignant pleural effusion: a randomized control study

    Directory of Open Access Journals (Sweden)

    Hojski Aljaz

    2015-12-01

    Full Text Available Background. Growth factors are key inducers of fibrosis but can also mediate inflammatory responses resulting in increasing pleural effusion and acute respiratory distress syndrome. The primary aim of the study was to analyse growth factors release after performing chemical and mechanical pleurodesis in the first 48 hours at the patients with malignant pleural effusion. The secondary endpoints were to evaluate the effectiveness of the both pleurodeses, symptoms release and the quality of life of patients after the treatment.

  19. Granulocyte-colony stimulating factor (G-CSF) producing malignant pleural mesothelioma: Report of a case

    OpenAIRE

    Fujiwara, Ayako; Higashiyama, Masahiko; Kanou, Takashi; OKAMI, JIRO; Tokunaga, Toshiteru; TOMITA, YASUHIKO; Kodama, Ken

    2015-01-01

    This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony-stimulating factor (G-CSF) that was treated by tumor resection. A 76-year-old male presented with a huge right-side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/?L) and C-reactive protein level (20.57?mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and h...

  20. Expression and activity of eIF6 trigger Malignant Pleural Mesothelioma growth in vivo

    OpenAIRE

    Miluzio, A.; Oliveto, S.; Pesce, E.; Mutti, L; Murer, B.; Grosso, S; Ricciardi, S.; Brina, D.; Biffo, S

    2015-01-01

    eIF6 is an antiassociation factor that regulates the availability of active 80S. Its activation is driven by the RACK1/PKC? axis, in a mTORc1 independent manner. We previously described that eIF6 haploinsufficiency causes a striking survival in the E?-Myc mouse lymphoma model, with lifespans extended up to 18 months. Here we screen for eIF6 expression in human cancers. We show that Malignant Pleural Mesothelioma tumors (MPM) and a MPM cell line (REN cells) contain high levels of hyperphosphor...

  1. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

    Directory of Open Access Journals (Sweden)

    Neragi-Miandoab Siyamek

    2008-01-01

    Full Text Available Abstract Malignant pleural mesothelioma (MPM is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes.

  2. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    Science.gov (United States)

    Kotova, Svetlana; Wong, Raymond M; Cameron, Robert B

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. PMID:25670913

  3. Fluorescence in situ hybridization as adjunct to cytology improves the diagnosis and directs estimation of prognosis of malignant pleural effusions

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    Han Jingquan

    2012-11-01

    Full Text Available Abstract Background The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity and specificity. The aim of this study was to investigate the value of fluorescence in situ hybridization (FISH as adjuncts to conventional cytologic examination in patients with malignant pleural effusions. Methods We conducted a retrospective cohort study of 93 inpatients with pleural effusions (72 malignant pleural effusions metastatic from 11 different organs and 21 benign over 23 months. All the patients came from Chinese northeast areas. Aspirated pleural fluid underwent cytologic examination and fluorescence in situ hybridization (FISH for aneuploidy. We used FISH in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations (chromosomes 7, 11, and 17 in effusion cells as markers of malignancy, to raise the diagnostic yield and identified the efficiency by diagnostic biopsy. Predominant cytogenetic anomalies and patterns of intratumor cytogenetic heterogeneity were brought in relation to overall survival rate. Results Cytology alone confirmed malignant pleural effusions in 45 of 72 patients (sensitivity 63%, whereas FISH alone positively identified 48 of 72 patients (sensitivity 67%. Both tests had high specificity in predicting benign effusions. If cytology and FISH were considered together, they exhibited 88% sensitivity and 94.5% specificity in discriminating benign and malignant effusions. Combined, the two assays were more sensitive than either test alone. Although the positive predictive value of each test was 94.5%, the negative predictive value of cytology and FISH combined was 78%, better than 47% and 44% for FISH and cytology alone, respectively. There was a significantly prolonged survival rate for patients with aneuploidy for chromosome 17. Conclusions FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting

  4. Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

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    Oluf Dimitri Røe

    2015-03-01

    Full Text Available Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.

  5. Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine 153 Malignant Pleural Effusion in Acute Myeloid Leukemia with Hepatitis B Virus Infection

    OpenAIRE

    C Suharti; Santosa, Santosa,; Budi Setiawan

    2016-01-01

    Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia a...

  6. Procedures Performed during Hospitalizations for Malignant Pleural Effusions: Data from the 2012 National Inpatient Sample.

    Science.gov (United States)

    Fortin, Marc; Taghizadeh, Niloofar; Tremblay, Alain

    2018-02-07

    Malignant pleural effusions (MPE) are a common clinical problem. Little is known about the burden of MPE and of the treatments used to alleviate its symptoms on the United States Health Care System. We aimed to obtain a better portrait of inpatient pleural procedures performed in the United States. We conducted a retrospective analysis of MPE-associated hospitalizations using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, Agency for Healthcare Research and Quality (HCUP-NIS 2012). Descriptive statistics were used to analyze procedures performed and their complications. Univariate and multivariate logistic regression models were used to explore the relationship between procedures performed and inpatient mortality and length of stay. Among the 126,825 hospital admissions with a diagnosis of MPE, 72,240 included one or more pleural procedures. Thoracentesis (54,070) was the most frequently performed procedure followed by chest tube placement (23,035), chemical pleurodesis (10,240), and thoracoscopy (6,615). Hospitalization for lung and breast cancer was more likely to include pleural procedures compared to hospitalization for other types of cancer (59.2 and 65.6%, respectively, p < 0.0001). Chemical pleurodesis through a chest tube compared to thoracoscopic chemical pleurodesis was performed more frequently (57 vs. 43%, p < 0.001) and associated with a longer hospital stay (4.9 vs. 5.9 days, p < 0.001). Hospital admissions for MPE represent a large burden on the US Health Care System. Many hospitalizations are associated with procedures not expected to reduce the recurrence rate of this condition. © 2018 S. Karger AG, Basel.

  7. Prognostic significance of pleural fluid data in patients with malignant effusion.

    Science.gov (United States)

    Bielsa, Silvia; Salud, Antonieta; Martínez, Montserrat; Esquerda, Aureli; Martín, Antonio; Rodríguez-Panadero, Francisco; Porcel, José M

    2008-07-01

    To determine the effects of the biochemical and cytological properties of the pleural fluid (PF) on the survival of patients with malignant pleural effusion (MPE). A retrospective study of 284 patients with MPE was performed, which measured overall survival, survival of patients with different types of primary tumors, and survival as a function of PF biochemical variables transformed into quartiles. Median overall survival of MPE patients was 5.4 months following diagnosis. Survival varied significantly depending on the type of the primary tumor: 17.4 months for mesothelioma, 13.2 months for breast cancer, 7 months for lymphoma and 2.6 months for lung cancer. A multivariate analysis of PF biochemical parameters showed that survival was lower as the concentration of lactate dehydrogenase (LDH) increased (11.3 months if LDH was between 140 U/L and 358 U/L vs 2.8 months if LDH was between 1027 U/L and 10,110 U/L) or the concentration of pleural proteins decreased (9.4 months if proteins were between 4.92 g/dL and 7.94 g/dL vs 2.2 months if proteins were between 0.97 g/dL and 3.85 g/dL). We also found that when mesotheliomas were excluded from the analysis, survival was lower in patients with a PF pH lower than 7.3 (2.4 months vs 6.8 months, p=0.03). Tumor type as well as some biochemical features of the pleural fluid, such as pH and concentrations of proteins and LDH, influence survival in patients with MPE.

  8. Radioimmunological detection of the tumor marker CA 12-5 in the serum of patients with benign and malignant pleural effusions

    Energy Technology Data Exchange (ETDEWEB)

    Scherer, J.H.; Krause, F.J.; Geier, G.

    1988-12-01

    In 44 patients with benign diseases and 16 patients with malignant diseases the tumour associated antigen CA 12-5 was determined in sera and pleural effusions. In 97% of the investigated pleural effusions and in 89% of the investigated sera we found pathologically elevated CA 12-5-concentrations. It could be shown, that the determination of CA 12-5 in sera of patients with pleural effusions does not permit to discriminate between benign and malignant origin, because there is no significant difference of the CA 12-5-concentrations between patient sera with benign diseases and patient sera with malignant diseases, when they have pleural effusions.

  9. High RRM1 Expression Is Associated with Adverse Outcome in Patients with Cisplatin/Vinorelbine-treated Malignant Pleural Mesothelioma

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Santoni-Rugiu, Eric; Bech, Cecilia

    2015-01-01

    BACKGROUND/AIM: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM). MATERIALS AND METH......BACKGROUND/AIM: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM). MATERIALS...

  10. Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells.

    Science.gov (United States)

    Hoda, M A; Münzker, J; Ghanim, B; Schelch, K; Klikovits, T; Laszlo, V; Sahin, E; Bedeir, A; Lackner, A; Dome, B; Setinek, U; Filipits, M; Eisenbauer, M; Kenessey, I; Török, S; Garay, T; Hegedus, B; Catania, A; Taghavi, S; Klepetko, W; Berger, W; Grusch, M

    2012-12-04

    Activins control the growth of several tumour types including thoracic malignancies. In the present study, we investigated their expression and function in malignant pleural mesothelioma (MPM). The expression of activins and activin receptors was analysed by quantitative PCR in a panel of MPM cell lines. Activin A expression was further analysed by immunohistochemistry in MPM tissue specimens (N=53). Subsequently, MPM cells were treated with activin A, activin receptor inhibitors or activin-targeting siRNA and the impact on cell viability, proliferation, migration and signalling was assessed. Concomitant expression of activin subunits and receptors was found in all cell lines, and activin A was overexpressed in most cell lines compared with non-malignant mesothelial cells. Similarly, immunohistochemistry demonstrated intense staining of tumour cells for activin A in a subset of patients. Treatment with activin A induced SMAD2 phosphorylation and stimulated clonogenic growth of mesothelioma cells. In contrast, treatment with kinase inhibitors of activin receptors (SB-431542, A-8301) inhibited MPM cell viability, clonogenicity and migration. Silencing of activin A expression by siRNA oligonucleotides further confirmed these results and led to reduced cyclin D1/3 expression. Our study suggests that activin A contributes to the malignant phenotype of MPM cells via regulation of cyclin D and may represent a valuable candidate for therapeutic interference.

  11. US Hospitalizations for Malignant Pleural Effusions: Data From the 2012 National Inpatient Sample.

    Science.gov (United States)

    Taghizadeh, Niloofar; Fortin, Marc; Tremblay, Alain

    2017-04-01

    Malignant pleural effusion (MPE) is a common complication of advanced malignancy, but little is known regarding its prevalence and overall burden on a population level. We conducted a retrospective analysis of MPE-associated hospitalizations using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, Agency for Healthcare Research and Quality (HCUP-NIS 2012). Cases were included if MPE was coded as a primary or secondary diagnosis or if an unspecified pleural effusion was coded in addition to a diagnosis of cancer with either of these being the primary diagnosis. A weighted sample of 126,825 admissions (0.35%) for MPE was identified among the 36,484,846 weighted admissions included in the database in 2012. Of these admissions, 70,750 (55.8%) were for female patients. The median age at admission was 68.0 years (interquartile range [IQR]), 58.4-77.2 years). Lung (37.8%), breast (15.2%), hematologic (11.2%), GI tract (11.0%), and gynecologic (9.0%) cancers were the most common primary malignancies associated with MPE. The median length of stay was 5.5 days (IQR, 2.7-10.1 days), and the inpatient mortality rate was 11.6%. Median hospitalization total charges were $42,376 (IQR, $21,618-$84,679). In the multivariate analyses, female sex, large fringe county residential area, Medicare insurance, and elective type of admission were independently associated with a lower risk of inpatient mortality. There is a considerable inpatient burden and high inpatient mortality associated with MPE in the United States, with potential demographic, geographic, and socioeconomic disparities. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. Methylation-associated Silencing of microRNA-126 and its Host Gene EGFL7 in Malignant Pleural Mesothelioma

    DEFF Research Database (Denmark)

    Andersen, Morten; Trapani, Davide; Ravn, Jesper

    2015-01-01

    BACKGROUND/AIM: We recently reported that miR-126 is down-regulated in malignant pleural mesothelioma (MPM) and can be combined into a 4-microRNA-classifier that can accurately diagnose MPM with high sensitivity and specificity. Herein we analyzed the epigenetic regulation of miR-126 and its host...

  13. SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    M. Ashton

    2018-01-01

    Full Text Available SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM. Standard palliative (20 Gy/5# or dose escalated treatment (36 Gy/6# will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM.

  14. Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

    2012-01-01

    The relationship between excision repair cross-complementation group 1 (ERCC1) expression and outcome, in patients with malignant pleural mesothelioma (MPM), treated with cisplatin/vinorelbine combination-therapy, was retrospectively evaluated in a patient population from a previously published...

  15. Extended Tumor Control After Dendritic Cell Vaccination With Low Dose Cyclophosphamide as Adjuvant Treatment in Patients With Malignant Pleural Mesothelioma

    NARCIS (Netherlands)

    R. Cornelissen (Robin); J.P.J.J. Hegmans (Joost); A.W.P.M. Maat (Alex); M.E.H. Lambers (Margaretha); K. Bezemer (Koen); R.W. Hendriks (Rudi); H.C. Hoogsteden (Henk); J.G.J.V. Aerts (Joachim)

    2015-01-01

    markdownabstract__Rationale:__ We demonstrated before that autologous tumor lysate-pulsed dendritic cell-based immunotherapy in patients with malignant pleural mesothelioma is feasible, well-tolerated, and capable of inducing immunological responses against tumors. In our murine model we found that

  16. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

    Directory of Open Access Journals (Sweden)

    Kota Washimi

    Full Text Available Malignant pleural mesothelioma (MPM is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

  17. [Update on epidemiology, pathophysiology, diagnosis and treatment of malignant pleural mesothelioma].

    Science.gov (United States)

    Gopar-Nieto, Rodrigo; Cabello-López, Alejandro; Juárez-Pérez, Cuauhtémoc Arturo; Haro-García, Luis Cuauhtémoc; Jiménez-Ramírez, Carmina; Aguilar-Madrid, Guadalupe

    2016-01-01

    Malignant pleural mesothelioma is an occupational tumor caused by asbestos exposure. In Mexico, as asbestos usage is not prohibited, an increase in the number of cases is expected. Asbestos exposure is ubiquitous due to the great amount of products in which it is present. Its carcinogenicity is caused as the inhaled asbestos fibers cannot be eliminated by macrophages and, thus, they travel to the pleura through lymphatic pathways, producing a persistent inflammatory response. Diagnosis approach includes occupational history, along with clinical signs and symptoms, and paraclinical studies, such as pleural fluid cytology, chest x-rays, computed tomography, magnetic resonance imaging, and biopsy with immunohistochemistry. The main differential diagnosis is lung adenocarcinoma. Regarding the treatment of this tumor, it mainly comprises palliative care, even though chemotherapy, radiotherapy, and, in selected cases, surgical treatments have been used. There is an urgent need for general physicians and specialists to identify asbestos exposure, in order to make a timely diagnosis. Research is necessary to develop screening and prompt diagnostic tools, along with an epidemiological surveillance program for the workers and the general population exposed to asbestos.

  18. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma.

    Science.gov (United States)

    Mogi, Ai; Koga, Kaori; Aoki, Mikiko; Hamasaki, Makoto; Uesugi, Noriko; Iwasaki, Akinori; Shirakusa, Takayuki; Tamura, Kazuo; Nabeshima, Kazuki

    2013-01-01

    Malignant cells supply their energy needs through increased glucose consumption, producing large quantities of lactic acid via glycolysis. Glucose transporters (GLUTs) and monocarboxylate transporters (MCTs) are therefore commonly up-regulated in human malignancies to mediate glucose influx and lactic acid efflux, respectively. However, their roles in malignant pleural mesothelioma (MPM) have not been fully elucidated. Here, we evaluated GLUT-1, MCT-1, and MCT-4 expression in human MPM and reactive mesothelial hyperplasia (RMH) and elucidated their biological role in vitro. GLUT-1, MCT-1, and MCT-4 expression was determined in human MPM (n = 35) and RMH (n = 20) specimens by immunohistochemistry and in frozen tissue, and MPM cell lines, by real-time reverse transcription-polymerase chain reaction and western blot analysis. GLUT-1, MCT-1, and MCT-4 functions in MPM were evaluated by transfection with small interfering RNA. Immunohistochemical analysis revealed higher levels of GLUT-1, MCT-1, and MCT-4 in MPM than in RMH. Additionally, GLUT-1, MCT-1, and MCT-4 mRNA levels were higher in MPM than in non-neoplastic mesothelial cell lines. The siRNA-mediated knockdown of GLUT-1 or MCT-1 significantly suppressed tumor cell proliferation, and MCT-1 silencing inhibited invasion and induced apoptosis. Taken together, these results indicate that combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating MPM from RMH and suggest that MCT-1plays an important biological role.

  19. Expression and activity of eIF6 trigger malignant pleural mesothelioma growth in vivo.

    Science.gov (United States)

    Miluzio, Annarita; Oliveto, Stefania; Pesce, Elisa; Mutti, Luciano; Murer, Bruno; Grosso, Stefano; Ricciardi, Sara; Brina, Daniela; Biffo, Stefano

    2015-11-10

    eIF6 is an antiassociation factor that regulates the availability of active 80S. Its activation is driven by the RACK1/PKCβ axis, in a mTORc1 independent manner. We previously described that eIF6 haploinsufficiency causes a striking survival in the Eμ-Myc mouse lymphoma model, with lifespans extended up to 18 months. Here we screen for eIF6 expression in human cancers. We show that Malignant Pleural Mesothelioma tumors (MPM) and a MPM cell line (REN cells) contain high levels of hyperphosphorylated eIF6. Enzastaurin is a PKC beta inhibitor used in clinical trials. We prove that Enzastaurin treatment decreases eIF6 phosphorylation rate, but not eIF6 protein stability. The growth of REN, in vivo, and metastasis are reduced by either Enzastaurin treatment or eIF6 shRNA. Molecular analysis reveals that eIF6 manipulation affects the metabolic status of malignant mesothelioma cells. Less glycolysis and less ATP content are evident in REN cells depleted for eIF6 or treated with Enzastaurin (Anti-Warburg effect). We propose that eIF6 is necessary for malignant mesothelioma growth, in vivo, and can be targeted by kinase inhibitors.

  20. Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.

    Science.gov (United States)

    Migliore, Marcello; Calvo, Damiano; Criscione, Alessandra; Palmucci, Stefano; Fuccio Sanzà, Giovanni; Caltabiano, Rosario; Spatola, Corrado; Privitera, Giuseppe; Aiello, Marco Maria; Parra, Hector Soto; Ciancio, Nicola; Di Maria, Giuseppe

    2015-01-01

    Cytoreductive surgery and hyperthermic intraoperative intrapleural chemotherapy (HITHOC) are a known option for malignant pleural mesothelioma (MPM). This prospective study was started to prove that pleurectomy/decortication and HITHOC could be successfully performed in a low volume center. Criteria of inclusion were a proven diagnosis of MPM, early-stage disease and good performance status. Six consecutive patients were enrolled. After pleurectomy/decortication, intrapleural cisplatin was administered for 60 min at 42.5 °C. Wedge resections and diaphragmatic reconstruction were added in two and one patient, respectively. Morbidity was 16.6%. Mortality was nil. Hospital stay was 7.8 days. Mean survival was 21.5 months (range: 6-30). This small experience confirms that pleurectomy/decortication and HITHOC are a good therapeutic option in the multimodality treatment of MPM. A randomized controlled trial is necessary.

  1. Radio-immunotherapy and chemo-immunotherapy as a novel treatment paradigm in malignant pleural mesothelioma

    Science.gov (United States)

    Wu, Licun

    2017-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor outcome. Novel radical radiation techniques using intensity modulated radiation therapy (IMRT) have become an important component of therapy in mesothelioma. Immunotherapy also provides new therapeutic options. However, how best to integrate immunotherapy with standard therapy such as radiation, chemotherapy and surgery remains unknown. A change of paradigm from adjuvant normofractionation to induction accelerated hypofractionated hemithoracic radiation could provide a platform to combine immunotherapy due to the potential benefit of short course high dose radiation on the immune system. Immunotherapy can also be combined with chemotherapy. Although chemotherapy is generally considered immunosuppressive, some chemotherapeutic agents do induce cell death that can be immunogenic and stimulate a specific immune response against the tumor. Immunotherapy could also be used in between cycles of chemotherapy to limit tumor cell repopulation and optimize the results of both treatments. The integration of immunotherapy into a multimodality approach is opening new avenue of treatment for mesothelioma. PMID:28713677

  2. Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients.

    Science.gov (United States)

    Lievense, Lysanne A; Bezemer, Koen; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Hegmans, Joost P J J; Aerts, Joachim G J V

    2017-05-01

    Clinical studies have proven the potential of immunotherapy in malignancies. To increase efficacy, a prerequisite is that treatment is tailored, so precision immune-oncology is the logical next step. In order to tailor treatment, characterization of the patient's tumor environment is key. Pleural effusion (PE) often accompanies malignant pleural mesothelioma (MPM) and is an important part of the MPM environment. Furthermore, the composition of PE is used as surrogate for the tumor. In this study, we provide an insight in the dynamics of the MPM environment through characterization of PE composition over time and show that the immunological characteristics of PE do not necessarily mirror those of the tumor. From 5 MPM patients, PE and tumor biopsies were acquired at the same time point. From one of these patients multiple PEs were obtained. PEs were acquired performing thoracocenteses and total cell amounts were determined. Immunohistochemistry was performed to quantify immune cell composition (T cells, macrophages) and tumor cells in PE derived cytospins and tumor biopsies. The PE amount and (immune) cellular composition varied considerably over time between multiple (n=10) thoracocenteses. These dynamics could in part be attributed to the treatment regimen consisting of standard chemotherapy and dendritic cell (DC)-based immunotherapy. In addition, the presence of T cells and macrophages in PE did not necessarily mirror the infiltration of these immune cells within tumor biopsies in 4 out of 5 patients. In this proof-of-concept study with limited sample size, we demonstrate that the composition of PE is dynamic and influenced by treatment. Furthermore, the immune cell composition of PE does not automatically reflect the properties of tumor tissue. This has major consequences when applying precision immunotherapy based on PE findings in patients. Furthermore, it implies a regulated trafficking of immune regulating cells within the tumor environment. Copyright

  3. Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine 153 Malignant Pleural Effusion in Acute Myeloid Leukemia with Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    C Suharti

    2016-05-01

    Full Text Available Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML. Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification. Key words: Acute myeloid leukemia, pleural effusion, infection.

  4. A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Okonogi Noriyuki

    2012-12-01

    Full Text Available Abstract Introduction Malignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy. Case presentation A 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent with a diagnosis of malignant pleural mesothelioma (sarcomatoid type. The tumor was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years. Conclusions The combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to

  5. National Trends in the Epidemiology of Malignant Pleural Mesothelioma: A National Cancer Data Base Study.

    Science.gov (United States)

    Saddoughi, Sahar A; Abdelsattar, Zaid M; Blackmon, Shanda H

    2018-02-01

    Malignant pleural mesothelioma (MPM) remains an aggressive malignancy that is difficult to cure. However, the treatment paradigm of MPM has evolved, and the national practice patterns are unknown. This study examined the national trends in the epidemiology, national treatment patterns, and survival of patients with this disease. We identified all patients (n = 19,134) with MPM from the National Cancer Data Base from 2004 to 2013. We analyzed patient, tumor characteristics, and treatment patterns using descriptive statistics and used Kaplan-Meier and Cox proportional hazards models to estimate survival stratified by the type of therapy administered. Four histologic subtypes were represented in the National Cancer Data Base, these included sarcomatoid (n = 2,355 [12.3%]), epithelioid (n = 6,858 [35.8%]), biphasic (n = 13,617 [11%]), and not otherwise specified (n = 8,560 [44.7%]). Across all subtypes, the prevalence of mesothelioma was highest among white men. Sarcomatoid had the worst survival (adjusted hazard ratio, 2.2; p Data Base. Although survival remains poor, multimodality therapy with surgical resection is associated with the best survival for MPM. Further research is needed to improve survival and overall patient outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Adenosine Deaminase Inhibitor EHNA Exhibits a Potent Anticancer Effect Against Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Yasuhiro Nakajima

    2015-01-01

    Full Text Available Background/Aims: Malignant pleural mesothelioma (MPM is an aggressive malignant tumor and an effective therapy has been little provided as yet. The present study investigated the possibility for the adenosine deaminase (ADA inhibitor EHNA as a target of MPM treatment. Methods: MTT assay, TUNEL staining, monitoring of intracellular adenosine concentrations, and Western blotting were carried out in cultured human MPM cell lines without and with knocking-down ADA. The in vivo effect of EHNA was assessed in mice inoculated with NCI-H2052 MPM cells. Results: EHNA induced apoptosis of human MPM cell lines in a concentration (0.01-1 mM- and treatment time (24-48 h-dependent manner, but such effect was not obtained with another ADA inhibitor pentostatin. EHNA increased intracellular adenosine concentrations in a treatment time (3-9 h-dependent manner. EHNA-induced apoptosis of MPM cells was mimicked by knocking-down ADA, and the effect was neutralized by the adenosine kinase inhibitor ABT-702. EHNA clearly suppressed tumor growth in mice inoculated with NCI-H2052 MPM cells. Conclusion: The results of the present study show that EHNA induces apoptosis of MPM cells by increasing intracellular adenosine concentrations, to convert to AMP, and effectively prevents MPM cell proliferation. This suggests that EHNA may be useful for treatment of the tragic neoplasm MPM.

  7. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  8. CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.

    Science.gov (United States)

    Zeltsman, Masha; Dozier, Jordan; McGee, Erin; Ngai, Daniel; Adusumilli, Prasad S

    2017-09-01

    Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell antitumor effector function and have gained momentum to investigate in solid tumors based on recent successes of clinical trials treating patients with B-cell hematologic malignancies. This review summarizes target antigens for CAR T-cell therapy that are being investigated in preclinical studies and clinical trials for both NSCLC and MPM patients. We discuss the rationale for combination immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the challenges and strategies for overcoming the obstacles facing translation of CAR T-cell therapy to solid tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Malignant Pleural Mesothelioma: State of the art and advanced cell therapy.

    Science.gov (United States)

    Facchetti, Giorgio; Petrella, Francesco; Spaggiari, Lorenzo; Rimoldi, Isabella

    2017-12-15

    Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy, with a response rate of 20% of patients and for this reason an efficient treatment is still a challenge. Platinum-based chemotherapy in association with a third-generation antifolate is the front-line standard of care whereas any second-line treatment was approved for MPM thus making it a pathology that evokes the need for new therapeutic agents. Different platinum-drugs were synthesised and tested as an option for patients who are not candidates to cisplatin-based therapy. Among these, monofunctional cationic antineoplastic platinum compounds received a special attention in the last decade. Alternative strategies to the commonly used combination-therapy resulted from the use of Mesenchymal Stromal Cells (MSC) widely used in the field of regenerative medicine and recently proposed as natural carriers for a selective delivery of chemotherapeutic agents and from the use of immune checkpoint and kinase inhibitors. The present short review shed light on the recent state of art and the future perspectives relative to MPM therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Pleural epitheliod hemangioendothelioma: What started as a liver fluke and ended up being almost mistaken for malignant mesothelioma

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    Omer H Jamy

    2015-01-01

    Full Text Available Epitheliod hemangioendothelioma (EHE is a rare tumor of vascular origin. The pleural variant has only been reported around 20 times in English literature. It commonly occurs in older men and carries a poor prognosis with average survival lasting from a few weeks to months. Pleural EHE (PEHE can be a diagnostic challenge due to its rarity as well as similarities to other pleural and vascular tumors. There is currently no standard treatment for EHE. Due to the rarity of this disease, reaching a final diagnosis is challenging. It′s clinical, radiological, and pathological resemblance to malignant mesothelioma can cause a delay in diagnosis. Special stains such as CD31, CD34, and factor VIII related antigen can help differentiate between the two. Ordering appropriate stains in a timely manner can help avoid misdiagnosing PEHE.

  11. Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

    Science.gov (United States)

    Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

    2017-08-01

    To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. MSLN gene silencing has an anti-malignant effect on cell lines overexpressing mesothelin deriving from malignant pleural mesothelioma.

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    Ombretta Melaiu

    Full Text Available Genes involved in the carcinogenetic mechanisms underlying malignant pleural mesothelioma (MPM are still poorly characterized. So far, mesothelin (MSLN has aroused the most interest. It encodes for a membrane glycoprotein, frequently over-expressed in various malignancies such as MPM, and ovarian and pancreatic cancers. It has been proposed as a diagnostic and immunotherapeutic target with promising results. However, an alternative therapeutic approach seems to rise, whereby synthetic molecules, such as antisense oligonucleotides, could be used to inhibit MSLN activity. To date, such a gene-level inhibition has been attempted in two studies only, both on pancreatic and ovarian carcinoma cell lines, with the use of silencing RNA approaches. With regard to MPM, only one cell line (H2373 has been employed to study the effects of MSLN depletion. Indeed, the knowledge on the role of MSLN in MPM needs expanding. Accordingly, we investigated the expression of MSLN in a panel of three MPM cell lines, i.e., NCI-H28, Mero-14, and IstMes2; one non-MPM cell line was used as reference (Met5A. MSLN knock-down experiments on MSLN-overexpressing cells were also performed through silencing RNA (siRNA to verify whether previous findings could be generalized to a different set of cell cultures. In agreement with previous studies, transient MSLN-silencing caused decreased proliferation rate and reduced invasive capacity and sphere formation in MSLN-overexpressing Mero-14 cells. Moreover, MSLN-siRNA combined with cisplatin, triggered a marked increase in apoptosis and a decrease in proliferation as compared to cells treated with each agent alone, thereby suggesting a sensitizing effect of siRNA towards cisplatin. In summary, our findings confirm that MSLN should be considered a key molecular target for novel gene-based targeted therapies of cancer.

  13. Ultrasound-guided intrapleural positioning of pleural catheters: influence on immediate lung expansion and pleurodesis in patients with recurrent malignant pleural effusion.

    Science.gov (United States)

    Araujo, Pedro Henrique Xavier Nabuco de; Terra, Ricardo Mingarini; Santos, Thiago da Silva; Chate, Rodrigo Caruso; Paiva, Antonio Fernando Lins de; Pêgo-Fernandes, Paulo Manuel

    2017-01-01

    To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE). This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure. Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35 patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in 10 (12%). No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL; interquartile range: -225 to 257 mL; p = 0.923), and clinical success of pleurodesis (85.8%; p = 0.676). Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE. Avaliar o papel do posicionamento intrapleural do cateter pleural na expansão pulmonar precoce e no sucesso da pleurodese em pacientes com derrame pleural maligno recorrente (DPMR). Trata-se de um estudo retrospectivo aninhado em um estudo prospectivo de

  14. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2013-09-01

    10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a...this project is to conduct a multicenter, double-blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to

  15. Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy.

    Science.gov (United States)

    Hoda, Mir Alireza; Mohamed, Amir; Ghanim, Bahil; Filipits, Martin; Hegedus, Balazs; Tamura, Masaya; Berta, Judit; Kubista, Bernd; Dome, Balazs; Grusch, Michael; Setinek, Ulrike; Micksche, Michael; Klepetko, Walter; Berger, Walter

    2011-05-01

    Human malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by frequent resistance to chemotherapy and radiotherapy. Here, we investigated the feasibility of mammalian target of rapamycin (mTOR) inhibition by temsirolimus as an antimesothelioma strategy. Phosphorylation of mTOR (p-mTOR) was assessed by immunohistochemistry in MPM surgical specimens (n = 70). Activation of mTOR and impact of mTOR inhibition by temsirolimus was determined in MPM cell lines in vitro (n = 6) and in vivo as xenografts in severe combined immunodeficiency mice (n = 2) either as single agent or in combination with cisplatin. Strong immunoreactivity for p-mTOR was predominantly detected in epitheloid and biphasic but not sarcomatoid MPM specimens while adjacent normal tissues remained widely unstained. Accordingly, all mesothelioma cell lines harbored activated mTOR, which was further confirmed by hyperphosphorylation of the downstream targets pS6K, S6, and 4EBP1. Temsirolimus potently blocked mTOR-mediated signals and exerted a cytostatic effect on mesothelioma cell lines in vitro cultured both as adherent monolayers and as nonadherent spheroids. Mesothelioma cells with intrinsic or acquired cisplatin resistance exhibited hypersensitivity against temsirolimus. Accordingly, cisplatin and temsirolimus exerted synergistic inhibition of the mTOR downstream signals and enhanced growth inhibition and/or apoptosis induction in mesothelioma cell lines. Finally, temsirolimus was highly active against MPM xenograft models in severe combined immunodeficiency mice both as a single agent and in combination with cisplatin. The mTOR inhibitor temsirolimus is active against mesothelioma in vitro and in vivo and synergizes with chemotherapy. These data suggest mTOR inhibition as a promising novel therapeutic strategy against MPM.

  16. Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Patil, Namrata S; Righi, Luisella; Koeppen, Hartmut; Zou, Wei; Izzo, Stefania; Grosso, Federica; Libener, Roberta; Loiacono, Marco; Monica, Valentina; Buttigliero, Consuelo; Novello, Silvia; Hegde, Priti S; Papotti, Mauro; Kowanetz, Marcin; Scagliotti, Giorgio V

    2018-01-01

    Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and relatively chemoresistant and radioresistant malignancy with limited therapeutic options. Our objective was to investigate the prevalence of programmed death ligand 1 (PD-L1) and the characteristics of the immune environment in this disease. A total of 99 archival tumors from advanced-stage MPM were immunohistochemically tested in parallel for PD-L1 in two different laboratories, and 87 of them were profiled for immune gene expression by NanoString analysis for 800 genes. A prior study on the same samples indicated a low mutational load with a complex mutational landscape of genetic variations more frequently associated with the p53/DNA repair and phosphoinisitide-3-kinase pathways. PD-L1 expression was found in 16% of the MPM tumor samples, either in the tumor cells or the infiltrating immune cells. Gene expression analysis suggested that MPM is an inflamed tumor type and can be classified into three different subgroups on the basis of the different expression profiles of immune-related genes, of which two groups showed varying degrees of expression of immune-related genes. Overall, these molecular findings suggest that these subgroups of MPM associated with PD-L1 positivity and expression of immune-related genes accounting for 60% of MPMs represent a candidate subtype that may respond to cancer immunotherapy. These data suggest that 60% of patients with MPM characterized by either PD-L1 expression or an inflamed status are attractive candidates for cancer immunotherapeutic options. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  17. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

    Science.gov (United States)

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-01-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. PMID:22289125

  18. Granulocyte-colony stimulating factor (G-CSF) producing malignant pleural mesothelioma: Report of a case.

    Science.gov (United States)

    Fujiwara, Ayako; Higashiyama, Masahiko; Kanou, Takashi; Okami, Jiro; Tokunaga, Toshiteru; Tomita, Yasuhiko; Kodama, Ken

    2015-01-01

    This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony-stimulating factor (G-CSF) that was treated by tumor resection. A 76-year-old male presented with a huge right-side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/μL) and C-reactive protein level (20.57 mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and histopathological analysis led to a diagnosis of sarcomatous type of MPM. Immunohistochemical findings for both anti-human G-CSF and interleukin-6 monoclonal antibodies were positive. Although the general condition of the patient quickly improved after surgery, local recurrence occurred two months later and he died of respiratory failure seven months after the operation, though surgery provided symptom relief. G-CSF-producing MPMs usually show a poor prognosis, though less-invasive surgery may be considered for relief of symptoms.

  19. Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma.

    Science.gov (United States)

    Ghanim, B; Hoda, M A; Klikovits, T; Winter, M-P; Alimohammadi, A; Grusch, M; Dome, B; Arns, M; Schenk, P; Jakopovic, M; Samarzija, M; Brcic, L; Filipits, M; Laszlo, V; Klepetko, W; Berger, W; Hegedus, B

    2014-02-18

    To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients. A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees. In total, 176 MPM patients (mean age: 63.5 years ± 10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (≥ 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (≤ 627 mg dl(-1)) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS). Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.

  20. miRNA regulation is important for DNA damage repair and recognition in malignant pleural mesothelioma.

    Science.gov (United States)

    Mairinger, Fabian Dominik; Werner, Robert; Flom, Elena; Schmeller, Jan; Borchert, Sabrina; Wessolly, Michael; Wohlschlaeger, Jeremias; Hager, Thomas; Mairinger, Thomas; Kollmeier, Jens; Christoph, Daniel Christian; Schmid, Kurt Werner; Walter, Robert Fred Henry

    2017-06-01

    Platin-containing regimes are currently considered as state-of-the-art therapies in malignant pleural mesotheliomas (MPM) but show dissatisfying response rates ranging from 6 to 16% only. Still, the reasons for the rather poor efficacy remain largely unknown. A clear stratification of patients based on new biomarkers seems to be a promising approach to enhance clinical management, which would be a long-needed improvement for MPM patients but does not seem likely soon unless new biomarkers can be validated. Twenty-four formalin-fixed, paraffin-embedded (FFPE) tumour specimens were subjected to a miRNA expression screening of 800 important miRNAs using digital quantification via the nCounter technique (NanoString). We defined a small subset of miRNAs regulating the key enzymes involved in the repair of platin-associated DNA damage. Particularly, the TP53 pathway network for DNA damage recognition as well as genes related to the term "BRCAness" are the main miRNA targets within this context. The TP53 pathway network for DNA damage recognition as well as genes related to the term "BRCAness" are the main players for risk stratification in patients suffering from this severe disease. Taking the specific molecular profile of the tumour into account can help to enhance the clinical management prospectively and to smooth the way to better response prediction.

  1. SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Yuen Yee Cheng

    2017-01-01

    Full Text Available Malignant pleural mesothelioma (MPM is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56% and SFRP5 (70% in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.

  2. Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.

    Science.gov (United States)

    Betti, Marta; Casalone, Elisabetta; Ferrante, Daniela; Aspesi, Anna; Morleo, Giulia; Biasi, Alessandra; Sculco, Marika; Mancuso, Giuseppe; Guarrera, Simonetta; Righi, Luisella; Grosso, Federica; Libener, Roberta; Pavesi, Mansueto; Mariani, Narciso; Casadio, Caterina; Boldorini, Renzo; Mirabelli, Dario; Pasini, Barbara; Magnani, Corrado; Matullo, Giuseppe; Dianzani, Irma

    2017-10-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  4. Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

    Science.gov (United States)

    Yang, Yi-Lin; Ni, Jian; Hsu, Ping-Chih; Mao, Jian-Hua; Hsieh, David; Xu, Angela; Chan, Geraldine; Au, Alfred; Xu, Zhidong; Jablons, David M; You, Liang

    2015-01-01

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma. PMID:26218750

  5. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    Directory of Open Access Journals (Sweden)

    Kotova S

    2015-01-01

    Full Text Available Svetlana Kotova,1,2 Raymond M Wong,1–3 Robert B Cameron1,2 1Veterans Affairs Greater Los Angeles Healthcare System, Division of Thoracic Surgery, Los Angeles, CA, USA; 2UCLA Division of Thoracic Surgery and Comprehensive Mesothelioma Program, Los Angeles, CA, USA; 3Pacific Meso Center at the Pacific Heart, Lung and Blood Institute, Los Angeles, CA, USA Abstract: Malignant pleural mesothelioma (MPM is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation, survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4 receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. Keywords: MPM, new targeted, systemic, local therapies

  6. Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position.

    Science.gov (United States)

    Datta, Avijit; Smith, Rhiannon; Fiorentino, Francesca; Treasure, Tom

    2014-02-01

    Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model. Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.

  7. Late cutaneous metastases to the face from malignant pleural mesothelioma: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Lawrence Julia

    2009-11-01

    Full Text Available Abstract Background Malignant Mesothelioma is a rare primary neoplasm affecting the serosal membranes. During its relative short course, this malignant neoplasm can give local and, rarely, distant haematogenous metastases in different organs. The reported metastatic sites include liver, lung, heart, brain, thyroid, adrenals, kidneys, pancreas, bone, soft tissue, skin and lymph nodes. Case Presentation We report a sixty one year-old man with a history of malignant pleural epithelioid mesothelioma treated with six cycles of Pemetrexed and Carboplatin completed 03/11/04 followed by radiotherapy to the drain site 250 Kv/TD20Gy/5F completed 13/12/2004. Then he developed multiple facial skin lesions 4 years later. These lesions were proved to be metastatic malignant sarcomatoid mesothelioma. Conclusion Mesothelioma metastases should be suspected in any known Mesothelioma patient with newly developed skin lesion.

  8. Defining the minimal important difference for the visual analogue scale assessing dyspnea in patients with malignant pleural effusions.

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    Eleanor K Mishra

    Full Text Available The minimal important difference (MID is essential for interpreting the results of randomised controlled trials (RCTs. Despite a number of RCTs in patients with malignant pleural effusions (MPEs which use the visual analogue scale for dyspnea (VASD as an outcome measure, the MID has not been established.Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD (24 hours after the pleural drainage, and in parallel assessed their breathlessness on a 7 point Likert scale.The mean decrease in VASD in patients with a MPE reporting a 'small but just worthwhile decrease' in their dyspnea (i.e. equivalent to the MID was 19mm (95% CI 14-24mm. The mean drainage volume required to produce a change in VASD of 19mm was 760ml.The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm. Thus choosing an improvement of 19mm in the VASD would be justifiable in the design and analysis of future MPE studies.

  9. P35. Fibroblast growth factor signals and their connection to micrornas in malignant pleural mesothelioma

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    Schelch, Karin; Kirschner, Michaela; Wagner, Christina; Hoda, Mir Alireza; Klepetko, Walter; Dome, Balazs; Hegedus, Balazs; Berger, Walter; Reid, Glen; Grusch, Michael

    2014-01-01

    Background Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy characterized by increasing incidence, poor outcome and limited therapeutic options due to frequent resistance to chemo- and radiotherapy. MicroRNAs (miRNAs) are highly conserved RNAs which control gene expression via translational repression of mRNA. Previous data show that the miR-15/16 family has tumor suppressor function and is downregulated in MPM. Fibroblast Growth Factors (FGFs) and their Receptors (FGFRs) are upregulated in MPM. Their signals are important players in MPM malignant behavior and inhibition leads to reduced growth in vitro and in vivo. Several FGFs/FGFRs are predicted mir-15/16 targets. Aim of this study was to investigate the interaction of the miR-15/16 family and FGF signals in MPM. Methods Target gene and miRNA expression was determined by TaqMan-based RT-qPCR and western blot. Mimics were used to restore miRNA expression and recombinant FGF2 or the FGFR1-specific inhibitor PD166866 (PD) to stimulate or inhibit FGF-mediated downstream signals. Effects on cell growth were assessed via SYBR green staining and colony formation assays. Results Expression analysis confirmed the loss of miR-15/16 in all cell lines tested and showed a consistent downregulation of target genes after transfection with miRNA mimics. Restoration of mir-15/16 led to dose-dependent growth inhibition and reduced colony formation. Cells which are more sensitive to FGFR inhibition exhibited a more pronounced response. FGF2 could reduce these effects, but only when added shortly (24 h) after transfection. Re-expression of miR-15/16 resulted in slightly decreased PD efficacy, indicating target competition. Taqman low density array screens showed several miRNAs changed after stimulation/inhibition of FGF signals. Conclusions These data suggest that miR-15/16 achieves a tumor-suppressor function due to translational repression of FGF signaling. Restoration of this miRNA family represses MPM cell

  10. Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells.

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    Maehara, Sachio; Usuda, Jitsuo; Ishizumi, Taichiro; Ichinose, Shuji; Ohtani, Keishi; Inoue, Tatsuya; Imai, Kentaro; Furumoto, Hideyuki; Kudo, Yujin; Kajiwara, Naohiro; Ohira, Tatsuya; Ikeda, Norihiko

    2015-02-01

    To identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer NPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell lines (MSTO‑211H, H2052, H2452 and H28) were assayed using the WST assay after treatment with pemetrexed and NPe6‑PDT. The treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre‑treatment enhanced the lethal effect of NPe6‑PDT in the four malignant mesothelioma cell lines, but NPe6‑PDT followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre‑treatment did not enhance the intracellular accumulation of NPe6, which is one of the determinants of the antitumor effect of PDT. In nude mice injected with MSTO‑211H cells and then treated using a combination of pemetrexed and NPe6‑PDT (10 mg/kg NPe6, 10 J/cm(2) laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre‑treatment value after 14 days. Pemetrexed treatment followed by NPe6‑PDT resulted in an 80% reduction in the tumor size and inhibited re‑growth. NPe6‑PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re‑growth. NPe6‑PDT induced the expression of thymidylate synthase (TS), which confers resistance to pemetrexed, and NPe6‑PDT followed by pemetrexed treatment did not enhance the treatment outcome in vivo. In conclusion, combination treatment, consisting of pemetrexed followed by NPe6‑PDT, should be further investigated as a new treatment modality for MPM. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.

  11. Characterization of human malignant mesothelioma cell lines orthotopically implanted in the pleural cavity of immunodeficient mice for their ability to grow and form metastasis

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    Orecchia Sara

    2006-05-01

    Full Text Available Abstract Background Malignant pleural mesothelioma (MPM is a tumor known to be resistant to conventional therapies. Thus, an in vivo model can represent an important tool for assessing the efficacy of novel approaches in the treatment of MPM. Presently, human MPM cells have been grown orthotopically in mice upon transplantation of tumor masses or tumor cell suspensions following surgery. In these models however, surgery can interfere with the tumor growth and the early stages of tumor development cannot be easily explored. Finally, results may not be so accurate due to implantation of potentially different tumor samples in different experimental groups. Our work aimed at establishing a nude mouse model xenotransplanted with human MPM cell lines in which tumor progression exhibits some features of the human disease. Methods Three distinct human MPM cell lines previously established from MPM patients displaying two different phenotypes, biphasic (MM-B1 and IST-Mes3 and epithelioid (IST-Mes2, were directly injected into the pleural cavity of nude mice. At different times, mice were sacrificed for autopsy, tumor nodules were counted and then removed for histology. Presence of metastases in visceral organs was also monitored. Results IST-Mes2 cells were unable to grow in nude mice. MM-B1 and IST-Mes3 cells were capable of growing in nude mice and formed tumor nodules in the pleura. Post-mortem examination showed that MPM cells progressively colonized the parietal and visceral pleura, the diaphragm, the mediastinum and, lastly the lung parenchyma. No pneumo-thorax was evidenced in the mice. Pleural effusions as well as lymph node metastases were observed only at later times. Conclusion This model mimics the progression of human malignant mesothelioma and it is easy to perform and reproducible; therefore it can be useful to study human MPM biology and evaluate the efficacy of novel therapies.

  12. Current practices in the management of malignant pleural effusions: a survey among members of the European Society of Thoracic Surgeons.

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    Scarci, Marco; Caruana, Edward; Bertolaccini, Luca; Bedetti, Benedetta; Brunelli, Alessandro; Varela, Gonzalo; Papagiannopoulos, Kostas; Kuzdzal, Jaroslaw; Massard, Gilbert; Ruffini, Enrico; Falcoz, Pierre Emmanuel; Opitz, Isabelle; Batirel, Hasan; Toker, Alper; Rocco, Gaetano

    2017-03-01

    Malignant pleural effusion (MPE) commonly complicates advanced malignancy and their exact management is still undefined. We undertook a survey to determine the current practice among members of the European Society of Thoracic Surgeons (ESTS). A cross-sectional survey focused on the current practice of management of MPE was developed by the authors. The questions were outlined after a review of the literature and circulated in an Internet-based survey format. Computed tomography (125, 92%) and chest X-ray (106, 78%) are the most common imaging modalities performed in the initial evaluation. Video-assisted thoracoscopic surgery for washout and pleurodesis (93, 68%) was reported as the preferred approach to patients with uncomplicated MPE. Sixty-one (45%) of the responding colleagues routinely use large bore chest tubes for draining malignant effusions. Forty-nine (35%) surgeons would not apply suction to the drainage system, whilst 50 (37%) would use -2 kPa or less. Talc (124, 91%) is the most commonly used sclerosing agent for pleurodesis in the context of malignant pleural effusion. The practice of 76 (56%) of the respondents is not informed by any clinical guidelines, whilst 60 (44%) reported adhering to the 2010 British Thoracic Society Pleural Disease Guideline. Seventy-one (52%) declared that the guidance was in need of updating or revision. This survey demonstrates the lacking adoption of the existing clinical guidance in this field, as well as the need for more contemporary guidelines for a better-informed practice. The ESTS Working Group on the management of MPE has been established for this purpose.

  13. Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.

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    Vino T Cheriyan

    Full Text Available Dithiocarbamate compound Disulfiram (DSF that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM suppressive effects of DSF-Cu and the molecular mechanisms involved. DSF-Cu inhibited growth of the murine as well as human MPM cells in part by increasing levels of ubiquitinated proteins. DSF-Cu exposure stimulated apoptosis in MPM cells that involved activation of stress-activated protein kinases (SAPKs p38 and JNK1/2, caspase-3, and cleavage of poly-(ADP-ribose-polymerase, as well as increased expression of sulfatase 1 and apoptosis transducing CARP-1/CCAR1 protein. Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes including matrix metallopeptidase 3 and 10. DSF inhibited MPM cell growth and survival by upregulating cell cycle inhibitor p27Kip1, IGFBP7, and inhibitors of NF-κB such as ABIN 1 and 2 and Inhibitory κB (IκBα and β proteins. DSF-Cu promoted cleavage of vimentin, as well as serine-phosphorylation and lysine-63 linked ubiquitination of podoplanin. Administration of 50 mg/kg DSF-Cu by daily i.p injections inhibited growth of murine MPM cell-derived tumors in vivo. Although podoplanin expression often correlates with metastatic disease and poor prognosis, phosphorylation of serines in cytoplasmic domain of podoplanin has recently been shown to interfere with cellular motility and migration signaling. Post-translational modification of podoplanin and cleavage of vimentin by DSF-Cu underscore a metastasis inhibitory property of this agent and together with our in vivo studies underscore its potential as an anti-MPM agent.

  14. Targeting of the Hedgehog signal transduction pathway suppresses survival of malignant pleural mesothelioma cells in vitro.

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    You, Min; Varona-Santos, Javier; Singh, Samer; Robbins, David J; Savaraj, Niramol; Nguyen, Dao M

    2014-01-01

    The present study sought to determine whether the Hedgehog (Hh) pathway is active and regulates the cell growth of cultured malignant pleural mesothelioma (MPM) cells and to evaluate the efficacy of pathway blockade using smoothened (SMO) antagonists (SMO inhibitor GDC-0449 or the antifungal drug itraconazole [ITRA]) or Gli inhibitors (GANT61 or the antileukemia drug arsenic trioxide [ATO]) in suppressing MPM viability. Selective knockdown of SMO to inhibit Hh signaling was achieved by small interfering RNA in 3 representative MPM cells. The growth inhibitory effect of GDC-0449, ITRA, GANT61, and ATO was evaluated in 8 MPM lines, with cell viability quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was determined by annexinV/propidium iodide staining and flow cytometry. SMO small interfering RNA mediated a two- to more than fivefold reduction of SMO and Gli1 gene expression as determined by real-time quantitative reverse-transcriptase polymerase chain reaction, indicating significant Hh pathway blockade. This was associated with significantly reduced cell viability (34% ± 7% to 61% ± 14% of nontarget small interfering RNA controls; P = .0024 to P = .043). Treating MPM cells with Hh inhibitors resulted in a 1.5- to 4-fold reduction of Gli1 expression. These 4 Hh antagonists strongly suppressed MPM cell viability. More importantly, ITRA, ATO, GANT61 induced significant apoptosis in the representative MPM cells. Hh signaling is active in MPM and regulates cell viability. ATO and ITRA were as effective as the prototypic SMO inhibitor GDC-0449 and the Gli inhibitor GANT61 in suppressing Hh signaling in MPM cells. Pharmaceutical agents Food and Drug Administration-approved for other indications but recently found to have anti-Hh activity, such as ATO or ITRA, could be repurposed to treat MPM. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

  15. Open access phone triage for veterans with suspected malignant pleural mesothelioma.

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    Siegert, Charles Jeff; Fisichella, Piero Marco; Moseley, Jennifer M; Shoni, Melina; Lebenthal, Abraham

    2017-01-01

    Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service. A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care. Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines. Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The malignant pleural effusion as a model to investigate intratumoral heterogeneity in lung cancer.

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    Saroj K Basak

    Full Text Available Malignant Pleural Effusions (MPE may be useful as a model to study hierarchical progression of cancer and/or intratumoral heterogeneity. To strengthen the rationale for developing the MPE-model for these purposes, we set out to find evidence for the presence of cancer stem cells (CSC in MPE and demonstrate an ability to sustain intratumoral heterogeneity in MPE-primary cultures. Our studies show that candidate lung CSC-expression signatures (PTEN, OCT4, hTERT, Bmi1, EZH2 and SUZ12 are evident in cell pellets isolated from MPE, and MPE-cytopathology also labels candidate-CSC (CD44, cMET, MDR-1, ALDH subpopulations. Moreover, in primary cultures that use MPE as the source of both tumor cells and the tumor microenvironment (TME, candidate CSC are maintained over time. This allows us to live-sort candidate CSC-fractions from the MPE-tumor mix on the basis of surface markers (CD44, c-MET, uPAR, MDR-1 or differences in xenobiotic metabolism (ALDH. Thus, MPE-primary cultures provide an avenue to extract candidate CSC populations from individual (isogenic MPE-tumors. This will allow us to test whether these cells can be discriminated in functional bioassays. Tumor heterogeneity in MPE-primary cultures is evidenced by variable immunolabeling, differences in colony-morphology, and differences in proliferation rates of cell subpopulations. Collectively, these data justify the ongoing development of the MPE-model for the investigation of intratumoral heterogeneity, tumor-TME interactions, and phenotypic validation of candidate lung CSC, in addition to providing direction for the pre-clinical development of rational therapeutics.

  17. Growth suppressive effect of pegylated arginase in malignant pleural mesothelioma xenografts.

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    Lam, Sze-Kwan; Li, Yuan-Yuan; Xu, Shi; Leung, Leanne Lee; U, Kin-Pong; Zheng, Yan-Fang; Cheng, Paul Ning-Man; Ho, James Chung-Man

    2017-05-02

    Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC 50 values at 13-24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth (p mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.

  18. Three-dimensional evaluation of chemotherapy response in malignant pleural mesothelioma

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    Ak, Guntulu [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)], E-mail: guntuluak@yahoo.com; Metintas, Muzaffer [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Metintas, Selma [Department of Public Health, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Yildirim, Huseyin [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozkan, Ragip [Department of Radiology, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozden, Hilmi [Department of Anatomy, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)

    2010-04-15

    Objectives: Measurement of tumor response to chemotherapy in malignant pleural mesothelioma (MPM) is problematic because of non-spherical tumor growth patterns and difficulty in choosing target lesion. In this study, we aimed to determine the effectiveness of tumor volume measurement for evaluating chemotherapy response. Methods: Fifty-seven MPM patients were included. Chemotherapy responses were evaluated by computed tomography (CT) using volumetric method, World Health Organization (WHO), and modified Response Evaluation Criteria in Solid Tumor (RECIST). The tumor volume was measured using the Cavalieri principle of stereological approaches. Results: According to the volumetric method, median survival was 10.0 months for progressive disease (PD), 14.0 months for stable disease (SD) and 16.0 months for objective response (OR). According to the WHO method, median survival was 11.3, 14.0, and 13.0 months, respectively. For modified RECIST, median survival was 10.0, 14.0, and 14.0 months, respectively. The correspondence between the WHO and modified RECIST methods was substantial (K = 0.66), as was that between the volumetric and WHO methods (K = 0.64); however the correspondence between the volumetric and modified RECIST methods was only moderate (K = 0.52). Conclusions: The most suitable chemotherapy response measurement technique is the volumetric method because of non-spherical tumor growth patterns in MPM. However, larger studies should be performed to better establish the suitability of this method. We recommend our method for determining the chemotherapy response in mesothelioma cases. However, modified RECIST criteria can also be applied due to favourable prediction of survival, ease of application, and moderate correspondence with the volumetric method.

  19. Gender-Specific Molecular and Clinical Features underlie Malignant Pleural Mesothelioma

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    Rienzo, Assunta De; Archer, Michael A.; Yeap, Beow Y.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Holman, Alexander G.; Wang, Yaoyu E.; Dal Cin, Paola S.; Fletcher, Jonathan A.; Rubio, Renee; Croft, Larry; Quackenbush, John; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Chirieac, Lucian R.; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert; Sugarbaker, David J.; Richards, William G.; Bueno, Raphael

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (p<0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that non-epitheliod histology (p=0.037), whereas CDKN2A deletions occurred more frequently in non-epithelioid subtypes among men (p=0.021) and were correlated with shorter overall survival for the entire cohort (p=0.002) and for men (p=0.012). Furthermore, women were more likely to harbor TP53 mutations (p=0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in non-epithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. PMID:26554828

  20. MicroRNA gene expression signatures in long-surviving malignant pleural mesothelioma patients

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    Ruby C.Y. Lin

    2016-09-01

    Full Text Available Malignant pleural mesothelioma (MPM is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4–18 months. Currently, no or few effective therapies exist for MPM. Trials of targeted agents such as antiangiogenic agents (VEGF, EGFR or ribonuclease inhibitors (ranpirnase largely failed to show efficacy in MPM Tsao et al. (2009 [1]. A recent study, however, showed that cisplatin/pemetrexed + bevacizumab (a recombinant humanized monoclonal antibody that inhibit VEGF treatment has a survival benefit of 2.7 months Zalcman et al. (2016 [2]. It remains to be seen if this targeted therapy will be accepted as a new standard for MPM. Thus the unmet needs of MPM patients remain very pronounced and almost every patient will be confronted with drug resistance and recurrence of disease. We have identified unique gene signatures associated with prolonged survival in mesothelioma patients undergoing radical surgery (EPP, extrapleural pneumonectomy, as well as patients who underwent palliative surgery (pleurectomy/decortication. In addition to data published in Molecular Oncology, 2015;9:715-26 (GSE59180 Kirschner et al. (2015 , we describe here additional data using a system-based approach that support our previous observations. This data provides a resource to further explore microRNA dynamics in MPM.

  1. Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma.

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    Baldini, Elizabeth H; Richards, William G; Gill, Ritu R; Goodman, Brian M; Winfrey, Olivia K; Eisen, Hannah M; Mak, Raymond H; Chen, Aileen B; Kozono, David E; Bueno, Raphael; Sugarbaker, David J

    2015-05-01

    We have previously described patterns of failure after extrapleural pneumonectomy and multimodality therapy for malignant pleural mesothelioma and sought to update our results with a larger cohort of recent patients. A total of 169 patients underwent extrapleural pneumonectomy without preoperative chemotherapy between 2001 and 2010. Data for treatment, recurrence, and survival were determined from medical records. A thoracic radiologist reviewed postoperative computed tomography or positron emission tomography computed tomography scans to determine sites of recurrence. Time to recurrence was estimated by the Kaplan-Meier method. Rates were compared using the Fisher exact test. The median age of patients was 62 years. Histology on final pathology was epithelial for 104 patients (62%) and nonepithelial for 65 patients (38%). A total of 132 patients (78%) received heated intraoperative chemotherapy; 77 patients (45%) received adjuvant chemotherapy, and 71 patients (42%) received adjuvant radiation therapy. Most chemotherapy regimens included platinum or pemetrexed. Median radiation therapy dose was 54 Gy. Among 158 evaluable patients, a recurrence developed in 118 (75%). Median follow-up was 83 months, median time to recurrence was 13.1 months, and median survival was 15 months. Sites of first recurrence were in the ipsilateral hemithorax or mediastinum for 54% of patients, in the abdomen for 39% of patients, in the contralateral hemithorax for 28% of patients, and in other distant sites for 5% of patients. Some patients had simultaneous recurrences in multiple sites. The most common site of recurrence after extrapleural pneumonectomy and planned multimodality therapy remains the ipsilateral hemithorax (including mediastinum), and true distant failure (other than the abdomen or contralateral hemithorax) remains unusual. The distribution of recurrences is strikingly similar to our prior report. Copyright © 2015 The American Association for Thoracic Surgery. Published

  2. Long non coding RNAs (lncRNAs are dysregulated in Malignant Pleural Mesothelioma (MPM.

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    Casey M Wright

    Full Text Available Malignant Pleural Mesothelioma (MPM is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P3-fold difference. Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2 15 cryopreserved MPM and 3 benign pleura, and (3 an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

  3. Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma.

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    Cao, Christopher; Tian, David H; Pataky, Kristopher A; Yan, Tristan D

    2013-09-01

    Pleurectomy/decortication (P/D) in the treatment of malignant pleural mesothelioma includes a number of procedures with different clinical indications and therapeutic intents. To unify the nomenclature, IMIG and IASLC recently defined P/D-related procedures according to surgical technique, including 'extended P/D', 'P/D' and 'partial pleurectomy'. The present systematic review aimed to assess the safety and efficacy of these techniques. A systematic review of relevant studies was performed by electronic search of five online databases from 1985 to 2012 by two independent reviewers according to predefined selection criteria. Thirty-four studies involving 1916 patients who underwent pleurectomy were included for quantitative analysis. These included 12 studies on 'extended P/D', 8 studies on 'P/D' and 14 studies on 'partial pleurectomy'. Perioperative mortality ranged from 0% to 11% and perioperative morbidity ranged from 13% to 43%. Median overall survival ranged from 7.1 to 31.7 months and disease-free survival ranged from 6 to 16 months. One study reported on quality-of-life outcomes using a standardized questionnaire suggesting superior outcomes for 'extended P/D' compared to extrapleural pneumonectomy. Results of the present systematic review suggested similar perioperative mortality outcomes between different P/D techniques but a trend towards higher morbidity and length of hospitalization for patients who underwent 'extended P/D'. However, overall and disease-free survival appeared to favour 'extended P/D' compared to less aggressive techniques. Future studies on P/D should adhere to recent definitions to enable accurate analysis of similar procedures. Direct comparisons of pleurectomy to extrapleural pneumonectomy remain challenging, and should be restricted to 'extended P/D' procedures only. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy.

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    Kimura, Tomoki; Doi, Yoshiko; Nakashima, Takeo; Imano, Nobuki; Katsuta, Tsuyoshi; Takahashi, Shigeo; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji; Nagata, Yasushi

    2015-03-01

    The purpose of this study was to evaluate the efficacy and safety of volumetric modulated arc therapy (VMAT) after extrapleural pneumonectomy (EPP) in patients with malignant pleural mesothelioma (MPM). A total of 15 patients who received VMAT after EPP were enrolled. All patients were males, and the median age was 67 years (Stage IB in two, II in six, and III in seven patients). The clinical target volume (CTV) included the entire preoperative ipsilateral hemithorax and involved nodal stations. The CTV was generally expanded by 10-15 mm beyond the planning target volume (PTV). The dose prescription was designed to cover 95% of the PTV with 54 Gy in 30 fractions. The median follow-up period was 11 months. Treatment-related toxicities were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) ver. 4. One-year local control, disease-free survival, and overall survival rates were 55.7% [95% confidence interval (CI): 25.6-85.8%], 29.3% (95% CI: 5.3-53.3%), and 43.1% (95% CI: 17.1-69.0%), respectively. According to the histological analysis, the one-year LC rate was significantly worse in patients with non-epithelial type (biphasic and sarcomatoid types) than in patients with epithelial type [epithelial type: 83.3% (95% CI, 53.5-100%), non-epithelial type: 0% (95% CI, 0%), P = 0.0011]. Grade 3 pneumonitis after VMAT was observed in three patients (20.0%); however, no patients died of pulmonary toxicity. VMAT appears to be relatively safe for patients with MPM after EPP because of the low pulmonary dose. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  5. Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma.

    Science.gov (United States)

    Cristaudo, Alfonso; Bonotti, Alessandra; Simonini, Silvia; Vivaldi, Agnese; Guglielmi, Giovanni; Ambrosino, Nicolino; Chella, Antonio; Lucchi, Marco; Mussi, Alfredo; Foddis, Rudy

    2011-09-01

    Malignant pleural mesothelioma (MPM) is a lethal tumor related to asbestos exposure. At present, the only instruments for screening and diagnosis are based on radiological tests, posing evident economic and radio-protectionist problems. Some authors are evaluating biological indicators, such as plasma osteopontin (pOPN) and serum soluble mesothelin-related peptides (SMRP). This study aimed to evaluate whether a combination of these two markers could increase sensitivity and specificity in diagnosis of epithelioid MPM. We enrolled 93 healthy subjects, 111 individuals with benign respiratory disease (BRD), and 31 patients with MPM, histologically and/or cytologically confirmed. SMRP and pOPN levels were determined using commercially available enzyme-linked immunosorbent assay kits. Though a logistic regression analysis, SMRP and pOPN were combined and translated into a new index, called "combined risk index." Differences in both SMRP and pOPN mean values between epithelial MPM patients and healthy subjects or BRD patients were statistically significant (p < 0.0001), whereas there was no difference in SMRP and pOPN mean values between healthy subjects and BRD patients. The performance in MPM diagnosis resulted improved by the combination of the two markers. The results of our study should be confirmed by a larger scale and, possibly, a multicenter study, which could better take into consideration the influence of some possible confounding factors such as glomerular filtration rate and other blood parameters. We combined SMRP and pOPN dosages to increase diagnostic accuracy. This study showed for the first time that combined SMRP and pOPN measurements can increase both sensitivity and specificity in terms of combined risk index.

  6. The role of microRNAs in the diagnosis and treatment of malignant pleural mesothelioma--a short review.

    Science.gov (United States)

    Sheff, Kelly W; Hoda, Mir A; Dome, Balazs; Hegedus, Balazs; Klepetko, Walter; Weiss, Glen J

    2012-01-01

    MicroRNAs are a class of small, non-coding RNAs that can function as tumor suppressors or oncogenes by regulating gene expression. This link was first reported in 2004, and has since been tied to a variety of malignancies, including malignant pleural mesothelioma (MPM). MPM is a malignancy arising in the mesothelial cells lining the lung pleura and is associated with chronic asbestos exposure. Despite the possibility for observing declining localized occurrence, global MPM is predicted to remain constant or increase slightly over the next decade. Global occurrence in combination with poor overall survival, difficulty in diagnosis, and limited effective treatment options signal the need for further exploration of miRNA involvement in MPM. Accordingly, this review highlights miRNA profiles associated with the diagnosis, prognosis, and therapeutic approaches in MPM.

  7. Congenital Giant Melanocytic Nevus with Malignant Melanoma of the Pleura: Do Primary Pleural Melanomas Exist?

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    Brijesh Sharma

    2017-09-01

    Full Text Available Cases of primary pleural and bronchial melanoma have been described in the literature in the absence of melanocytic cells in the pleura and bronchi. We described a case of congenital giant melanocytic nevus that had a presentation suggestive of primary pleural melanoma. However, biopsy of a chest wall lesion confirmed the presence of another melanoma deposit in a subcutaneous swelling concealed within the congenital giant melanocytic nevus. Histopathology with immunohistochemistry results showed that the pleural and chest wall swelling were similar. The difficult clinical detection of the primary tumor contributes to the fact that 24% of cases of congenital giant melanocytic nevus receive a diagnosis of metastatic melanoma without identification of the primary site. We propose that it is probable that the entity “primary pleural melanoma” may, in fact, not exist. Instead, all such reported tumors in the pleura may actually be metastatic from an unknown, regressed, or missed primary site.

  8. Extended Pleurectomy and Decortication for Malignant Pleural Mesothelioma Is an Effective and Safe Cytoreductive Surgery in the Elderly.

    Science.gov (United States)

    Williams, Trevor; Duraid, Hadi; Watson, Sydeaka; Durkin, Amy; Todd, Kristy; Kindler, Hedy L; Vigneswaran, Wickii T

    2015-11-01

    A survival advantage has been observed among patients with malignant pleural mesothelioma undergoing maximal cytoreductive surgery and adjuvant therapy. Elderly patients are considered higher risk for these radical operations and are commonly not offered surgical treatment. We reviewed our experience with extended pleurectomy and decortication among patients 70 years or older and compared them with a cohort of younger patients undergoing extended pleurectomy and decortication for malignant pleural mesothelioma. We performed a retrospective review of 117 consecutive patients undergoing extended pleurectomy and decortication at a university hospital from January 2008 to December 2013. Patients 70 years and older were compared with younger patients for postoperative outcome and survival. Survival was estimated using the Kaplan-Meier method. Fifty-four patients were 70 years or older; 63 were younger than 70 years. Older patients had more hypertension (71.2% versus 45.2%; p = 0.004) and coronary artery disease (22.6% versus 6.5%; p = 0.006). Major complications occurred in 3 patients (5.5%) in the older group and in 7 patients (11.1%) of the younger group (not significant). There were 2 deaths in each group after surgery (3.7% older versus 3.2% younger; not significant). Median survival was 15.6 months in the older patients and 14.0 months in the younger patients (not significant). Kaplan-Meier survival curves based on age groups were not significantly different with 1- and 2-year survivals of 64% versus 55% and 29% versus 32%, respectively. Our study demonstrates that whereas age may be associated with more comorbid conditions in patients with malignant pleural mesothelioma undergoing extended pleurectomy and decortication, this does not necessarily translate into increased operative morbidity or mortality or shorter long-term survival. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Fine Needle Aspiration Biopsies for Gene Expression Ratio-based Diagnostic and Prognostic Tests in Malignant Pleural Mesothelioma

    Science.gov (United States)

    De Rienzo, Assunta; Dong, Lingsheng; Yeap, Beow Y.; Jensen, Roderick V.; Richards, William G.; Gordon, Gavin J.; Sugarbaker, David J.; Bueno, Raphael

    2010-01-01

    Purpose Malignant pleural mesothelioma (MPM) is an aggressive disease associated with median survival between 9 and 12 months. The correct diagnosis of MPM is sometimes challenging and usually requires solid tissue biopsies rather than fine needle aspiration biopsies (FNA). We postulated that the accuracy of FNA-based diagnosis might be improved by the addition of molecular tests using a gene expression ratio-based algorithm and that prognostic tests could be similarly performed. Experimental Design Two MPM and two lung cancer cell lines were used to establish the minimal RNA amount required for ratio tests. Based on these results, 276 ex-vivo FNA biopsies from 63 MPM patients, and 250 ex-vivo FNA samples from 92 lung cancer patients were analyzed using previously described diagnostic and prognostic tests based on gene expression ratios. Results We found that the sensitivity of the diagnostic test for MPM was 100% (95% CI: 95–100%), and the specificity in primary lung adenocarcinoma was 90% (95% CI: 81–95%). The FNA-based prognostic classification was concordant among 76% (95% CI: 65–87%) of patients with the risk assignment in a subset of the matched surgical specimens previously analyzed by the prognostic test. Conclusions Sufficient RNA can be extracted from most FNA biopsies to perform gene expression molecular tests. In particular, we show that the gene expression ratio algorithms performed well when applied to diagnosis and prognosis in MPM. This study provides support for the development of additional RNA molecular tests that may enhance the utility of FNA in the management of other solid cancers. PMID:21088255

  10. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

    Science.gov (United States)

    Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

    2017-04-01

    Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

  11. A benchmarking project on the quality of previous guidelines about the management of malignant pleural effusion from the European Society of Thoracic Surgeons (ESTS) Pleural Diseases Working Group.

    Science.gov (United States)

    Bertolaccini, Luca; Bedetti, Benedetta; Brunelli, Alessandro; Marinova, Katerina; Raveglia, Federico; Rocco, Gaetano; Shargall, Yaron; Solli, Piergiorgio; Varela, Gonzalo; Papagiannopoulos, Kostas; Kuzdzal, Jaroslaw; Massard, Gilbert; Ruffini, Enrico; Falcoz, Pierre-Emmanuel; Martinez-Barenys, Carlos; Opitz, Isabelle; Batirel, Hasan F; Toker, Alper; Scarci, Marco

    2017-08-01

    In the European Society of Thoracic Surgeons (ESTS) survey about management of malignant pleural effusions (MPE), 56% of respondents are not informed of any relevant clinical guidelines and 52%, who are aware of the existence of guidelines, declared that they are in need of updating or revision. The ESTS Pleural Diseases Working Group developed a benchmarking project on quality of previous guidelines on the management of MPE. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used to assess each guideline. Each item was scored on a 7-point scale. Scores for each domain were calculated. Economic data for the nations which have issued the guidelines were collected from the Organisation for Economic Cooperation and Development health statistics database. Six guidelines fitted the inclusion criteria and were assessed. Five out of 6 guidelines were produced by a multinational collaboration. Observers would recommend only 2 guidelines with minimal modification. Two areas that received the best score were clarity of presentation and scope and purpose (objectives and health questions target population). The applicability of guideline domain had the lowest score. Multivariate analysis demonstrated that clarity of presentation, international guidelines and publication through medical journal were related to improved scores. A strong correlation was observed between the measures of economic status. The quality of guidelines assessed by the AGREE II criteria was found to be extremely variable. Guidelines achieving higher AGREE II scores were more likely to come from the European Union with the direct involvement of scientific societies in their development. It was also recognized that some fundamental unanswered questions remain about the management of MPE.

  12. Survival in Good Performance Malignant Pleural Mesothelioma Patients; Prognostic Factors and Predictors of Response

    Science.gov (United States)

    Rahouma, Mohamed; Aziz, Hala; Ghaly, Galal; Kamel, Mohamed; Loai, Iman; Mohamed, Abdelrahman

    2017-08-27

    Purpose: Malignant pleural mesothelioma (MPM) has a poor prognosis in general. Here we sought to evaluate prognostic factors and predictors of response to chemotherapy in good performance (PS=0-I) patients. Methods: We retrospectively reviewed our database and enrolled patients with MPM who received platinum containing chemotherapy (2012-2014). Clinico-pathological and laboratory data were retrieved and Cox and logistic regression multivariate analyses (MVA) were respectively used to identify predictors of survival and response to chemotherapy. Comparison of good vs poor performance status (PS≥II) was accomplished using the Chi (X2) test. Kaplan–Meier survival curves were also obtained and propensity-score matching was performed for survival comparison. Results: Among 114 patients listed during the study period, 82 had good PS=0-I (median age 45years, 43 men, 30 smokers, median weight=77Kg, pretreatment haemoglobin (Hb) level=12g/dL, platelet count=372,000/μL, leukocytes=9,700/μL, neutrophils=6,100/μL, lymphocytes=1,890/μL and neutrophil/lymphocyte ratio (NLR)=3.60 ). Some 65 had asbestosis, 23 had chronic disease, 55 (67.1%) were responders to platinum containing first line chemotherapy. A total of 49 (59.8%) had epithelial MPM. Median-OS and PFS in good PS cases were 17 and 9 months, respectively, as compared to 16 and 8 months for the poor PS group. After matching, better OS was observed among good PS vs poor PS patients (p=0.024) but there was no PFS difference (p=0.176). Significant decrease in PFS was observed among those with advanced nodal N disease (median PFS in N0 and N+ was 10 and 5 months, respectively), non-responders (p=0.012), NLR (p=0.026) and those with an epithelial pathology (p=0.062). MVA demonstrated that advanced (N) status (p=0.015), being a non-responder (pgood PS. Early detection before development of metastasis warrants greater focus to allow better responses to be obtained. Creative Commons Attribution License

  13. Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Goricar, Katja; Kovac, Viljem; Dolzan, Vita

    2014-06-01

    A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM. MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival. Patients with at least one polymorphic MTHFD1 rs2236225 allele had a significantly lower response rate (p = 0.005; odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03-0.54) and shorter progression-free survival (p = 0.032; hazard ratio [HR] = 3.10; 95% CI = 1.10-8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028; OR = 0.23; 95% CI = 0.06-0.85), SLCO1B1 rs4149056 (p = 0.028; OR = 0.23; 95% CI = 0.06-0.85) and rs11045879 (p = 0.014; OR = 0.18; 95% CI = 0.05-0.71) alleles compared to non-carriers, as well as in patients with SLCO1B1 GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03-0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15-52.85) and ABCC2 CAG haplotype (p = 0.006; OR = 5.67; 95% CI = 1.64-19.66). MTHFD1 polymorphism affected treatment response and survival, while polymorphisms in ABCC2 and SLCO1B1 transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential markers of

  14. Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma.

    Science.gov (United States)

    Kostron, Arthur; Friess, Martina; Crameri, Ornella; Inci, Ilhan; Schneiter, Didier; Hillinger, Sven; Stahel, Rolf; Weder, Walter; Opitz, Isabelle

    2016-05-01

    To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment. Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records. The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local

  15. Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma.

    Science.gov (United States)

    Cristaudo, Alfonso; Foddis, Rudy; Bonotti, Alessandra; Simonini, Silvia; Vivaldi, Agnese; Guglielmi, Giovanni; Ambrosino, Nicolino; Canessa, Pier Aldo; Chella, Antonio; Lucchi, Marco; Mussi, Alfredo; Mutti, Luciano

    2010-01-01

    A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos. The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients. We found that both serum and plasma OPN levels were influenced by storage at -80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack

  16. Tomotherapy PET-guided dose escalation. A dosimetric feasibility study for patients with malignant pleural mesothelioma

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    Maggio, Angelo; Cutaia, Claudia; Di Dia, Amalia; Bresciani, Sara; Miranti, Anna; Poli, Matteo; Stasi, Michele [Candiolo Cancer Institute - FPO, IRCCS, Medical Physics, Turin (Italy); Del Mastro, Elena; Garibaldi, Elisabetta; Gabriele, Pietro [Candiolo Cancer Institute - FPO, IRCCS, Radiotherapy Department, Turin (Italy)

    2016-02-15

    The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV{sub 1}) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV{sub 2}). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV{sub 1} and 56 Gy (2.24 Gy/fraction) to the PTV{sub 2}, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V{sub 20}, V{sub 30}, and V{sub 40} DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs. (orig.) [German] Ziel war es, zu untersuchen, ob mit der helikalen Tomotherapie (HT) eine

  17. Unusually high incidence of malignant pleural mesothelioma in a town of eastern Sicily: an epidemiological and environmental study.

    Science.gov (United States)

    Paoletti, L; Batisti, D; Bruno, C; Di Paola, M; Gianfagna, A; Mastrantonio, M; Nesti, M; Comba, P

    2000-01-01

    In a recent epidemiological study, researchers investigated mortality from malignant pleural neoplasms in Italy, and they detected some geographic clusters of cases of this disease. We found a town located in a volcanic area of eastern Sicily to be of special interest. The residents, some of whom were diagnosed with pleural mesothelioma, had never had any relevant exposure to asbestos during their professional lives. The results of an environmental survey suggested that a possible cause of asbestos exposure was the stone quarries near the town. The products of the quarries contain fibrous amphiboles, which are used widely in the local building industry. These fibrous amphiboles were identified as intermediate phases between tremolite and actinolite. Samples were collected from buildings in the town, and concentrations of amphibole fibers were evaluated. Fibrous phases were detected in 71% of the samples, and fiber concentrations ranged from a few thousand to more than 4 x 10(4) fibers/mg of material. In addition, we conducted a study on the mineral fiber lung burden in a pleural mesothelioma case. Many mineral fibers that were classified as the same tremolite-actinolite fibrous amphibole found in the quarries and in the building materials were detected in the lung tissue. The results suggest that the inhabitants of the town we studied had been exposed for several decades to asbestos fibers that were present in the material extracted from the local stone quarries. The material was subsequently used in the building industry, and this has caused an increased risk of pleural mesothelioma in the area.

  18. Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed.

    Science.gov (United States)

    Ando, Hidenori; Kobayashi, Sakiko; Abu Lila, Amr S; Eldin, Noha Essam; Kato, Chihiro; Shimizu, Taro; Ukawa, Masami; Kawazoe, Kazuyoshi; Ishida, Tatsuhiro

    2015-12-28

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Pleural Touch Preparations and Direct Visualization of the Pleura during Medical Thoracoscopy for the Diagnosis of Malignancy.

    Science.gov (United States)

    Grosu, Horiana B; Vial-Rodriguez, Macarena; Vakil, Erik; Casal, Roberto F; Eapen, George A; Morice, Rodolfo; Stewart, John; Sarkiss, Mona G; Ost, David E

    2017-08-01

    During diagnostic thoracoscopy, talc pleurodesis after biopsy is appropriate if the probability of malignancy is sufficiently high. Findings on direct visual assessment of the pleura during thoracoscopy, rapid onsite evaluation (ROSE) of touch preparations (touch preps) of thoracoscopic biopsy specimens, and preoperative imaging may help predict the likelihood of malignancy; however, data on the performance of these methods are limited. To assess the performance of ROSE of touch preps, direct visual assessment of the pleura during thoracoscopy, and preoperative imaging in diagnosing malignancy. Patients who underwent ROSE of touch preps during thoracoscopy for suspected malignancy were retrospectively reviewed. Malignancy was diagnosed on the basis of final pathologic examination of pleural biopsy specimens. ROSE results were categorized as malignant, benign, or atypical cells. Visual assessment results were categorized as tumor studding present or absent. Positron emission tomography (PET) and computed tomography (CT) findings were categorized as abnormal or normal pleura. Likelihood ratios were calculated for each category of test result. The study included 44 patients, 26 (59%) with a final pathologic diagnosis of malignancy. Likelihood ratios were as follows: for ROSE of touch preps: malignant, 1.97 (95% confidence interval [CI], 0.90-4.34); atypical cells, 0.69 (95% CI, 0.21-2.27); benign, 0.11 (95% CI, 0.01-0.93); for direct visual assessment: tumor studding present, 3.63 (95% CI, 1.32-9.99); tumor studding absent, 0.24 (95% CI, 0.09-0.64); for PET: abnormal pleura, 9.39 (95% CI, 1.42-62); normal pleura, 0.24 (95% CI, 0.11-0.52); and for CT: abnormal pleura, 13.15 (95% CI, 1.93-89.63); normal pleura, 0.28 (95% CI, 0.15-0.54). A finding of no malignant cells on ROSE of touch preps during thoracoscopy lowers the likelihood of malignancy significantly, whereas finding of tumor studding on direct visual assessment during thoracoscopy only moderately increases the

  20. Combination of DNA ploidy analysis and miR-21 or miR-24 in screening malignant pleural effusion.

    Science.gov (United States)

    Liu, Chongmei; Huang, Liuyan; Zhang, Xuechun; Yang, Juan

    2017-10-24

    The study aimed to assess the combination of DNA ploidy analysis (DPA) and the expression of microRNA-21 (miR-21) or microRNA-24 (miR-24) in the detection of malignant pleural effusion (MPE). In this prospective research, a total of 40 samples (20 benign and 20 malignant effusions), flexural effusion exfoliated cells and cell-free miR-21 and miR-24 were collected. DPA and exfoliative cytology examinations were conducted to diagnose flexural effusion exfoliated cells. Quantitative reverse transcriptase polymerase chain reaction was carried out to measure the expressions of miR-21 and miR-24. Receiver operating characteristic curve and the area under the curve were applied to evaluate the accuracy rate of different diagnostic approaches on MPE. In the MPE group, DPA demonstrated a higher rate of accuracy in MPE diagnosis than exfoliative cytology. The expressions of miR-21 and miR-24 were significantly higher in MPE than in benign pleural effusion (P < 0.05). Furthermore, area under the curve, sensitivity and specificity were 0.942, 95% and 90% for the combination of miR-21 and DPA and 0.973, 100% and 80% for the union of miR-24 and DPA, respectively, representing a significant improvement in both accuracy and sensitivity. Therefore, the combination of DPA and miR-21 or miR-24 appears to be a better biomarker for discriminating MPE from benign pleural effusion. The combination of DPA and miR-21 or miR-24 may function as a promising diagnostic tool of MPE. ChiCTR-TRC-14004719.

  1. Comparing the results of VATS pleurectomy and talc pleurodesis with small sized catheter in randomised patients with malign pleural effusion

    Directory of Open Access Journals (Sweden)

    Bülent Tunçözgür

    2012-06-01

    Full Text Available Objectives: Pleural effusion occurs as a result of detoriationin equilibrium between absorption and secretion.We aimed to investigate the clinical responses of talkpleurodesis and pleurectomy with video assisted thoracoscopicsurgery (VATS in patients with malignant pleuraleffusion.Materials and methods: Forty-five patients with malignantpleural effusion between June 2007 and June 2008were included in this study. Thoracentesis was performedin order to study the biochemical, microbiologic, cytologicalanalysis. Glucose, total protein, albumin, lactic dehydrogenasesand cytological examination were studied ineffusion and blood sample simultaneously. Cases wereclassified into two groups; in group I (n=25, small calibratedcatheter and talk pleurodesis were performed. Ingroup II (n=20, VATS pleurectomy was performed.Results: There were 32 females and 13 males with meanage 51.58 (27-75 years. Diagnosis was made with cytologicexamination of pleural fluid that was aspirated withthoracentesis. Transudate- exudate discrimination wasdone according to Light’s criteria. Success rates of thegroups were as complete response; 84% (n=21 in groupI, 85% (n=17 in group II. Unsuccessful response was16% (n=4 in group I and 15% (n=3 in group II. Therewas no statistically significant difference between hospitalstay and tube duration of groups when compared to eachother.Conclusion: The treatment of malignant pleural effusionis palliative due to poor prognosis. The purpose isto eliminate dyspnea in patients with short survival time.There was no significant difference between the VATSpleurectomy and talc pleurodesis that has been known aseffective sclerosant agent. J Clin Exp Invest 2012; 3(2:223-228

  2. The evolution of the diminishing role of extrapleural pneumonectomy in the surgical management of malignant pleural mesothelioma

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    Azzouqa AG

    2016-11-01

    Full Text Available Abdel-Ghani Azzouqa,1 James P Stevenson2 1Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 2Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: Malignant pleural mesothelioma is an uncommon and aggressive thoracic malignancy that is rarely curable, even when multimodality therapy is used. Systemic chemotherapy is the primary treatment for the majority of patients with this disease; however, surgical resection may benefit a subset of patients with early-stage disease. The surgical approach that offers the best outcomes remains an area of controversy, with data from retrospective comparisons being the only guide. Historically, extrapleural pneumonectomy (EPP has been the standard procedure, carrying with it a cost of significant morbidity and impact on quality of life that has raised questions regarding its routine application. Over the past two decades as surgical techniques have been refined and survival data with EPP in large case series have been reported, the paradigm has evolved toward the use of lung-sparing pleural resections such as pleurectomy/decortication (P/D and extended P/D. The identification of patients who may benefit from EPP over pleurectomy has proven problematic, and the larger question regarding the impact of any type of surgical intervention on outcomes for pleural mesothelioma patients is still an area of investigation. Uniform treatment approaches have been difficult to develop due to the relatively small numbers of patients with this disease, the use of a staging system that does not readily identify those who may benefit from more aggressive therapy, and the institutional biases that have resulted from the growth of multimodality centers of excellence. Keywords: mesothelioma, pneumonectomy, thoracic surgical procedure, multimodal treatment 

  3. Clinical effects of thermotherapy in combination with intracavitary infusion of traditional Chinese medicine in the treatment of malignant pleural effusion.

    Science.gov (United States)

    Gu, Y; Jiang, L; Miao, J H; Liang, T S; Kan, Q C; Yang, D K

    2016-01-01

    Malignant fluid, a commonly seen tumor associated complication, mainly includes peritoneal effusion, malignant pleural effusion and pericardial effusion. It can produce huge negative influence on the quality of life of patients and even lead to death. Treatment of malignant effusion is one of the effective measures for improving life expectancy of patients. To evaluate the effect of thermotherapy in combination with intracavitary infusion of Kangai injection in treating malignant pleural effusion, 195 patients who received treatment from April 2010 to October 2014 in the First Affiliated Hospital of Zhengzhou University were selected and divided into an observation group and two control groups (group A and B). The observation group was treated by thermotherapy in combination with intracavitary infusion of kangai injection. Control group A was treated by intracavitary infusion of kangai injection and control group B was treated by hyperthermal perfusion in combination with intracavity chemotherapy. Clinical effects, quality of life, treatment safety and untoward reactions were compared between the groups. It was found that differences of WBC, RBC and PLT levels before and after treatment had no statistical significance comparisons within group and comparisons between groups (P>0.05); hepatic and renal functions of the groups had no remarkable difference before or after treatment (P>0.05). The clinical effect of the observation group was superior to that of control groups A and B (P less than 0.05); the Karnofsky performance status (KPS) score of the observation group was much higher than that of control groups A and B (79.34±10.58 vs 71.11±9.64), but the difference of the ZPS score between groups had no statistical significance (P>0.05). It can be concluded that thermotherapy in combination with intracavitary infusion of traditional Chinese medicine can be safely applied as it has positive effects and remarkably improves quality of life, therefore it is clinically

  4. Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007.

    Science.gov (United States)

    Finley, Brent L; Pierce, Jennifer S; Paustenbach, Dennis J; Scott, Laura L F; Lievense, Laura; Scott, Paul K; Galbraith, David A

    2012-10-01

    Until the 1980s, chrysotile asbestos was a component of automotive brakes manufactured in the US. The current OSHA Bulletin (2006) for brake repair cites a single study (Lemen, 2004) which concluded that the number of mesothelioma cases reported in the literature in "end-product users of friction materials" indicated an asbestos-related risk for auto mechanics. However, Lemen (2004) did not compare the reported number of cases to an "expected" value, even though pleural mesothelioma occurs in the general population in the absence of asbestos exposure. We compare the number of malignant pleural mesothelioma (MPM) cases reported in the US literature among auto mechanics between 1975-2007 to an expected value derived from estimated numbers of current and former auto mechanics. A total of 106 cases categorized as mesothelioma or malignant neoplasm of the pleura were found in the literature. Using background incidence rates for MPM of two and three cases per million individuals per year, we estimated that a range of 278-515 cases of non-asbestos-related MPM, respectively, would have occurred in current or former auto mechanics from 1975-2007. Our findings are consistent with the numerous epidemiology studies that have found no increased risk of MPM in auto mechanics. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Role of bevacizumab in the management of the patient with malignant pleural effusion: more questions than answers.

    Science.gov (United States)

    Sabang, Ralph Llewel; Gandhiraj, Deepthi; Fanucchi, Michael; Epelbaum, Oleg

    2018-02-01

    Malignant pleural effusion (MPE) is a feature of metastatic cancer associated with significant morbidity and cost. The typical management of MPE is systemic chemotherapy and mechanical intervention. Vascular endothelial growth factor (VEGF), an inducer of vascular permeability, has been shown to mediate fluid formation. Therefore, bevacizumab, an inhibitor of VEGF, offers theoretical promise for abolishing fluid formation in MPE. Areas covered: This review begins with a summary of VEGF physiology and evidence of its role in MPE pathogenesis. This is followed by an overview of bevacizumab and major trials that put it on the map of non-small cell lung cancer (NSCLC). The majority of the article is devoted to a review of the current evidence base for the use of bevacizumab for MPE control in metastatic pleural malignancy. The review concludes with considerations of patient selection and toxicity. Expert commentary: Evidence in support of bevacizumab administration for MPE management remains flawed. Small studies suggest efficacy of both intravenous and intrapleural routes, but their design raises bias concerns. Bevacizumab appears to be safe in properly selected cases. The future of MPE management may de-emphasize VEGF inhibition in favor of precise molecular therapeutics that could address the root cause of tumorigenesis.

  6. Mesotelioma pleural maligno: experiência multidisciplinar em hospital público terciário Malignant pleural mesothelioma: multidisciplinary experience in a public tertiary hospital

    Directory of Open Access Journals (Sweden)

    Ricardo Mingarini Terra

    2008-01-01

    Full Text Available OBJETIVOS: Avaliar a experiência com o diagnóstico e a terapêutica do mesotelioma pleural maligno (MPM acumulada durante 5 anos em um hospital público terciário. MÉTODOS: Avaliação retrospectiva dos prontuários dos pacientes com diagnóstico de MPM entre janeiro de 2000 e fevereiro de 2005. RESULTADOS: Foram analisados 17 pacientes, 14 homens e 3 mulheres, com idade média de 54,1 (13-75 anos. Os espécimes de biópsia para exame histopatológico foram obtidos por meio de pleuroscopia em 9 pacientes (53%, agulha de Cope em 5 (29,5% e biópsia pleural aberta em 3 (17,5%. Os tipos histológicos foram: epitelial em 14 pacientes (82%, sarcomatóide em 1 (6% e bifásico em 2 (12%. As terapêuticas instituídas foram: multimodal (pleuropneumonectomia com radioterapia e quimioterapia adjuvante em 6 pacientes (35%, quimioterapia e radioterapia em 6 (35%, radioterapia exclusiva em 3 (17,5% e quimioterapia exclusiva em 2 (12%. A sobrevida média foi de 11 (1-26 meses. CONCLUSÕES: Na presente experiência foi empregada a abordagem multidisciplinar integrada, e contou-se com uma estrutura hospitalar de alta complexidade para o diagnóstico e tratamento do MPM, como preconizado na literatura. Apesar disso, a sobrevida média observada foi de apenas 11 meses, refletindo a agressividade da doença.OBJECTIVE: To evaluate the experience in diagnosing and treating malignant pleural mesothelioma (MPM accumulated over 5 years in a tertiary public hospital. METHODS: The medical charts of the patients diagnosed with MPM between January of 2000 and February of 2005 were evaluated retrospectively. RESULTS: Of the 17 patients analyzed, 14 were male and 3 were female. The mean age was 54.1 years (range, 13-75 years. The biopsy specimens for histopathological examination were obtained through thoracoscopy in 9 patients (53%, Cope needle in 5 (29.5%, and open pleural biopsy in 3 (17.5%. The following histological types were identified: epithelial, in 14 patients

  7. A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Welch, B. T., E-mail: Welch.brian@mayo.edu; Eiken, P. W.; Atwell, T. D. [Mayo Clinic, Department of Radiology (United States); Peikert, T. [Mayo Clinic, Department of Pulmonary and Critical Care Medicine (United States); Yi, E. S. [Mayo Clinic, Department of Pathology (United States); Nichols, F. [Mayo Clinic, Department of Thoracic Surgery (United States); Schmit, G. D. [Mayo Clinic, Department of Radiology (United States)

    2017-06-15

    PurposeMesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma.Materials and MethodsRetrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)].ResultsPercutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract.ConclusionPercutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

  8. A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Welch, B T; Eiken, P W; Atwell, T D; Peikert, T; Yi, E S; Nichols, F; Schmit, G D

    2017-06-01

    Mesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma. Retrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)]. Percutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract. Percutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

  9. Re-directed T cells for the treatment of fibroblast activation protein (FAP-positive malignant pleural mesothelioma (FAPME-1

    Directory of Open Access Journals (Sweden)

    Petrausch Ulf

    2012-12-01

    Full Text Available Abstract Background Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. Methods/design This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT. No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. Discussion Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of

  10. Trabectedin Is Active against Malignant Pleural Mesothelioma Cell and Xenograft Models and Synergizes with Chemotherapy and Bcl-2 Inhibition In Vitro.

    Science.gov (United States)

    Hoda, Mir A; Pirker, Christine; Dong, Yawen; Schelch, Karin; Heffeter, Petra; Kryeziu, Kushtrim; van Schoonhoven, Sushilla; Klikovits, Thomas; Laszlo, Viktoria; Rozsas, Anita; Ozsvar, Judit; Klepetko, Walter; Döme, Balazs; Grusch, Michael; Hegedüs, Balazs; Berger, Walter

    2016-10-01

    Malignant pleural mesothelioma (MPM) is characterized by widespread resistance to systemic therapy. Trabectedin is an antineoplastic agent targeting both the malignant cells and the tumor microenvironment that has been approved for the treatment of advanced soft tissue sarcoma and ovarian cancer. In this preclinical study, we evaluated the antineoplastic potential of trabectedin as a single agent and in drug combination approaches in human MPM. Therefore, we utilized an extended panel of MPM cell lines (n = 6) and primary cell cultures from surgical MPM specimens (n = 13), as well as nonmalignant pleural tissue samples (n = 2). Trabectedin exerted a dose-dependent cytotoxic effect in all MPM cell cultures in vitro when growing as adherent monolayers or nonadherent spheroids with IC50 values ≤ 2.6 nmol/L. Nonmalignant mesothelial cells were significantly less responsive. The strong antimesothelioma activity was based on cell-cycle perturbation and apoptosis induction. The activity of trabectedin against MPM cells was synergistically enhanced by coadministration of cisplatin, a drug routinely used for systemic MPM treatment. Comparison of gene expression signatures indicated an inverse correlation between trabectedin response and bcl-2 expression. Accordingly, bcl-2 inhibitors (Obatoclax, ABT-199) markedly synergized with trabectedin paralleled by deregulated expression of the bcl-2 family members bcl-2, bim, bax, Mcl-1, and bcl-xL as a consequence of trabectedin exposure. In addition, trabectedin exerted significant antitumor activity against an intraperitoneal MPM xenograft model. Together, these data suggest that trabectedin exerts strong activity in MPM and synergizes with chemotherapy and experimental bcl-2 inhibitors in vitro Thus, it represents a promising new therapeutic option for MPM. Mol Cancer Ther; 15(10); 2357-69. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma.

    LENUS (Irish Health Repository)

    Jennings, Cormac J

    2012-02-01

    INTRODUCTION: Estrogen receptor beta (ERbeta) overexpression by malignant pleural mesothelioma (MPM) tumor cells correlates with enhanced patient survival. ER-regulated transcription is mediated by the p160 family of steroid receptor coactivators (SRCs), and SRC isoform overexpression is associated with worse prognosis in many steroid-related malignancies. The aim of this study was to establish whether SRC isoform expression varied between individual MPM tumors with positive or negative prognostic significance. METHODS: Immunohistochemical analysis of tumor biopsies from 89 subjects with confirmed histological diagnosis of MPM and biopsies from 3 normal control subjects was performed to detect the expression of SRC-1, SRC-2 (TIF-2), SRC-3 (AIB-1), and ERbeta. Allred scores for expression of ERbeta and each of the SRCs were determined, and Kaplan-Meier survival curves were calculated to correlate biomarker expression, gender, and histology type with postdiagnosis survival. RESULTS: ERbeta and all the SRCs were expressed at high levels in normal pleural mesothelium, and expression of each biomarker was reduced or lost in a subset of the MPM subjects; however, postdiagnosis survival only significantly correlated with TIF-2 expression. Low or intermediate expression of TIF-2 correlated with reduced median postdiagnosis survival (9 months) compared with those subjects whose tumors highly expressed TIF-2 (20 months) (p = 0.036, log-rank test). CONCLUSIONS: Maintained high expression of TIF-2 in tumor cells is a positive prognostic indicator for postdiagnosis survival in patients with confirmed MPM. This is the first clinical study to correlate high TIF-2 expression with improved patient prognosis in any malignancy.

  12. Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma.

    Science.gov (United States)

    Inaguma, Shingo; Lasota, Jerzy; Wang, Zengfeng; Czapiewski, Piotr; Langfort, Renata; Rys, Janusz; Szpor, Joanna; Waloszczyk, Piotr; Okoń, Krzysztof; Biernat, Wojciech; Ikeda, Hiroshi; Schrump, David S; Hassan, Raffit; Miettinen, Markku

    2018-01-01

    Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1-expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1-positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1-positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. miR-130A as a diagnostic marker to differentiate malignant mesothelioma from lung adenocarcinoma in pleural effusion cytology.

    Science.gov (United States)

    Cappellesso, Rocco; Galasso, Marco; Nicolè, Lorenzo; Dabrilli, Paolo; Volinia, Stefano; Fassina, Ambrogio

    2017-08-01

    Malignant pleural mesothelioma is a rare tumor with a dismal prognosis, usually presenting with recurrent effusions. However, the majority of malignant pleural effusions are due to lung adenocarcinoma (AdC). The distinction between these tumors has considerable therapeutic and medicolegal implications and can be very challenging both histologically and cytologically. Appropriate immunohistochemistry (IHC) is required to support the diagnosis. MicroRNA (miRNA) expression analysis could be a viable diagnostic tool for distinguishing between these tumors. The purpose of the current study was to assess the reliability of miRNAs as diagnostic markers to differentiate epithelioid malignant mesothelioma (MM) from lung AdC. Bioinformatic analysis of publicly searchable data sets regarding miRNA expression profiling was performed to select the most significant differentially expressed miRNAs. These were analyzed by quantitative polymerase chain reaction on histologic (41 MM cases and 40 lung AdC cases) and cytological (26 MM cases and 27 lung AdC cases) specimens and the diagnostic performances were assessed. miR-130a, miR-193a, miR-675, miR-141, miR-205, and miR-375 were found to be the best distinguishing markers. Of these, only miR-130a was significantly overexpressed in MM compared with lung AdC (P =.029 in histologic and P =.014 in cytological samples). miR-130a demonstrated a sensitivity of 77%, a specificity of 67%, a positive predictive value of 69%, a negative predictive value of 75%, and an accuracy of 72% in identifying MM. The diagnostic performances of miR-130a expression analysis and IHC appear to be similar. miR-130a quantification could be used reliably as second-level diagnostic tool to differentiate MM from lung AdC in pleural effusion cytology, mainly in those cases with ambiguous or negative IHC. Further validation is needed. Cancer Cytopathol 2017;125:635-43. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. The inhibition of FGF receptor 1 activity mediates sorafenib antiproliferative effects in human malignant pleural mesothelioma tumor-initiating cells.

    Science.gov (United States)

    Pattarozzi, Alessandra; Carra, Elisa; Favoni, Roberto E; Würth, Roberto; Marubbi, Daniela; Filiberti, Rosa Angela; Mutti, Luciano; Florio, Tullio; Barbieri, Federica; Daga, Antonio

    2017-05-25

    Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro. Three fully characterized tumorigenic cultures, named MM1, MM3, and MM4, were selected and used to assess antiproliferative effects of the multi-kinase inhibitor sorafenib. Cell viability was investigated by MTT assay, and cell cycle analysis as well as induction of apoptosis were determined by flow cytometry. Western blotting was performed to reveal the modulation of protein expression and the phosphorylation status of pathways associated with sorafenib treatment. We analyzed the molecular mechanisms of the antiproliferative effects of sorafenib in mesothelioma TIC cultures. Sorafenib inhibited cell cycle progression in all cultures, but only in MM3 and MM4 cells was this effect associated with Mcl-1-dependent apoptosis. To investigate the mechanisms of sorafenib-mediated antiproliferative activity, TICs were treated with epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) causing, in MM3 and MM4 cells, MEK, ERK1/2, Akt, and STAT3 phosphorylation. These effects were abolished by sorafenib only in bFGF-treated cells, while a modest inhibition occurred after EGF stimulation, suggesting that sorafenib effects are mainly due to FGF receptor (FGFR) inhibition. Indeed, FGFR1 phosphorylation was inhibited by sorafenib. Moreover, in MM1 cells, which release high levels of bFGF and showed autocrine activation of FGFR1 and constitutive phosphorylation/activation of MEK-ERK1/2, sorafenib induced a more effective antiproliferative response

  15. Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience.

    Science.gov (United States)

    Porcel, José M; Civit, Carme; Esquerda, Aureli; Salud, Antonieta; Bielsa, Silvia

    2017-08-01

    To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination. PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion. The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%. Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Andersen, Morten; Grauslund, Morten; Ravn, Jesper

    2014-01-01

    Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 mi...

  17. Improving Outcome in Malignant Pleural Mesothelioma (MPM) Using Pulsed-Protracted External Beam Radiation (PERT) and Intrapleural Delivery of Stem Cells

    Science.gov (United States)

    2014-09-01

    Malignant Pleural Mesothelioma (MPM) survival remains poor despite multidisciplinary treatment involving aggressive surgery, chemotherapy and... Mesothelioma (MPM) survival remains poor despite multidisciplinary treatment involving aggressive surgery, chemotherapy and adjuvant radiotherapy (RT... Mesothelioma (MPM) Using Pulsed-Protracted External Beam Radiation (PERT) and Intrapleural Delivery of

  18. Frequency of EGFR mutations in lung adenocarcinoma with malignant pleural effusion: Implication of cancer biological behaviour regulated by EGFR mutation.

    Science.gov (United States)

    Zou, JianYong; Bella, Amos Ela; Chen, ZhenGuang; Han, XiangQian; Su, ChunHua; Lei, YiYan; Luo, HongHe

    2014-10-01

    A retrospective single-centre study to compare the clinical features of patients with lung adenocarcinoma with and without epidermal growth factor receptor (EGFR) mutations. Pretreatment medical records of patients with lung adenocarcinoma were reviewed. DNA was extracted from paraffin wax-embedded tumour tissue for analysis of EGFR mutations. Malignant pleural effusion (MPE) was diagnosed by cytopathological testing of pleural fluid. EGFR mutations (19-Del and L858R) were recorded in 81/283 patients (28.6%). MPE was found in 42/283 patients (14.8%). In patients with stage IV disease, the frequency of EGFR mutations was higher in those with MPE than in those without MPE. EGFR mutations were independently associated with female sex, no history of smoking and presence of MPE. There was a positive association between EGFR mutation and the presence of MPE. EGFR mutations may play an important role in the formation of MPE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Komiya, Eriko [Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Ohnuma, Kei, E-mail: kohnuma@juntendo.ac.jp [Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Yamazaki, Hiroto; Hatano, Ryo; Iwata, Satoshi; Okamoto, Toshihiro [Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Dang, Nam H. [Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road, Box 100278, Room MSB M410A, Gainesville, FL 32610 (United States); Yamada, Taketo [Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Morimoto, Chikao [Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2014-05-16

    Highlights: • CD26-expressing MPM cells upregulate production of periostin. • The intracytoplasmic region of CD26 mediates the upregulation of periostin. • CD26 expression leads to nuclear translocation of Twist1 via phosphorylation of Src. • Secreted periostin enhances migration and invasion of MPM cells. - Abstract: Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.

  20. Diagnostic delay in malignant pleural mesothelioma due to physicians fixation on history with non-exposure to asbestos

    DEFF Research Database (Denmark)

    Madsen, Poul Henning; Laursen, Christian B.; Davidsen, Jesper Rømhild

    2013-01-01

    To establish the diagnosis of virtually any disease, the clinician must combine a variety of information. Often emphasised in this context is thorough medical history-taking including information on exposure to factors leading to or being associated with the disease in question. Continuous...... assessment of all available information is of utmost importance, as fixation on single details can be misguiding with inappropriate consequences in both the diagnostic and therapeutic approach. This case report presents how an atypical medical history led to a delay in the diagnosis of malignant pleural...... mesothelioma due to a low a priori likelihood of the disease because of non-exposure to asbestos. We highlight the fact that postrationalisation and attempts to renew a diagnostic approach must be carried out each time diagnostic dilemmas emerge, and when some or all diagnostic clues disagree....

  1. FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Giovenzio Genestreti, Andrea Moretti, Sara Piciucchi, Noemi Giovannini, Riccardo Galassi, Emanuela Scarpi, Marco Angelo Burgio, Dino Amadori, Stefano Sanna, Venerino Poletti, Federica Matteucci, Giampaolo Gavelli

    2012-01-01

    Full Text Available Purpose: Talc pleurodesis (TP is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F FDG PET/CT response evaluation in malignant pleural mesothelioma (MPM patients treated with TP and chemotherapy.Methods: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq 18F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM iterative reconstruction algorithm.Results: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic, with a median age of 65 years (range: 54-77, were evaluated. Median follow-up was 31 months (range: 4-44. After TP treatment, there was a mean interval of 14 days (range: 9-22 and 125 days (range: 76-162 between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75% and 3 (37.5% patients, respectively.Conclusion: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax.

  2. Chromosomal aberrations of malignant pleural effusions of lung adenocarcinoma: different cytogenetic changes are correlated with genders and smoking habits.

    Science.gov (United States)

    Yen, Chueh-Chuan; Liang, Shu-Ching; Jong, Yiin-Jeng; Chen, Yann-Jang; Lin, Chi-Hung; Chen, Yuh-Min; Wu, Yu-Chung; Su, Wu-Chou; Huang, Chi-Ying F; Tseng, Szu-Wen; Whang-Peng, Jacqueline

    2007-09-01

    Chromosomal aberrations of malignant cells from pleural effusions of 31 cases of lung adenocarcinoma were analyzed. Pooled CGH results showed frequent amplifications on chromosome arms 1p (22.6%), 1q (35.5%), 2q (25.8%), 3q (38.7%), 4q (41.9%), 5p (41.9%), 5q (51.6%), 6p (19.4%), 6q (25.8%), 7p (41.9%), 7q (35.5%), 8q (32.3%), 12q (38.7%), 13q (22.6%), 14q (35.5%), 17q (19.4%), Xp (22.6%), and Xq (38.7%). Frequent deletions were found on 1p (19.4%), 3p (16.1%), 4q (16.1%), 8p (25.8%), 9p (22.6%), 9q (29.0%), 10q (22.6%), 13q (22.6%), 16p (19.4%), 16q (22.6%), 17p (29.0%), 18q (16.1%), 19p (41.9%), 19q (32.3%), 20p (19.4%) and 22q (29%). These genomic changes were generally found consistent with previous reports of CGH analysis of primary tumors of lung adenocarcinoma. Loss of 19q and 22q were more frequently found in our studies (32.3% and 29.0%, respectively) than studies of primary tumors (less than 7% for both genetic changes). Gain of 11p, although not a frequent finding, was relatively more common in this (16%) than other studies (range, 2.9-11.8%). Interestingly, occurrences of 3p loss and 11p gain were higher in smokers than non-smokers, and deletion of 3p and increased copy number of 11p and Xp appeared more often in male than female patients. Among 17 male patients, gain of chromosomal 11p was a frequent aberration in tumors of smokers, while gain of Xp was more easily found in tumors of non-smokers. One candidate gene located within 11p15, lactate dehydrogenase C (LDHC), was selected for further study. Three cases with 11p gain had amplified FISH signals of LDHC. Also tumors from smokers or male had significantly higher transcript level of LDHC than non-smokers or female, respectively. The results demonstrate that different cytogenetic changes of malignant pleural effusions from lung adenocarcinoma are correlated with genders and smoking habits. The role of LDHC in the carcinogenesis of smoking-related lung adenocarcinoma, especially in male patients with

  3. An unusual presentation of malignant hepatic epithelioid haemangioendothelioma with left pleural and pulmonary localization

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Luca, Angelo [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Department of Radiology, Palermo (Italy); Spada, Marco; Gridelli, Bruno [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Department of Transplantation Surgery, Palermo (Italy); Vitulo, Patrizio [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Department of Medicine, Pneumology, Palermo (Italy); Minervini, Marta Ida [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), Department of Pathology, Palermo (Italy)

    2008-09-15

    Hepatic epithelioid haemangioendothelioma (HEHE) is extremely rare in children. We present an adolescent who presented with a scoliosis due to left thoracic pain. Multifocal HEHE was incidentally found during CT scan of the thorax, and confirmed with a multiphase CT scan of the abdomen, biopsy and immunochemistry. Left pleural and pulmonary involvement was suspected and later confirmed with biopsy and histopathological examination. The patient died 1 year after diagnosis. To the best of our knowledge, scoliosis has not previously been reported as the first symptom of EHE. (orig.)

  4. Early and late morbidity and mortality and life expectancy following thoracoscopic talc insufflation for control of malignant pleural effusions: a review of 400 cases

    Directory of Open Access Journals (Sweden)

    Lyriti Konstantina

    2010-04-01

    Full Text Available Abstract Background Malignant pleural effusion is a common sequelae in patients with certain malignancies. It represents a terminal condition with short median survival (in terms of months and the goal is palliation. Aim of our study is to analyze morbidity, mortality and life expectancy following videothoracoscopic talc poudrage. Materials and methods From September 2004 to October 2009, 400 patients underwent video-assisted thoracic surgery (VATS for malignant pleural effusion. The conditions of patients were assessed and graded before and after treatment concerning morbidity, mortality, success rate of pleurodesis and median survival. Results The median duration of follow up was 40 months (range 4-61 months. All patients demonstrated notable improvement in dyspnea. Intraoperative mortality was zero. The procedure was well tolerated and no significant adverse effects were observed. In hospital mortality was 2% and the pleurodesis success rate was 85%. A poor Karnofsky Performance Status and delay between diagnosis of pleural effusion and pleurodesis were statistically significant factors for in-hospital mortality. The best survival was seen in breast cancer, followed by ovarian cancer, lymphoma and pleural mesothelioma. Conclusions Video-assisted thoracoscopic talc poudrage is an effective and safe procedure that yields a high rate of successful pleurodesis and achieves long-term control with marked dyspnea decrease.

  5. Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins.

    Science.gov (United States)

    Giusti, Laura; Da Valle, Ylenia; Bonotti, Alessandra; Donadio, Elena; Ciregia, Federica; Ventroni, Tiziana; Foddis, Rudy; Giannaccini, Gino; Guglielmi, Giovanni; Cristaudo, Alfonso; Lucacchini, Antonio

    2014-04-01

    Malignant mesothelioma is a neoplastic disease linked to asbestos exposure whose diagnosis is limited, so detection methods for an early diagnosis and treatment result essential. Here, we compared proteomic profiles of malignant pleural mesothelioma (MPM) and benign biopsies to search potential biomarkers useful in differential diagnosis. Tissue biopsies were obtained from 53 patients who were subjected to a diagnostic thoracoscopy. 2DE/MS based approach was used for proteomic analysis and protein validation was carried out by Western blot analysis versus benign and lung carcinoma samples. Among the proteins identified we confirmed known MPM biomarkers such as calretinin and suggested the new ones as prelamin A/C, desmin, vimentin, calretinin, fructose-bisphosphate aldolase A, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myosin light chain 3 and myosin light chain 6B. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network. Overall, our results suggest potential biomarkers that can be useful in occupational medicine for the early identification of the onset of disease in health surveillance of past asbestos-exposed workers, for monitoring the progress of disease and for assessing the response to treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Successful use of central venous catheters in the management of recurrent malignant pleural effusions: one new option.

    Science.gov (United States)

    Yazdanbod, Abbas; Salehifar, Azita; Maleki, Nasrollah; Habibzadeh, Shahram; Tavosi, Zahra

    2015-08-01

    Malignant pleural effusion (MPE) is a common clinical problem in patients with malignancy. To date, placement of various catheters has been suggested as an effective alternative method for traditional treatment of recurrent MPE. In this study, we report our experience in managing treatment of recurrent MPE by placing a central vein catheter without a radiologic guide. Patients with recurrent MPE who underwent triple-lumen central vein catheter insertion (2010-2013) were retrospectively reviewed. Clinical, procedural, complication, and outcome details were analyzed. Patients were carefully selected, and the central catheters were inserted as a palliative measure. We assessed the quality of life of patients using the EORTC QLQ-C30. A total of 84 patients with recurrent MPE were enrolled in this study. Fifty-six males and 28 females with mean age of 57.8 ± 12.4 years old underwent the procedure. There were no preoperative or postoperative complications related to the procedure. The EORTC QLQ-C30 questionnaire showed a significant improvement following catheter placement in symptom scales at 30 days (p = 0.01) and at 60 days (p = 0.002). Triple-lumen central catheter insertion is a simple, noninvasive option in patients with recurrent MPE that can be performed the patient's bedside. Further research is needed to confirm the results and to assess the impact of central catheter insertion on the quality of life of these patients.

  7. Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.

    Science.gov (United States)

    Hoda, Mir Alireza; Dong, Yawen; Rozsas, Anita; Klikovits, Thomas; Laszlo, Viktoria; Ghanim, Bahil; Stockhammer, Paul; Ozsvar, Judit; Jakopovic, Marko; Samarzija, Miroslav; Brcic, Luka; Bendek, Matyas; Szirtes, Ildiko; Reid, Glen; Kirschner, Michaela B; Kao, Steven C; Opitz, Isabelle; Weder, Walter; Frauenfelder, Thomas; Nguyen-Kim, Thi Dan Linh; Aigner, Clemens; Klepetko, Walter; van Zandwijk, Nico; Berger, Walter; Dome, Balazs; Grusch, Michael; Hegedus, Balazs

    2016-08-01

    The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM. Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables. Plasma activin A level was significantly elevated in MPM patients (862 ± 83 pg/ml) when compared to healthy controls (391 ± 21 pg/ml; P < 0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625 ± 95 pg/ml; P = 0.0067). Sarcomatoid (n = 10, 1629 ± 202 pg/ml, P = 0.0019) and biphasic (n = 23, 1164 ± 233 pg/ml, P = 0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n = 94, 712 ± 75 pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365 d, P < 0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM. Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Trimodality therapy for malignant pleural mesothelioma: Results from an EORTC phase II multicentre trial

    NARCIS (Netherlands)

    P.E.Y. van Schil (Paul); P. Baas (Paul); R.M. Gaafar (Rabab); A.W.P.M. Maat (Alex); F. Van De Pol (Francien); B. Hasane (B.); H.M. Klomp (Houke); A.M. Abdelrahman (A.); J. Welche (J.); J.P. van Meerbeeck (Jan)

    2010-01-01

    textabstractThe European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant

  9. Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion.

    Science.gov (United States)

    Qi, Nan; Li, Fang; Li, Xiaosong; Kang, Huanrong; Zhao, Hui; Du, Nan

    2016-11-01

    The current study is conducted to investigate efficacy of the chemotherapy drug paclitaxel in combination with Avastin (Roche Diagnostics GmbH., Mannheim, Germany) (antiangiogenic agent) in treatment of malignant pleural effusions (MPEs).Twenty-four patients with non-small cell lung cancer were randomly assigned for 2 treatment approaches. Ten patients received paclitaxel (175 mg/m) alone, and 14 patients took a combination therapy of paclitaxel and Avastin (5 mg/kg). Efficacy of the treatment approaches in the patients was validated with the change in the MPE volume. Pharmacokinetic (PK) profile and urinary excretion rate of paclitaxel were analyzed with serum vascular endothelial growth factor (VEGF) level, and adverse events were examined as well.The combination therapy reduced the MPE level with a successful rate of 29% and a survival rate of 25% over the single paclitaxel treatment in the study cohort (both P < 0.05). PKs for the combined treatment displayed a rapid distribution of the anticancer drug paclitaxel with an obvious increase in its elimination half-life in the pleural fluid (both P < 0.01). Mean residence time of paclitaxel increased in the presence of Avastin (P < 0.01). Serum VEGF levels significantly reduced in the Avastin-treated patients as compared to the paclitaxel-treated ones (P < 0.01). The urinary excretion rate was similar in the study cohort. Incidence of adverse events for the 2 treatment approaches was similar in the patients.Intervention of Avastin enhances potency of paclitaxel in treatment of MPEs with the increased survival rate of the patients through inhibiting VEGF production and prolonging time of ongoing interaction between the chemotherapy drug and the tumor tissues.

  10. Quality of life and personality traits in patients with malignant pleural mesothelioma and their first-degree caregivers

    Directory of Open Access Journals (Sweden)

    Granieri A

    2013-08-01

    Full Text Available Antonella Granieri,1 Stella Tamburello,2 Antonino Tamburello,2 Silvia Casale,3 Chiara Cont,1 Fanny Guglielmucci,1 Marco Innamorati21Università degli Studi di Torino, Turin, Italy; 2Università Europea di Roma, Rome, Italy; 3Università di Firenze, Firenze, ItalyAbstract: Asbestos exposure causes significant pleural diseases, including malignant pleural mesothelioma (MPM. Taking into account the impact of MPM on emotional functioning and wellbeing, this study aimed to evaluate the quality of life and personality traits in patients with MPM and their first-degree caregivers through the World Health Organization Quality of Life–BREF (WHOQOL-BREF and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF. The sample was composed of 27 MPM patients, 55 first-degree relatives enrolled in Casale Monferrato and Monfalcone (Italy, and 40 healthy controls (HC. Patients and relatives reported poorer physical health than the HC. Patients had a higher overall sense of physical debilitation and poorer health than relatives and the HC, more numerous complaints of memory problems and difficulties in concentrating, and a greater belief that goals cannot be reached or problems solved, while often claiming that they were more indecisive and inefficacious than the HC. First-degree relatives reported lower opinions of others, a greater belief that goals cannot be reached or problems solved, support for the notion that they are indecisive and inefficacious, and were more likely to suffer from fear that significantly inhibited normal activities than were HC. In multinomial regression analyses, partial models indicated that sex, physical comorbidities, and the True Response Inconsistency (TRIN-r, Malaise (MLS, and Behavior-Restricting Fears (BRF dimensions of the MMPI-2-RF had significant effects on group differences. In conclusion, health care providers should assess the ongoing adjustment and emotional wellbeing of people with MPM and their

  11. Quality of life and personality traits in patients with malignant pleural mesothelioma and their first-degree caregivers

    Science.gov (United States)

    Granieri, Antonella; Tamburello, Stella; Tamburello, Antonino; Casale, Silvia; Cont, Chiara; Guglielmucci, Fanny; Innamorati, Marco

    2013-01-01

    Asbestos exposure causes significant pleural diseases, including malignant pleural mesothelioma (MPM). Taking into account the impact of MPM on emotional functioning and wellbeing, this study aimed to evaluate the quality of life and personality traits in patients with MPM and their first-degree caregivers through the World Health Organization Quality of Life–BREF (WHOQOL-BREF) and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). The sample was composed of 27 MPM patients, 55 first-degree relatives enrolled in Casale Monferrato and Monfalcone (Italy), and 40 healthy controls (HC). Patients and relatives reported poorer physical health than the HC. Patients had a higher overall sense of physical debilitation and poorer health than relatives and the HC, more numerous complaints of memory problems and difficulties in concentrating, and a greater belief that goals cannot be reached or problems solved, while often claiming that they were more indecisive and inefficacious than the HC. First-degree relatives reported lower opinions of others, a greater belief that goals cannot be reached or problems solved, support for the notion that they are indecisive and inefficacious, and were more likely to suffer from fear that significantly inhibited normal activities than were HC. In multinomial regression analyses, partial models indicated that sex, physical comorbidities, and the True Response Inconsistency (TRIN-r), Malaise (MLS), and Behavior-Restricting Fears (BRF) dimensions of the MMPI-2-RF had significant effects on group differences. In conclusion, health care providers should assess the ongoing adjustment and emotional wellbeing of people with MPM and their relatives, and provide support to reduce emotional distress. PMID:23983468

  12. Management of malignant pleural effusion by suicide gene therapy in advanced stage lung cancer: a case series and literature review.

    Science.gov (United States)

    Zarogoulidis, P; Chatzaki, E; Hohenforst-Schmidt, W; Goldberg, E P; Galaktidou, G; Kontakiotis, T; Karamanos, N; Zarogoulidis, K

    2012-09-01

    Gene therapy can be defined as the transfer of genetic material into a cell for therapeutic purposes. Cytosine deaminase (CD) transferred into tumor cells by an adenoviral vector (Ad.CD), can convert the antifungal drug fluorocytosine (5-FC) to the antimetabolite 5-fluorouracil (5-FU), which kills not only the transfected tumor cells but also their neighbors by the so-called 'bystander effect'. After testing a protocol for Ad.CD transfer and lung tumor burden control in a Lewis mouse model, we used this technique in the management of lung cancer patients with malignant pleural effusion (MPE): two cases are presented investigating the possible enhancement of anticancer effect in both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by local activation of the pro-drug 5-FC. Results were discussed in parallel to a literature review on the topic. 5-FC and Ad.CD were administered intratumorally to Lewis mouse lung carcinoma and the effect was monitored by tumor size and electromicroscopy. Two patients with advanced stage lung cancer (1SCLC, 1NSCLC), which developed MPE during first-line treatment were administered 10(12) plaque-forming unit (pfu) Ad.CD by intrapleural instillation, in two doses (day 1 and day 7). Instillation was performed when the pleural fluid was ≤200 ml. In addition, they received 5-FC 500 mg four times daily for 14 days. Lung tumor regression and successful transfer of adenoviral particles were observed in treated animals. Patients presented complete regression of pleural effusion as monitored by computerized tomography scan. Neutrapenia and anemia were the most severe adverse effect presented (grade III/grade IV 100%). The increased toxicity followed by the intrapleural gene therapy indicates the augmentation of anticancer effect of transformed pro-drug 5-FC to active 5-FU. The obtained data indicate that intrapleural gene therapy may be a useful tool, adjunct to chemotherapy, in the management of MPE related to lung cancer.

  13. Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma.

    Science.gov (United States)

    Laszlo, Viktoria; Hoda, Mir Alireza; Garay, Tamas; Pirker, Christine; Ghanim, Bahil; Klikovits, Thomas; Dong, Yawen W; Rozsas, Anita; Kenessey, Istvan; Szirtes, Ildiko; Grusch, Michael; Jakopovic, Marko; Samarzija, Miroslav; Brcic, Luka; Kern, Izidor; Rozman, Ales; Popper, Helmut; Zöchbauer-Müller, Sabine; Heller, Gerwin; Altenberger, Corinna; Ziegler, Barbara; Klepetko, Walter; Berger, Walter; Dome, Balazs; Hegedus, Balazs

    2015-10-01

    Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity. Reduced expression of the novel tumour suppressor integrin α7 (ITGA7) was found in highly motile cells. A significant negative correlation was observed between ITGA7 transcript levels and average displacement of cells. Forced overexpression of ITGA7 in MPM cells with low endogenous ITGA7 expression inhibited cell motility, providing direct evidence for the regulatory role of ITGA7 in MPM cell migration. MPM cells showed decreased ITGA7 expressions at both transcription and protein levels when compared to non-malignant mesothelial cells. The majority of MPM cell cultures displayed hypermethylation of the ITGA7 promoter when compared to mesothelial cultures. A statistically significant negative correlation between ITGA7 methylation and ITGA7 expression was also observed in MPM cells. While normal human pleura samples unambiguously expressed ITGA7, a varying level of expression was found in a panel of 200 human MPM samples. In multivariate analysis, ITGA7 expression was found to be an independent prognostic factor. Although there was no correlation between histological subtypes and ITGA7 expression, importantly, patients with high tumour cell ITGA7 expression had an increased median overall survival compared to the low- or no-expression groups (463 versus 278 days). In conclusion, our data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human MPM. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Metabonomics by proton nuclear magnetic resonance in human pleural effusions: A route to discriminate between benign and malignant pleural effusions and to target small molecules as potential cancer biomarkers.

    Science.gov (United States)

    Zennaro, Lucio; Vanzani, Paola; Nicolè, Lorenzo; Cappellesso, Rocco; Fassina, Ambrogio

    2017-05-01

    Cytopathology is a noninvasive and cost-effective method for detecting cancer cells in pleural effusions (PEs), although in many cases, the diagnostic performance is hindered by the paucity of significant cells or the lack of clear morphological criteria. This study presents the results of an omics approach to improving the diagnostic performance of PE cytology. Metabolic profiling with proton nuclear magnetic resonance (1 H-NMR) was performed for 92 PEs (44 malignant cases of 8 different cancers and 48 benign cases of 7 nonneoplastic conditions). Light's criteria were used to further classify PEs as transudates or exudates, and 1 H-NMR spectroscopy was used to differentiate malignant pleural effusions (mPEs) from benign pleural effusions (bPEs). 1 H-NMR metabolic analysis showed clearly different spectra for mPEs and bPEs in the regions of the signals due to lipids, branched amino acids, and lactate, which were increased in mPEs. Transudates and exudates in bPEs were differentiated as well on the basis of the 1 H-NMR signals from lipids and lipoproteins, which were increased in exudates. Subject to validation in further larger studies, 1 H-NMR metabonomics could be an effective and reliable ancillary tool for PE investigations and diagnoses. Cancer Cytopathol 2017;125:341-348. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Effects of extended pleurectomy and decortication on quality of life and pulmonary function in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Burkholder, David; Hadi, Duraid; Kunnavakkam, Rangesh; Kindler, Hedy; Todd, Kristy; Celauro, Amy Durkin; Vigneswaran, Wickii T

    2015-05-01

    Maximal cytoreductive surgeries--extrapleural pneumonectomy and extended pleurectomy and decortication (EPD)--are effective surgical treatments in selected patients with malignant pleural mesothelioma. Extended pleurectomy and decortication results in equivalent survival yet better health-related quality of life (HRQoL). Patients with malignant pleural mesothelioma were studied for the effects of EPD on HRQoL and pulmonary function. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionaire-C30 was used to evaluate HRQoL before operation, and at 4 to 5 and 7 to 8 months postoperatively. Pulmonary function tests were measured immediately before and 5 to 7 months after the operation. Patients were compared according to World Health Organization baseline performance status (PS). Of the 36 patients enrolled, 17 were PS 0 and 19 were PS 1 or PS 2 at baseline. Patients in groups PS 1 and PS 2 had significantly worse global health, functional, and symptoms scores. After EPD, PS 0 patients had no change in global health or function and symptoms scores except for emotional function, whereas PS 1 or PS 2 patients showed improvements at 4 to 5 months with further improvements at 7 to 8 months. The PS 0 patients demonstrated a significant decrease in forced vital capacity (p = 0.001), forced expiratory volume in 1 second (p = 0.002), total lung capacity (p = 0.0006) and diffusing capacity of the lung for carbon monoxide (p = 0.003) after EPD, whereas no change was observed in PS 1 and PS 2 patients. Extended pleurectomy and decortication did not improve overall HRQoL and had a negative impact in pulmonary function in minimally symptomatic patients. In symptomatic patients, a significant improvement in HRQoL was observed after EPD, which continued at late follow-up, although the pulmonary function was not affected. As changes in HRQoL are multidimensional, the preservation of the pulmonary function may have contributed to the net benefit

  16. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Minatel, Emilio [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Di Maso, Matteo [Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Drigo, Annalisa; Barresi, Loredana [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Furlan, Carlo [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Pordenone (Italy); Bruschi, Gioia [Department of Pneumology, Pordenone General Hospital, Pordenone (Italy); Fontana, Paolo [Department of Thoracic Surgery, Mestre General Hospital, Mestre (Italy); Pagan, Vittore [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Franchin, Giovanni [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2015-11-01

    Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and

  17. SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H [The University of Chicago, Chicago, IL (United States)

    2015-06-15

    Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology.

  18. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors.

    Science.gov (United States)

    Minatel, Emilio; Trovo, Marco; Bearz, Alessandra; Di Maso, Matteo; Baresic, Tania; Drigo, Annalisa; Barresi, Loredana; Furlan, Carlo; Del Conte, Alessandro; Bruschi, Gioia; Fontana, Paolo; Pagan, Vittore; Franchin, Giovanni

    2015-11-01

    To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and acceptable toxicity rates. The similarity of survival between

  19. Unexpandable lung from pleural disease.

    Science.gov (United States)

    Huggins, John T; Maldonado, Fabien; Chopra, Amit; Rahman, Najib; Light, Richard

    2017-10-24

    Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post-procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment. © 2017 Asian Pacific Society of Respirology.

  20. An Unusual Case of Metastatic Malignant Melanoma Presenting as Pseudomesothelioma with Intense Diffuse Pleural FDG Uptake Demonstrated on FDG PET/CT

    Directory of Open Access Journals (Sweden)

    Rosamma Bency

    2015-06-01

    Full Text Available A 75-year-old male, non-smoker with history of asbestos exposure, and excision of 2 mm Clark IV cutaneous malignant melanoma 15 months earlier, presented with rapidly progressive dyspnea, left pleuritic chest pain, and weight loss. CT Pulmonary Angiography (CTPA demonstrated bilateral pulmonary emboli and findings suspicious of mesothelioma. There was no evidence of infection or malignancy in the hemorrhagic pleural fluid aspirate. FDG PET-CT revealed extensive intense FDG uptake throughout the pleura of left hemi-thorax, bilateral hilar and mediastinal lymph nodes, bilateral adrenals and left gluteal musculature. Subsequent pleural biopsy was consistent with metastatic melanoma. The patient was referred for palliative therapy but died 10 days later

  1. First reported finding of a malignant pleural mesothelioma in a patient post liver transplant

    LENUS (Irish Health Repository)

    Gleeson, J

    2016-03-01

    The case history of a liver transplant recipient is presented, who presented with acute dyspnoea after an innocuous fall. His early management was complicated and he was eventually diagnosed with malignant mesothelioma. This is the first such case report in the literature.

  2. A phase II study of gemcitabine in patients with malignant pleural mesothelioma

    NARCIS (Netherlands)

    van Meerbeeck, JP; Bass, P; Debruyne, C; Groen, HJ; Manegold, C; Ardizzoni, A; Gridelli, C; van Marck, EA; Lentz, M; Giaccone, G

    1999-01-01

    BACKGROUND, Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer

  3. Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

    Science.gov (United States)

    Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

    2017-08-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. SU-F-T-391: Comparative Study of Treatment Planning Between IMRT and IMAT for Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Duan, J [Shandong Cancer Hospital and Institute, Jinan, Shandong province (China)

    2016-06-15

    Purpose: The purpose of this study was to compare the dosimetric differences between intensitymodulated radiation therapy (IMRT) and intensity modulated arc therapy (IMAT) for malignant pleural mesothelioma (MPM) patients with regard to the sparing effect on organs at risk (OARs), plan quality, and delivery efficiency. Methods: Ten MPM patients were recruited in this study. To avoid the inter-operator variability, IMRT and IMAT plans for each patient were performed by one experienced dosimetrist. The treatment planning optimization process was carried out using the Eclipse 13.0 software. For a fair comparison, the planning target volume (PTV) coverage of the two plans was normalized to the same level. The treatment plans were evaluated on the following dosimetric variables: conformity index (CI) and homogeneity index (HI) for PTV, OARs dose, and the delivery efficiency for each plan. Results: All plans satisfied clinical requirements. The IMAT plans gained better CI and HI. The IMRT plans performed better sparing for heart and lung. Less MUs and control points were found in the IMAT plans. IMAT shortened delivery time compared with IMRT. Conclusion: For MPM, IMAT gains better conformity and homogeneity for PTV with IMRT, but increases the irradiation dose for OARs. IMAT shows an advantage in delivery efficiency.

  5. Preclinical demonstration of synergistic Active Nutrients/Drug (AND combination as a potential treatment for malignant pleural mesothelioma.

    Directory of Open Access Journals (Sweden)

    Viviana Volta

    Full Text Available Malignant pleural mesothelioma (MPM is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug. In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

  6. Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date

    Directory of Open Access Journals (Sweden)

    Levin PA

    2017-04-01

    Full Text Available Pavel A Levin,1 Jonathan E Dowell1,2 1Division of Hematology/Oncology, University of Texas Southwestern Medical Center, 2Section of Hematology/Oncology, Veteran Affairs North Texas Health Care System, Dallas, TX, USA Abstract: Malignant pleural mesothelioma (MPM is a rare, but aggressive cancer. Surgery and radiation offer limited benefit, and systemic chemotherapy remains the primary treatment modality for the majority of patients. Vascular endothelial growth factor (VEGF and its receptor have been recognized as important players in the biology of this disease. Bevacizumab is a monoclonal antibody that binds VEGF and blocks its interaction with the VEGF receptor. Recent studies have shown benefit with the addition of bevacizumab to the combination of cisplatin and pemetrexed in MPM. This combination is now included in the National Comprehensive Cancer Network guidelines (with a category 2A recommendation as a possible first-line treatment for unresectable MPM in appropriately selected patients. This review discusses the rationale behind the use of bevacizumab in MPM, as well as summarizes the pharmacology, efficacy, safety, and toxicity of bevacizumab across multiple trials. The use of small-molecule inhibitors of angiogenesis in the treatment of MPM is also discussed. Keywords: angiogenesis, monoclonal antibody, VEGF

  7. Evaluation of the efficacy of the guideline on reading CT images of malignant pleural mesothelioma with reference CT films for improving the proficiency of radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Huashi, E-mail: zhouhua@u-fukui.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Tamura, Taro, E-mail: tarou@u-fukui.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Kusaka, Yukinori, E-mail: kusakayk@gmail.com [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Suganuma, Narufumi, E-mail: nsuganuma@kochi-u.ac.jp [Department of Environmental Medicine, Kochi University School of Medicine (Japan); Subhannachart, Ponglada, E-mail: pongladas@gmail.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Vijitsanguan, Chomphunut, E-mail: Chompoo_vj@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Noisiri, Weeraya, E-mail: weeraya_tat@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Hering, Kurt G., E-mail: k.g.hering@t-online.de [Department of Diagnostic Radiology, Radiooncology and Nuclear Medicine, Radiological Clinic, Miner' s Hospital, Radiologische Klinik, Lansppaschaftskranhaus Dortmund, Wieckesweg 27, 44309, Dortmund (Germany); Akira, Masanori, E-mail: akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8555 (Japan); Itoh, Harumi, E-mail: hitoh@fmsrsa.fukui-med.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Department of Radiology, School of Medicine, University of Fukui, 23-3 Shimoaitsuki Matsuoka, Eiheizi-cho, Fukui Prefecture, 910-1193 (Japan); and others

    2013-01-15

    Purpose: To assess the efficacy of the developed guideline on reading CT images of malignant pleural mesothelioma for improving radiologists’ reading proficiency. Materials and Methods: Three radiologists independently read the CT films of 22 cases including definite mesothelioma and non-mesothelioma cases at two times before and after studying the malignant pleural mesothelioma CT Guideline. The sensitivity and specificity for mesothelioma were calculated and compared between the 1st and 2nd trials. The kappa statistics was examined for agreement with experts for mesothelioma probability and for mesothelioma features recorded by three radiologists. Results: After studying the mesothelioma CT Guideline, the sensitivity for mesothelioma shown by the three radiologists at the 2nd trial was 100%, 100% and 80%, which were higher than 80%, 85% and 60% at the 1st trial, respectively. The average kappa for agreement between radiologists and experts on dichotomized mesothelioma probability were 0.69 (good) at the 2nd trial vs. 0.38 (fair) at the 1st trial. The average kappa for the agreement with experts for each of 7 features by three radiologists were 0.52–0.80 at the 2nd trial, which were significantly higher than 0.34–0.58 at the 1st trial (Wilcoxon Signed Rank Test: P < 0.01), and as to five features “unilateral pleural effusion”, “nodular pleural thickening”, “tumoral encasement of lung”, “mediastinal pleural thickening”, and “diminished lung”, they achieved good agreement with average kappa of 0.61–0.80. Conclusion: The developed mesothelioma CT Guideline was suggested to have substantial effect in improving the radiologists’ proficiency for reading CT images of mesothelioma, and may contribute to accurate diagnosis of mesothelioma.

  8. Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma.

    Science.gov (United States)

    Verma, Akash; Chopra, Akhil; Lee, Yeo W; Bharwani, Lavina D; Asmat, Atasha B; Aneez, Dokeu B A; Akbar, Fazuludeen A; Lim, Albert Y H; Chotirmall, Sanjay H; Abisheganaden, John

    2016-01-01

    Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are effective against lung adenocarcinoma. However, limited data is available assessing the effectiveness of EGFR-TKI use in preventing re-accumulation of MPE. To our knowledge, there is no literature on comparison of talc pleurodesis with EGFR-TKIs alone on re-accumulation of MPE in Asian population. We investigated if EGFR-TKI therapy for advanced lung adenocarcinoma with malignant pleural effusion (MPE) is also successful in preventing pleural fluid re-accumulation following initial drainage. An observational cohort study of patients with lung adenocarcinoma and MPE in the year 2012 was conducted. 70 patients presented with MPE from lung adenocarcinoma. Fifty six underwent EGFR mutation testing of which 39 (69.6%) had activating EGFR mutation and 34 (87.1%) received TKI. 20 were managed by pleural fluid drainage only whereas 14 underwent talc pleurodesis following pleural fluid drainage. Time taken for the pleural effusion to re-accumulate in those with and without pleurodesis was 9.9 vs. 11.7 months, p=0.59 respectively. More patients (n=10, 25.6%) with activating EGFR mutation presented with complete opacification (white-out) of the hemithorax compared to none without activating EGFR mutation (p=0.02). In TKI eligible patients, early talc pleurodesis may not confer additional benefit in preventing re-accumulation of pleural effusion and may be reserved for non-adenocarcinoma histology, or EGFR negative adenocarcinoma. Complete opacification of the hemithorax on presentation may serve as an early radiographic signal of positive EGFR mutation status.

  9. Pleural needle biopsy

    Science.gov (United States)

    ... may reveal cancer (including primary lung cancer , malignant mesothelioma , and metastatic pleural tumor ), tuberculosis, other infections, or ... any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should ...

  10. The efficacy of indwelling pleural catheter placement versus placement plus talc sclerosant in patients with malignant pleural effusions managed exclusively as outpatients (IPC-PLUS): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Bhatnagar, Rahul; Kahan, Brennan C; Morley, Anna J; Keenan, Emma K; Miller, Robert F; Rahman, Najib M; Maskell, Nick A

    2015-02-12

    Malignant pleural effusions (MPEs) remain a common problem, with 40,000 new cases in the United Kingdom each year and up to 250,000 in the United States. Traditional management of MPE usually involves an inpatient stay with placement of a chest drain, followed by the instillation of a pleural sclerosing agent such as talc, which aims to minimise further fluid build-up. Despite a good success rate in studies, this approach can be expensive, time-consuming and inconvenient for patients. More recently, an alternative method has become available in the form of indwelling pleural catheters (IPCs), which can be inserted and managed in an outpatient setting. It is currently unknown whether combining talc pleurodesis with IPCs will provide improved pleural symphysis rates over those of IPCs alone. IPC-PLUS is a patient-blind, multicentre randomised controlled trial (RCT) comparing the combination of talc with an IPC to the use of an IPC alone for inducing pleurodesis in MPEs. The primary outcome is successful pleurodesis at five weeks post-randomisation. This study will recruit 154 patients, with an interim analysis for efficacy after 100 patients, and aims to help to define the future gold standard for outpatient management of patients with symptomatic MPEs. IPC-PLUS is the first RCT to examine the practicality and utility of talc administered via an IPC. The study remains in active recruitment and has the potential to significantly alter how patients requiring pleurodesis for MPE are approached in the future. This trial was registered with Current Controlled Trials (identifier: ISRCTN73255764 ) on 23 August 2012.

  11. Development of a guideline on reading CT images of malignant pleural mesothelioma and selection of the reference CT films.

    Science.gov (United States)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G; Akira, Masanori; Itoh, Harumi; Arakawa, Hiroaki; Ishikawa, Yuichi; Kumagai, Shinji; Kurumatani, Norio

    2012-12-01

    International experts developed a guideline on reading CT images of malignant pleural mesothelioma for radiologists and physicians. It is intended that it act as a supplement to the current International Classification of HRCT for Occupational and Environmental Respiratory Diseases. The research literatures on mesothelioma CT features were systematically reviewed. Ten mesothelioma CT features were adopted into the guideline prepared according to experts' opinion. The terminology of mesothelioma CT features and mesothelioma probability were agreed by consensus of experts. The CT reference films for each mesothelioma feature were selected based on agreement by experts from 22 definite mesothelioma cases confirmed pathologically and immunohistochemically. To support the validity of the mesothelioma probability, 4 experts' readings of CT films from 57 cases with or without mesothelioma were analyzed by kappa statistics between the experts; sensitivity and specificity for mesothelioma were also assessed. The mesothelioma CT Guideline was developed, providing the terminology of CT features and the mesothelioma probability, the judgement of severity, the distribution of mesothelioma, and the revised CT reading sheet including mesothelioma items. The CT reference films with ten mesothelioma typical features were selected. The average linearly and quadratically weighted kappa of the agreement on the 4-point scale mesothelioma probability were 0.58 and 0.71, respectively. The average sensitivity and specificity for mesothelioma were 93.2% and 65.6%, respectively. The evidence-based mesothelioma CT Guideline developed may serve as a good educational tool to facilitate physicians in recognising mesothelioma and improve their proficiency in diagnosis of mesothelioma. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Molecular Profiling of Malignant Pleural Effusion in Metastatic Non-Small-Cell Lung Carcinoma. The Effect of Preanalytical Factors.

    Science.gov (United States)

    Carter, Jamal; Miller, James Adam; Feller-Kopman, David; Ettinger, David; Sidransky, David; Maleki, Zahra

    2017-07-01

    Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. This study evaluates diagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) for ALK gene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and high-throughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. A total of 50 NSCLC-associated MPE cases were identified where molecular testing was requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50 MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR ( 9 ) and KRAS ( 7 ). Six cases had ALK FISH only, of which one showed rearrangement. MPE volume was not associated with overall cellularity or tumor cellularity (P = 0.360). Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in 59% of samples with minimal risk of false negative.

  13. Development of a guideline on reading CT images of malignant pleural mesothelioma and selection of the reference CT films

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Huashi, E-mail: zhouhua@u-fukui.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Tamura, Taro, E-mail: tarou@u-fukui.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Kusaka, Yukinori, E-mail: kusakayk@gmail.com [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Suganuma, Narufumi, E-mail: nsuganuma@kochi-u.ac.jp [Department of Environmental Medicine, Kochi University School of Medicine (Japan); Subhannachart, Ponglada, E-mail: pongladas@gmail.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Vijitsanguan, Chomphunut, E-mail: Chompoo_vj@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Noisiri, Weeraya, E-mail: weeraya_tat@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Hering, Kurt G., E-mail: k.g.hering@t-online.de [Department of Diagnostic Radiology, Radiooncology and Nuclear Medicine, Radiological Clinic, Miner' s Hospital, Radiologische Klinik, Lansppaschaftskranhaus Dortmund, Wieckesweg 27 44309, Dortmund (Germany); Akira, Masanori, E-mail: akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8555 (Japan); Itoh, Harumi, E-mail: hitoh@fmsrsa.fukui-med.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Department of Radiology, School of Medicine, University of Fukui, 23-3 Shimoaitsuki Matsuoka, Eiheizi-cho, Fukui Prefecture 910-1193 (Japan); and others

    2012-12-15

    Purpose: International experts developed a guideline on reading CT images of malignant pleural mesothelioma for radiologists and physicians. It is intended that it act as a supplement to the current International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Methods: The research literatures on mesothelioma CT features were systematically reviewed. Ten mesothelioma CT features were adopted into the guideline prepared according to experts’ opinion. The terminology of mesothelioma CT features and mesothelioma probability were agreed by consensus of experts. The CT reference films for each mesothelioma feature were selected based on agreement by experts from 22 definite mesothelioma cases confirmed pathologically and immunohistochemically. To support the validity of the mesothelioma probability, 4 experts’ readings of CT films from 57 cases with or without mesothelioma were analyzed by kappa statistics between the experts; sensitivity and specificity for mesothelioma were also assessed. Results: The mesothelioma CT Guideline was developed, providing the terminology of CT features and the mesothelioma probability, the judgement of severity, the distribution of mesothelioma, and the revised CT reading sheet including mesothelioma items. The CT reference films with ten mesothelioma typical features were selected. The average linearly and quadratically weighted kappa of the agreement on the 4-point scale mesothelioma probability were 0.58 and 0.71, respectively. The average sensitivity and specificity for mesothelioma were 93.2% and 65.6%, respectively. Conclusion: The evidence-based mesothelioma CT Guideline developed may serve as a good educational tool to facilitate physicians in recognising mesothelioma and improve their proficiency in diagnosis of mesothelioma.

  14. The association of {sup 18}F-FDG PET/CT parameters with survival in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Klabatsa, Astero; Lang-Lazdunski, Loic [Guys and St Thomas' NHS Foundation Trust, Department of Thoracic Oncology, London (United Kingdom); Chicklore, Sugama; Barrington, Sally F.; Goh, Vicky [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Cook, Gary J.R. [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Kings College London, Clinical PET Centre, Division of Imaging Sciences and Biomedical Engineering, St Thomas' Hospital, London (United Kingdom)

    2014-02-15

    Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[{sup 18}F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT). In order to determine the relationships between metabolic activity and prognosis we reviewed all {sup 18}F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes. Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUV{sub max} was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes. {sup 18}F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials. (orig.)

  15. Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution.

    Science.gov (United States)

    Bece, Andrej; Tin, Mo Mo; Martin, Darren; Lin, Robert; McLean, Jocelyn; McCaughan, Brian

    2015-06-01

    We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution. Between July 2004 and March 2013, 53 patients were referred for radiation treatment following EPP, of whom 49 were suitable for adjuvant treatment. Radiation treatment initially involved a 3D conformal, mixed electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients) and subsequently a nine-field intensity-modulated radiotherapy technique, delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of patients also received pre-operative chemotherapy. We assessed toxicity, disease-specific and overall survival in patients who commenced radiation treatment. Forty-one patients (84%) completed treatment as prescribed. Six patients stopped prematurely due to toxicity, and two with disease progression. Most patients discontinuing due to toxicity received over 90% of the prescribed dose. Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe early toxicities were rare. Late toxicities were uncommon, with the exception of a persistent elevation in liver enzymes in those with right-sided disease. Neither clinical hepatitis nor radiation pneumonitis was documented. With a median follow up of 18.7 months, median disease-free and overall survival were 21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%. Hemithoracic radiotherapy following EPP, although associated with significant early toxicity, is well tolerated. Most patients complete the prescribed treatment, and clinically significant late toxicities are rare. © 2015 The Royal Australian and New Zealand College of Radiologists.

  16. Long-Term Survival Outcomes of Cancer-Directed Surgery for Malignant Pleural Mesothelioma: Propensity Score Matching Analysis.

    Science.gov (United States)

    Nelson, David B; Rice, David C; Niu, Jiangong; Atay, Scott; Vaporciyan, Ara A; Antonoff, Mara; Hofstetter, Wayne L; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Tsao, Anne; Gomez, Daniel; Giordano, Sharon H; Mehran, Reza; Sepesi, Boris

    2017-10-10

    Purpose Small observational studies have shown a survival advantage to undergoing cancer-directed surgery for malignant pleural mesothelioma (MPM); however, it is unclear if these results are generalizable. Our purpose was to evaluate survival after treatment of MPM with cancer-directed surgery and to explore the effect surgery interaction with chemotherapy or radiation therapy on survival by using the National Cancer Database. Patients and Methods Patients with microscopically proven MPM were identified within the National Cancer Database (2004 to 2014). Propensity score matching was performed 1:2 and among this cohort, a Cox proportional hazards regression model was used to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results Of 20,561 patients with MPM, 6,645 were identified in the matched cohort, among whom 2,166 underwent no therapy, 2,015 underwent chemotherapy alone, 850 underwent cancer-directed surgery alone, 988 underwent surgery with chemotherapy, and 274 underwent trimodality therapy. The remaining 352 patients underwent another combination of surgery, radiation, or chemotherapy. Thirty-day and 90-day mortality rates were 6.3% and 15.5%. Cancer-directed surgery, chemotherapy, and radiation therapy were independently associated with improved survival (hazard ratio, 0.77, 0.74, and 0.88, respectively). Stratified analysis revealed that surgery-based multimodality therapy demonstrated an improved survival compared with surgery alone, with no significant difference between surgery-based multimodality therapies; however, the largest estimated effect was when cancer-directed surgery, chemotherapy, and radiation therapy were combined (hazard ratio, 0.52). For patients with the epithelial subtype who underwent trimodality therapy, median survival was extended from 14.5 months to 23.4 months. Conclusion MPM is an aggressive and rapidly fatal disease. Surgery-based multimodality therapy was associated with

  17. A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience.

    Science.gov (United States)

    Opitz, Isabelle; Friess, Martina; Kestenholz, Peter; Schneiter, Didier; Frauenfelder, Thomas; Nguyen-Kim, Thi Dan Linh; Seifert, Burkhardt; Hoda, Mir Alireza; Klepetko, Walter; Stahel, Rolf A; Weder, Walter

    2015-11-01

    Treatment of malignant pleural mesothelioma (MPM) remains a clinical challenge. The aim of this study was to identify selection factors for allocation of MPM patients to multimodal therapy based on survival data from 12 years of experience. Eligible patients had MPM of all histological subtypes with clinical stage T1-3 N0-2 M0. Induction chemotherapy consisted of cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess independent prognosticators for overall survival (OS). A Multimodality Prognostic Score was developed based on clinical variables available before surgery. From May 1999 to August 2011, 186 MPM patients were intended to be treated with induction chemotherapy followed by EPP. Hematologic toxicity was significantly less frequent after cis/pem compared to cis/gem, but there was no difference in response or OS between the regimens. One hundred and twenty-eight patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the patients received adjuvant radiotherapy. The median OS of patients undergoing EPP was significantly longer with 22 months (95% confidence interval: 20-24) when compared to 11 months (9-12) for patients treated without EPP. A prognostic score was defined considering tumor volume, histology, C-reactive protein level, and response to chemotherapy that identified patient groups not benefitting from multimodality treatment which was confirmed in an independent cohort. Patients receiving induction chemotherapy followed by EPP for MPM of all histological subtypes and irrespective of nodal status showed a median survival of 22 months. A prognostic score is proposed to help patient allocation for surgery after validation in an independent cohort.

  18. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma.

    Science.gov (United States)

    Cho, B C John; Feld, Ron; Leighl, Natasha; Opitz, Isabelle; Anraku, Masaki; Tsao, Ming-Sound; Hwang, David M; Hope, Andrew; de Perrot, Marc

    2014-03-01

    We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART). All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure. Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002). SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.

  19. Pemetrexed-related interstitial lung disease reported from post marketing surveillance (malignant pleural mesothelioma/non-small cell lung cancer).

    Science.gov (United States)

    Tomii, Keisuke; Kato, Terufumi; Takahashi, Masashi; Noma, Satoshi; Kobashi, Yoichiro; Enatsu, Sotaro; Okubo, Sumiko; Kobayashi, Noriko; Kudoh, Shoji

    2017-04-01

    Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised.

  20. Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma

    Science.gov (United States)

    Gayosso-Gómez, LV; Zárraga-Granados, G; Paredes-Garcia, P; Falfán-Valencia, R; Vazquez-Manríquez, ME; Martinez-Barrera, LM; Castillo-Gonzalez, P; Rumbo-Nava, U; Guevara-Gutierrez, R; Rivera-Bravo, B; Ramirez-Venegas, A; Sansores, R; Negrete-Garcia, MC; Ortiz-Quintero, Blanca

    2014-01-01

    Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed. PMID:26417297

  1. Characterization of novel transforming growth factor-beta type I receptors found in malignant pleural effusion tumor cells

    Directory of Open Access Journals (Sweden)

    Leu Sy-Jye C

    2007-08-01

    Full Text Available Abstract Background Tumors expressing a transforming growth factor-beta type I receptor (TβRI mutant with sequence deletions in a nine-alanine (9A stretch of the signal peptide are reported to be highly associated with disease progression. Expression of this mutant could interfere with endogenous TGFβ signaling in the cell. However, little is known about the importance of the remaining part of the signal peptide on the cellular function of TβRI. Results We cloned and identified four new in-frame deletion variants of TβRI, designated DM1 to DM4, in pleural effusion-derived tumor cells. Intriguingly, DM1 and DM2, with a small region truncated in the putative signal peptide of TβRI, had a serious defect in their protein expression compared with that of the wild-type receptor. Using serial deletion mutagenesis, we characterized a region encoded by nucleotides 16–51 as a key element controlling TβRI protein expression. Consistently, both DM1 and DM2 have this peptide deleted. Experiments using cycloheximde and MG132 further confirmed its indispensable role for the protein stability of TβRI. In contrast, truncation of the 9A-stretch itself or a region downstream to the stretch barely affected TβRI expression. However, variants lacking a region C-terminal to the stretch completely lost their capability to conduct TGFβ-induced transcriptional activation. Intriguingly, expression of DM3 in a cell sensitive to TGFβ made it significantly refractory to TGFβ-mediated growth inhibition. The effect of DM3 was to ablate the apoptotic event induced by TGFβ. Conclusion We identified four new transcript variants of TβRI in malignant effusion tumor cells and characterized two key elements controlling its protein stability and transcriptional activation. Expression of one of variants bestowed cancer cells with a growth advantage in the presence of TGFβ. These results highlight the potential roles of some naturally occurring TβRI variants on the

  2. FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

    Energy Technology Data Exchange (ETDEWEB)

    Gerbaudo, Victor H.; Mamede, Marcelo [Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston, MA (United States); Trotman-Dickenson, Beatrice; Hatabu, Hiroto [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Radiology, Boston, MA (United States); Sugarbaker, David J. [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Surgery, Boston, MA (United States)

    2011-05-15

    This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 {+-} 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

  3. Impact of a nursing education program about caring for patients in Japan with malignant pleural mesothelioma on nurses' knowledge, difficulties and attitude: a randomized control trial.

    Science.gov (United States)

    Nagamatsu, Yasuko; Natori, Yuji; Yanai, Haruo; Horiuchi, Shigeko

    2014-07-01

    In Japan nursing care lags behind the growing population of patients with malignant pleural mesothelioma. This study evaluated an educational program for nurses about caring for patients with malignant pleural mesothelioma in Japan. In this randomized controlled study relative to care for malignant pleural mesothelioma, Knowledge, Difficulties and Attitude were measured at baseline, at post-test and at follow-up one month later. The two-day program with a half-day follow-up program included lectures, group work, role-playing and group discussion. 188 participants were randomly assigned to the intervention group (program, n=96) and control group (n=92; self-study by a similar content handbook). At baseline the groups showed no statistical differences in Knowledge (p=0.921), Difficulty (p=0.458) and Attitude (p=0.922). Completing the study were 177 participants yielding 88 in the intervention group and 89 in the control group. Human rights and privacy of participants were protected. The Knowledge score was significantly higher in the intervention post-test (t=14.03, p=0.000) and follow-up test (t=8.98, p=0.000). Difficulty score was significantly lower in the intervention at post-test (t=-3.41, p=0.001) and follow-up test (t=-3.70, p=0.000). The Attitude score was significantly higher in the intervention post-test (t=7.11, p=0.000) and follow-up test (t=4.54, p=0.000). The two-way analysis of variance with repeated measures on time showed an interaction between time and group; the subsequent simple main effect test found significant differences (p=0.000-0.001) between groups for after-program and at follow-up and a significant difference (p=0.000) in time only within the intervention group. The educational program was effective in improving the nurses' knowledge and attitude toward malignant pleural mesothelioma care and decreasing the difficulty in MPM care, therefore this program has potential for nurses' in-service education throughout Japan. Copyright © 2014

  4. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial.

    Science.gov (United States)

    Alley, Evan W; Lopez, Juanita; Santoro, Armando; Morosky, Anne; Saraf, Sanatan; Piperdi, Bilal; van Brummelen, Emilie

    2017-05-01

    Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort. Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria included measurable disease, failure of standard therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 positivity was defined as expression in 1% or more of tumour cells by immunohistochemistry. Response was assessed based on investigator review using the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Primary endpoints were safety and tolerability, analysed in the all-patients-as-treated population, and objective response, analysed for the full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT02054806, and is ongoing but not recruiting participants. As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%]). Five (20%) patients reported grade 3 treatment-related adverse events. Three (12%) patients required dose interruption because of immune-related adverse events: one (4%) of 25 each had grade 3 rhabdomyolysis and grade 2 hypothyroidism; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema; and grade 2 infusion-related reaction. No treatment-related deaths or discontinuations occurred. Five (20

  5. Pleurectomy-decortication in malignant pleural mesothelioma: are different surgical techniques associated with different outcomes? Results from a multicentre study.

    Science.gov (United States)

    Marulli, Giuseppe; Breda, Cristiano; Fontana, Paolo; Ratto, Giovanni Battista; Leoncini, Giacomo; Alloisio, Marco; Infante, Maurizio; Luzzi, Luca; Paladini, Piero; Oliaro, Alberto; Ruffini, Enrico; Benvenuti, Mauro Roberto; Pariscenti, Gianluca; Spaggiari, Lorenzo; Casiraghi, Monica; Rusca, Michele; Carbognani, Paolo; Ampollini, Luca; Facciolo, Francesco; Leuzzi, Giovanni; Mucilli, Felice; Camplese, Pierpaolo; Romanello, Paola; Perissinotto, Egle; Rea, Federico

    2017-07-01

    The potential benefit of surgery for malignant pleural mesothelioma (MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the literature. The aim of this study was to evaluate the outcome after multimodality treatment of MPM involving different types of P/D and to analyse the prognostic factors. We reviewed 314 patients affected by MPM who were operated on in 11 Italian centres from 1 January 2007 to 11 October 2014. The characteristics of the population were male/female ratio: 3.7/1, and median age at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III disease was found following a pathological analysis in 62.3% of cases. A total of 162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was delivered in 39.2% of patients. Median overall survival time after surgery was 23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox) analysis, pathological Stage III-IV [ P  = 0.004, hazard ratio (HR):1.34; 95% CI: 1.09-1.64], EP/D and P/D ( P  = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P  = 0.01, HR: 1.52; 95% CI: 1.09-2.12) and pathological status T4 ( P  = 0.0003, HR: 1.38; 95% CI: 1.14-1.66) were found to be independent significant predictors of overall survival. Whether the P/D is extended or not, it shows similarly good outcomes in terms of early results and survival rate. In contrast, a partial pleurectomy, which leaves gross tumour behind, has no impact on survival.

  6. Physical function and health-related quality of life in patients undergoing surgical treatment for malignant pleural mesothelioma.

    Science.gov (United States)

    Tanaka, Takashi; Morishita, Shinichiro; Hashimoto, Masaki; Itani, Yusuke; Mabuchi, Satoshi; Kodama, Norihiko; Hasegawa, Seiki; Domen, Kazuhisa

    2017-08-01

    Malignant pleural mesothelioma (MPM) is a rare cancer that affects the thin cell wall lining of internal organs and structures. Studies have shown that patients with lung cancer have decreased pulmonary function and exercise capacity after pneumonectomy. However, to date, physical function and health-related quality of life (HRQOL) in surgically treated MPM patients have not been evaluated in detail. The aim of this study was to assess physical function and HRQOL of MPM patients following pleurectomy/decortication (P/D). The subjects were 22 MPM patients (20 men and 2 women) who completed P/D between December 2013 and March 2015. Physical function was assessed using handgrip strength and knee extensor strength tests, the 6-min walk distance (6MWD), and pulmonary function tests, including forced expiratory vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). HRQOL was assessed using the Medical Outcome Study 36-item Short Form Health Survey (SF-36). The handgrip strength (P < 0.05), 6MWD, FVC, and FEV1 values following P/D decreased significantly compared to baseline (P < 0.001 for each comparison). Additionally, scores of three of the eight SF-36 domains were significantly lower following P/D: physical functioning (P < 0.001), body pain (P = 0.002), and vitality (P = 0.005). 6MWD correlated role physical (P < 0.05) and vitality (P < 0.01). Significant correlations were also observed between FEV1 and physical functioning (P < 0.05) and social functioning (P < 0.05). Patients with MPM who completed P/D have decreased physical function and HRQOL. Following surgery, exercise capacity and pulmonary function decreased more than limb muscle strength. Physicians, nurses, and rehabilitation staff should note these findings, which may provide insight into the development of customized rehabilitation strategies for patients with MPM who completed P/D.

  7. Malignant Pleural Effusion

    Science.gov (United States)

    ... and make echoes. The echoes form a picture of body tissues called a sonogram . The picture can be printed to be looked at later. It is important ... use this content on your website or other digital platform? Our syndication services page shows you how. National Cancer Institute at the National Institutes of Health FOLLOW US ... ...

  8. Evaluation of the efficacy of the guideline on reading CT images of malignant pleural mesothelioma with reference CT films for improving the proficiency of radiologists.

    Science.gov (United States)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G; Akira, Masanori; Itoh, Harumi; Arakawa, Hiroaki; Ishikawa, Yuichi; Kumagai, Shinji; Kurumatani, Norio

    2013-01-01

    To assess the efficacy of the developed guideline on reading CT images of malignant pleural mesothelioma for improving radiologists' reading proficiency. Three radiologists independently read the CT films of 22 cases including definite mesothelioma and non-mesothelioma cases at two times before and after studying the malignant pleural mesothelioma CT Guideline. The sensitivity and specificity for mesothelioma were calculated and compared between the 1st and 2nd trials. The kappa statistics was examined for agreement with experts for mesothelioma probability and for mesothelioma features recorded by three radiologists. After studying the mesothelioma CT Guideline, the sensitivity for mesothelioma shown by the three radiologists at the 2nd trial was 100%, 100% and 80%, which were higher than 80%, 85% and 60% at the 1st trial, respectively. The average kappa for agreement between radiologists and experts on dichotomized mesothelioma probability were 0.69 (good) at the 2nd trial vs. 0.38 (fair) at the 1st trial. The average kappa for the agreement with experts for each of 7 features by three radiologists were 0.52-0.80 at the 2nd trial, which were significantly higher than 0.34-0.58 at the 1st trial (Wilcoxon Signed Rank Test: Preading CT images of mesothelioma, and may contribute to accurate diagnosis of mesothelioma. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma.

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    Meerang, Mayura; Bérard, Karima; Friess, Martina; Bitanihirwe, Byron K Y; Soltermann, Alex; Vrugt, Bart; Felley-Bosco, Emanuela; Bueno, Raphael; Richards, William G; Seifert, Burkhardt; Stahel, Rolf; Weder, Walter; Opitz, Isabelle

    2016-10-01

    Alterations of the tumor suppressor Neurofibromatosis type II (NF2) have been reported in about 40% of Malignant pleural mesothelioma (MPM) patients. NF2 (Merlin) deficiency leads to alterations of the Hippo pathway; resulting in activation of the oncogenic Yes Associated Protein-1 (YAP1). Our aim was to investigate the association between these alterations and clinical outcomes. Tissue microarrays composed of MPM tumors derived from 2 independent MPM cohorts were employed for this study. Immunohistochemical expression of Merlin, YAP1 and its target genes, Survivin and connective tissue growth factor (CTGF) were assessed in nuclear and cytoplasmic fractions. Cohort 1 was comprised of 145 patients intended to be treated with chemotherapy (CTX) followed by extrapleural pneumonectomy (EPP), thus both pre- and post-CTX tissues were available. Cohort 2 was comprised of 59 patients treated with EPP followed by intraoperative hyperthermic cisplatin and/or adjuvant CTX and/or radiotherapy. Marker expression was quantified by means of labeling index (%) for nuclear Survivin and by H-score for the other markers. The dichotomized marker expression was tested for the association with overall survival (OS) and freedom from recurrence (FFR). Kaplan-Meier survival curves revealed a significant association between low cytoplasmic Merlin expression in pre-induction CTX tissues of cohort 1 with shorter FFR (p = 0.02) and OS (p = 0.03). The same tendency was observed in the chemotherapy naïve tissues obtained during EPP of cohort 2. Low nuclear Merlin expression in post-CTX tissues (available from cohort 1 only) was associated with shorter FFR (p = 0.04) and OS (p = 0.05). High nuclear Survivin labeling indices in both pre- and post-CTX tissues of cohort 1 was associated with shorter FFR (p = 0.02). In cohort 2, this was associated with both FFR and OS (p = 0.046 and p = 0.002, respectively). In multivariate analysis, low expression of cytoplasmic Merlin remained an

  10. Quantitative analyses at baseline and interim PET evaluation for response assessment and outcome definition in patients with malignant pleural mesothelioma

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    Lopci, Egesta; Chiti, Arturo [Humanitas Research Hospital, Nuclear Medicine Department, Rozzano, Milan (Italy); Zucali, Paolo Andrea; Perrino, Matteo; Gianoncelli, Letizia; Lorenzi, Elena; Gemelli, Maria; Santoro, Armando [Humanitas Research Hospital, Oncology, Rozzano (Italy); Ceresoli, Giovanni Luca [Humanitas Gavazzeni, Oncology, Bergamo (Italy); Giordano, Laura [Humanitas Research Hospital, Biostatistics, Rozzano (Italy)

    2015-04-01

    Quantitative analyses on FDG PET for response assessment are increasingly used in clinical studies, particularly with respect to tumours in which radiological assessment is challenging and complete metabolic response is rarely achieved after treatment. A typical example is malignant pleural mesothelioma (MPM), an aggressive tumour originating from mesothelial cells of the pleura. We present our results concerning the use of semiquantitative and quantitative parameters, evaluated at the baseline and interim PET examinations, for the prediction of treatment response and disease outcome in patients with MPM. We retrospectively analysed data derived from 131 patients (88 men, 43 women; mean age 66 years) with MPM who were referred to our institution for treatment between May 2004 and July 2013. Patients were investigated using FDG PET at baseline and after two cycles of pemetrexed-based chemotherapy. Responses were determined using modified RECIST criteria based on the best CT response after treatment. Disease control rate, progression-free survival (PFS) and overall survival (OS) were calculated for the whole population and were correlated with semiquantitative and quantitative parameters evaluated at the baseline and interim PET examinations; these included SUV{sub max}, total lesion glycolysis (TLG), percentage change in SUV{sub max} (ΔSUV{sub max}) and percentage change in TLG (ΔTLG). Disease control was achieved in 84.7 % of the patients, and median PFS and OS for the entire cohort were 7.2 and 14.3 months, respectively. The log-rank test showed a statistically significant difference in PFS between patients with radiological progression and those with partial response (PR) or stable disease (SD) (1.8 vs. 8.6 months, p < 0.001). Baseline SUV{sub max} and TLG showed a statistically significant correlation with PFS and OS (p < 0.001). In the entire population, both ΔSUV{sub max} and ΔTLG were correlated with disease control based on best CT response (p < 0

  11. Role of postoperative radiotherapy in the management of malignant pleural mesothelioma. A propensity score matching of the SEER database

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    Abdel-Rahman, Omar [Ain Shams University, Clinical Oncology department, Faculty of medicine, Cairo (Egypt)

    2017-04-15

    This study assessed the prognostic impact of postoperative radiotherapy in patients with surgically resected malignant pleural mesothelioma (MPM). MPM patients diagnosed between 2000 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. A propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TNM stage, and type of surgery). A total of 2166 patients were identified. The median age was 60 years (range 25-85 years), and 469 patients received postoperative radiotherapy. Both before and after propensity score matching, overall survival (P < 0.0001 and P = 0.012, respectively) was better in the postoperative radiotherapy group. When the overall survival was stratified by histology, postoperative radiotherapy did not improve the survival in sarcomatoid histology patients both before and after matching (P = 0.424 and P = 0.281, respectively). In multivariate analysis of the matched population, not receiving postoperative radiotherapy did not correlate with worse survival (hazard ratio: 1.175; P = 0.12). Factors associated with worse survival include sarcomatoid histology, nodal positivity, and age ≥70. Evidence from this analysis is insufficient on its own to routinely recommend postoperative radiotherapy for surgically resected MPM. However, large-scale prospective clinical trials are warranted to further evaluate this intervention in nonsarcomatoid histology. (orig.) [German] In der vorliegenden Studie wurde der prognostische Einfluss der postoperativen Strahlentherapie bei Patienten mit chirurgisch reseziertem malignem Pleuramesotheliom (MPM) untersucht. In der SEER-Datenbank (Surveillance, Epidemiology, and End Results) wurden Patienten ermittelt, bei denen zwischen 2000 und 2013 die Diagnose eines MPM gestellt worden war. Unter Beruecksichtigung der Ausgangsmerkmale (Alter, Geschlecht, Ethnizitaet, Histologie, TNM-Stadium und Art des chirurgischen Eingriffs) wurde eine

  12. CT appearances of pleural tumours

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    Salahudeen, H.M. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)], E-mail: hmdsal@gmail.com; Hoey, E.T.D. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom); Department of Radiology, Papworth Hospital, Cambridge (United Kingdom); Robertson, R.J.; Darby, M.J. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)

    2009-09-15

    Computed tomography (CT) is the imaging technique of choice for characterizing pleural masses with respect to their location, composition, and extent. CT also provides important information regarding invasion of the chest wall and surrounding structures. A spectrum of tumours can affect the pleura of which metastatic adenocarcinoma is the commonest cause of malignant pleural disease, while malignant mesothelioma is the most common primary pleural tumour. Certain CT features help differentiate benign from malignant processes. This pictorial review highlights the salient CT appearances of a range of tumours that may affect the pleura.

  13. Vascular endothelial growth factor in diagnosis of pleural effusion

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    Nasr H. Khalil

    2017-01-01

    Conclusion: VEGF pleural fluid level could differentiate between malignant and non malignant effusion, while could not differentiate between tuberculous and nontuberculous, or between parapneumonic and nonparapneumonic exudative effusions.

  14. Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China.

    Science.gov (United States)

    Gao, Zhibin; Hiroshima, Kenzo; Wu, Xiaodong; Zhang, Jixian; Shao, Dichu; Shao, Huajiang; Yang, Hanqing; Yusa, Toshikazu; Kiyokawa, Takako; Kobayashi, Makio; Shinohara, Yasushi; Røe, Oluf D; Zhang, Xing; Morinaga, Kenji

    2015-10-01

    Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking. All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected. Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%. This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma. © 2015 Wiley Periodicals, Inc.

  15. Are the days of closed pleural biopsy over? Yes

    Directory of Open Access Journals (Sweden)

    Dharmesh Patel

    2015-01-01

    Full Text Available In the modern management of pleural diseases, thoracoscopy has a clear advantage over closed pleural biopsy. By way of its high yield, both in malignant pleural disease and pleural Tuberculosis – the two commonest cause of undiagnosed pleural effusion, thoracoscopy has the added advantage of faster symptom relief and offering effective pleurodesis. This makes it an attractive diagnostic and therapeutic procedure of choice and features high in the algorithms of many international guidelines on the approach to pleural diseases.

  16. Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced by Mycobacterium bovis BCG▿

    Science.gov (United States)

    Souza, Mariana C.; Penido, Carmen; Costa, Maria F. S.; Henriques, Maria Graças

    2008-01-01

    Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 × 105 bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-γ). Accordingly, in vivo IL-2 or IFN-γ neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ. PMID:18809659

  17. Minor regression and long-time survival (56 months) in a patient with malignant pleural mesothelioma under Viscum album and Helleborus niger extracts-a case report.

    Science.gov (United States)

    Werthmann, Paul G; Saltzwedel, Gerhard; Kienle, Gunver S

    2017-12-01

    Malignant pleural mesothelioma (MPM) is a rare cancer with a dismal prognosis. Viscum album extracts (VAE) have strong immune stimulatory properties, cytotoxic effects, can downregulate cancer genes and inhibit angiogenesis. VAE are often used as an adjunct treatment in cancer patients but have rarely been investigated in MPM. Helleborus niger extracts (HNE) have been used in anticancer therapy since antiquity, and also show tumor specific cytotoxic effects. We present a case of a 64-year old woman with epithelioid MPM of the right chest with node involvement (T2N1M0, stage III). Deciding against the recommended radio-chemotherapy, surgery and pleurodesis, she opted for an integrative treatment approach and was treated with VAE and HNE. After 6 weeks' treatment, the pleural and nodal MPM manifestations were reduced by about 15%. Subsequent tumor growth was slow, and the patient remained in good health, enabling her to remain physically active until shortly before her death 56 months after the initial diagnosis. This is a rare case of an MPM patient not receiving any standard anticancer treatment; it still shows an extraordinary long survival and good performance status. We presume that VAE and HNE might had an impact on this clinically relevant outcome and therefore should be further investigated in MPM.

  18. A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma.

    Science.gov (United States)

    Shimokawa, Mototsugu; Hasegawa, Seiki; Fukuoka, Kazuya; Okada, Morihito; Yokoi, Kohei; Tanaka, Fumihiro; Yamanaka, Takeharu; Daimon, Takashi; Nakano, Takashi

    2013-05-01

    A prospective multi-institutional study has been initiated in Japan to evaluate the feasibility of induction chemotherapy using pemetrexed plus cisplatin, followed by pleurectomy/decortication aimed at macroscopic complete resection in patients with resectable malignant pleural mesothelioma. The study was initiated on September 2012, for which 24 patients will be recruited over a period of 2 years. The primary endpoint is the macroscopic complete resection rate, regardless of the surgical technique employed (i.e. pleurectomy/decortication or extrapleural pneumonectomy). The secondary endpoints are the pleurectomy/decortication rate, macroscopic complete resection rate by pleurectomy/decortication, pulmonary function at 3 months after surgery, adverse events, treatment-related mortality, response rate to chemotherapy and 3-year overall survival rate.

  19. Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Di Salvo, Maurizio; Gambaro, Giuseppina; Pagella, Simonetta; Manfredda, Irene; Casadio, Caterina; Krengli, Marco (Radiotherapy, Univ. of Piemonte Orientale-Hospital Maggiore della Carit, Novara (Italy))

    2008-07-15

    Introduction. Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. Material and methods. Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. Results. After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). Discussion. The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.

  20. Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Ulger, Sukran; Cetin, Eren; Catli, Serap; Sarac, Hilal; Kilic, Diclehan; Bora, Huseyin

    2017-06-01

    To investigate high conformality on target coverage and the ability on creating strict lung dose limitation of intensity-modulated radiation therapy in malignant pleural mesothelioma. Twenty-four radiation therapy plannings were evaluated and compared with dosimetric outcomes of conformal radiation therapy and intensity-modulated radiation therapy. Hemithoracal radiation therapy was performed on 12 patients with a fraction of 1.8 Gy to a total dose of 50.4 Gy. All organs at risk were contoured. Radiotherapy plannings were differed according to the technique; conformal radiation therapy was planned with conventionally combined photon-electron fields, and intensity-modulated radiation therapy was planned with 7 to 9 radiation beam angles optimized in inverse planning. Strict dose-volume constraints were applied. Intensity-modulated radiation therapy was statistically superior in target coverage and dose homogeneity (intensity-modulated radiation therapy-planning target volume 95 mean 100%; 3-dimensional conformal radiation therapy-planning target volume 95 mean 71.29%, P = .0001; intensity-modulated radiation therapy-planning target volume 105 mean 11.14%; 3-dimensional conformal radiation therapy-planning target volume 105 mean 35.69%, P = .001). The dosimetric results of the remaining lung was below the limitations on intensity-modulated radiation therapy planning data (intensity-modulated radiation therapy-lung mean dose mean 7.5 [range: 5.6%-8.5%]; intensity-modulated radiation therapy-lung V5 mean 55.55% [range: 47%-59.9%]; intensity-modulated radiation therapy-lung V20 mean 4.5% [range: 0.5%-9.5%]; intensity-modulated radiation therapy-lung V13 mean 13.43% [range: 4.2%-22.9%]). With a complex and large target volume of malignant pleural mesothelioma, intensity-modulated radiation therapy has the ability to deliver efficient tumoricidal radiation dose within the safe dose limits of the remaining lung tissue.

  1. Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells

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    Mara A. Bonelli

    2017-08-01

    Full Text Available Malignant pleural mesothelioma (MPM is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16INK4a and p14ARF, deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991, a highly selective inhibitor of cyclin-dependent kinase (CDK 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM. All the MPM cell lines, as well as the primary cultures, were sensitive to palbociclib with a significant blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the expression of myc with a concomitant increased phosphorylation of AKT. Based on these results, we tested the efficacy of the combination of palbociclib with the PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the sequential association with PI3K inhibitors synergistically hampered cell proliferation and strongly increased the percentage of senescent cells. In addition, AKT activation was repressed while p53 and p21 were up-regulated. Interestingly, two cycles of sequential drug administration produced irreversible growth arrest and senescent phenotype that were maintained even after drug withdrawal. These findings suggest that the sequential association of palbociclib with PI3K inhibitors may represent a valuable therapeutic option for the treatment of MPM.

  2. Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Cornelissen, Robin; Hegmans, Joost P J J; Maat, Alexander P W M; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; Hendriks, Rudi W; Hoogsteden, Henk C; Aerts, Joachim G J V

    2016-05-01

    We demonstrated previously that autologous tumor lysate-pulsed dendritic cell-based immunotherapy in patients with malignant pleural mesothelioma is feasible, well-tolerated, and capable of inducing immunologic responses against tumor cells. In our murine model, we found that reduction of regulatory T cells with metronomic cyclophosphamide increased the efficacy of immunotherapy. To assess the decrease in number of peripheral blood regulatory T cells during combination therapy of low-dose cyclophosphamide and dendritic cell immunotherapy and determine the induction of immunologic responses with this treatment in patients with mesothelioma. Ten patients with malignant pleural mesothelioma received metronomic cyclophosphamide and dendritic cell-based immunotherapy. During the treatment, peripheral blood mononuclear cells were analyzed for regulatory T cells and immunologic responses. Administration of dendritic cells pulsed with autologous tumor lysate combined with cyclophosphamide in patients with mesothelioma was safe, the only side effect being moderate fever. Dendritic cell vaccination combined with cyclophosphamide resulted in radiographic disease control in 8 of the 10 patients. Overall survival was promising, with 7 out of 10 patients having a survival of greater than or equal to 24 months and two patients still alive after 50 and 66 months. Low-dose cyclophosphamide reduced the percentage of regulatory T cells of total CD4 cells in peripheral blood from 9.43 (range, 4.34-26.10) to 4.51 (range, 0.27-10.30) after 7 days of cyclophosphamide treatment (P = 0.02). Consolidation therapy with autologous tumor lysate-pulsed dendritic cell-based therapy and simultaneously reducing the tumor-induced immune suppression is well-tolerated and shows signs of clinical activity in patients with mesothelioma. Clinical trial registered with www.clinicaltrials.gov (NCT 01241682).

  3. Fatores clínicos e anatomopatológicos que influenciam a sobrevida de pacientes com câncer de mama e derrame pleural neoplásico Clinical and pathological factors influencing the survival of breast cancer patients with malignant pleural effusion

    Directory of Open Access Journals (Sweden)

    Giovana Tavares dos Santos

    2012-08-01

    Full Text Available OBJETIVO: O objetivo deste estudo foi identificar os fatores clínicos e anatomopatológicos que possam influenciar o prognóstico de pacientes com câncer de mama e sintomas clínicos de derrame pleural neoplásico. MÉTODOS: Trata-se de um estudo clínico de coorte, no qual foram analisados os prontuários médicos de pacientes que receberam diagnóstico de derrame pleural neoplásico entre 2006 e 2010. Por meio da análise dos prontuários, identificamos as pacientes com história de câncer de mama. Para essas pacientes, coletamos dados anatomopatológicos relacionados ao tumor primário e dados citopatológicos relacionados à metástase pleural. RESULTADOS: Das 145 pacientes avaliadas, 87 (60% apresentaram, no exame citológico, resultado positivo para células neoplásicas no líquido pleural; além disso, 119 (82% apresentaram tipo histológico ductal. O fenótipo triplo-negativo foi observado em 25 pacientes (17%, as quais apresentaram o pior prognóstico, com queda acentuada na curva de sobrevida. Das 25 pacientes, 20 (80% evoluíram a óbito durante o período de seguimento (até junho de 2011. A sobrevida média após a identificação de derrame pleural neoplásico foi de 6 meses. CONCLUSÕES: Em pacientes com câncer de mama triplo-negativo e exame citológico com resultado positivo para células neoplásicas no líquido pleural, o prognóstico é ruim e a sobrevida é menor.OBJECTIVE: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. METHODS: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related

  4. STUDY OF 200 CASES OF PLEURAL FLUID

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    Ramakrishna R

    2016-09-01

    Full Text Available BACKGROUND We have studied 200 patients of pleural fluid presenting to our tertiary care centre. Presence of cases of pleural fluid is a common presentation both in pulmonary and extrapulmonary diseases. We analysed the patients having both exudates and transudates and studied the results. MATERIALS AND METHODS We selected patients above 20 years of age and classified the patients with pleural fluid as having transudates and exudates. We studied the causes of transudates and exudates. A total of 200 patients are studied in this prospective study. Diagnosis of pleural exudates is made on the basis of Light’s criteria, chest x-ray, pleural fluid analysis, CT scan in selected patients, sputum examination, bronchoscopy and bronchial washings. Moribund and non-cooperative patients and HIV positives were excluded from the study. RESULTS Among the 200 patients, 91% have exudates. 9% have transudates by Light’s criteria. Tuberculosis is the commonest cause of effusions (64.83% followed by malignancy (13.73% and sympneumonic or parapneumonic effusions (9.89%. Pleural effusions occurred predominantly in males. Prevalence of diabetes Mellitus among cases of tuberculous pleural effusions is 13.56%. Tuberculous effusions are predominantly right-sided. CONCLUSION Predominant cases of pleural fluid are exudates. Commonest cause of pleural effusion is Tuberculosis followed by malignancy both pulmonary and extrapulmonary and sym. and parapneumonic effusions. Prevalence of Diabetes among Tuberculous pleural effusion cases is more or less same as in general population. Cough, expectoration fever, chest pain and breathlessness are the common symptoms occurring in three fourths of the patients of tuberculous pleural effusion. Most of the cases of Tuberculous effusion are above 30 years of age. In the diagnosis of tuberculous pleural effusion, Pleural fluid ADA is very important. Pleural fluid cytology, pleural biopsy, bronchoscopy, bronchial washings and sputum

  5. IMPAIRED NEOVASCULARIZATION AND REDUCED CAPILLARY SUPPLY IN THE MALIGNANT VERSUS NON-MALIGNANT COURSE OF EXPERIMENTAL RENOVASCULAR HYPERTENSION

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    Andrea Hartner

    2016-08-01

    Full Text Available Malignant hypertension develops in some cases of hypertension but not in others. We hypothesized that an impaired neovascularization and a reduced capillary supply characterizes the malignant course of experimental hypertension. Two-kidney, one-clip renovascular hypertension was induced in rats; controls (sham were sham operated. To distinguish malignant hypertension from non-malignant hypertension, we considered two factors: weight loss, and the number of typical vascular lesions (onion skin lesions and fibrinoid necroses per kidney section of the nonclipped kidney. Animals in the upper half for both criteria were defined as malignant hypertensives. After 5 weeks, mean arterial blood pressure was elevated to the same degree in malignant hypertension and non-malignant hypertension whereas plasma renin and aldosterone were significantly higher in malignant hypertensives. The expression of plasminogen activator inhibitor-1 was elevated (up to 14-fold in non-malignant but significantly more increased (up to 36-fold in malignant hypertensive rats, compared to sham. As a bioassay for neovascularization, the area of granulation tissue ingrowth in polyvinyl discs (implanted subcutaneously was reduced in malignant hypertension compared to non-malignant hypertension and sham, while there was no difference between non-malignant hypertension and sham. The number of renal and left ventricular capillaries was significantly lower in malignant hypertension compared to non-malignant hypertension, as was the number of proliferating endothelial cells. We conclude that an impaired neovascularization and capillarization occurs in malignant renovascular hypertension but not in the non-malignant course of the disease despite comparable blood pressure levels. This might contribute to the unique vascular lesions and progressive target organ damage observed in malignant hypertension.

  6. Extended pleurectomy decortication for malignant pleural mesothelioma in the elderly: the need for an inclusive yet selective approach.

    Science.gov (United States)

    Sharkey, Annabel Jane; Bilancia, Rocco; Tenconi, Sara; Nakas, Apostolos; Waller, David A

    2017-11-01

    The median age at diagnosis of patients with pleural mesothelioma in the UK is 73 years. Recent series have shown the feasibility of extended pleurectomy decortication in the elderly, but with continuing debate about the efficacy of this treatment, we reviewed our experience to identify more detailed selection criteria. We reviewed prospectively collected data on all patients from 1999 to 2016 undergoing extended pleurectomy decortication. We compared clinical and pathological outcomes and survival data from patients 70 years and older (≥70 years) with those younger than 70 years (mesothelioma, in the elderly, a more rigorous preoperative evaluation of nodal disease and an additional assessment of fitness for adjuvant chemotherapy are recommended.

  7. Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England.

    Science.gov (United States)

    Damhuis, R A; Khakwani, A; De Schutter, H; Rich, A L; Burgers, J A; van Meerbeeck, J P

    2015-08-01

    Pleural mesothelioma has a dismal prognosis and is refractory to local treatment. Combination chemotherapy can increase median survival by several months and was gradually introduced in the period 2003-2006. Elderly patients may be unfit for chemotherapy but little is known about age-related treatment practice. To determine treatment patterns and current survival outcome, three large population-based registries were queried in a uniform manner. Data from the Belgian Cancer Registry, the Netherlands Cancer Registry and the UK National Lung Cancer Audit were analyzed for patients diagnosed with pleural mesothelioma since 2007. Treatment patterns and survival rates were compared between countries and age-groups. The study included 900, 2306 and 5808 patients from Belgium, the Netherlands and England, respectively. Fifty-nine percent of patients were 70 years or older and 84% were men. Chemotherapy use decreased with advancing age and was used more often in Belgium (60%) than in the Netherlands (41%) and England (37%). For patients aged 70-79 years, chemotherapy use was 55%, 36% and 34% in the respective countries. Median survival was 10.7 months in Belgium versus 9.2 months for the Netherlands and 9.5 months for England. Survival rates decreased with advancing age. On average, median survival was 5.6 months longer for patients treated with chemotherapy, irrespective of age. Combined analysis of data from three countries with high mesothelioma rates demonstrates that chemotherapy has become standard treatment for younger patients. Elderly patients currently account for more than half of all cases and less toxic treatment options will be required to improve their prospects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival.

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    Paajanen, Juuso; Laaksonen, Sanna; Ilonen, Ilkka; Wolff, Henrik; Husgafvel-Pursiainen, Kirsti; Kuosma, Eeva; Ollila, Hely; Myllärniemi, Marjukka; Vehmas, Tapio

    2018-02-01

    Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. As part of our study that included all MPM patients diagnosed in Finland 2000-2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients.

    Science.gov (United States)

    Shin, Saeam; Kim, Juwon; Kim, Yoonjung; Cho, Sun-Mi; Lee, Kyung-A

    2017-10-26

    EGFR mutation is an emerging biomarker for treatment selection in non-small-cell lung cancer (NSCLC) patients. However, optimal mutation detection is hindered by complications associated with the biopsy procedure, tumor heterogeneity and limited sensitivity of test methodology. In this study, we evaluated the diagnostic utility of real-time PCR using malignant pleural effusion samples. A total of 77 pleural fluid samples from 77 NSCLC patients were tested using the cobas EGFR mutation test (Roche Molecular Systems). Pleural fluid was centrifuged, and separated cell pellets and supernatants were tested in parallel. Results were compared with Sanger sequencing and/or peptide nucleic acid (PNA)-mediated PCR clamping of matched tumor tissue or pleural fluid samples. All samples showed valid real-time PCR results in one or more DNA samples extracted from cell pellets and supernatants. Compared with other molecular methods, the sensitivity of real-time PCR method was 100%. Concordance rate of real-time PCR and Sanger sequencing plus PNA-mediated PCR clamping was 98.7%. We have confirmed that real-time PCR using pleural fluid had a high concordance rate compared to conventional methods, with no failed samples. Our data demonstrated that the parallel real-time PCR testing using supernatant and cell pellet could offer reliable and robust surrogate strategy when tissue is not available.

  10. Pleural fluid characteristics of pleuropulmonary paragonimiasis masquerading as pleural tuberculosis.

    Science.gov (United States)

    Hwang, Ki-Eun; Song, Hyo-Yeop; Jung, Jae-Wan; Oh, Su-Jin; Yoon, Kwon-Ha; Park, Do-Sim; Jeong, Eun-Taik; Kim, Hak-Ryul

    2015-01-01

    Pleuropulmonary paragonimiasis produces no specific symptoms or radiologic findings, allowing for the possibility of misdiagnosis. We evaluated the specific clinical and pleural fluid features of pleuropulmonary paragonimiasis masquerading as pleural tuberculosis. We retrospectively analyzed the clinical and radiologic characteristics of 20 patients diagnosed with pleuropulmonary paragonimiasis between 2001 and 2011. In total, 17 patients presented with respiratory symptoms, including dyspnea (30%), hemoptysis (20%), cough (20%), and pleuritic chest pain (15%). Chest radiographs revealed intrapulmonary parenchymal lesions, including air-space consolidation (30%), nodular opacities (20%), cystic lesions (15%), ground-glass opacities (10%), and pneumothorax (5%). A pleural fluid examination revealed eosinophilia, low glucose levels, and high lactate dehydrogenase (LDH) levels in 87%, 76%, and 88% of the patients, respectively. These traits helped to distinguish pleuropulmonary paragonimiasis from other pleural diseases such as parapneumonic effusion, malignancy, and pleural tuberculosis. Pleuropulmonary paragonimiasis is often initially misdiagnosed as other pleural diseases. Therefore, it is important to establish the correct diagnosis. In patients with unexplained pleural effusion living in paragonimiasis-endemic areas, pleural fluid obtained by thoracentesis should be examined to distinguish pleuropulmonary paragonimiasis. When marked eosinophilia, high LDH levels, and low glucose levels are identified in pleural fluid, physicians could consider a diagnosis of pleuropulmonary paragonimiasis.

  11. The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Ak, Guntulu; Metintas, Selma; Akarsu, Muhittin; Metintas, Muzaffer

    2015-07-09

    We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma. One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy. The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second-line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 ± 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 ± 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 ± 0.99 months (95% CI: 9.06-12.94) for group 1 and 11.0 ± 1.52 months (95% CI: 8.02-13.97) for group 2 (Log-Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 ± 0.61 months for group I and 6.0 ± 1.56 months for group II (Log-Rank: 0.522; p = 0

  12. Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery.

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    Frischknecht, Lukas; Meerang, Mayura; Soltermann, Alex; Stahel, Rolf; Moch, Holger; Seifert, Burkhardt; Weder, Walter; Opitz, Isabelle

    2015-06-01

    Survival and response to platinum-based induction chemotherapy are heterogeneous among patients with malignant pleural mesothelioma. The aim of the present study was to assess the prognostic role of DNA repair markers, such as excision repair cross-complementation group 1 and ribonucleotide reductase M1, in multimodally treated patients with malignant pleural mesothelioma. Tumor tissue of a malignant pleural mesothelioma cohort (n = 107) treated with platinum/gemcitabine (n = 46) or platinum/pemetrexed (n = 61) induction chemotherapy followed by extrapleural pneumonectomy was assembled on a tissue microarray. Immunohistochemical expression of excision repair cross-complementation group 1 (nuclear) and ribonucleotide reductase M1 (nuclear and cytoplasmic) was assessed for its prognostic impact (association with overall survival or freedom from recurrence). Patients with high nuclear ribonucleotide reductase M1 expression before chemotherapy showed significantly longer freedom from recurrence (P = .03). When specifically analyzed in the subgroup of patients receiving platinum/gemcitabine followed by extrapleural pneumonectomy, high nuclear ribonucleotide reductase M1 was associated with prolonged freedom from recurrence (P = .03) and overall survival (P = .02). Low excision repair cross-complementation group 1 expression in prechemotherapy tumor tissues was associated with significantly longer freedom from recurrence (P = .04). Nuclear ribonucleotide reductase M1 and excision repair cross-complementation group 1 were independent prognosticators of freedom from recurrence in addition to pT stage in multivariate analysis. In the present study, nuclear ribonucleotide reductase M1 and excision repair cross-complementation group 1 expression were identified as independent prognosticators for freedom from recurrence of malignant pleural mesothelioma in patients undergoing induction chemotherapy followed by extrapleural pneumonectomy. Copyright © 2015 The American

  13. The impact of lymph node station on survival in 348 patients with surgically resected malignant pleural mesothelioma: implications for revision of the American Joint Committee on Cancer staging system.

    Science.gov (United States)

    Flores, Raja M; Routledge, Tom; Seshan, Venkatraman E; Dycoco, Joseph; Zakowski, Maureen; Hirth, Yael; Rusch, Valerie W

    2008-09-01

    The propensity of malignant pleural mesothelioma to metastasize to N1 or N2 nodes and their corresponding prognostic value is unclear. The American Joint Committee on Cancer staging system groups N1 and N2 disease together as stage III. The goal of this study was to define the prognostic value of specific nodal stations. Patients with malignant pleural mesothelioma who underwent resection were identified from an institutional database. Nodal stations were defined by the American Joint Committee on Cancer lung cancer node map classification. Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. From 1990 to 2006, 348 patients were identified: 279 men and 69 women with a median age of 67 years (range 26-85 years). Extrapleural pneumonectomy was performed in 223 cases, and pleurectomy/decortication was performed in 125 cases. Survival differences (P gender (hazard ratio 1.4, P < .01). This study confirms a preferential pattern of drainage of malignant pleural mesothelioma to N2 rather than N1 lymph nodes, but suggests that N1 only nodal involvement should be classified as lower stage disease. Multiple N2 nodal site involvement could potentially be classified as higher stage disease than single station N2. Our results emphasize the need for larger, confirmatory multicenter studies that could lead to revision of the current staging system.

  14. Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study.

    Science.gov (United States)

    Ghanim, B; Klikovits, T; Hoda, M A; Lang, G; Szirtes, I; Setinek, U; Rozsas, A; Renyi-Vamos, F; Laszlo, V; Grusch, M; Filipits, M; Scheed, A; Jakopovic, M; Samarzija, M; Brcic, L; Stancic-Rokotov, D; Kern, I; Rozman, A; Dekan, G; Klepetko, W; Berger, W; Glasz, T; Dome, B; Hegedus, B

    2015-03-03

    Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

  15. Is less also better? A single-institution experience on treatment of early stage Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Bertoglio, P; Ambrogi, M C; Chella, A; Aprile, V; Dini, P; Korasidis, S; Fanucchi, O; Mussi, A

    2017-07-01

    No clear evidence of which surgical procedure should be performed for early stage mesothelioma is available to date. We analyzed our 10-year experience in the treatment of early stage mesothelioma with surgery and Hyperthermic IntraTHOracic Chemotherapy. We retrospectively analyzed all cases of histologically proven epithelioid or biphasic IMIG stage I and II mesothelioma that we operated between 2005 and 2014. We performed an open pleurectomy and partial decortication of any visible lesion on the visceral pleura in all cases and both diaphragm and pericardium were always spared; Hyperthermic IntraTHOracic Chemotherapy was ran using Cisplatin 80 mg/m 2 and Doxorubicin 25 mg/m 2 at a target temperature of 42.5 °C for 60 min. We operated on 26 patients (23 male and 3 female); epithelioid tumor was diagnosed in 23 cases. Twelve patients were in IMIG stage I and 14 in IMIG stage II; median overall survival for all patients, stage I and II were 35.6, 46 and 23 months respectively and disease free survival was 18, 18 and 16 months respectively. Our results for stage I were better than those reported in literature and were similar for stage II. We observe no 30- and 90- mortality and the rate of severe complication (all CTCAE stage 3) were 30%; the median postoperative stay was 7.5 days. Our lung sparing approach for the treatment of pleural mesothelioma in early stages allows promising long term outcomes with a complete sparing of pulmonary and diaphragmatic function. Larger studies are needed to confirm our good results. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  16. Effect of Increasing Experience on Dosimetric and Clinical Outcomes in the Management of Malignant Pleural Mesothelioma With Intensity-Modulated Radiation Therapy

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    Patel, Pretesh R., E-mail: patel073@mc.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Cancer Center Biostatistics, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Miles, Edward F. [Naval Medical Center, Portsmouth, Virginia (United States); D' Amico, Thomas A.; Harpole, David [Department of Surgery, Division of Thoracic Surgery, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-05-01

    Purpose: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Methods and Materials: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Results: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. Conclusions: With increasing experience, target volume coverage improved and dose to the

  17. Pleural effusion: Role of pleural fluid cytology, adenosine deaminase level, and pleural biopsy in diagnosis

    Science.gov (United States)

    Biswas, Biswajit; Sharma, Sudershan Kumar; Negi, Rameshwar Singh; Gupta, Neelam; Jaswal, Virender Mohan Singh; Niranjan, Narsimhalu

    2016-01-01

    Objective: The present study is designed to evaluate the role of pleural fluid analysis in diagnosing pleural diseases and to study the advantages and disadvantages of thoracocentasis and pleural biopsy. Materials and Methods: We prospectively included 66 consecutive indoor patients over a duration of 1 year. Pleural fluid was collected and cytological smears were made from the fluid. Plural biopsy was done in the same patient by Cope needle. Adequate pleural biopsy tissue yielding specific diagnosis was obtained in 47 (71.2%) cases. Results: Tuberculosis was the commonest nonneoplastic lesion followed by chronic nonspecific pleuritis comprising 60% and 33.3% of the nonneoplastic cases respectively and tuberculosis was predominantly diagnosed in the younger age group. Majority (70.8%) of malignancy cases were in the age group of >50-70. Adenocarcinoma was found to be the commonest (66.7%) malignant neoplasm in the pleurae followed by small-cell carcinoma (20.8%). Conclusion: Pleural biopsy is a useful and minimally invasive procedure. It is more sensitive and specific than pleural fluid smears. PMID:27756990

  18. Pleural effusion: Role of pleural fluid cytology, adenosine deaminase level, and pleural biopsy in diagnosis

    Directory of Open Access Journals (Sweden)

    Biswajit Biswas

    2016-01-01

    Full Text Available Objective: The present study is designed to evaluate the role of pleural fluid analysis in diagnosing pleural diseases and to study the advantages and disadvantages of thoracocentasis and pleural biopsy. Materials and Methods: We prospectively included 66 consecutive indoor patients over a duration of 1 year. Pleural fluid was collected and cytological smears were made from the fluid. Plural biopsy was done in the same patient by Cope needle. Adequate pleural biopsy tissue yielding specific diagnosis was obtained in 47 (71.2% cases. Results: Tuberculosis was the commonest nonneoplastic lesion followed by chronic nonspecific pleuritis comprising 60% and 33.3% of the nonneoplastic cases respectively and tuberculosis was predominantly diagnosed in the younger age group. Majority (70.8% of malignancy cases were in the age group of >50-70. Adenocarcinoma was found to be the commonest (66.7% malignant neoplasm in the pleurae followed by small-cell carcinoma (20.8%. Conclusion: Pleural biopsy is a useful and minimally invasive procedure. It is more sensitive and specific than pleural fluid smears.

  19. Thymidylate Synthase and Folyl-polyglutamate synthase (FPGS) Are Not Clinically Useful Markers of Response to Pemetrexed [Pem] in Patients with Malignant Pleural Mesothelioma [MPM

    Science.gov (United States)

    Schwed Lustgarten, Daniel E.; Deshpande, Charuhas; Aggarwal, Charu; Wang, Liang-Chuan; Saloura, Vassiliki; Vachani, Anil; Wang, Li-Ping; Litzky, Leslie; Feldman, Michael; Creaney, Jeanette; Nowak, Anna K.; Langer, Corey; Inghilleri, Simona; Stella, Giulia; Albelda, Steven M.

    2013-01-01

    Purpose Thymidylate synthase (TS) is a potential predictor of outcome after pemetrexed (Pem) in patients with malignant pleural mesothelioma (MPM), and assays measuring TS levels are commercially marketed. The goal of this study was to further evaluate the value of TS and to study another potential biomarker of response, the enzyme, folyl-polyglutamate synthase (FPGS), which activates Pem intracellularly. Patients and Methods Levels of TS and FPGS were semi-quantitatively determined immunohistochemically using H-scores on tissue samples from 85 MPM patients receiving Pem as primary therapy. H-score was correlated with radiographic disease control rate (DCR), time to progression (TTP) and overall survival (OS). In addition, expression levels of TS and FPGS in MPM cell lines were determined using immunoblotting and correlated with their sensitivity to Pem-induced cell death. Results H-scores from patients with disease control versus progressive disease showed extensive overlap. There were no significant correlations of DCR, TTP, or OS to either TS levels (p = 0.73, 0.93, and 0.59, respectively), FPGS levels (p = 0.95, 0.77 and 0.43 respectively) or the ratio of FPGS/TS using the median scores of each test as cutoffs. There was no correlation between TS or FPGS expression and chemosensitivity of mesothelioma cells to Pem in vitro. Conclusions Although previous retrospective data suggest that TS and FPGS expression might be potential markers of Pem efficacy in MPM, our data indicate these markers lack sufficient predictive value in individual patients and should not be used to guide therapeutic decisions in the absence of prospective studies. PMID:23486267

  20. Pretreatment serum C-reactive protein levels predict benefit from multimodality treatment including radical surgery in malignant pleural mesothelioma: a retrospective multicenter analysis.

    Science.gov (United States)

    Ghanim, Bahil; Hoda, Mir Alireza; Winter, Max-Paul; Klikovits, Thomas; Alimohammadi, Arman; Hegedus, Balazs; Dome, Balazs; Grusch, Michael; Arns, Madeleine; Schenk, Peter; Pohl, Wolfgang; Zielinski, Christoph; Filipits, Martin; Klepetko, Walter; Berger, Walter

    2012-08-01

    To evaluate the prognostic and predictive relevance of pretreatment serum C-reactive protein (CRP) in malignant pleural mesothelioma (MPM) patients. MPM is a rare but aggressive disease with poor treatment outcome. Therapeutic decision is challenging, and predictive biomarkers for better treatment stratification are urgently needed. Clinical data, including survival and pretreatment CRP levels, were retrospectively collected from 115 patients with histologically proven MPM. Patients with any evidence for infectious disease were excluded. The association between CRP levels and survival was analyzed using Cox models adjusted for clinical and pathological factors. Median pretreatment CRP of all patients was 1.19 mg/dL (range: 0.00-22.62 mg/dL). Patients with elevated CRP levels (≥1 mg/dL; n = 62, 53.9%) had a significantly shorter overall survival compared with those with normal CRP (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.82-4.33; P < 0.001). In multivariate survival analyses, elevated CRP was confirmed as an independent prognostic factor in MPM (HR 2.07, 95% CI 1.23-3.46; P = 0.01). Most interestingly, we observed a significant interaction between CRP and treatment modality (P < 0.001). Among patients with normal CRP levels, radical tumor resection within multimodality therapy was associated with distinctly prolonged overall survival when compared with treatment protocols without surgery (HR 7.26, 95% CI 3.40-15.49; P < 0.001). In contrast among patients with elevated CRP, no survival benefit was achieved by radical surgery within multimodality approaches (HR 0.911, 95% CI 0.53-1.58; P = 0.74). Our results suggest that multimodality regimens including radical resection increase survival selectively in MPM patients with normal pretreatment serum CRP levels.

  1. A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.

    Science.gov (United States)

    Nowak, A K; Cook, A M; McDonnell, A M; Millward, M J; Creaney, J; Francis, R J; Hasani, A; Segal, A; Musk, A W; Turlach, B A; McCoy, M J; Robinson, B W S; Lake, R A

    2015-12-01

    Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry. Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival. ACTRN12609000294257. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Role of doxycycline to resolve different types of non-malignant lung and pleural pathology: The results of a pilot observation

    Directory of Open Access Journals (Sweden)

    Parthasarathi Bhattacharyya

    2015-01-01

    Full Text Available Background: Lung lesions may develop from tissue reactions to known or unknown stimuli and present with different morphological descriptions. The pathogenesis may be induced and maintained by different bioactive substances, of which, the upregulation matrix metalloproteinases (MMPs play a vital role. Inhibition of the MMPs, therefore, may be a prospective mode of therapy for such lesions. Materials and Methods: A number of patients with lung lesions of different morphologies and presentations were treated empirically with long-term oral doxycycline (100 mg BID upon exclusion of malignancy and infection in an open, single-arm, prospective, observational pilot study. The effect of the treatment was recorded on serial x-rays/computed tomography (CT scans and the impact of treatment was measured with a visual analog scale (VAS or a Likert-like scale. Furthermore, six independent pulmonologists′ opinion (expressed on a ′0′ to ′100′ scale were pooled with regard to the significance and the expectedness of such a change. Results: Twenty-six patients (mean age 49.33 years and male: female ratio = 10:3 with different types of pulmonary parenchymal/pleural lesions were treated with long-term oral doxycycline for a mean duration of 386.88 days related to the available radiological comparison. They showed a mean improvement of 3.99 on the Likert-like scale and 78% on the VAS scale. The mean significance of the change was 83.33%, with a mean expectedness of 18% as per the pooled opinion of the pulmonologists. Inference: The significant and unexpected resolution of different tissue lesions from long-term doxycycline appears to be a novel observation. This needs proper scientific validation.

  3. TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.

    Science.gov (United States)

    Uramoto, Hidetaka; Onitsuka, Takamitsu; Shimokawa, Hidehiko; Hanagiri, Takeshi

    2010-10-01

    Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non-SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment.

  4. Adjuvant intensity-modulated proton therapy in malignant pleural mesothelioma. A comparison with intensity-modulated radiotherapy and a spot size variation assessment

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    Lorentini, S. [Agenzia Provinciale per la Protonterapia (ATreP), Trento (Italy); Padova Univ. (Italy). Medical Physics School; Amichetti, M.; Fellin, F.; Schwarz, M. [Agenzia Provinciale per la Protonterapia (ATreP), Trento (Italy); Spiazzi, L. [Brescia Hospital (Italy). Medical Physics Dept.; Tonoli, S.; Magrini, S.M. [Brescia Hospital (Italy). Radiation Oncology Dept.

    2012-03-15

    Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT. We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions. IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D{sub mean} reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V{sub 20} reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints. Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 x 3 mm (up to 9 x 9 mm) does not compromise dosimetric results and allows a shorter delivery time.

  5. Role of protein kinase C β and vascular endothelial growth factor receptor in malignant pleural mesothelioma: Therapeutic implications and the usefulness of Caenorhabditis elegans model organism

    Directory of Open Access Journals (Sweden)

    Sivakumar Loganathan

    2011-01-01

    Full Text Available Purpose: To examine the role of both protein kinase C (PKC-β and vascular endothelial growth factor receptor (VEGFR-2 in malignant pleural mesothelioma (MPM using respective inhibitors, enzastaurin and KRN633. Materials and Methods: MPM cell lines, control cells, and a variety of archived MPM tumor samples were used to determine the protein expression levels of PKC-β, VEGFR-2, VEGF, and p-AKT. Effects of enzastaurin and KRN633 on phosphorylation status of key signaling molecules and viability of the mesothelioma cells were determined. The common soil nematode, Caenorhabditis elegans, was treated with enzastaurin to determine its suitability to screen for highly potent kinase inhibitors. Results: PKC-β1, PKC-β2 and VEGFR-2/KDR were overexpressed in MPM cell lines and MPM tumor tissues. Enzastaurin treatment resulted in significant loss in viability of VEGF induced cell proliferation; however, the effect of KRN633 was much less. Enzastaurin also dramatically decreased the phosphorylation of PKC-β, its downstream target p-AKT, and surprisingly, the upstream VEGFR-2. The combination of the two drugs at best was additive and similar results were obtained with respect to cell viability. Treatment of C. elegans with enzastaurin resulted in clear phenotypic changes and the worms were hypermotile with abnormal pattern and shape of eggs, suggesting altered fecundity. Conclusions: PKC-β1 and VEGFR-2 are both excellent therapeutic targets in MPM. Enzastaurin was better at killing MPM cells than KRN633 and the combination lacked synergy. In addition, we show here that C. elegans can be used to screen for the next generation inhibitors as treatment with enzastaurin resulted in clear phenotypic changes that could be assayed.

  6. Update on pleural diseases - 2007

    Directory of Open Access Journals (Sweden)

    Bishay Ayman

    2007-01-01

    Full Text Available Background : New information is available on pleural diseases. The authors selected articles to make recommendations on diagnostic and treatment aspects of pleural diseases. Materials and Methods: Eleven articles published in the English language between 2004 and 2007 were chosen. The basis of selection of the articles was the impact on daily practice, change in prior thinking of a disease process or specific treatment modality, as well as proper design and execution of the study. 5-amino-laevulinic acid with fluorescent light combined with white light may allow further diagnostic yield in undiagnosed pleural disease. FDG-PET may allow prognostication of patients with pleural tumors. Utilizing ultrasound by trained Emergency Department physicians is a rapid and effective technique to evaluate non-traumatic pleural effusions in symptomatic patients. Serum osteopontin levels may distinguish patients exposed to asbestos with benign disease from those with pleural mesothelioma. Administration of streptokinase in patients with empyema does not need for surgical drainage, length of hospital stay, or mortality as compared to conventional treatment with chest tube drainage and intravenous antibiotics. Silver nitrate may be an alternative agent to talc for producing pleurodesis. Routine use of graded talc (50% particles greater than 25 microns is recommended to reduce the morbidity associated with talc pleurodesis. Study design does not permit us to conclude that aspiration of spontaneous pneumothorax is as effective as chest tube drainage. Pleural catheter may prove to be an important palliative modality in treating debilitated patients or patients with trapped lung who show symptomatic improvement with drainage; however, at the present time, these catheters cannot be considered a first line treatment option for patients with malignant pleural effusion. One of the studies reviewed showed no significant difference in tract metastasis in patients with

  7. Significance of pleural effusion in neuroblastoma.

    Science.gov (United States)

    Gupta, Himesh; Conrad, John; Khoury, Joseph D; McGregor, Lisa M; Krasin, Matthew J; Dome, Jeffrey S; Santana, Victor M; Davidoff, Andrew M

    2007-12-01

    Pleural effusion is uncommon at diagnosis of neuroblastoma in children. Because the presence of malignant cells in pleural fluid may significantly change the management and outcome of patients with neuroblastoma, we retrospectively analyzed a cohort of neuroblastoma patients who presented with pleural effusion at the time of diagnosis to determine the incidence, presentation, stage, treatment, and outcome of these patients. We reviewed the presenting features of 295 patients with the diagnosis of neuroblastoma who received treatment at St. Jude Children's Research Hospital between 1991 and 2005. Patients were chosen for further analysis if pleural effusion had been identified on chest radiographs or computed tomography (CT) scans at diagnosis Thirty-one out of 295(10.5%) patients with neuroblastoma had pleural effusion identified at time of presentation. International neuroblastoma staging system (INSS) risk stratification was high risk in 29 cases and intermediate risk and low risk in 1 case each. The primary site of disease was abdomen in 26 patients; mediastinum in 5. We conducted cytologic analysis of pleural fluid of nine patients; the specimen of seven contained malignant cells. Eighteen of 31 patients died of progressive or recurrent disease. In patients with neuroblastoma, pleural effusion is usually associated with unfavorable biologic features and high-risk disease. Pleural fluid should be examined cytologically and at a time when the results would change the risk stratification. There was no statistically significant difference in the survival rate of the patients with high-risk neuroblastoma with or without malignant pleural effusion. 2007 Wiley-Liss, Inc

  8. Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Lee Kyung-Ae

    2012-06-01

    Full Text Available Abstract Background Malignant pleural mesothelioma (MPM is a highly aggressive cancer with a very poor prognosis. Several clinical studies such as immunotherapy, gene therapy and molecular targeting agents have been tried for treatment of malignant mesothelioma, however, there is no application for effective clinical treatment. Coffee has various biological functions such as anti-oxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities. The therapeutic activities of the bioactive compounds in coffee was sugested to influence intracellular signaling of MPM. Regarding to the cancer-related functions, In this study, suppression of Sp1 protein level followed by induction of MSTO-211H cell apoptosis by cafestol and kahweol were investigated in oreder to determine Sp1's potential as a significant target for human MPM therapy as well. Methods Cells were treated separately with final concentration of cafestol and kahweol and the results were analyzed by MTS assay, DAPI staining, PI staining, luciferase assay, RT-PCR, and immunoblotting. Results Viability of MSTO-211H and H28 cells were decreased, and apoptotic cell death was increased in MSTO-211H as a result of cafestol and kahweol treatment. Cafestol and kahweol increased Sub-G1 population and nuclear condensation in MSTO-211H cells. Roles of Sp1 in cell proliferation and apoptosis of the MSTO-211H cells by the Sp1 inhibitor of Mithramycin A were previously confirmed. Cafestol and kahweol significantly suppressed Sp1 protein levels. Kahweol slightly attenuated Sp1 mRNA, while Cafestol did not affect in MSTO-211H cells. Cafestol and kahweol modulated the promoter activity and protein expression level of the Sp1 regulatory genes including Cyclin D1, Mcl-1, and Survivin in mesothelioma cells. Apoptosis signaling cascade was activated by cleavages of Bid, Caspase-3, and PARP with cafestol and by upregulation of Bax, and downregulation of Bcl-xl by kahweol. Conclusions Sp1 can be a novel

  9. Role of fibulin-3 in the diagnosis of malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Mohammed A. Agha

    2014-01-01

    Conclusions: Fibulin-3 in the serum and pleural fluid is a good biomarker in the diagnosis of MPM and in differentiation between MPM from malignant pleural metastasis other than mesothelioma and also from benign pleural effusions.

  10. Recurrent pleural effusion as a clinical manifestation of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Marcelo Torquato Toneline

    2013-12-01

    Multiple myeloma is a hematologic malignant tumor of plasma cells, sometimes associated with pleural effusion. This, in most cases, is associated to infectious complications. Pleural effusion as the onset or progression of the disease itself is rare. This case reports a young male, who presented recurrent pleural effusions, diagnosed with multiple myeloma at diagnosis.

  11. Vascular Endothelial Growth Factor in Pleural Effusions and ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... and eosinophil values in the pleura (P < 0.05). Pleural VEGF levels were also higher in patients with massive effusions and pleural thickening (both P < 0.001). Conclusions: The overlap of pleural VEGF levels between the groups may limit the value of VEGF in discriminating between malignant versus ...

  12. Vascular Endothelial Growth Factor in Pleural Effusions and ...

    African Journals Online (AJOL)

    Materials and Methods: The study included patients with pleural effusion. VEGF levels in the pleural fluid were measured by enzyme‑linked immunosorbent assay. Results: A total of 97 patients who had exudative pleural effusion related to lung cancer (n = 17), nonpulmonary malignancies (n = 25), mesothelioma (n = 9), ...

  13. Microfilaria in pleural fluid cytology: A rare finding

    Directory of Open Access Journals (Sweden)

    Subrata Pal

    2017-01-01

    Full Text Available Lymphatic filariasis is endemic in India and Southeast Asia. Detection of microfilaria is infrequently reported during cytological evaluation of various lesions or body cavity fluids. Presence of microfilaria in pleural fluid cytology is very rare finding even in endemic areas. Few cases of accidental finding of microfilaria have been reported in association with malignant pleural effusion. But pleural effusion of filarial origin is extremely rare manifestation. Here we report a classical case of microfilaria in pleural fluid cytology.

  14. Microfilaria in pleural fluid cytology: A rare finding.

    Science.gov (United States)

    Pal, Subrata; Bose, Kingshuk; Sharma, Abhishek; Sikder, Mrinal

    2017-01-01

    Lymphatic filariasis is endemic in India and Southeast Asia. Detection of microfilaria is infrequently reported during cytological evaluation of various lesions or body cavity fluids. Presence of microfilaria in pleural fluid cytology is very rare finding even in endemic areas. Few cases of accidental finding of microfilaria have been reported in association with malignant pleural effusion. But pleural effusion of filarial origin is extremely rare manifestation. Here we report a classical case of microfilaria in pleural fluid cytology.

  15. Sea-urchin-like Au nanocluster with surface-enhanced raman scattering in detecting epidermal growth factor receptor (EGFR) mutation status of malignant pleural effusion.

    Science.gov (United States)

    Wang, Lei; Guo, Ting; Lu, Qiang; Yan, Xiaolong; Zhong, Daixing; Zhang, Zhipei; Ni, Yunfeng; Han, Yong; Cui, Daxiang; Li, Xiaofei; Huang, Lijun

    2015-01-14

    Somatic mutations in the epidermal growth factor receptor (EGFR) gene are common in patients with lung adenocarcinomas and are associated with sensitivity to the small-molecule tyrosine kinase inhibitors (TKIs). For 10%-50% of the patients who experienced malignant pleural effusion (MPE), pathological diagnosis might rely exclusively on finding lung cancer cells in the MPE. Current methods based on polymerase chain reaction were utilized to test EGFR mutation status of MPE samples, but the accuracy of the test data was very low, resulting in many patients losing the chance of TKIs treatment. Herein, we synthesized the sea-urchin-like Au nanocluster (AuNC) with an average diameter of 92.4 nm, composed of 15-nm nanopricks. By introducing abundant sharp nanopricks, the enhancement factor of AuNC reached at 1.97 × 10(7). After capped with crystal violet (CV), polyethylene glycol, and EGFR mutation specific antibody, the AuNC-EGFR had excellent surface-enhanced Raman scattering (SERS) activity and EGFR mutation targeted recognition capability in lung cancer cells. Characteristic SERS signal at 1617 cm(-1) of CV was linear correlation with the number of H1650 cells, demonstrating the minimum detection limit as 25 cells in a 1-mL suspension. The gold mass in single H1650 cells exposed to AuNC-E746_750 for 2 h ranged from 208.6 pg to 231.4 pg, which approximately corresponded to 56-62 AuNCs per cell. Furthermore, SERS was preclinically utilized to test EGFR mutation status in MPE samples from 35 patients with lung adenocarcinoma. Principal component analysis (PCA) and the support vector machine (SVM) algorithm were constructed for EGFR mutation diagnostic analysis, yielding an overall accuracy of 90.7%. SERS measurement based on sea-urchin-like AuNC was an efficient method for EGFR mutation detection in MPE, and it might show great potential in applications such as predicting gene typing of clinical lung cancer in the near future.

  16. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.

    Science.gov (United States)

    Grosso, Federica; Steele, Nicola; Novello, Silvia; Nowak, Anna K; Popat, Sanjay; Greillier, Laurent; John, Thomas; Leighl, Natasha B; Reck, Martin; Taylor, Paul; Planchard, David; Sørensen, Jens Benn; Socinski, Mark A; von Wangenheim, Ute; Loembé, Arsène Bienvenu; Barrueco, José; Morsli, Nassim; Scagliotti, Giorgio

    2017-11-01

    Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with

  17. Therapy response in malignant pleural mesothelioma-role of MRI using RECIST, modified RECIST and volumetric approaches in comparison with CT

    Energy Technology Data Exchange (ETDEWEB)

    Plathow, Christian [University of Freiburg, Department of Nuclearmedicine, Freiburg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Klopp, Michael [Clinic for Thoracic Diseases, Department of Thoracic Surgery, Heidelberg (Germany); Thieke, Christian [German Cancer Research Center Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Herth, Felix [Clinic for Thoracic Diseases, Department of Pneumology, Heidelberg (Germany); Thomas, Andreas [Clinic for Thoracic Diseases, Department of Oncology, Heidelberg (Germany); Schmaehl, Astrid [Clinic for Thoracic Diseases, Department of Radiology, Heidelberg (Germany); Zuna, Ivan; Kauczor, Hans-Ulrich [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

    2008-08-15

    To evaluate and compare early therapy response according to RECIST (response evaluation criteria in solid tumours) and modified RECIST criteria using MRI techniques in patients with malignant pleural mesothelioma (MPM) in comparison with CT. Fifty patients with MPM (32 male/18 female) were included in this study. Early therapy response was evaluated after 9 weeks [three of six chemotherapy (CHT)] cycles. Additionally patients were examined before chemotherapy, 4 weeks after early therapy response evaluation and after six cycles to evaluate diagnostic follow-up. RECIST and modified RECIST criteria were applied using CT and MRI (HASTE, VIBE, T2-TSE sequences). In MRI additionally a volumetric approach measuring tumour weight (overall segmented tumour volume) was applied. Additionally vital capacity (VC) was measured for correlation. Image interpretation was performed by three independent readers independently and in consensus. The 'gold standard' was follow-up examination. Twenty-eight patients showed partial response, 12 patients stable disease and 10 patients progressive disease at early therapy response evaluation. In the follow-up these results remained. For MRI, in 46 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as gold standards in all cases, whereas using RECIST criteria in four cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST criteria ({kappa}=0.9-1.0 vs. 0.7-1.0). For CT, in 44 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as in gold standards in 48 out of 50 patients, whereas using RECIST criteria in 6 cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST

  18. Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, Andreas, E-mail: andreas.tyler@medbio.umu.se [Department of Medical Biosciences, Umeå University, S-901 85 Umea (Sweden); Johansson, Anders [Department of Odontology, Umeå University, S-901 85 Umea (Sweden); Karlsson, Terese [Department of Radiation Sciences, Oncology, S-901 85 Umea (Sweden); Gudey, Shyam Kumar; Brännström, Thomas; Grankvist, Kjell; Behnam-Motlagh, Parviz [Department of Medical Biosciences, Umeå University, S-901 85 Umea (Sweden)

    2015-08-01

    Background: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expression of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance. Methods: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analyzed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72 h on expression and cisplatin cytotoxicity was tested. Results: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. Conclusions: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin

  19. Pleural drainage and pleurodesis: implementation of guidelines in four hospitals

    NARCIS (Netherlands)

    Burgers, J. A.; Kunst, P. W. A.; Koolen, M. G. J.; Willems, L. N. A.; Burgers, J. S.; van den Heuvel, M.

    2008-01-01

    The aim of the present study was to evaluate the implementation of the 2003 Dutch guideline on the diagnosis and treatment of malignant pleural effusions, and the potential effect of the implementation on the clinical outcome of pleurodesis. All patients with malignant pleural effusion who had a

  20. Pleural drainage and pleurodesis: implementation of guidelines in four hospitals.

    NARCIS (Netherlands)

    Burgers, J.A.; Kunst, P.W.; Koolen, M.G.; Willems, L.N.; Burgers, J.S.

    2008-01-01

    The aim of the present study was to evaluate the implementation of the 2003 Dutch guideline on the diagnosis and treatment of malignant pleural effusions, and the potential effect of the implementation on the clinical outcome of pleurodesis. All patients with malignant pleural effusion who had a

  1. Diagnosis and Management of Pleural Transudates.

    Science.gov (United States)

    Ferreiro, Lucía; Porcel, José M; Valdés, Luis

    2017-11-01

    Various clinical trials have been published on the optimal clinical management of patients with pleural exudates, particularly those caused by malignant tumors, while little information is available on the diagnosis and treatment of pleural transudates. The etiology of pleural transudates is wide and heterogeneous, and they can be caused by rare diseases, sometimes constituting a diagnostic challenge. Analysis of the pleural fluid can be a useful procedure for establishing diagnosis. Treatment should target not only the underlying disease, but also management of the pleural effusion itself. In cases refractory to medical treatment, invasive procedures will be necessary, for example therapeutic thoracentesis, pleurodesis with talc, or insertion of an indwelling pleural catheter. Little evidence is currently available and no firm recommendations have been made to establish when to perform an invasive procedure, or to determine the safest, most efficient approach in each case. This article aims to describe the spectrum of diseases that cause pleural transudate, to review the diagnostic contribution of pleural fluid analysis, and to highlight the lack of evidence on the efficacy of invasive procedures in the management and control of pleural effusion in these patients. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. [Pulmonary and pleural reaction patterns to artificial mineral fibers --rockwool].

    Science.gov (United States)

    Respondek, M; Voss, B; Wiethege, T; Kerenyi, T; Müller, K M

    1993-01-01

    Epidemiological and animal studies about the fibrogenic and carcinogenic properties of natural mineral fibers required the development of man made vitreous fibers as substitutes for asbestos containing material. The question about the possible fibrogenic and carcinogenic properties of man-made vitreous fibers is not yet answered. By means of different experimental animal studies we tried to investigate the man made vitreous fibers-related pulmonary and pleural diseases. The experimental administration of rockwool induce lesions in the lung of the rats. The lung showed an extensive granulomatous inflammation. In the observation time of 10 months we did not find any malignant tumor of the lung and the pleura.

  3. Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

    Energy Technology Data Exchange (ETDEWEB)

    Mould, Richard F [41 Ewhurst Avenue, South Croydon, Surrey CR2 0DH (United Kingdom); Lahanas, Michael [Klinikum Offenbach, Strahlenklinik, 66 Starkenburgring, 63069 Offenbach am Main (Germany); Asselain, Bernard [Institut Curie, Biostatistiques, 26 rue d' Ulm, 75231 Paris Cedex 05 (France); Brewster, David [Director, Scottish Cancer Registry, Information Services (NHS National Services Scotland) Area 155, Gyle Square, 1 South Gyle Crescent, Edinburgh EH12 9EB (United Kingdom); Burgers, Sjaak A [Department of Thoracic Oncology, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The (Netherlands); Damhuis, Ronald A M [Rotterdam Cancer Registry, Rochussenstraat 125, PO Box 289, 3000 AG Rotterdam, The (Netherlands); Rycke, Yann De [Institut Curie, Biostatistiques, 26 rue d' Ulm, 75231 Paris Cedex 05 (France); Gennaro, Valerio [Liguria Mesothelioma Cancer Registry, Etiology and Epidemiology Department, National Cancer Research Institute, Pad. Maragliano, Largo R Benzi, 10-16132 Genoa (Italy); Szeszenia-Dabrowska, Neonila [Department of Occupational and Environmental Epidemiology, National Institute of Occupational Medicine, PO Box 199, Swietej Teresy od Dzieciatka Jezus 8, 91-348 Lodz (Poland)

    2004-09-07

    A truncated left-censored and right-censored lognormal model has been validated for representing pleural mesothelioma survival times in the range 5-200 weeks for data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years and for all ages combined for females. The cases available for study were from Europe and USA and totalled 5580. This is larger than any other pleural mesothelioma cohort accrued for study. The methodology describes the computation of reference baseline probabilities, 5-200 weeks, which can be used in clinical trials to assess results of future promising treatment methods. This study is an extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol. 47 3893-924) to predict long-term cancer survival from short-term data where the proportion cured is denoted by C and the uncured proportion, which can be represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case when C = 0.

  4. The case against performing pleural biopsies for the aetiological diagnosis of exudates.

    Science.gov (United States)

    Porcel, J M

    2017-10-01

    In most cases, the etiological diagnosis of pleural exudates does not require a pleural biopsy. However, when it is considered necessary, the biopsy should seldom be conducted using invasive methods such as thoracoscopy. Two paradigmatic examples are pleural tuberculosis and malignant effusions. In many centres, pleural fluid adenosine deaminase measurement has replaced closed pleural biopsies in the diagnosis of tuberculosis. Similarly, pathological and molecular studies on pleural fluid cell blocks or alternatively, image-guided pleural biopsies have drastically reduced the need for thoracoscopy. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. Spontaneous and experimental malignancies in non-human primates.

    Science.gov (United States)

    Lapin, Boris A; Yakovleva, Lelita A

    2014-04-01

    Contrary to earlier established opinion that tumors in monkeys are found rarely, now the large material confirms that monkey tumors are frequent phenomenon. Tumor incidence clearly increases with age. Frequencies of benign and malignant tumors of various locations and histogenesis are slightly different. Tumors of hematopoietic system are the most frequent. Sporadic cases and enzootic outbreaks of lymphomas are described for different kinds of monkeys, including apes, and probably are caused by viruses. Two viruses were isolated by us from sick monkeys - the retrovirus C-type STLV-1 and the herpes virus papio HVP. Inoculation of virus cultures into monkeys and rabbits induces neoplasms. Monkey neoplasms can be induced by exposure to various chemical agents, and by oncogenic and non-oncogenic viruses. There is no strict species specificity of tumor viruses. The role of polyoma viruses in neoplasms etiology is discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Diagnostic performance of different pleural fluid biomarkers in tuberculous pleurisy.

    Science.gov (United States)

    Klimiuk, J; Krenke, R; Safianowska, A; Korczynski, P; Chazan, R

    2015-01-01

    Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7%) patients with tuberculous pleural effusion, 88 (43.3%) patients with malignant pleural effusion, 35 (17.2%) with parapneumonic effusion/pleural empyema, 30 (14.8%) with pleural transudates, and 6 (3%) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97%, 98%, 95.5%, 99.4%, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC≥0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.

  7. Pleural ultrasound for clinicians.

    Science.gov (United States)

    Porcel, J M

    2016-11-01

    Pleural ultrasonography is useful for identifying and characterising pleural effusions, solid pleural lesions (nodules, masses, swellings) and pneumothorax. Pleural ultrasonography is also considered the standard care for guiding interventionist procedures on the pleura at the patient's bedside (thoracentesis, drainage tubes, pleural biopsies and pleuroscopy). Hospitals should promote the acquisition of portable ultrasound equipment to increase the patient's safety. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  8. State-of-the-art: Radiological investigation of pleural disease.

    Science.gov (United States)

    Hallifax, R J; Talwar, A; Wrightson, J M; Edey, A; Gleeson, F V

    2017-03-01

    Pleural disease is common. Radiological investigation of pleural effusion, thickening, masses, and pneumothorax is key in diagnosing and determining management. Conventional chest radiograph (CXR) remains as the initial investigation of choice for patients with suspected pleural disease. When abnormalities are detected, thoracic ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) can each play important roles in further investigation, but appropriate modality selection is critical. US adds significant value in the identification of pleural fluid and pleural nodularity, guiding pleural procedures and, increasingly, as "point of care" assessment for pneumothorax, but is highly operator dependent. CT scan is the modality of choice for further assessment of pleural disease: Characterising pleural thickening, some pleural effusions and demonstration of homogeneity of pleural masses and areas of fatty attenuation or calcification. MRI has specific utility for soft tissue abnormalities and may have a role for younger patients requiring follow-up serial imaging. MRI and PET/CT may provide additional information in malignant pleural disease regarding prognosis and response to therapy. This article summarises existing techniques, highlighting the benefits and applications of these different imaging modalities and provides an up to date review of the evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma.

    Science.gov (United States)

    Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy; Onda, Masanori; Czapiewski, Piotr; Langfort, Renata; Rys, Janusz; Szpor, Joanna; Waloszczyk, Piotr; Okoń, Krzysztof; Biernat, Wojciech; Ikeda, Hiroshi; Schrump, David S; Hassan, Raffit; Pastan, Ira; Miettinen, Markku

    2017-04-18

    Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy. Also, characterization of selected mesothelin-positive tumors was performed by immunohistochemistry and oncogene sequencing. Among the tumors analyzed, the highest frequencies of mesothelin-positivity were detected in ovarian serous carcinoma (90% in 5B2 and 94% in MN-1). Both antibodies showed frequent positivity in pancreatic adenocarcinoma (71% using 5B2 and 87% using MN-1) and malignant pleural mesothelioma (75% using 5B2 and 78% using MN-1). In malignant mesothelioma, overall survival was significantly longer in the cohort of patients with diffuse membranous expression of mesothelin (P < 0.001). Both antibodies showed positive staining in thymic carcinoma (77% in 5B2 and 59% in MN-1), however, no expression was detected in thymoma. No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas. Mesothelin immunohistochemistry may assist the differential diagnosis of thymoma vs. thymic carcinoma as well as prognostication of mesothelioma patients. Our results demonstrate that patients with solid tumors expressing mesothelin could be targeted by anti-mesothelin therapies.

  10. Spontaneous hemothorax: primary pleural epithelioid angiosarcoma

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    Amit Panjwani

    2016-01-01

    Full Text Available Spontaneous hemothorax is a rare condition seen in coagulation and vascular disorders. Uncommonly, malignant neoplasms may cause spontaneous hemothorax. Primary pleural epithelioid angiosarcomas (excluding the cases with pleuropulmonary or chest wall involvement are extremely rare pleural tumors, which may be mistaken for mesothelioma or adenocarcinoma, and only 19 cases (one of them from India have been reported in the English literature, to date. It commonly occurs in older men, has a nonspecific clinicoradiological presentation, and carries a poor prognosis with no survivors beyond a year of establishing the diagnosis. We report a case of primary pleural epithelioid angiosarcoma presenting as a life-threatening spontaneous hemothorax. We also present a brief literature review on pleural angiosarcoma.

  11. Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities.

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    Wang, Xingyu; Gronchi, Fabrizio; Bensimon, Michael; Mercier, Thomas; Decosterd, Laurent Arthur; Wagnières, Georges; Debefve, Elodie; Ris, Hans-Beat; Letovanec, Igor; Peters, Solange; Perentes, Jean Yannis

    2015-12-01

    Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural

  12. Diagnostic approach to pleural effusion.

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    Saguil, Aaron; Wyrick, Kristen; Hallgren, John

    2014-07-15

    Pleural effusion affects more than 1.5 million people in the United States each year and often complicates the management of heart failure, pneumonia, and malignancy. Pleural effusion occurs when fluid collects between the parietal and visceral pleura. Processes causing a distortion in body fluid mechanics, such as in heart failure or nephrotic syndrome, tend to cause transudative effusions, whereas localized inflammatory or malignant processes are often associated with exudative effusions. Patients can be asymptomatic or can present with cough, dyspnea, and pleuritic chest pain. Dullness to percussion on physical examination suggests an effusion; chest radiography can confirm the diagnosis. Thoracentesis may be indicated to diagnose effusion and relieve symptoms. Ultrasound guidance is preferred when aspirating fluid. Routine assays for aspirated fluid include protein and lactate dehydrogenase levels, Gram staining, cytology, and pH measurement. Light's criteria should be used to differentiate exudative from transudative effusions. Additional laboratory assays, bronchoscopy, percutaneous pleural biopsy, or thoracoscopy may be required for diagnosis if the initial test results are inconclusive.

  13. Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma.

    Science.gov (United States)

    Pasello, Giulia; Urso, Loredana; Silic-Benussi, Micol; Schiavon, Marco; Cavallari, Ilaria; Marulli, Giuseppe; Nannini, Nazarena; Rea, Federico; Ciminale, Vincenzo; Favaretto, Adolfo

    2014-07-01

    Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT combination was also effective in blocking the growth of MPM cell lines in a SCID mice preclinical model. CPT increases MPM cell death in vitro and in vivo compared with CP. In vitro results suggest that chemotherapy sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs.

  14. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.

    Science.gov (United States)

    van Zandwijk, Nico; Pavlakis, Nick; Kao, Steven C; Linton, Anthony; Boyer, Michael J; Clarke, Stephen; Huynh, Yennie; Chrzanowska, Agata; Fulham, Michael J; Bailey, Dale L; Cooper, Wendy A; Kritharides, Leonard; Ridley, Lloyd; Pattison, Scott T; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Reid, Glen

    2017-10-01

    TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma. In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3 + 3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5 × 10 9 , 7 × 10 9 , and 9 × 10 9 TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1 × 10 9 TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based

  15. Characteristics of Patients with Tuberculous Pleural Effusion in Rural Nepal

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    M S Paudel

    2013-06-01

    admitted with pleural effusion were included in the study. Hundred cases diagnosed with pleural effusion by clinical Examination or chest X-ray or ultrasonography’s (USG of the chest were included in the studied. The following parameters patients demographic profile, causes of pleural effusion, location (unilateral/bilateral, hemoglobin and complete blood count, sputum stain and culture sensitivity, Monteux test, chest X-ray and USG findings and Pleural fluid analysis (biochemical, hematological, microbiological and cytological were analyzed by using SPSS 21.   Results: Out of 100 cases, the cause of pleural effusion in 59 patients was tuberculosis, 14 by malignancy, next 14 by Para pneumonic Effusion, 12 by congestive cardiac failure and three cases by alcoholic liver disease. Patients with tuberculous pleural effusion were younger, predominantly males, had unilateral effusion, lower blood hemoglobin, lower Pleural fluid neutrophils, higher pleural fluid Adenosine Deaminase (ADA levels and higher level of pleural fluid to serum protein ratio as compared to the patients with non-tuberculous effusion.   Conclusion: Tuberculosis is the most common cause of pleural effusion in patients of rural Nepal.

  16. An IR Navigation System for Pleural PDT.

    Science.gov (United States)

    Zhu, Timothy C; Liang, Xing; Kim, Michele M; Finlay, Jarod C; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles B; Friedberg, Joseph S; Cengel, Keith A

    2015-03-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light fluence uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

  17. An IR Navigation System for Pleural PDT

    Directory of Open Access Journals (Sweden)

    Timothy C Zhu

    2015-03-01

    Full Text Available Pleural photodynamic therapy (PDT has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM. In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

  18. An IR Navigation System for Pleural PDT

    Science.gov (United States)

    Zhu, Timothy; Liang, Xing; Kim, Michele; Finlay, Jarod; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Friedberg, Joseph; Cengel, Keith

    2015-03-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

  19. MASSIVE PLEURAL EFFUSION: A CASE REPORT

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    Putu Bayu Dian Tresna Dewi

    2013-03-01

    Full Text Available Pleural effusion is abnormal fluid accumulation within pleural cavity between the parietal pleura and visceralis pleura, either transudation or exudates. A 47 year-old female presented with dyspneu, cough, and decreased of appetite. She had history of right lung tumor. Physical examination revealed asymmetric chest movement where right part of lung was lagged during breathing, vocal fremitus on the right chest was decreased, dullness at the right chest, decreased vesicular sound in the right chest, enlargement of supraclavicular and colli dextra lymph nodes, and hepatomegali. Complete blood count showed leukocytosis. Clinical chemistry analysis showed hipoalbumin and decreased liver function. Blood gas analysis showed hypoxemia. Pleural fluid analysis showed an exudates, murky red liquid color filled with erythrocytes, number of cells. Cytological examination showed existence of a non-small cell carcinoma tends adeno type. From chest X-ray showed massive right pleural effusion. Based on history, physical examination and investigations, she was diagnosed with massive pleural effusion et causa suspected malignancy. She had underwent pleural fluid evacuation and treated with analgesics and antibiotics.

  20. Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Sahay, Sandeep; Jimenez, Carlos A

    2014-07-01

    Pulmonary manifestations have been well described in leukemia, but pleural disease is less common. This review highlights pleural effusions in acute and chronic leukemia and myelodysplastic syndrome (MDS) based on the evidence to date. Diagnostic workup and recommendations for the management of these effusions are also outlined. Pleural effusions in patients with leukemia are most often due to infection and to a lesser extent leukemic infiltration of the pleura. The prognostic implications of these effusions are unclear, but survival is most likely determined by the underlying malignancy and its response to treatment. New therapies have changed survival in these patients, and some of these treatments, such as tyrosine kinase inhibitors, have emerged as important causes for these effusions. Pleural interventions may be accomplished with few complications. Pleural effusions may occur with acute and chronic leukemia and MDS. Infection remains the most common cause. Malignant pleural effusions tend to occur in advanced disease in chronic leukemia, but they can be seen at any time with acute leukemia and MDS. With standard precautions, pleural procedures may be performed safely in this population. In cases of unclear cause, pleural and bone marrow biopsy should be considered.

  1. Image-guided pleural biopsy: diagnostic yield and complications

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    Benamore, R.E. [Department of Radiology and Department of Histopathology, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester (United Kingdom)]. E-mail: rachelbenamore@doctors.org.uk; Scott, K. [Department of Radiology and Department of Histopathology, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester (United Kingdom); Richards, C.J. [Department of Radiology and Department of Histopathology, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester (United Kingdom); Entwisle, J.J. [Department of Radiology and Department of Histopathology, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester (United Kingdom)

    2006-08-15

    Background: Pleural biopsy and cytology are standard procedures for the investigation of pleural disease. Recent medical literature has suggested that image-guided pleural biopsy shows improved sensitivity for the diagnosis of pleural malignancy, when compared with the more commonly performed reverse bevel needle biopsy such as Abrams' needle. In our centre there has been an increasing trend towards performing image-guided pleural biopsies, and to our knowledge there is no large published series documenting the complication rate and diagnostic yield. Methods: The radiology and pathology databases were searched for all image-guided [computed tomography (CT) and ultrasound (US)] pleural biopsies from January 2001 to December 2004. All imaging and histology were reviewed, and final diagnostic information about patients was obtained from the respiratory multidisciplinary team database and patient notes. A record was made of complications following biopsy, presence of pleura in the biopsy, and adequacy of tissue for histological diagnosis. Results: A total of 82 patients underwent 85 image-guided pleural biopsies over a 4-year period. 80 cases were performed under CT and five under US guidance. The rate of new pneumothorax detected by chest radiography was 4.7%. No patient required a chest drain or blood transfusion to treat complications. In 10 (12%) cases, there was inadequate tissue to reach a confident histological diagnosis and in eight (9%) of these, no pleura was present. Assuming all suspicious and inadequate biopsies are treated as benign, which is the worst case scenario, image-guided pleural biopsy has a sensitivity and specificity of 76% and 100%, respectively, for the diagnosis of malignant disease. Conclusions: Image-guided pleural biopsy is a safe procedure with few associated complications and has a higher sensitivity than previously published series for reverse cutting needle biopsy in the diagnosis of malignant pleural disease.

  2. A potential role for VEGF in the diagnostic approach of pleural effusions

    Science.gov (United States)

    Psatha, Aggeliki; Makris, Demosthenes; Daniil, Zoe; Kiropoulos, Theodoros; Gourgoulianis, Konstantinos

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) may play a role in pleural fluid formation, as it represents a potent inducer of capillary permeability. We aimed to investigate the diagnostic utility of VEGF levels in pleural fluid and serum in patients with pleural effusions with initially negative diagnostic work up. Methods Seventy-one patients with exudative lymphocytic pleural effusions undiagnosed after initial diagnostic work up were enrolled in this prospective study and their clinical course was followed up to 24 months. VEGF levels were measured in serum and pleural fluid by using immunoenzymometric assay. Results During the follow up period, in 43 patients the pleural effusion was eventually attributed to malignancy while in the rest 28 patients it was due to non-malignant causes (benign and unknown origin). Patients with malignancy had significantly higher VEGF levels in pleural fluid compared to patients with non-malignant effusions (1,506 vs. 588 pg/dL, P=0.0001), while no statistically significant difference was found in the VEGF serum levels between the two groups. Conclusions Pleural VEGF levels may be helpful in identifying malignant pleural effusion (MPE) in patients with negative diagnostic work up at the initial assessment and help in selecting patients for more invasive procedures. PMID:27499957

  3. Status of Exudative Pleural Effusion in Adults of South Khorasan Province, Northeast Iran: Pleural Tuberculosis Tending toward Elderly

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    Sayyed Gholam Reza Mortazavi-Moghaddam

    2016-07-01

    Full Text Available The causes and situation of exudative pleural effusion vary from one area to another. A cross-sectional study was conducted on 327 patients with exudative pleural effusion in South Khorasan province (Iran. The patients were older than 12 years and comprised 172 (52.6% males and 155 (47.4% females. The study commenced in 2007 with seven years duration. The Light’s criteria were used to define exudative effusion. Procedures including pleural fluid analysis, microbiological study, pleural biopsy, and systemic investigations were conducted to determine the special cause of pleural effusion. The mean age of the patients was 63.4±18.4 years. Malignancies, tuberculosis, and parapneumonia pleural exudation were diagnosed in 125 (38.2%, 48 (14.7%, and 45 (13.8% cases, respectively. Among malignant effusions, metastasis from lung cancer made 48 (38.4% of the cases. The origin of metastasis was not determined in 44 (35.2% patients. The mean age of patients was not significantly different between malignant (66.9±14.3 years and tuberculosis (63.9±19.7 years cases (P=0.16. The older age of tuberculosis patients could be a new discussion point on the overall impression created on the subject of tuberculosis pleural exudation (TB-PLE occurring in young people.

  4. Ultrasound guided pleural biopsy in undiagnosed exudative pleural effusion patients

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    Adel S. Ahmed

    2016-04-01

    In conclusion: Thoracic ultrasound (TUS guided pleural biopsy had a diagnostic yield which was slightly lower but comparable to both CT guided pleural biopsy and medical thoracoscopic pleural biopsy (MT.

  5. The effectiveness of single port thoracoscopic approach in pleural effusions

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    Yasemin Bilgin Büyükkarabacak

    2014-12-01

    Full Text Available Objective: Currently, thoracoscopic procedures have been used frequently in diagnosis and treatment of pleural effusions. It was reported, high diagnosis and treatment success with thoracoscopy in pleural effusion, which was not, diagnosed using cytology and blinding pleural biopsy procedures. In this study, it was aimed to evaluate of the patient was performed video-assisted thoracic surgery (VATS due to pleural effusion. Methods: Between 2011 and 2014 years, it was evaluated 52 patients was performed VATS because of pleural effusion. The procedure was performed under general anesthesia and single lung ventilation in 50 patients, and local anesthesia in 2 patients. Results: Histopathological results were reported as carcinoma infiltration in 29 patients, benign disease in 23 patients. Cytological examination of liquid was executed before thoracoscopy in all of the patients with malignity positive. In addition, in eight patients pleura biopsy, on which blinding was executed, evaluated as malignity negative. The diagnostic value of our procedure has 100% in malign group and 98% in benign group. In patients with malignant disease, pleurodesis was performed peroperatively. Mean hospital stay was 5 days (3-15. Mean duration of terminating chest tube was 3 days (3-15. There were no morbidity and mortality due to procedure. Conclusion: Single port VATS is an effective and safe procedure in diagnosis and palliative treatment of patient with pleural effusion, and it has high success rate and reduces hospital stay.

  6. Long-term Outcome of Patients With Undiagnosed Pleural Effusion.

    Science.gov (United States)

    Gunluoglu, Gulsah; Olcmen, Aysun; Gunluoglu, Mehmet Zeki; Dincer, Ibrahim; Sayar, Adnan; Camsari, Gungor; Yilmaz, Veysel; Altin, Sedat

    2015-12-01

    The cause of exudative pleural effusion cannot be determined in some patients. The longterm outcomes of patients with undiagnosed pleural effusion were analyzed. Patients with exudative pleural effusion whose diagnostic procedures included pleural biopsy using video-assisted thoracoscopic surgery carried out between 2008 and 2012 were evaluated retrospectively. Patients diagnosed with non-specific pleuritis were included. Fifty-three patients with available follow-up data were included in the study. Forty men and 13 women (mean age 53.9±13.9 years) were included. Median follow-up time was 24 months. No diagnosis was given in 27 patients (51%), and a clinical diagnosis was given in 26 patients (49%) during the follow-up period. Malignant disease (malignant mesothelioma) was diagnosed in 2 (3.7%) patients. Other diseases were parapneumonic effusion in 12, congestive heart failure in 8, and miscellaneous in 4 patients. Volume of effusion at the time of initial examination and re-accumulation of fluid after video-assisted thoracoscopic surgery were associated with malignant disease (P=.004 and .0001, respectively). Although the probability is low, some patients with exudative pleural effusion undiagnosed after pleural biopsy via video-assisted thoracoscopic surgery may have malignant disease. Patients with an initially large volume of effusion that re-accumulates after examination should be closely monitored. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  7. Detection of minute pleural fluid in the pleural retracted space associated with peripheral lung cancer. Evaluation with MR imaging

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    Shiotani, Seiji; Endoh, Hideho; Wada, Mitsuyoshi [Tsukuba Medical Center Hospital, Ibaraki (Japan); Sugimura, Kazuro; Sugihara, Masaki; Kawamitsu, Hideaki; Maruyama, Riruke; Yamauchi, Masanobu

    2000-02-01

    To evaluate the efficacy of magnetic resonance imaging (MRI) in detecting minute pleural fluid in the pleural retracted space (PRS) associated with peripheral lung cancer. Our subjects were 20 patients with peripheral lung cancer in whom thin-section CT in the lung window setting demonstrated lesions adjacent to the pleural surface, and who were referred for MR imaging. The imaging findings were retrospectively evaluated and correlated with the histopathologic specimens. Pleural fluid was aspirated for cytology under ultrasound (US) guidance in six patients. STIR MR images revealed water SI areas beneath the chest wall associated with the lung cancer, whereas, on CT images, lung cancer and minute pleural fluid in the PRS showed similar soft-tissue density without enabling easy differentiation. Two of the six patients who underwent aspiration cytology showed malignancy. All histopathologic specimens obtained from 18 patients who underwent surgery showed pleural retraction corresponding to the water SI areas on STIR images. Histopathological study revealed that the fibrotic focus of the tumor tended to occur more intensively when the shape of pleural retraction was thinner and deeper. Water SI areas on STIR images were thought to suggest pleural fluid retention in the PRS. MRI was sensitive in detecting minute pleural fluid in the PRS and may help to avoid overdiagnosis of chest wall invasion induced from peripheral lung cancers. (author)

  8. Persistent benign pleural effusion.

    Science.gov (United States)

    Porcel, J M

    In this narrative review we describe the main aetiologies, clinical characteristics and treatment for patients with benign pleural effusion that characteristically persists over time: chylothorax and cholesterol effusions, nonexpansible lung, rheumatoid pleural effusion, tuberculous empyema, benign asbestos pleural effusion and yellow nail syndrome. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  9. Pleural function and lymphatics.

    Science.gov (United States)

    Negrini, D; Moriondo, A

    2013-02-01

    The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  10. Silicone Breast Implants: A Rare Cause of Pleural Effusion

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    Imam H. Shaik

    2015-01-01

    Full Text Available Pleural effusions are one of the rarest complications reported in patients with silicone gel filled breast implants. The silicone implants have potential to provoke chronic inflammation of pleura and subsequent pulmonary complications such as pleural effusion. Herein, we report a 44-year-old female who presented with left sided pleural effusion, six weeks after a silicone breast implantation surgery. The most common infectious, inflammatory, and malignant causes of pleural effusion were excluded with pleural fluid cytology and cultures. With recurrent effusion in the setting of recent surgery, the chemical reaction to silicone breast implants was sought and exploration was performed which revealed foreign body reaction (FBR to silicone material. The symptoms dramatically improved after the explantation.

  11. Behaviour of nucleated cells in various types of pleural effusion.

    Science.gov (United States)

    Ferreiro, L; Pereiro, T; San José, E; Toubes, M E; Suárez-Antelo, J; Álvarez Dobaño, J M; González Barcala, F J; Rodríguez Núñez, N; Lama, A; Valdés, L

    2017-04-01

    To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories RESULTS: 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  12. A simple solution for complicated pleural effusions.

    Science.gov (United States)

    Murthy, Sudish C; Okereke, Ikenna; Mason, David P; Rice, Thomas W

    2006-09-01

    Complicated pleural effusions are difficult to manage with conventional strategies. In this study, we review the safety, efficacy, and durability of PleurX catheters (Denver Biomedical, Golden, CO) for managing complicated pleural effusions and describe a patient population who might benefit. From July 1999 to February 2003, 63 PleurX catheters were placed in 58 symptomatic patients (an additional five had bilateral catheters) to manage complicated pleural effusions. Patients selected for catheter placement tended to have poor performance status (Eastern Cooperative Oncology Group < or =2) or had failed standard therapies. Of the 63 catheters, 52 (83%) were placed because of malignant complicated pleural effusions. A registry of patients was constructed, and data were obtained from review of medical records. Nonparametric estimates of freedom from reintervention and overall survival were obtained by the Kaplan-Meier method. Catheter-related complications were noted in four of 58 patients (7%) and included one each of pneumothorax, seroma, empyema, and pain syndrome. Freedom from reintervention for effusion management was 95%. Of the patients, 86% (50 of 58) experienced dyspnea relief. There were no procedure-related mortalities. Catheters remained functional up to 330 days, and four of 63 (6%) required one-time thrombolysis with tissue plasminogen activator. PleurX catheters are safe, effective, and durable solutions for complicated pleural effusions and seem to provide an attractive alternative for patients who have few other palliative options. We consider the catheters as first-line therapy for these patients.

  13. Efficacy of mistletoe for chemical pleurodesis in rats without malignancy

    Science.gov (United States)

    Ahn, Hyo Yeong; Cho, Jeong Su; Kim, Yeong Dae; I, Hoseok; Kim, Yeon Ji; Kim, Ahrong; Lee, Chang Hun

    2015-01-01

    Chemical pleurodesis is an effective treatment modality to reduce recurrence of malignant effusion. Several agents have been used in chemical pleurodesis but, it is not yet clear which is better. Eighteen Sprague-Dawley rats were used and classified into three groups: a group intrapleurally injected normal saline (group A, n=6), 400mg/kg talc (group B, n=6), and 9mg/kg mistletoe extraction (ME) (group C, n=6). Autopsy was performed to evaluate the pleural adhesion, pathologic examination of pleura and lung and bronchoalveolar lavage fluid analysis 4 weeks after pleurodesis. Both group B and C showed an obvious pleural adhesion and there was no significant difference in grade of pleural adhesion between two groups (p=0.58). The parietal pleural thickness in talc group than ME group was significantly thicker (p=0.002) and the visceral pleura of talc group showed marked foreign body reaction with fibrosis and many multinucleated giant cells associated with talc crystal. This study suggests that pleurodesis using ME in condition without malignancy has comparable effect to pleurodesis using talc. However, additional experimental study in large animal or clinical trials would be required to prove a safety and an efficacy of pleurodesis using ME. PMID:28352717

  14. Experimental immunotherapy for malignant glioma: lessons from two decades of research in the GL261 model.

    Science.gov (United States)

    Maes, Wim; Van Gool, Stefaan W

    2011-02-01

    Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered promising, it is clear that immunotherapy does not on its own represent the magic bullet in glioma therapy. In this review, we summarize the major immunotherapeutic achievements in the mouse GL261 glioma model, which has emerged as the gold standard syngeneic model for experimental glioma therapy. Gene therapy, monoclonal antibody treatment, cytokine therapy, cell transfer strategies and dendritic cell therapy were hereby considered. Apart from the considerable progress made in understanding glioma immunology in this model, we also addressed its most pertinent issues and shortcomings. Despite these, the GL261 model will remain indispensable in glioma research since it is a fast, highly reproducible and easy-to-establish model system.

  15. Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Akansha Chhabra

    2015-05-01

    Full Text Available Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis.

  16. Pleural biopsy for indeterminate cases of pleural effusion | Ukadike ...

    African Journals Online (AJOL)

    Materials and Methods: This is a retrospective study of all consecutive cases of pleural biopsies done for indeterminate cause of pleural effusion in the University of Benin Teaching Hospital from December 2008 to May 2010, a total of 18months. Blind pleural biopsy was carried out using the Abram's Pleural Biopsy Needle.

  17. Atypical pleural tuberculosis presenting as an isolated pleural tuberculoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Sook Min; Rho, Ji Young; Yoo, Seung Min; Jung, Hae Kyoung (Department of Radiology, CHA Bundang Medical Center, CHA University, Gyeonggi-do (Korea, Republic of)), Email: rhoji@naver.com; Cho, Sang Ho (Department of Pathology, CHA Bundang Medical Center, CHA University, Gyeonggi-do (Korea, Republic of))

    2012-02-15

    Pleural tuberculosis is the most common extrapulmonary manifestation of tuberculosis, and is generally characterized by an effusion. The effusion is usually unilateral and residual pleural thickening or calcification is also observed in some cases. Manifestations of multiple pleural tuberculomas without associated effusion and history of tuberculosis or antituberculous therapy are rare and an isolated pleural tuberculoma is exceedingly rare. Herein, we report the first documented case of an isolated pleural tuberculoma, diagnosed by chest CT and pathological findings. Although rare, an isolated pleural tuberculoma should be added to the differential diagnosis of focal nodular pleural tumors, particularly in areas of high tuberculosis prevalence

  18. Value of Detection of CAIX in the Pleural Effusion and Its Sediment in the Diagnosis of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lina PENG

    2015-11-01

    Full Text Available Background and objective Carbonic anhydrase IX (CAIX is widely expressed in a variety of malignant tumors, including-lung cancer. Our previous study has shown that the serum level of soluble form of carbonic anhydrase IX (s-CAIX was significantly higher in patients with lung cancer than that in the healthy group. The aim of this study is to detect the s-CAIX level in the pleural effusion and its sediment, and to evaluate the significance of CAIX detection in the diagnosis of lung cancer. Methods The s-CAIX level in pleural effusion of 29 lung cancer patients and 27 patients with tuberculosis was detected by ELISA. The expression of CAIX in the pleural effusion sediment of 21 lung cancer patients with malignant pleural effusion and 6 patients with benign pleural effusion was examined by immunohistochemistry. With pathological diagnosis as the gold standard, receiver operating characteristic (ROC curve of pleural effusion s-CAIX was established for the diagnosis of lung cancer with malignant pleural effusion. Results The s-CAIX level in the malignant pleural effusion was significantly higher than that in the tuberculosis group (P<0.05. The AUC of pleural effusion s-CAIX level was 0.761. At a threshold level of 109.135 pg/mL, sensitivity and specificity were 92.3% and 58.3%, respectively. The CAIX expression in all samples of the benign pleural effusion sediment was negative. The positive rate of CAIX expression in malignant pleural effusion sediment was 66.67%. Conclusion Detection of CAIX in the pleural effusion and its sediment exhibits high sensitivity and specificity, and is helpful in diagnosis of lung cancer with malignant pleural effusion.

  19. Pleural effusions in patients with acute leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Bashoura, Lara; Lei, Xiudong; Sampat, Keeran R; Brown, Tiffany C; Eapen, George A; Morice, Rodolfo C; Ferrajoli, Alessandra; Jimenez, Carlos A

    2013-02-01

    Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

  20. Indwelling Tunneled Pleural Catheters for the Management of Hepatic Hydrothorax. A Pilot Study.

    Science.gov (United States)

    Chen, Alexander; Massoni, Jennifer; Jung, Diana; Crippin, Jeffrey

    2016-06-01

    Hepatic hydrothorax is a complication of cirrhosis in which hydrostatic imbalances result in fluid accumulation within the pleural space. Although uncommon, this may cause significant morbidity, resulting in dyspnea requiring repeated pleural drainage procedures. Liver transplantation is curative, but it is rarely immediately available to qualified patients, presenting the clinical challenge of managing recurrent pleural effusions. Indwelling tunneled pleural catheters (ITPCs) have been used successfully to palliate dyspnea associated with recurrent malignant pleural effusions. This study was performed to evaluate the feasibility of using ITPCs for the management of hepatic hydrothorax. A single-center prospective feasibility study was performed to evaluate the use of ITPCs for the management of recurrent hepatic hydrothorax in patients who were eligible for liver transplant evaluation. Twenty-five ITPCs were placed in 24 patients. The mean number of pleural drainage procedures before ITPC placement was 1.9, with no further pleural drainages required in any patient after ITPC placement. Spontaneous pleurodesis occurred in 8 of 24 patients (33%). All eight catheters were successfully removed without pleural fluid reaccumulation. Mean time to pleurodesis was 131.8 days. Pleural fluid infection occurred in 4 of 24 patients (16.7%), requiring catheter removal in 3 of the 4 patients. ITPCs may be successfully and safely used to control symptoms associated with hepatic hydrothorax. The rate of spontaneous pleurodesis that occurs is similar to that observed with ITPCs placed for malignant pleural effusion, although the infection rate may be higher. Clinical trial registered with www.clinicaltrials.gov (NCT02595567).

  1. Extramedullary Acute Myeloid Leukemia (AML: Leukemic Pleural Effusion, Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Naveen ePemmaraju

    2014-06-01

    Full Text Available Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML with fewer than 20 cases reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical presentation: In this case, a 55 year old man with previous history of myeloproliferative neoplasm (MPN experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based upon extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization (FISH testing are recommended. Futhermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. Objective and ImportancePleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML, but may be more common than previously thought. Fewer than 20 cases have been reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature.

  2. A randomized controlled trial comparing indwelling pleural catheters with talc pleurodesis (NVALT-14)

    NARCIS (Netherlands)

    Boshuizen, R. C.; vander Noort, V.; Burgers, J. A.; Herder, G. J. M.; Hashemi, S. M. S.; Hiltermann, T. J. N.; Kunst, P. W.; Stigt, J. A.; van den Heuvel, M. M.

    Background: Symptomatic malignant pleural effusion (MPE) occurs frequently in patients with metastatic cancer. The associated prognosis is poor and the success rate of talc pleurodesis (TP) is low. Indwelling pleural catheters (IPCs) are commonly inserted when TP has been unsuccessful. Methods: We

  3. A randomized controlled trial comparing indwelling pleural catheters with talc pleurodesis (NVALT-14)

    NARCIS (Netherlands)

    Boshuizen, R. C.; van der Noort, V.; Burgers, J. A.; Herder, G. J. M.; Hashemi, S. M. S.; Hiltermann, T. J. N.; Kunst, P. W.; Stigt, J. A.; van den Heuvel, M. M.

    2017-01-01

    Background: Symptomatic malignant pleural effusion (MPE) occurs frequently in patients with metastatic cancer. The associated prognosis is poor and the success rate of talc pleurodesis (TP) is low. Indwelling pleural catheters (IPCs) are commonly inserted when TP has been unsuccessful. Methods: We

  4. Metastatic pleural tumor

    Science.gov (United States)

    ... spread from another organ to the thin membrane (pleura) surrounding the lungs. ... can spread to the lungs and involve the pleura. ... the chest Procedure to remove and examine the pleura ( open pleural biopsy ) Test that examines a sample ...

  5. The management of benign non-infective pleural effusions

    Directory of Open Access Journals (Sweden)

    Oliver J. Bintcliffe

    2016-09-01

    Full Text Available The evidence base concerning the management of benign pleural effusions has lagged behind that of malignant pleural effusions in which recent randomised trials are now informing current clinical practice and international guidelines. The causes of benign pleural effusions are broad, heterogenous and patients may benefit from individualised management targeted at both treating the underlying disease process and direct management of the fluid. Pleural effusions are very common in a number of non-malignant pathologies, such as decompensated heart failure, and following coronary artery bypass grafting. Pleural fluid analysis forms an important basis of the diagnostic evaluation, and more specific assays and imaging modalities are helpful in specific subpopulations. Options for management beyond treatment of the underlying disorder, whenever possible, include therapeutically aspirating the fluid, talc pleurodesis and insertion of an indwelling pleural catheter. Randomised trials will inform clinicians in the future as to the risks and benefits of these options providing a guide as to how best to manage patient symptoms in this challenging clinical setting.

  6. [Imaging of pleural diseases: evaluation of imaging methods based on chest radiography].

    Science.gov (United States)

    Poyraz, Necdet; Kalkan, Havva; Ödev, Kemal; Ceran, Sami

    2017-03-01

    The most commonly employed radiologic method in diagnosis of pleural diseases is conventional chest radiograph. The commonest chest- X-Ray findings are the presence of pleural effusion and thickening. Small pleural effusions are not readily identified on posteroanterior chest radiograph. However, lateral decubitus chest radiograph and chest ultrasonography may show small pleural effusions. These are more efficient methods than posteroanterior chest radiograph in the erect position for demonstrating small amounts of free pleural effusions. Chest ultrasonograph may be able to help in distinguishing the pleural pathologies from parenchymal lesions. On chest radiograph pleural effusions or pleural thickening may obscure the visibility of the underlying disease or parenchymal abnormality. Thus, computed tomography (CT) may provide additional information of determining the extent and severity of pleural disease and may help to differentiate malign pleural lesions from the benign ones. Moreover, CT may provide the differentiation of parenchmal abnormalities from pleural pathologies. CT (coronal and sagittal reformatted images) that also show invasion of chest wall, mediastinum and diaphragm, as well as enlarged hilar or mediastinal lymph nodes. Standart non-invasive imaging techniques may be supplemented with magnetic resonans imaging (MRI).

  7. Time to diagnosis and time to therapy in patients with malignant pleural mesothelioma (MPM) compared to patients with lung cancer in Denmark 2007 to 2011. A quality assurance analysis

    DEFF Research Database (Denmark)

    Hansen, Niels-Chr. G.; Laursen, Christian B.; Olsen, Karen Ege

    2014-01-01

    In Denmark patients with pleural diseases are usually first seen by departments taking care of patients with suspected lung cancer. When "diagnostic packages" was published in 2008 by the National Board of Health a 28 days maximal time to diagnosis and a 42 days maximal time to treatment were sta...

  8. Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.

  9. Effect of Peganum harmala (wild rue extract on experimental ovine malignant theileriosis : pathological and parasitological findings

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    A. Derakhshanfar

    2008-09-01

    Full Text Available Malignant theileriosis of sheep is a highly fatal, acute or subacute disease is caused by the tick-borne protozoan parasite, Theileria hirci. In this investigation ten healthy male lambs aged 5-6 months were randomly divided into two groups, A and B and were kept in isolated tick-proof pens. They were treated for internal and external parasite before commencement of the experiment. The lambs were experimentally infected with T. hirci by placing ticks Hyalomma anatolicum anatolicum infected with T. hirci on them. The ticks used in this survey had originally been isolated from sheep and colonies of them were established in an insectarium. Before and after infection rectal temperatures and clinical signs of the lambs were recorded, blood and prescapular lymph node smears were prepared and examined to determine the extent of the parasitaemia, and blood samples were analyzed to evaluate their haemoglobin (Hb and packed cell volume (PCV rates. Three days after the commencement of a febrile reaction and appearance of the schizonts in the lymph node smears, treatment of the lambs in Group A with an extract containing the alkaloids of Peganum harmala (wild rue was commenced. Group B lambs were kept untreated controls. Before treatment there were no significant differences in the rectal temperature, parasitaemia rate, and the Hb and PCV values between animals in the two groups but after treatment significant differences in these values was detected (P < 0.05. After treatment, the clinical signs and parasites in the lymph node smears of the animals in Group A disappeared and they all animals recovered. These parameters in the animals of Group B progressed until their death. Pathological studies showed the characteristic lesions of theileriosis in lambs in Group B, but not in Group A. The results indicate a therapeutic effect of the alkaloids of P. harmala for treatment of ovine malignant theileriosis.

  10. Needle biopsy of the pleura in the diagnosis of pleural effusion

    Science.gov (United States)

    McAleer, J J A; Murphy, G J J; Quinn, R J

    1987-01-01

    Needle biopsy of the parietal pleura was undertaken in 64 patients with undiagnosed pleural effusion. An adequate specimen was obtained in 96% of procedures. This was diagnostic in 45% of those due to malignancy and in 50% of those due to tuberculosis. A second biopsy improved the combined diagnostic yield in these two diseases from 32% to 46%. Pleural fluid cytology was unhelpful in establishing the presence of a malignancy, and culture of the biopsy specimen was helpful in one case. PMID:3590388

  11. Intracytoplasmic eosinophilic inclusions (Melamed-Wolinska bodies). Association with metastatic transitional cell carcinoma in pleural fluid.

    Science.gov (United States)

    Renshaw, A A; Madge, R; Granter, S R

    1997-01-01

    To determine if eosinophilic cytoplasmic inclusions (Melamed-Wolinska bodies) (ECIs) can help to distinguish metastatic transitional cell carcinoma (TCC) from pulmonary carcinoma (PC) in pleural effusions. The presence of ECIs was evaluated in malignant pleural effusions from 8 cases (5 patients) of TCC and 38 cases of pulmonary carcinoma (PC). ECIs were categorized as absent, rare ( 2 per high-power field). In pleural fluids with TCC, ECIs were numerous in 1 case, frequent in 2 cases, occasional in 3 cases and absent in 2 cases. In contrast, in pleural fluids with PC, ECIs were occasional in 1 case, rare in 5 cases and absent in 32 cases. While not present in every case, frequent ECIs in a malignant pleural effusion are suggestive of TCC rather than PC.

  12. Pleural FDG Uptake More Than a Decade after Talc Pleurodesis

    NARCIS (Netherlands)

    Peek, H.; Bruggen, W. van der; Limonard, G.

    2009-01-01

    Talc pleurodesis induces a strong local inflammatory reaction which can be detected by PET scan for years after the procedure. When patients undergo PET scanning in the workup of a suspected malignancy later in life, pleural FDG uptake may unnecessarily lead to an additional invasive diagnostic

  13. Physician-based ultrasound-guided biopsy for diagnosing pleural disease.

    Science.gov (United States)

    Hallifax, Robert J; Corcoran, John P; Ahmed, Asia; Nagendran, Myura; Rostom, Hussam; Hassan, Neelam; Maruthappu, Mahiben; Psallidas, Ioannis; Manuel, Ari; Gleeson, Fergus V; Rahman, Najib M

    2014-10-01

    Definitive diagnosis of pleural disease (particularly malignancy) depends upon histologic proof obtained via pleural biopsy or positive pleural fluid cytology. Image-guided sampling is now standard practice. Local anesthetic thoracoscopy has a high diagnostic yield for malignant and nonmalignant disease, but is not always possible in frail patients, if pleural fluid is heavily loculated, or where the lung is adherent to the chest wall. Such cases can be converted during the same procedure as attempted thoracoscopy to cutting-needle biopsy. This study aimed to determine the diagnostic yield of a physician-led service in both planned biopsies and cases of failed thoracoscopy. This study was a retrospective review of all ultrasound-guided, cutting-needle biopsies performed at the Oxford Centre for Respiratory Medicine between January 2010 and July 2013. Histologic results were assessed for the yield of pleural tissue, final diagnosis, and clinical follow-up in nonmalignant cases. Fifty ultrasound-guided biopsies were undertaken. Overall, 47 (94.0%) successfully obtained sufficient tissue for histologic diagnosis. Of the 50 biopsy procedures, 13 were conducted after failed thoracoscopy (5.2% of 252 attempted thoracoscopies over the same time period); of these 13, 11 (84.6%) obtained sufficient tissue. Thirteen of 50 biopsy specimens (26.0%) demonstrated pleural malignancy on histology (despite previous negative pleural fluid cytology), while 34 specimens (68.0%) were diagnosed as benign. Of the benign cases, 10 were pleural TB, two were sarcoidosis, and 22 were benign pleural thickening. There was one "false negative" of mesothelioma (median follow-up, 16 months). Within this population, physician-based, ultrasound-guided, cutting-needle pleural biopsy obtained pleural tissue successfully in a high proportion of cases, including those of failed thoracoscopy.

  14. Medical image of the week: septated pleural effusion

    Directory of Open Access Journals (Sweden)

    Wong C

    2015-09-01

    Full Text Available No abstract available. Article truncated at 150 words. An 83 year old man with a history of metastatic malignant melanoma and atrial fibrillation on warfarin was admitted for shortness of breath. He underwent a diagnostic and therapeutic thoracentesis for a large right sided pleural effusion, suspected to be malignancy related. Three days later, he had transferred to the ICU for respiratory distress. An ultrasound of the thorax revealed a large loculated effusion with multiple septations (Figure 1. A large bore chest tube was placed and revealed a hemothorax, which may have been related to the previous thoracentesis. In an observational study of ultrasound characteristics of pleural effusions, complex septations were more commonly seen in non-malignant effusions than malignant effusions (25.4% vs. 7.5%. In non-malignant effusions, the septated pattern was associated with infections, specifically tuberculosis and pneumonia (1. While metastases in melanoma commonly involve the thoracic cavity, malignant pleural effusions are rare and are seen in about 2% of ...

  15. Pleural fluid cholesterol in differentiating exudative and transudative pleural effusion.

    Science.gov (United States)

    Hamal, A B; Yogi, K N; Bam, N; Das, S K; Karn, R

    2013-01-01

    Objectives. To study the diagnostic value of pleural fluid cholesterol in differentiating transudative and exudative pleural effusion. To compare pleural fluid cholesterol level for exudates with Light's criteria. Design. Cross sectional descriptive study. Settings. Medical wards of Tribhuvan University Teaching Hospital. Methods. Sixty two cases of pleural effusion with definite clinical diagnosis admitted in TUTH were taken and classified as transudates (19) and exudates (43). The parameters pleural fluid protein/serum protein ratio (pfP/sP), pleural fluid LDH/ serum LDH ratio, pleural fluid LDH (pfLDH) and pleural fluid cholesterol (pCHOL) were compared with clinical diagnosis with regard to their usefulness for distinguishing between pleural exudates and transudates. Results. The pCHOL values determined were 1.92 ± 0.75 for exudates, 0.53 ± 0.28 for transudates, the differences between the transudates and others are statistically significant (P pfLDH/sLDH ratio has a sensitivity of 86% and specificity of 94.7% and pCHOL with sensitivity of 97.7% and specificity of 100% for differentiating exudative and transudative PE. Conclusion. The determination of pCHOL is of great value for distinguishing between pleural exudates and transudates and should be included in routine laboratory analysis of pleural effusion.

  16. Pleural Fluid Cholesterol in Differentiating Exudative and Transudative Pleural Effusion

    Directory of Open Access Journals (Sweden)

    A. B. Hamal

    2013-01-01

    Full Text Available Objectives. To study the diagnostic value of pleural fluid cholesterol in differentiating transudative and exudative pleural effusion. To compare pleural fluid cholesterol level for exudates with Light’s criteria. Design. Cross sectional descriptive study. Settings. Medical wards of Tribhuvan University Teaching Hospital. Methods. Sixty two cases of pleural effusion with definite clinical diagnosis admitted in TUTH were taken and classified as transudates (19 and exudates (43. The parameters pleural fluid protein/serum protein ratio (pfP/sP, pleural fluid LDH/ serum LDH ratio, pleural fluid LDH (pfLDH and pleural fluid cholesterol (pCHOL were compared with clinical diagnosis with regard to their usefulness for distinguishing between pleural exudates and transudates. Results. The pCHOL values determined were for exudates, for transudates, the differences between the transudates and others are statistically significant (. It is seen that pfP/sP ratio has a sensitivity of 81.4% and specificity of 82.6%; pfLDH/sLDH ratio has a sensitivity of 86% and specificity of 94.7% and pCHOL with sensitivity of 97.7% and specificity of 100% for differentiating exudative and transudative PE. Conclusion. The determination of pCHOL is of great value for distinguishing between pleural exudates and transudates and should be included in routine laboratory analysis of pleural effusion.

  17. Primary Pleural Angiosarcoma in a 63-Year-Old Gentleman

    Directory of Open Access Journals (Sweden)

    Ahmed Abu-Zaid

    2013-01-01

    Full Text Available Primary pleural angiosarcomas are extremely rare. As of 2010, only around 50 case reports have been documented in the literature. Herein, we report the case of a 63-year-old gentleman who presented with a 3-month history of right-sided chest pain, dyspnea, and hemoptysis. Chest X-ray showed bilateral pleural effusion with partial bibasilar atelectasis. Ultrasound-guided thoracocentesis showed bloody and exudative pleural fluid. Cytologic examination was negative for malignant cells. An abdominal contrast-enhanced computed tomography (CT scan showed two right diaphragmatic pleural masses. Whole-body positron emission tomography/computed tomography (PET/CT scan showed two hypermetabolic fluorodeoxyglucose- (FDG- avid lesions involving the right diaphragmatic pleura. CT-guided needle-core biopsy was performed and histopathological examination showed neoplastic cells growing mainly in sheets with focal areas suggestive of vascular spaces lined by cytologically malignant epithelioid cells. Immunohistochemical analysis showed strong positivity for vimentin, CD31, CD68, and Fli-1 markers. The overall pathological and immunohistochemical features supported the diagnosis of epithelioid angiosarcoma. The patient was scheduled for surgery in three weeks. Unfortunately, the patient died after one week after discharge secondary to pulseless ventricular tachycardia arrest followed by asystole. Moreover, we also present a brief literature review on pleural angiosarcoma.

  18. [Sarcoid pleural effusion].

    Science.gov (United States)

    Rodríguez-Núñez, Nuria; Rábade, Carlos; Valdés, Luis

    2014-12-09

    Pleural effusion (PE) is a very uncommon manifestation of sarcoidosis. It is equally observed in men and women, can appear at any age and in all radiologic stages, though it is more common in stages i and ii. Effusions have usually a mild or medium size and mainly involve the right side. Various mechanisms can be implicated. PE will be a serous exudate if there is an increase in the capillary permeability due to direct involvement of the pleural membrane, a chylothorax if mediastinum lymph nodes compress the thoracic duct and/or the lymphatic drainage from the pleural cavity, an hemothorax if granuloma compress or invade pleural small vessels or capillaries, and even a transudate if there is compression of the inferior vena cava, atelectasis due to complete bronchial obstruction or when the resolution of the PE is incomplete with chronic thickening of visceral pleura (trapped lung). It manifests biochemically as a pauci-cellular exudate with a predominance of lymphocytes, though there can be a preponderance of eosinophils or neutrophils. Protein concentrations are usually proportionately higher than lactate dehidrogenase, adenosine deaminase is normally low and it is possible to find increased levels of CA-125 in women. The tuberculin test is negative and pleural or lung biopsies yield the diagnosis by confirming the presence of non-caseating granulomata. These PE can have a favorable self-limited outcome, even though in most cases treatment with corticosteroids is needed, while surgery is required in a few cases. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  19. Extramedullary Acute Myeloid Leukemia: Leukemic Pleural Effusion, Case Report and Review of the Literature

    Science.gov (United States)

    Pemmaraju, Naveen; Chang, Elaine; Daver, Naval; Patel, Keyur; Jorgensen, Jeffrey; Sabloff, Bradley; Verstovsek, Srdan; Borthakur, Gautam

    2014-01-01

    Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML) with fewer than 20 cases reported (1–11). We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical Presentation: In this case, a 55-year-old man with previous history of myeloproliferative neoplasm experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based on the extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization testing are recommended. Furthermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. PMID:24918086

  20. Study of immunoglobulins in pleura and pleural effusions.

    Science.gov (United States)

    Telvi, L; Jaubert, F; Eyquem, A; Andreux, J P; Labrousse, F; Chrétien, J

    1979-01-01

    The protein concentration of 35 pleural effusions was compared with that in the serum. The ratio of the pleural and serum concentration of albumin, IgG, IgA, and IgM is always below unity and appears to have no diagnostic value. However, the ratio of the concentration of these proteins was inversely related to their molecular weight. The underlying mechanism in malignant and inflammatory effusions appear similar and is in keeping with a diffusion process. Immunofluorescent staining of the pleura suggests the intercellular passage of the proteins through the mesothelial barrier. Images PMID:384578

  1. Development of a time-resolved fluoroimmunoassay of CFP-10 for rapid diagnosis of tuberculous pleural effusion.

    Science.gov (United States)

    Lu, Jianyi; Zou, Lilin; Liu, Bin; Li, Xiaoqing; Tan, Jinrong; Zhao, Ai; Xiong, Chunhui; Li, Xiang; Lu, Jianxin; Gao, Jimin

    2015-07-01

    Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis, which is very difficult to rapidly distinguish from malignant pleural effusion in the clinical setting. A time-resolved fluoroimmunoassay (TRF) of CFP-10, a low molecular weight protein secreted by pathogenic Mycobacterium tuberculosis, was developed to differentiate tuberculous pleural effusion from malignant one. The measuring range was 0.3-187.5 ng/ml with the dose-response coefficient of 0.9998 and detection limit of 0.036 ng/ml. The intra-assay and inter-assay coefficients of variation were 3.6-9.2% and 10.0-12.4%, respectively. The concentration of CFP-10 in malignant pleural effusion was less than 0.8 ng/ml. The negative predictive value was 93.1% in malignant pleural effusion (n = 247) while the positive predictive value was 83.0% in tuberculous pleural effusion (n = 235). Moreover, there was a statistically significant difference in the CFP-10 concentration of pleural effusion between the groups before and after clinical therapy of tuberculosis (P CFP-10 may be used for the rapid diagnosis of tuberculous pleural effusion and further monitoring the clinical therapeutic efficacy of tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Prognostic features of residual pleural thickening in parapneumonic pleural effusions.

    Science.gov (United States)

    Jiménez Castro, D; Díaz, G; Pérez-Rodríguez, E; Light, R W

    2003-06-01

    The objective of the study was the identification of predictive factors for the development of residual pleural thickening (RPT) in patients with parapneumonic effusion. The design of the prospective study involved investigating patients with parapneumonic pleural effusions diagnosed between March 1991 and December 2000 in the respiratory department of Hospital Ramón y Cajal (Madrid, Spain) which is a 1,500 tertiary-care hospital. The clinical and radiological characteristics and measurements of microbiological and biochemical variables in the pleural fluid taken from the patients were studied. RPT was defined in a posteroanterior chest radiograph as pleural thickening of > or = 10 mm measured at the lateral chest wall at the level of an imaginary line, tangent to the diaphragmatic dome. A total of 48 of the 348 patients studied (13.79%) were found to have RPT. Among the factors studied, only presence of pus in the pleural space, Fine classes IV and V, temperature > or = 38 degrees C and delayed resolution of pleural effusions after diagnosis (> 15 days) were independently associated with the risk of RPT. This study showed that significant residual pleural thickening was not a common complication of parapneumonic pleural effusions. There are certain risk factors for the development of residual pleural thickening. However, this complication was not associated with long-term functional repercussions in the series of patients involved in this study.

  3. [Contribution of pleural fluid analysis to the diagnosis of pleural effusion].

    Science.gov (United States)

    Ferreiro, Lucía; Toubes, María Elena; Valdés, Luis

    2015-08-21

    Analysis of pleural fluid can have, on its own, a high diagnostic value. In addition to thoracocentesis, a diagnostic hypothesis based on medical history, physical examination, blood analysis and imaging tests, the diagnostic effectiveness will significantly increase in order to establish a definite or high probable diagnosis in a substantial number of patients. Differentiating transudates from exudates by the classical Light's criteria helps knowing the pathogenic mechanism resulting in pleural effusion, and it is also useful for differential diagnosis purposes. An increased N-terminal pro-brain natriuretic peptide, both in the fluid and in blood, in a due clinical context, is highly suggestive of heart failure. The presence of an increased inflammatory marker, such as C-reactive protein, together with the presence of over 50% of neutrophils is highly suggestive of parapneumonic pleural effusion. If, in these cases, the pH ispleural effusion is high. There remains to be demonstrated the usefulness of other markers to differentiate complicated from uncomplicated effusions. An adenosine deaminase > 45 U/L and>50% lymphocytes is suggestive of tuberculosis. If a malignant effusion is suspected but the cytological result is negative, increased concentrations of some markers in the pleural fluid can yield high specificity values. Increased levels of mesothelin and fibruline-3 are suggestive of mesothelioma. Immunohistochemical studies can be useful to differentiate reactive mesothelial cells, mesothelioma and metastatic adenocarcinoma. An inadequate use of the information provided by the analysis of pleural fluid would results in a high rate of undiagnosed effusions, which is unacceptable in current clinical practice. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. Primary pleural thymoma mimicking signs of another tumor

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-12-01

    Owing to their peculiar location and a variety of manifested histologic patterns, pleural thymomas may be confused with other neoplasms and may cause diagnostic problems clinically, radiologically, and morphologically,” the researchers explained. In their case report, Monaco and his co-authors highlighted several instances of lesions that need to be examined more closely by physicians during differential diagnosis in order to distinguish primary pleural thymoma from other neoplasms, especially malignant mesotheliomas, as in their case study. In rare instances, according to the authors, malignant mesotheliomas may have a significant infiltration of the lymphoid, thus giving rise to diagnostic mistakes. In addition, they pointed out that close similarities may exist between thymic tumors and malignant mesothelioma in small biopsies, thus making analysis problematic. “An awareness of these interpretative pitfalls is important to prevent misdiagnosis of malignant pleural mesothelioma,” they cautioned. “Because of their ectopic site and variety of histologic patterns, as well as the occurrence of an ‘invasive’ border, diagnosis of primary pleural thymomas via pleural biopsy can be very difficult, especially if the pathologist is not aware of this entity or if the typical features of thymoma are lacking,” the researchers said. Owing to the possibility of thymomas mimicking both radiological and microscopical lesions, Monaco and fellow authors stressed upon the consideration of a primary pleural thymoma in the diagnostic approach concerning pleural pathology. Their diagnosis of pleural thymoma in their patient, outlined in their case report, was established based on careful examination of histological features, combined with radiographic, and surgical findings — which they argued “should be considered essential for excluding any mediastinal involvement.” Hence, “[a] combination of clinical information, histopathologic appearance of the tumor, and

  5. Gastric schwannoma as a rare differential diagnosis of pleural effusion.

    Science.gov (United States)

    Janowitz, P; Meier, F; Reisig, J

    2002-11-01

    We report a case of solitary gastric schwannoma that initially manifested with recurrent left pleural effusion caused by an inflammatory reaction. A 75-year-old female was primarily admitted with progressive dyspnoea and left sided effusion. History as well as clinical examination, gastroscopy, computed tomography (CT) and transabdominal ultrasound of the abdomen suggested the diagnosis of a benign tumour of the stomach. The tumour was resected and a fundectomy with a security distance of 3-5 cm performed. Histological assessment revealed a large intramural schwannoma of the gastric wall, arising from the submucosal layer. There was no evidence of malignancy. During a three year follow-up the patient has not shown any evidence of relapse or pleural effusion. This is a very rare manifestation of this benign tumour, representing a rare differential diagnosis in a case of left sided pleural effusion.

  6. Tuberculous pleural effusion.

    Science.gov (United States)

    Ferreiro, Lucía; San José, Esther; Valdés, Luis

    2014-10-01

    Tuberculous pleural effusion (TBPE) is the most common form of extrapulmonary tuberculosis (TB) in Spain, and is one of the most frequent causes of pleural effusion. Although the incidence has steadily declined (4.8 cases/100,000population in 2009), the percentage of TBPE remains steady with respect to the total number of TB cases (14.3%-19.3%). Almost two thirds are men, more than 60% are aged between 15-44years, and it is more common in patients with human immunodeficiency virus. The pathogenesis is usually a delayed hypersensitivity reaction. Symptoms vary depending on the population (more acute in young people and more prolonged in the elderly). The effusion is almost invariably a unilateral exudate (according to Light's criteria), more often on the right side, and the tuberculin test is negative in one third of cases. There are limitations in making a definitive diagnosis, so various pleural fluid biomarkers have been used for this. The combination of adenosine deaminase and lymphocyte percentage may be useful in this respect. Treatment is the same as for any TB. The addition of corticosteroids is not advisable, and chest drainage could help to improve symptoms more rapidly in large effusions. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  7. Novel therapy for malignant pleural mesothelioma based on anti-energetic effect: an experimental study using 3-Bromopyruvate on nude mice.

    Science.gov (United States)

    Zhang, Xiaodong; Varin, Emilie; Briand, Mélanie; Allouche, Stéphane; Heutte, Natacha; Schwartz, Laurent; Poulain, Laurent; Icard, Philippe

    2009-04-01

    Most cancer cells exhibit increased anaerobic glycolysis and use this metabolic pathway for the generation of ATP as a main source of energy. This impaired metabolism of glucose, leading to the secretion of lactic acid even in the presence of oxygen, is named the Warburg effect. Because cancer cells are partly or mainly dependent on such a pathway to generate ATP, inhibition of glycolysis may slow down the proliferation or kill cells. The effect of 3-Bromopyruvate (3-BrPA) alone or associated to cisplatin on nude mice presenting intraperitoneal carcinomatosis developed after intraperitoneal injection of human mesothelioma cells (MSTO-211H) was investigated. 3-BrPA significantly prolonged survival of animals. Combined with cisplatin, it demonstrated significant benefit on survival whereas cisplatin alone had no or a mild effect. 3-BrPA may thus constitute an interesting novel anticancer drug that could be tested in humans.

  8. Ultrasound guided closed pleural biopsy versus medical thoracoscopic pleural biopsy in diagnosis of pleural diseases

    Directory of Open Access Journals (Sweden)

    K. Sobhy

    2017-01-01

    Conclusion: Both TUS guided pleural biopsy and medical thoracoscopic pleural biopsy are available to diagnose different pleural lesions each of which has its advantages and disadvantages. The proper selection of the patients for each modality will result in raising the diagnostic yield of both modalities. TUS examination before medical thoracoscopy will allow proper selection of patients, reduce incidence of complications, guide for the best site of entry and raisethe diagnostic yield of medical thoracoscopy.

  9. The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma

    Science.gov (United States)

    2012-12-01

    11-1-0574 TITLE: The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma PRINCIPAL...Mice with Pleural Mesothelioma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0574 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jonathan M...stem cells (BMSCs) as potential therapeutics against malignant mesothelioma (MM). Our over-arching goal was to determine whether fluorescently

  10. Blood culture bottle culture of pleural fluid in pleural infection.

    Science.gov (United States)

    Menzies, Sarah M; Rahman, Najib M; Wrightson, John M; Davies, Helen E; Shorten, Robert; Gillespie, Stephen H; Davies, Christopher W H; Maskell, Nick A; Jeffrey, Andrew A; Lee, Y C Gary; Davies, Robert J O

    2011-08-01

    Pleural infection is common, and has a >30% major morbidity and mortality-particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform. To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce. 62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for 'false-positive' results. The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference -2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative. Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.

  11. Pleural complications of hydatid disease

    National Research Council Canada - National Science Library

    Aribas, Olgun Kadir; Kanat, Fikret; Gormus, Niyazi; Turk, Emel

    2002-01-01

    ... into the pleural or pericardial cavity, severe and life-threatening problems can be encountered. 4-6 We present 43 cases of hydatid disease with pleural and pericardial complications and share our experiences by discussing the diagnostic and therapeutic procedures. Materials and methods The records of 145 patients with hydatid disease who had been hos...

  12. Pleurodese nos derrames pleurais malignos: um inquérito entre médicos em países da América do Sul e Central Pleurodesis for malignant pleural effusions: a survey of physicians in South and Central America

    Directory of Open Access Journals (Sweden)

    Evaldo Marchi

    2010-12-01

    Full Text Available OBJETIVO: A pleurodese é uma alternativa eficaz no controle dos derrames pleurais malignos, mas existem controvérsias a respeito de sua indicação e técnica. O objetivo deste estudo foi avaliar como é realizada a pleurodese em países da América do Sul e Central. MÉTODOS: Profissionais que realizam pleurodese responderam um questionário sobre critérios de indicação para pleurodese, técnicas utilizadas e desfechos. RESULTADOS: Nossa amostra envolveu 147 profissionais no Brasil, 49 em outros países da América do Sul e 36 em países da América Central. Mais de 50% dos participantes realizavam pleurodese somente se confirmada a malignidade no derrame pleural. Entretanto, escalas de dispneia e de status de performance eram raramente utilizadas para indicar o procedimento. Aproximadamente 75% dos participantes no Brasil e na América Central preferiam realizar a pleurodese somente no caso de recidiva do derrame, e a expansão pulmonar deveria variar de 90% a 100%. O talco slurry foi o agente mais utilizado, instilado via drenos de calibre intermediário. A toracoscopia foi realizada em menos de 25% dos casos. Febre e dor torácica foram os efeitos adversos mais comuns, e empiema ocorreu em OBJECTIVE: Pleurodesis is an effective alternative for the control of malignant pleural effusions. However, there is as yet no consensus regarding the indications for the procedure and the techniques employed therein. The objective of this study was to evaluate how pleurodesis is performed in South and Central America. METHODS: Professionals who perform pleurodesis completed a questionnaire regarding the indications for the procedure, the techniques used therein, and the outcomes obtained. RESULTS: Our sample comprised 147 respondents in Brazil, 49 in other South American countries, and 36 in Central America. More than 50% of the respondents reported performing pleurodesis only if pleural malignancy had been confirmed. However, scores on dyspnea and

  13. The diagnostic role of glycosaminoglycans in pleural effusions: A pilot study

    Directory of Open Access Journals (Sweden)

    Dougekou Georgia

    2009-02-01

    Full Text Available Abstract Background Pleural effusions are classified into transudates and exudates. Various criteria have been used with Light's et al being the most accepted ones. Glycosaminoglycans (GAGs have been detected during pleural fluids (PF analysis in various causes. In this pilot study, we investigated: (a the usefulness of GAGs in the assessment of pleural effusions, and (b whether and in what way GAGs correlate with established criteria used to indicate an exudate. Methods LDH, total protein, cholesterol and GAG levels were measured in pleural fluid and serum from 50 patients with pleural effusion. GAG levels were defined by the photometric method of Hata. The discriminative properties of pleural GAGs (pGAG, pleural fluid/serum GAG ratio (GAGR, serum GAGs (sGAG and serum LDH (sLDH were explored with ROC analysis. Results According to ROC analysis, pGAG and GAGR exhibited satisfactory discriminative properties in the separation of pleural effusions. For GAGR, at a 1.1 cut off point, sensitivity and specificity reached 75.6%; 95%CI: 60.5–87.1 and 100%; 95%CI: 47.8–100, respectively. For pGAG at a cut off value of 8.4 μg/ml, these percentages changed to 86.7%; 95%CI: 73.2–94.9 and 100%; 95%CI: 47.8–100. The study also revealed the differential role of sGAG between malignancies and benign cases, scoring 68.8%; 95%CI: 50.0–83.9 for sensitivity, and 84.6%; 95%CI: 54.5–97.6 for specificity at a 7.8 μg/ml cut off. Conclusion Our results suggest that glycosaminoglycan measurement of both serum and pleural effusions could be useful for simultaneous differentiation of exudates from transudates, and of malignant from benign exudates.

  14. The Impact of Pleural Lavage Cytology Before and After Resection on Prognosis

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    Serdar Ozkan

    2016-09-01

    Full Text Available Aim: Regardless of pleural effusion, presence of tumor in pleural cavity indicates presence of more aggressive tumor. In this study, we analysed positive tumor results in preoperative pleural lavage in operable malignant cases with no pleural fluid according to the mass and mediastinal lymph node characteristics. Material and Method: Pleural lavage before preoperative dissection and after resection was performed on 199 cases that underwent surgery for non small cell lung cancer (NSCLC. Findings of lavage were statistically evaluated based on gender, lesion shape and size, lymph node involvement in positron emission tomography- computed tomography (PET-CT, SUV-max value of lesion, localisation of the lesion, N1 and N2 metastases, local invasion findings, histopathological type of tumor and type of resection. Results: Cases included in this study were followed for four years. Ten of the cases (5% had tumor recurrence and 12 of them (6% had distant organ metastasis. In multivariable analysis, significant correlation was found between the first positive pleural lavage cytology and postoperative distant organ metastasis; the last pleural lavage cytology and tumor recurrence; postoperative distant organ metastasis and lymph node metastasis and the first positive lavage cytology; tumor recurrence and PET-CT lymph node uptake, lymph node metastasis and the last positive pleural lavage cytology. Discussion: Recently there has been an increase in studies on pleural lavage analysis and there is a need for standardization in lavage timing and sampling. We hope that positive lavage cytology, like malign effusion, will be accepted as a prognostic factor in staging as more studies based on wider series are conducted.

  15. Dosagem da atividade da adenosina deaminase no líquido pleural para o diagnóstico da tuberculose pleural Pleural fluid adenosine deaminase detection for the diagnosis of pleural tuberculosis

    Directory of Open Access Journals (Sweden)

    Morrys Casagrande Kaisemann

    2004-12-01

    Full Text Available INTRODUÇÃO: O diagnóstico da tuberculose pleural permanece um desafio, pois a sensibilidade dos testes tradicionais é baixa. O exame histopatológico da pleura é o método mais preciso, com até 80% de sensibilidade. A dosagem da adenosina deaminase foi introduzida mais recentemente, mas sua utilidade no diagnóstico da tuberculose pleural no Brasil não foi suficientemente esclarecida. OBJETIVO: Verificar a sensibilidade e a especificidade de um método experimental de dosagem da atividade da adenosina deaminase em uma série de pacientes com derrame pleural investigados entre agosto de 1998 e novembro de 2002 no Rio de Janeiro (RJ. RESULTADOS: De 137 casos, em 111 havia amostras de líquido pleural disponíveis, das quais 83 pertenciam a pacientes com tuberculose pleural. Entre os 67 pacientes testados com tuberculose pleural, 10 apresentavam co-infecção pelo vírus da imunodeficiência humana (14,9%. O valor de corte da adenosina deaminase de 35U/L foi determinado por uma curva receiver operator characteristic. A sensibilidade, especificidade, e razões de verossimilhança positiva e negativa da adenosina deaminase foram de 92,8%, 93,2%, 25,8 e 13,9, respectivamente. A média de adenosina deaminase no grupo com tuberculose pleural foi de 84,7 ± 43,1 U/L e no grupo com outras doenças de 15,9 ±11,1 U/L. Não houve diferença significativa na dosagem da adenosina deaminase entre pacientes com tuberculose pleural co-infectados ou não pelo vírus da imunodeficiência humana. CONCLUSÃO: A dosagem da adenosina deaminase no líquido pleural é um método sensível e específico para o diagnóstico da tuberculose pleural e seu uso rotineiro pode reduzir a necessidade de realização de biópsias pleurais na abordagem inicial de um derrame pleural. O valor de corte de 35U/L para a adenosina deaminase é recomendado.BACKGROUND: The diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional

  16. [Benign pleural effusion caused by asbestos exposure].

    Science.gov (United States)

    Vieira, J R; Alfarroba, E; Viegas, J; Freitas e Costa, M

    1992-05-01

    The Authors present the first case described among us of benign pleural effusion of an asbestotic origin. They stress the importance of thoracoscopy (pleuroscopy) in the diagnosis of this situation. Attention is drawn to the fact that asbestotic lesions and asbestotic bodies have been found in the lung and, in particular, in the parietal pleura as well. They emphasize the fact that exposure to asbestos was not realized by the patient, which made the clarification of the situation more difficult. It was a CT scan that showed the signs suggestive of exposure to asbestos which raised the diagnostic suspicion. They conclude that every patient with a pleural effusion must be thoroughly questioned about exposure to asbestos. Even if the exposure is accepted, they consider that one should proceed to a pleuro-pulmonar biopsy by thoracoscopy. This biopsy allows demonstration of the characteristic histopathological lesions and rule out other etiologies, namely malignancy and tuberculosis. They suggest that these patients must be highly motivated to stop any smoking and kept under periodic surveillance.

  17. Role of video-assisted thoracoscopy in patients with ovarian cancer and pleural effusion.

    Science.gov (United States)

    Cohen-Mouly, Sandra; Badia, Alain; Bats, Anne-Sophie; Barthes, Françoise; Bensaïd, Chérazade; Riquet, Marc; Lécuru, Fabrice

    2009-12-01

    To evaluate the feasibility of video-assisted thoracoscopy (VAT) for staging advanced ovarian cancer, to measure the performance of preoperative computed tomography (CT) for diagnosing pleural metastases, to assess the correlation between pleural and abdominal involvement, and to measure the impact of VAT on patient management. We retrospectively evaluated 16 VAT procedures in 15 patients with advanced ovarian malignancies and pleural effusions. The reason for VAT was either to evaluate unilateral or bilateral pleural effusions (n = 15) or to evaluate pleural metastases after neoadjuvant chemotherapy (n = 1). Preoperative CT was performed routinely, and findings were compared with those of VAT. The rates of involvement of the hepatic pedicle, mesentery, and right side of the diaphragm were compared with the rate of pleural involvement. The right side of the chest was examined 12 times; and the left side, 4 times. There were no complications; 1 procedure was stopped because of ventilatory intolerance. Video-assisted thoracoscopy identified metastases smaller than 1 cm in 5 patients and larger than 1 cm in 2 additional patients; there was no evidence of pleural involvement in 6 patients. Computed tomography had 14% sensitivity and 25% specificity for pleural status determination, using VAT biopsy as the reference standard. Pleural involvement did not correlate with involvement of the hepatic pedicle, mesentery, or right side of the diaphragm. Video-assisted thoracoscopy performs better than CT for evaluating pleural involvement in ovarian cancer. Video-assisted thoracoscopy supplies accurate data on thoracic involvement, which does not seem predictable from the peritoneal involvement. Video-assisted thoracoscopy may impact patient management.

  18. Role of pleural fluid adenosine deaminase activity and lymphocytosis in the etiological diagnosis

    Directory of Open Access Journals (Sweden)

    K Pande

    2016-09-01

    Full Text Available Background: Pleural effusion is a common medical condition with many possible underlying etiologies. However, Tuberculosis is the most common cause of pleural effusion especially in countries like Nepal. Pleural uid lymphocytosis is seen in tuberculosis, malignancy and few auto-immune diseases. Adenosine Deaminase activity (ADA level in tubercular pleural effusion is markedly increased compared to non-tubercular effusions. ADA estimation being a simple colorimetric method is suitable for the rapid diagnosis of tubercular effusion. This study aims to correlate the diagnostic ef cacy of ADA with the value of differential count (lymphocytosis in establishing different etiology of pleural effusion. Materials and Methods: This is a cross sectional study of 50 cases with pleural effusion carried out in the department of Pathology, Green city hospital for the duration of Twenty one month’s dating from October 2014 to July 2016 AD. Results: Of all, tubercular pleural effusion accounted for 26%. ADA level was raised (≥40U/L in 92% of Tubercular pleural effusion. The sensitivity and speci city of ADA alone to diagnose tubercular pleural effusion was 92% each and when lymphocytosis alone was considered sensitivity was 85% with speci city of 32% whereas the combined effect of both ADA with lymphocytosis was 100% (sensitivity and 87% (speci city, 83% (positive predictive value and 100% (negative predictive value respectively with statistically signi cant p value (<0.05. Conclusion: We can conclude that the combination of pleural uid differential count (lymphocytosis >50% and ADA level >40U/L provides with much more positive result than each component alone in differentiating tubercular effusion from other etiologies. 

  19. Pleurisy and Other Pleural Disorders

    Science.gov (United States)

    ... arthritis Cancer, such as lung cancer, lymphoma, and mesothelioma (MEZ-o-thee-lee-O-ma) Chest and ... medicine to make you sleep during the procedure. Treatment Pleurisy and other pleural disorders are treated with ...

  20. Pleural effusion following ovarian hyperstimulation.

    Science.gov (United States)

    Junqueira, Jader Joel Machado; Bammann, Ricardo Helbert; Terra, Ricardo Mingarini; Castro, Ana Cristina P; Ishy, Augusto; Fernandez, Angelo

    2012-01-01

    Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that occurs in the luteal phase of an induced hormonal cycle. In most cases, the symptoms are self-limited and spontaneous regression occurs. However, severe cases are typically accompanied by acute respiratory distress. The objective of the present study was to describe the clinical presentation, treatment, and outcome of pleural effusion associated with OHSS in three patients undergoing in vitro fertilization. The patients ranged in age from 27 to 33 years. The onset of symptomatic pleural effusion (bilateral in all cases) occurred, on average, 43 days (range, 27-60 days) after initiation of hormone therapy for ovulation induction. All three patients required hospitalization for massive fluid resuscitation, and two required noninvasive mechanical ventilation. Although all three patients initially underwent thoracentesis, early recurrence of symptoms and pleural effusion prompted the use of drainage with a pigtail catheter. Despite the high output from the pleural drain (mean, 1,000 mL/day in the first week) and prolonged drainage (for 9-22 days), the outcomes were excellent: all three patients were discharged from hospital. Although pleural effusion secondary to OHSS is probably underdiagnosed, the associated morbidity should not be underestimated, especially because it affects potentially pregnant patients. In this study, early diagnosis and appropriate supportive measures yielded favorable results, limiting the surgical approach to adequate pleural drainage.

  1. Automated anatomical description of pleural thickening towards improvement of its computer-assisted diagnosis

    Science.gov (United States)

    Chaisaowong, Kraisorn; Jiang, Mingze; Faltin, Peter; Merhof, Dorit; Eisenhawer, Christian; Gube, Monika; Kraus, Thomas

    2016-03-01

    Pleural thickenings are caused by asbestos exposure and may evolve into malignant pleural mesothelioma. An early diagnosis plays a key role towards an early treatment and an increased survival rate. Today, pleural thickenings are detected by visual inspection of CT data, which is time-consuming and underlies the physician's subjective judgment. A computer-assisted diagnosis system to automatically assess pleural thickenings has been developed, which includes not only a quantitative assessment with respect to size and location, but also enhances this information with an anatomical description, i.e. lung side (left, right), part of pleura (pars costalis, mediastinalis, diaphragmatica, spinalis), as well as vertical (upper, middle, lower) and horizontal (ventral, dorsal) position. For this purpose, a 3D anatomical model of the lung surface has been manually constructed as a 3D atlas. Three registration sub-steps including rigid, affine, and nonrigid registration align the input patient lung to the 3D anatomical atlas model of the lung surface. Finally, each detected pleural thickening is assigned a set of labels describing its anatomical properties. Through this added information, an enhancement to the existing computer-assisted diagnosis system is presented in order to assure a higher precision and reproducible assessment of pleural thickenings, aiming at the diagnosis of the pleural mesothelioma in its early stage.

  2. Pleural Nodules and Mediastinal Lymphadenopathy in a Smoker: An Unusual Case Report

    Directory of Open Access Journals (Sweden)

    Damien Desbuquoit

    2016-08-01

    Full Text Available The authors report a case of thoracic splenosis, which is the autotransplantation of splenic tissue into the pleural cavity. Splenosis in the chest is a rare entity and most often an incidental finding on chest computed tomography, typically showing solitary or multiple well-defined, noncalcified pleural nodules of variable size in the left hemithorax. It is important to include this benign pathology in the differential diagnosis among other, generally malignant, pleural lesions. Imaging clues to the diagnosis are absence of the spleen and/or associated rib fractures. Early identification of thoracic splenosis as a cause of pleural nodules can prevent unnecessary and risky invasive procedures, such as biopsy or surgery.

  3. Bilateral presentation of pleural desmoplastic small round cell tumors: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Won, You Sun; Park, Jai Soung; Jeong, Sun Hye; Paik, Sang Hyun; Lee, Heon; Cha, Jang Gyu; Koh, Eun Suk [Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-04-15

    Desmoplastic small round cell tumor (DSRCT) is a highly aggressive malignant small cell neoplasm occurring mainly in the abdominal cavity, but it is extremely rare in the pleura. In this case, a 15-year-old male presented with a 1-month history of left chest pain. Chest radiographs revealed pleural thickening in the left hemithorax and chest computed tomography showed multifocal pleural thickening with enhancement in both hemithoraces. A needle biopsy of the left pleural lesion was performed and the final diagnosis was DSRCT of the pleura. We report this unusual case arising from the pleura bilaterally. The pleural involvement of this tumor supports the hypothesis that it typically occurs in mesothelial-lined surfaces.

  4. The case for performing pleural biopsies for the aetiological diagnosis of exudates. Yes.

    Science.gov (United States)

    Rodriguez-Panadero, F

    2017-10-01

    Pleural biopsies are especially indicated in the following circumstances: a) inconclusive pleural fluid analysis and negative sputum study, if adenosine deaminase (ADA) levels are unavailable; b) suspected multi-resistant tuberculosis; c) a need for differentiating tuberculous pleurisy (if it progresses with neutrophilia) and complicated parapneumonic effusion; d) malignant pleural effusion coexisting with very high ADA levels; e) effusion coexisting with lung cancer and negative pleural cytology; f) suspected mesothelioma; and g) need for implementing re-treatment for patients with relapse after chemotherapy. Image-guided needle biopsy is recommended for cases a and b, while thoracoscopy is preferable for the other cases. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. Applications of Magnetic Resonance Imaging of the Thorax in Pleural Diseases: A State-of-the-Art Review.

    Science.gov (United States)

    Pessôa, Fernanda Miraldi Clemente; de Melo, Alessandro Severo Alves; Souza, Arthur Soares; de Souza, Luciana Soares; Hochhegger, Bruno; Zanetti, Gláucia; Marchiori, Edson

    2016-08-01

    The aim of this review was to present the main aspects of pleural diseases seen with conventional and advanced magnetic resonance imaging (MRI) techniques. This modality is considered to be the gold standard for the evaluation of the pleural interface, characterization of complex pleural effusion, and identification of exudate and hemorrhage, as well as in the analysis of superior sulcus tumors, as it enables more accurate staging. The indication for MRI of the thorax in the identification of these conditions is increasing in comparison to computerized tomography, and it can also be used to support the diagnosis of pulmonary illnesses. This literature review describes the morphological and functional aspects of the main benign and malignant pleural diseases assessed with MRI, including mesothelioma, metastasis, lymphoma, fibroma, lipoma, endometriosis, asbestos-related pleural disease, empyema, textiloma, and splenosis.

  6. CYTOLOGICAL STUDY OF PLEURAL FLUIDS AND ITS CLINICOBIOCHEMICAL CORRELATION

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    Shikha

    2015-10-01

    Full Text Available A study of analysis of 50 pleural fluids was carried out at major teaching hospital, in Mumbai over a period of three years . Of these 50 fluids were 33 were transudates and 17 exudates. Male predominance (72% was observed with the majority in 3 rd decade. Tuberculosis (30 cases was the commonest conditions associated with exudates followed by synpneumonic effusions. Majority of the tuberculous cases (80% showed WBC count between 1000 - 5000 cells/cmm. Polymorphs were predominant in synpneumonic effusions. Of the 2 cases of malignant effusion, malignant cells (well differentiated adenocarcinoma were detected in both the cases, with total WBC counts ranging between 1000 - 5000cell/cmm. The correct diagnosis of the fluid as transudate or exudate is important be cause if the fluid is exudative then further diagnostic procedures like cytopathology , pleural biopsy and other invasive procedure can be done for definite diagnosis . On the other hand, if the fluid is transudative then treatment for underlying conditions like CCF, nephrotic syndrome, cirrhosis is given. The presence of cancer cells in the fluid is a proof positive of malignancy related fluid but in 30 to 60 percent of cancer cases, cancer cells are not detected. Exfoliative cytology for malignant cells is highly specific though less sensitive (40 - 60%. Definitive diagnosis may depend upon clinical correlation and histological examination

  7. Derrame pleural de origem indeterminada Undiagnosed pleural effusion

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    Eduardo Genofre

    2006-08-01

    Full Text Available Apesar do progresso nos métodos diagnósticos, cerca de 20% dos derrames pleurais podem permanecer sem diagnóstico etiológico definido após os exames convencionais. Para tentar determinar a origem destes derrames, métodos não convencionais e procedimentos mais invasivos devem ser utilizados com o objetivo de tentar esclarecer a etiologia do derrame pleural e instituir a terapêutica mais adequada.In spite of the progress in the diagnostic methods, about 20% of the pleural effusions may remain without a proper diagnosis after the use of conventional exams. In order to determine the origin of these effusions, alternative methods and invasive procedures shall be used aiming to determine the etiology of the undiagnosed pleural effusions and institute the most appropriate therapeutics.

  8. Early dislodgement of Indwelling Pleural Catheter (IPC): a balancing act.

    Science.gov (United States)

    Tung, Alvin Hon Man; Ngai, Jenny Chun Li; Ng, Susanna So Shan; Ko, Fanny Wai San; Hui, David Shu-Cheong

    2014-03-01

    A 63-year-old nonsmoker with right malignant pleural effusion derived symptomatic benefit following drainage of his effusion. Following insertion of indwelling pleural catheter (IPC), 1.3 L of blood-stained fluid was drained into underwater sealed bottle (Atrium®), but the IPC dislodged 26 h after continuous connection. We believe that the weight of the drainage bottle (including the un-emptied fluid) and the prolonged connection time contributed to this uncommon event reported in the literature. There was no recurrence when his second IPC was connected to a drainage bag which was emptied at every 500 mL, capped at 2 h each time. An anchoring stitch should also be considered when drainage devices heavier than the manufacturer bottles are used to drain IPC.

  9. Radiology in the management of pleural disease

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    Patel, M.C.; Flower, C.D.R. [Department of Radiology, Addenbrookes Hospital, Hills Road, Cambridge CB 2 2QQ (United Kingdom)

    1997-12-01

    This is a review of the role of radiological intervention in the pleural space. It discusses the radiological management of effusions, empyemas (including the use of fibrinolytic agents), pneumothoraces and pleural thickening. (orig.) With 10 figs., 101 refs.

  10. Derrame pleural de origem indeterminada Undiagnosed pleural effusion

    OpenAIRE

    Eduardo Genofre; Antonio Monteiro da Silva Chibante; Alex Gonçalves Macedo

    2006-01-01

    Apesar do progresso nos métodos diagnósticos, cerca de 20% dos derrames pleurais podem permanecer sem diagnóstico etiológico definido após os exames convencionais. Para tentar determinar a origem destes derrames, métodos não convencionais e procedimentos mais invasivos devem ser utilizados com o objetivo de tentar esclarecer a etiologia do derrame pleural e instituir a terapêutica mais adequada.In spite of the progress in the diagnostic methods, about 20% of the pleural effusions may remain w...

  11. Evaluation of usefulness of pleural fluid adenosine deaminase in diagnosing tuberculous pleural effusion from empyema

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    Vijetha Shenoy

    2014-02-01

    Full Text Available Objective: To evaluate the utility of adenosine deaminase activity in the pleural fluid for the diagnosis of tuberculous pleural effusion from empyema of non-tubercular origin. Method: A retrospective analysis of data was performed on patients who were diagnosed to have tuberculous pleural effusion and empyema of non tubercular origin. Among 46 patients at Kasturba Hospital, Manipal University, Manipal, Karnataka, India, from November 201 2 to February 2013 who underwent pleural fluid adenosine deaminase estimation, 25 patients with tuberculous pleural effusion and 21 patients with empyema were diagnosed respectively. Adenosine deaminase in pleural fluid is estimated using colorimetric, Galanti and Guisti method. Results: Pleural fluid Adenosine Deaminase levels among tuberculous pleural effusion(109.38依 53.83 , empyema (141.20依71.69 with P=0.27. Conclusion: Pleural fluid adenosine deaminase alone cannot be used as a marker for the diagnosis of tuberculous pleural effusion.

  12. Selective accumulation and strong photodynamic effects of a new photosensitizer, ATX-S10.Na (II), in experimental malignant glioma.

    Science.gov (United States)

    Yamamoto, Junkoh; Hirano, Toru; Li, Shaoyi; Koide, Masayo; Kohno, Eiji; Inenaga, Chikanori; Tokuyama, Tsutomu; Yokota, Naoki; Yamamoto, Seiji; Terakawa, Susumu; Namba, Hiroki

    2005-11-01

    We investigated the feasibility of a novel photosensitizer, ATX-S10.Na (II), in photodynamic therapy (PDT) for glioma. First, PDT was performed in various brain tumor cell lines in vitro. Cytotoxicity depended upon both drug concentration and laser energy and the 50% inhibitory concentration ranged from 3.5 to 20 microg/ml. Next, PDT was performed in the subcutaneous and intracranial 9L tumor models in Fischer rats using ATX-S10.Na (II) and light from a 670-nm diode laser delivered by intratumoral insertion of an optical fiber. The effect of PDT on brain tumors was evaluated using magnetic resonance imaging. Sequential changes of the ATX-S10.Na (II) concentrations were also measured quantitatively by fluorospectrometry up to 12 h after intravenous administration in rats with intracranial and subcutaneous tumors. The concentration of ATX-S10.Na (II) in the brain tumor reached a maximum at 2 h after administration and the tumor/normal brain concentration ratio was as high as 131 at 8 h. Intratumoral PDT for intracranial tumors irradiated at this timing showed an obvious anti-tumor effect without severe side effects. The present study demonstrated the highly selective accumulation of ATX-S10.Na (II) in tumor tissue and its potent photodynamic effect in an experimental malignant glioma model.

  13. Silver nanoparticles alter the permeability of sheep pleura and of sheep and human pleural mesothelial cell monolayers.

    Science.gov (United States)

    Arsenopoulou, Zoi V; Taitzoglou, Ioannis A; Molyvdas, Paschalis-Adam; Gourgoulianis, Konstantinos I; Hatzoglou, Chrissi; Zarogiannis, Sotirios G

    2017-03-01

    Nanoparticles have been implicated in the development of pleural effusions in exposed factory workers while in experimental animal studies it has been shown that they induce inflammation, fibrosis and carcinogenesis in the pleura. The scope of this study was to investigate the direct effects of silver nanoparticles exposure on the membrane permeability of sheep parietal pleura, of primary sheep pleural cell monolayers and on a human mesothelial cell line. Our findings suggest that acute (30min) exposure increases the pleural permeability ex vivo, while longer (24h) exposure in vivo leads to late decrease of the pleural cell monolayers permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. PERCUTANEOUS PLEURAL BIOPSY

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    M. Bahadori

    1966-01-01

    Full Text Available I have carried out 22 biopsies in 20 Patients, in fifteen I used a Vim _ Silverman Needle, and in the remainder a curetting type Needle, In 12 cases (60% the diagnosis that was made; in 3 cases, inadequate tissue, was obtained; in two cases a fibromuscular tissue, in one case a fatty tissue and in one case the specimen was of hepatic tissue. Even with the small biopsy specimen obtained with the Needle it is easy to recognize malignant tissue if present.

  15. Diagnostic Value and Safety of Medical Thoracoscopy in the Management of Exudative Pleural Effusion

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    Mehmet Akif Özgül

    2016-12-01

    Full Text Available Objective: Medical thoracoscopy is a minimally invasive procedure that is performed by experienced pulmonologists under local anesthesia and conscious intravenous sedation. It allows direct observation and evaluation of the pleural space. Our aim is to evaluate the diagnostic efficacy and safety of this procedure while presenting our results of medical thoracoscopy performed by rigid thoracoscopy in our clinic. Methods: Thirty-seven patients who had gone thorough medical thoracoscopy between March 2011 and August 2014 were evaluated retrospectively. Results: Of these 37 patients, 26 were male and the average age was 50.94±15.38 years. Fourteen patients had right-sided pleural effusion, whereas 23 had left-sided pleural effusion. Closed pleural biopsy was performed previously in 16 patients with no diagnostic results. In 36 patients (97.3%, a specific diagnosis was achieved. One patient, diagnosed as lymphocytic pleuritis by medical thoracoscopy, underwent decortication and the pathology was consistent with biphasic malignant pleural mesothelioma. Another patient, diagnosed as chronic nonspecific pleuritis with medical thoracoscopy, underwent decortication and the diagnosis was fibrinous pleuritis characterized by extensive fibrosis. Three patients had expansion defects during the post-operative period. Hemothorax occurred in one patient that died of respiratory failure on day 34 of hospitalization. The median length of stay in the hospital after the procedure was 5 days (1–34. Conclusion: Medical thoracoscopy is a secure procedure with high diagnostic value in the management of exudative pleural effusion.

  16. Surgery for metastatic pleural extension of non-small-cell lung cancer.

    Science.gov (United States)

    Mordant, Pierre; Arame, Alex; Foucault, Christophe; Dujon, Antoine; Le Pimpec Barthes, Françoise; Riquet, Marc

    2011-12-01

    Malignant cells in the pleural fluid or pleural metastases are now classified stage IV in lung cancer and alter the treatment. Our purpose was to question the role of surgery in such patients. The clinical records of 4668 patients, who underwent lung cancer surgery, were reviewed. In some, an undiagnosed pleural malignant disease (M1a) was discovered during thoracotomy. When feasible, selected patients underwent complete surgical resection of the primary tumor and pleural nodules. We analyzed the epidemiology, pathology, and prognosis characteristics of that group (study group), as compared with the population undergoing pulmonary resection in a curative attempt (overall population) or exploratory thoracotomy in case of unexpected disseminated carcinomatous pleuritis (control group). The study group included 32 patients (25 males), mean age 59 ± 8.8 years, who underwent pneumonectomy (n = 9) or lobectomy (n = 23), associated with mediastinal lymph nodes dissection and surgical resection of associated pleural nodules. There were 21 adenocarcinomas, seven squamous cell carcinomas, two undifferentiated large cell carcinomas, and two miscellaneous tumors. Pathological node (pN) was: N0 in 10 patients (31.3%), N1 in four (12.5%), and N2 in 18 (56.3%). Five-year survival rate was 16% after resection, and 21% if the resection was a lobectomy. Complete surgical resection of non-small-cell lung cancer (NSCLC) associated with limited metastatic pleural involvement is associated with long-term survival in 16% of the cases. A review of the published data, together with the results of this series, may justify the inclusion of surgery in multimodality treatment of NSCLC patients with metastatic pleural extension. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  17. Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma

    DEFF Research Database (Denmark)

    Jepsen, Rikke Karlin; Skov, Anne Guldhammer; Skov, Birgit Guldhammer

    2014-01-01

    . The pathogenesis is unclear but might be explained by circulating tumor-associated growth factors. We present two thoracic malignancies associated with LT: adenocarcinoma of the lung (ACL) and pleural malignant mesothelioma (MM). Both malignant tumors expressed high levels of epidermal growth factor receptors...

  18. Experimental evaluation of the influence of gold nanoparticles and cerium dioxide on normal and malignant cells and tissues

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    Reznikov A.G.

    2017-10-01

    Full Text Available The results of experimental studies of the effect of gold nanoparticles (AuNPs on the organs of the reproductive system of male rats, cells and tissues of androgen-dependent prostate cancer (PCa are presented, as well as the effect of cerium dioxide nanoparticles (CeO2NPs on the testes and fertility of aging male rats. Addition of polydisperse colloidal solution of AuNPs (10-50 nm to the culture medium in a final concentration of 10 μg/ml inhibited the growth of the LNCaP culture, PCa cells, while monodisperse solution of AuNPs (20 nm caused no effect. The polydisperse colloidal solution of AuNPs arrested the growth of PCa xenografts in mice, when administered parenterally at a dose range of 0.64-6.4 μg/kg body weight. The selectivity of the drug effect on the malignant epithelium is confirmed by signs of its destruction and decrease in the epithelial stromal ratio on histological preparations of xenografts. There was no significant damaging effect of poly- and monodisperse AuNPs solutions on the organs of the reproductive system of male rats when administered for up to two weeks. The stimulating effect of a low dose of CeO2NPs (1 mg/kg b.w. administered orally on hormonal function of testes and spermatogenesis, proliferative and secretory processes in the prostate of aging male rats was established. However, fertility of animals was reduced in comparison with the control group due to immaturity of the part of spermatozoa. Thus, metal nanoparticles and their salts can have both a stimulating and destructive effect on organs and tissues, which should be taken into consideration when studying their therapeutic potential and in toxicology.

  19. Varicella-zoster infection with pleural involvement. A cytologic and ultrastructural study of a case.

    Science.gov (United States)

    Charles, R E; Katz, R L; Ordóñez, N G; MacKay, B

    1986-04-01

    Cytologic evidence of herpes viral infection within cells from body cavity effusions is extremely uncommon. The authors report the case of a 57-year-old woman who was treated with chemotherapy and irradiation for malignant lymphoma and subsequently developed disseminated varicella-zoster infection with pleural involvement. Cytologic examination of pleural fluid revealed cytopathic changes caused by the varicella-zoster virus, which were confirmed by electron microscopy and viral culture of the effusion. The cytologic and ultrastructural features of the virus-infected cells are described, and the pathogenesis of the effusion and sequence of events in varicella-zoster virus-cell interaction are discussed.

  20. [Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma].

    Science.gov (United States)

    Kishimoto, Takumi; Fujimoto, Nobukazu; Nishi, Hideyuki

    2016-05-01

    For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.

  1. Superior vena caval syndrome and ipsilateral pleural effusion: A rare presentation of anterior mediastinal thymoma

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    Anirban Das

    2014-01-01

    Full Text Available Incidence of thymic malignancies is very low. Thymoma, a tumor of thymus gland, is of epithelial origin and is most common anterior mediastinal tumor. In most cases, thymomas are localized and locally advanced thymomas may rarely present with superior vena caval obstruction (SVCO and malignant pleural deposits. Microscopically, capsular invasion is noted in case of locally advanced thymomas, which behave like a malignant neoplasm. Complete surgical removal of the tumor along with intact capsule is the treatment modality of choice in case of localized tumors. Neoadjuvant radiotherapy (RT and chemotherapy followed by surgical resection of residual tumor is useful in case of locally advanced tumors. RT is especially useful in case of SVCO to relieve the distressing respiratory symptoms. Here, we report a rare case of locally advanced thymoma, complicated by SVCO and ipsilateral pleural effusion in a 53-year-old male patient.

  2. Isolated secondary fungal infections of pleural cavity

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    Makbule Ergin

    2013-12-01

    Full Text Available Objectives: Pleural fungal infections are rare, but the incidence has been increasing with immunosuppressant diseases and use of immunosuppressive medications. In this report, we present 6 patients with pleural effusions that have been determined fungal infection. Methods: The medical records of patients with followed and treated due to fungal infection of the pleural were retrospectively reviewed. Result: The 6 cases whom was 58 of the value median for age were treated as surgical and medical due to fungal infection of the pleural cavity. Dyspnea, cough and chest pain were the most common symptoms. Fever, night sweats and expectoration are relatively rare. In 4 patients, the infections of pleural cavity developed on the bases of rheumatoid arthritis, tuberculosis, pleural mesothelioma and esophagopleural fistula. In two patients had isolated fungal infections. Cultural positivity was seen in 5 patients. Fungal hyphae were determined by cytopathology in all of the patients. As a surgical procedure, all of the patients underwent decortication or pleural biopsy and pleural irrigation. In all patients, antifungal agents were added to surgical procedures. Full recovery of infection was seen in 5 patients. One patient died. Conclusion: In immunosuppressive patients, the incidence of pleural effusions due to or associated with fungal infections are more common. Addition to culture of pleural fluid, histopathological evaluation of pleura will aid diagnosis. J Clin Exp Invest 2013; 4 (4: 443-446

  3. Ability of procalcitonin to discriminate infection from non-infective inflammation using two pleural disease settings.

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    Fiona J McCann

    Full Text Available Procalcitonin has been shown to be useful in separating infection from non-infective disorders. However, infection is often paralleled by tissue inflammation. Most studies supporting the use of procalcitonin were confounded by more significant inflammation in the infection group. Few studies have examined the usefulness of procalcitonin when adjusted for inflammation.Pleural inflammation underlies the development of most exudative effusions including pleural infection and malignancy. Pleurodesis, often used to treat effusions, involves provocation of intense aseptic pleural inflammation. We conducted a two-part proof-of-concept study to test the specificity of procalcitonin in differentiating infection using cohorts of patients with pleural effusions of infective and non-infective etiologies, as well as subjects undergoing pleurodesis.We measured the blood procalcitonin level (i in 248 patients with pleural infection or with non-infective pleural inflammation, matched for severity of systemic inflammation by C-reactive protein (CRP, age and gender; and (ii in patients before and 24-48 hours after induction of non-infective pleural inflammation (from talc pleurodesis.1 Procalcitonin was significantly higher in patients with pleural infection compared with controls with non-infective effusions (n = 32 each group that were case-matched for systemic inflammation as measured by CRP [median (25-75%IQR: 0.58 (0.35-1.50 vs 0.34 (0.31-0.42 µg/L respectively, p = 0.003]. 2 Talc pleurodesis provoked intense systemic inflammation, and raised serum CRP by 360% over baseline. However procalcitonin remained relatively unaffected (21% rise. 3 Procalcitonin and CRP levels did not correlate. In 214 patients with pleural infection, procalcitonin levels did not predict the survival or need for surgical intervention.Using a pleural model, this proof-of-principle study confirmed that procalcitonin is a biomarker specific for infection and is not affected by non

  4. High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment.

    Science.gov (United States)

    Parisi, E; Romeo, A; Sarnelli, A; Ghigi, G; Bellia, S R; Neri, E; Micheletti, S; Dipalma, B; Arpa, D; Furini, G; Burgio, M A; Genestreti, G; Gurioli, C; Sanna, S; Bovolato, P; Rea, F; Storme, G; Scarpi, E; Arienti, C; Tesei, A; Polico, R

    2017-12-01

    The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25Gy in five fractions over 5 consecutive days. We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3-54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5-24.1] compared to 19.4 months for patients not submitted to surgery. Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  5. Monitoring and assessment of tumor hemodynamics during pleural PDT

    Science.gov (United States)

    Ong, Yi Hong; Kim, Michele M.; Penjweini, Rozhin; Rodriguez, Carmen E.; Dimofte, Andrea; Finlay, Jarod C.; Busch, Theresa M.; Yodh, Arjun G.; Cengel, Keith A.; Singhal, Sunil; Zhu, Timothy C.

    2017-02-01

    Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor vasculature and stimulates the body's anti-tumor immune response. Although light fluence rate and photosensitizer concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration (FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper, we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT. A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32% higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).

  6. Pleural mesothelioma: a descriptive analysis based on a case-control study and mortality data in Ile de France, 1987-1990.

    Science.gov (United States)

    Iwatsubo, Y; Pairon, J C; Archambault de Beaune, C; Chamming's, S; Bignon, J; Brochard, P

    1994-07-01

    Incidence rates of pleural mesothelioma in Ile de France were examined for the period 1987-1990, on the basis of information collected in a case-control study. This study was designed to include all new cases of pleural mesothelioma occurring in the region. On the other hand, mortality rates from pleural malignancies in the same region were examined on the basis of death certificates recorded by INSERM for the same period. A large difference was found between the two types of data. Average annual incidence rates were 7.5 per million among men and 1.6 per million among women. Average annual mortality rates due to primary pleural malignancies were 25.2 per million in males and 8.9 per million in females. This study confirms discordances between incidence and mortality data for pleural malignancies already reported in several countries. However, contrasting with some previous reports, the annual mortality rate from pleural malignancies was higher than the incidence rate of mesothelioma in this study. This emphasizes the usefulness of a specific investigation to explain such discordances, prior to comparison of data from one country to another.

  7. The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: an institutional experience.

    Science.gov (United States)

    Rossi, Esther Diana; Bizzarro, Tommaso; Schmitt, Fernando; Longatto-Filho, Adhemar

    2015-04-01

    Fine-needle aspiration cytology (FNAC) of serous membrane effusions may fulfil a challenging role in the diagnostic analysis of both primary and metastatic disease. From this perspective, liquid-based cytology (LBC) represents a feasible and reliable method for empowering the performance of ancillary techniques (ie, immunocytochemistry and molecular testing) with high diagnostic accuracy. In total, 3171 LBC pleural and pericardic effusions were appraised between January 2000 and December 2013. They were classified as negative for malignancy (NM), suspicious for malignancy (SM), or positive for malignancy (PM). The cytologic diagnoses included 2721 NM effusions (2505 pleural and 216 pericardic), 104 SM effusions (93 pleural and 11 pericardic), and 346 PM effusions (321 pleural and 25 pericardic). The malignant pleural series included 76 unknown malignancies (36 SM and 40 PM effusions), 174 metastatic lesions (85 SM and 89 PM effusions), 14 lymphomas (3 SM and 11 PM effusions), 16 mesotheliomas (5 SM and 11 SM effusions), and 3 myelomas (all SM effusions). The malignant pericardic category included 20 unknown malignancies (5 SM and 15 PM effusions), 15 metastatic lesions (1 SM and 14 PM effusions), and 1 lymphoma (1 PM effusion). There were 411 conclusive immunocytochemical analyses and 47 molecular analyses, and the authors documented 88% sensitivity, 100% specificity, 98% diagnostic accuracy, 98% negative predictive value, and 100% positive predictive value for FNAC. FNAC represents a primary diagnostic tool for effusions and a reliable approach with which to determine the correct follow-up. Furthermore, LBC is useful for ancillary techniques, such as immunocytochemistry and molecular analysis, with feasible diagnostic and predictive utility. © 2015 American Cancer Society.

  8. Effectiveness and safety of iodopovidone in an experimental pleurodesis model

    Directory of Open Access Journals (Sweden)

    Lisete R. Teixeira

    2013-04-01

    Full Text Available OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine and immunological (Interleukin-8 [IL-8], VEGF and TGFβ parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura and microscopic (pleura and retina analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10% correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.

  9. Spontaneous esophageal-pleural fistula

    Directory of Open Access Journals (Sweden)

    Sameer Vyas

    2011-01-01

    Full Text Available Spontaneous esophageal-pleural fistula (EPF is a rare entity. We describe a case in a middle-aged female who presented with severe retrosternal chest pain and shortness of breadth. Chest computed tomography showed right EPF and hydropneumothorax. She was managed conservatively keeping the chest tube drainage and performing feeding jejunostomy. A brief review of the imaging finding and management of EPF is discussed.

  10. Talc pleurodesis in the management of persistent pleural effusion in an infant

    Directory of Open Access Journals (Sweden)

    Ali Ozdemir

    2016-06-01

    Full Text Available Pleural effusion is excessive fluid that accumulates in the pleural cavity. It predominantly occurs by infectious agents. Other various causes include congestive heart diseases, malignancies, viral diseases, trauma, hypoalbuminemia, connective tissue diseases and chromosomal abnormalities. Treatment strategies should target the responsible cause. Herein, we present a 16-month old male infant with persistent pleural effusion occuring after uncomplicated Morgagni hernia surgery who had no response to antibiotics, parenteral nutritional support and octreotide therapy that was eventually treated by pediatric surgery with talc pleurodesis. No significant advers effect was observed after administration of talc as a sclerozing agent for pleurodesis. This procedure has been rarely reported at this age group. [Cukurova Med J 2016; 41(2.000: 390-392

  11. Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Friedberg, Joseph S; Culligan, Melissa J; Mick, Rosemarie; Stevenson, James; Hahn, Stephen M; Sterman, Daniel; Punekar, Salman; Glatstein, Eli; Cengel, Keith

    2012-05-01

    Radical pleurectomy (RP) for mesothelioma is often considered either technically unfeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. Thirty-eight patients (42-81 years) underwent RP-PDT. Thirty five of 38 (92%) patients also received systemic therapy. Standard statistical techniques were used for analysis. Thirty seven of 38 (97%) patients had stage III/IV cancer (according to the American Joint Committee on Cancer [AJCC manual 7th Edition, 2010]) and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was 1 postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) patients with epithelial subtypes, and 6.8 months for the 7/38 (18%) patients with nonepithelial subtypes. Median progression-free survival (PFS) was 9.6, 15.1, and 4.8 months, respectively. The median survival and PFS for the 20/31 (64%) patients with N2 epithelial disease were 31.7 and 15.1 months, respectively. It was possible to achieve a macroscopic complete resection using lung-sparing surgery in 97% of these patients with stage III/IV disease. The survival we observed with this approach was unusually long for the patients with the epithelial subtype but, interestingly, the PFS was not. The reason for this prolonged survival despite recurrence is not clear but is potentially related to preservation of the lung or some PDT-induced effect, or both. We conclude that the results of this lung-sparing approach are safe, encouraging, and warrant further investigation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Nonselective transarterial chemoperfusion: a palliative treatment for malignant pleural mesothelioma

    National Research Council Canada - National Science Library

    Vogl, Thomas J; Lindemayr, Sebastian; Naguib, Nagy N N; Gurung, Jessen; Nour-Eldin, Nour-Eldin A; Zangos, Stephan; Mbalisike, Emmanuel C

    2013-01-01

    ... nonselective transarterial chemoperfusion as a palliative treatment option. This retrospective study was approved by the hospital ethical committee, and all patients signed an informed consent prior to treatment...

  13. Recurrence of Malignant Pleural Effusion Following Pleurodesis: Is ...

    African Journals Online (AJOL)

    Consecutive patients were enrolled by simple randomization (coin tossing) into either cyclophosphamide or povidone iodine groups by two of the authors (AS ..... J Surg. 2011;17:29-38. 11. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the East Cooperative. Oncology Group. Am J Clin Oncol.

  14. Malignant Pleural Mesothelioma Prognostic Marker: A Review of ...

    African Journals Online (AJOL)

    Erah

    extracellular matrix were positive for osteopontin. Osteopontin expression was observed in ... vesicles. In the LS (long-term survival) group, the distribution of HScore values of osteopontin expression varied from 5 to 250 (median, 50), whereas in the SS (short term survival) group, HScore values varied from 30 to 297.

  15. Postoperative pleural effusion following upper abdominal surgery

    DEFF Research Database (Denmark)

    Nielsen, P H; Jepsen, S B; Olsen, A D

    1989-01-01

    Of 128 patients who underwent upper abdominal surgery, examined by standard preoperative and postoperative chest roentgenograms for the formation of postoperative pleural effusions, 89 had postoperative pleural effusions. Their presence was not related to the type of operation, infection, serum...... to postoperative sodium and water retention, and aggravated by an age-related relative cardiac decompensation. Early postoperative pleural effusions are common and do not require specific treatment....

  16. Pleural small cell carcinoma in pre-existent asbestos related pleural disease.

    NARCIS (Netherlands)

    Heijden, E. van der; Heijdra, Y.F.; Bulten, J.; Festen, J.

    2002-01-01

    Extrapulmonary small cell carcinoma (SCC) is a very rare disease, and a primary pleural manifestation is extremely rare. A case of SCC of the pleura in a 66-year-old man with pre-existent asbestos-related pleural plaques is presented. This is the first case of pleural SCC in a patient with

  17. Discrimination between pleural thickening and minimal pleural effusion using color Doppler chest ultrasonography

    Directory of Open Access Journals (Sweden)

    Ali A. Hasan

    2013-07-01

    Conclusions: Application of color Doppler examination increases the accuracy of real time chest ultrasound to discriminate pleural thickening from minimal pleural effusion and hence color Doppler examination proved to be a useful diagnostic tool to real-time gray-scale ultrasound for diagnosis of minimal pleural effusion.

  18. A PILOT AND FEASIBILITY CLINICAL TRIAL EVALUATING IMMUNO-GENE THERAPY OF MALIGNANT PLEURAL MESOTHELIOMA (MPM) USING INTRAPLEURAL DELIVERY OF ADENOVIRUS- INTERFERON-ALPHA (Ad.hIFN-α2b) IN COMBINATION WITH HIGH-DOSE CELECOXIB AND SYSTEMIC CHEMOTHERAPY

    Science.gov (United States)

    Sterman, Daniel H; Alley, Evan; Stevenson, James; Friedberg, Joseph; Metzger, Susan; Recio, Adri; Moon, Edmund; Haas, Andrew R; Vachani, Anil; Katz, Sharyn I; Sun, Jing; Heitjan, Daniel F; Hwang, Wei-Ting; Litzky, Leslie; Yearley, Jennifer H; Tan, Kay See; Papasavvas, Emmanouil; Kennedy, Paul; Montaner, Luis J.; Cengel, Keith; Simone, Charles B; Culligan, Melissa; Langer, Corey J; Albelda, Steven M

    2016-01-01

    Purpose “In situ vaccination” using immuno-gene therapy has the ability to induce polyclonal anti-tumor responses directed by the patient’s immune system. Experimental Design Patients with unresectable MPM received two intrapleural doses of a replication-defective adenoviral vector containing the human interferon-alpha2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Bio-correlates on blood and tumor were measured. Results Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n=7) or gemcitabine (n=15). Treatment was generally well tolerated. The overall response rate was 25% and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with non-epithelial histology. MOS in the first-line cohort was 12.5 months, while MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of interferon-α in blood or pleural fluid, induction of anti-tumor antibodies, nor an immune-gene signature in pretreatment biopsies. Conclusions The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. Overall survival rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multi-center randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. PMID:26968202

  19. Advanced medical interventions in pleural disease

    Directory of Open Access Journals (Sweden)

    Rahul Bhatnagar

    2016-06-01

    Full Text Available The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease.

  20. [Pleural effusion--which diagnosis is significant?].

    Science.gov (United States)

    Hügel, Ulrike

    2007-01-01

    Although many different diseases may cause a pleural effusion the most common causes are congestive heart failure, pneumonie, and cancer. The first step in the diagnosis of pleural effusion is the distinction between exudates and transudates. Because of their high sensitivity Light's criteria, which differentiate transudative effusions from exudative effusions by measuring the levels of total protein and lactate dehydrogenase in the pleural fluid and serum, have become the standard method for making this distinction. Aim of this article was to mention the various parameters and their usefulness in closer characterication of pleural effusion.

  1. Microfilaria in pleural effusion: An unusual association

    Directory of Open Access Journals (Sweden)

    Rehena Sarkar

    2016-01-01

    Full Text Available Lymphatic filariasis is a major public health problem in tropical countries and India is endemic for it. However, lymphatic filariasis presenting as pleural effusion is an unusual manifestation and finding microfilaria in pleural effusion without any lung pathology is rare. We report a case of pleural effusion without any underlying lung pathology and normal blood picture. Clinical cure occurred after treatment with diethyl-carbamazepine. Filariasis should be kept in view while considering the differential diagnosis of idiopathic pleural effusion, especially in endemic countries.

  2. Tru-cut needle pleural biopsy and cytology as the initial procedure in the evaluation of pleural effusion.

    Science.gov (United States)

    Botana Rial, Maribel; Briones Gómez, Andrés; Ferrando Gabarda, José Ramón; Cifuentes Ruiz, José Fernando; Guarín Corredor, María Juliana; Manchego Frach, Nuria; Cases Viedma, Enrique

    2014-08-01

    The evaluation of pleural effusion (PE) includes various techniques, including pleural biopsy (PB). Our aim was to study the diagnostic yield of Tru-Cut needle PB (TCPB) and to define clinical/radiological situations in which TCPB might be indicated as an initial procedure. Retrospective study of TCPB in a hospital centre (2010-2012). Cases of pleural lesions without effusion were excluded. Clinical and radiological variables, diagnostic yield, TCPB complications and factors associated with the diagnostic yield of the combination of TCPB and thoracocentesis as initial procedure were analysed. One hundred and twenty-seven (127) TCPB were reviewed: 29.1% were cases of malignant PE and in 18.9% the cause of the PE could not be determined. The diagnostic yield of TCPB for tuberculosis was 76.5% (13/17) and 54% (20/37) for malignant PE. Complications occurred in 4.7% of the cases. In 72 patients with a final definitive diagnosis, TCPB was performed at the same time as the initial thoracocentesis. Diagnostic yield for the combination of TCPB/cytology as an initial technique was 43% (31/72) compared to 12.5% (9/72) for cytology only (p=0.01). The only predictive variable for the indication of TCBP as an initial technique was a PE volume>2/3 (P=.04). TCPB is safe and provides an acceptable diagnostic yield, particularly when combined with simultaneous cytology in the evaluation of PE of various aetiologies. Radiological criteria may help guide the selection of patients who could benefit from this technique as an initial procedure combined with thoracocentesis. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  3. Tumor markers in pleural effusion caused by bronchogenic carcinoma and tuberculosis

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2002-01-01

    Full Text Available Concentrations of carcinoembryonic antigen (CEA and carbon hydrate antigen (CA 50 were measured in pleural effusion and sera of 57 patients with bronchogenic carcinoma and in 73 patients in whom the effusion was the sequelae of tuberculosis pleurisy. In the group with bronchogenic carcinomas plan cellular was confirmed in 19, micro cellular in 17, macro cellular in 2 and adenocarcinoma in 18, while in 1 patient it was not possible to determine the histopathologic structure. The diagnosis of pleural disease was established upon the cytologic examination of the effusion and histopathologic examination of the pleural sample obtained by blind percutaneous needle biopsy or following pleuroscopy. CEA concentration in the sera of patients with bronchogenic carcinoma was significantly higher than in the patients with tuberculosis (p<0.001, with sensitivity of 44% and ideal specificity and positive predictive value of 100%. In the same group highly significant difference of mean values of CEA concentrations in pleural effusion (p<0.001, was also found with sensitivity of 60%, significant specificity of 99% and positive predictive value of 97%. CA 50 concentrations in the sera of patients with lung carcinoma were significantly higher than those in the sera of patients with tuberculosis pleurisy (p<0.05, and the sensitivity was 50%, while the specificity was 94% and positive predictive value was 75%. Significantly higher was also the value in the pleural effusion (p<0.05, but the sensitivity was slightly lower - 40%, but specificity was favorable as well as the positive predictive value (94 and 86%, respectively. The results indicate the significance of the determination of CEA and CA 50 in the sera and pleural effusion in the differentiation of malignant from tuberculosis pleural effusion.

  4. Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.

    Science.gov (United States)

    Solari, Lely; Soto, Alonso; Van der Stuyft, Patrick

    2017-10-01

    Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT. © 2017 John Wiley & Sons Ltd.

  5. Pleural infections: a 9-year review of bacteriology, case characteristics and mortality.

    Science.gov (United States)

    White, Heath D; White, Bobbie Ann A; Song, Juhee; Fader, Robert; Quiroga, Pedro; Arroliga, Alejandro C

    2013-05-01

    Despite advances in medical therapies, pleural infections remain a common disease. The characteristics of this disease seem to change over time, with alterations in patient characteristics and bacteriology. The purpose of this study was to provide a retrospective descriptive analysis of pleural infections during a 9-year period. We performed a single-center retrospective review of all culture-positive pleural infections between January 2000 and December 2008. The primary outcome was assessment of long-term survival and associated independent risk factors affecting survival. Length of survival was determined using the Social Security Death Index. Case characteristics and bacteriology were reviewed for descriptive analysis. During a 9-year period, 187 culture-positive pleural infections were identified. Review of bacteriology revealed gram-positive cocci as the predominate organisms, most commonly Streptococcus and Staphylococcus. Anaerobes were found in 9.1% of the cases. Independent risk factors associated with risk of death based on multivariable survival analysis were age older than 65, cirrhosis and past and present malignancy. The hospital mortality was 10.7%, and the 1-year, 3-year and 5-year estimated survival rates were 73.8%, 63.3% and 60.6%, respectively. Pleural infections continue to remain a major health problem and carry significant morbidly and mortality. The importance of Staphylococcus aureus in this population has yet to be fully examined, and although potentially underestimated in this study, anaerobic infections remain a common pathogen.

  6. Factors influencing pleural drainage in parapneumonic effusions.

    Science.gov (United States)

    Porcel, J M; Valencia, H; Bielsa, S

    2016-10-01

    The identification of parapneumonic effusions (PPE) requiring pleural drainage is challenging. We aimed to determine the diagnostic accuracy of radiological and pleural fluid findings in discriminating between PPE that need drainage (complicated PPE (CPPE)) and those that could be resolved with antibiotics only (uncomplicated PPE (UPPE)). A retrospective review of 641 consecutive PPE, of which 393 were categorized as CPPE and 248 as UPPE. Demographics, radiological (size and laterality on a chest radiograph) and pleural fluid parameters (pus, bacterial cultures, biochemistries) were compared among groups. Logistic regression was performed to determine variables useful for predicting chest drainage, and receiver-operating characteristic curves assisted in the selection of the best cutoff values. According to the likelihood ratios (LR), findings increasing the probability of chest tube usage the most were: effusions occupying ≥1/2 of the hemithorax (LR 13.5), pleural fluid pH ≤7.15 (LR 6.2), pleural fluid glucose ≤40mg/dL (LR 5.6), pus (LR 4.8), positive pleural fluid cultures (LR 3.6), and pleural fluid lactate dehydrogenase >2000U/L (LR 3.4). In the logistic regression analysis only the first two were selected as significant predictors of CPPE. In non-purulent effusions, the effusion's size and pleural fluid pH retained their discriminatory properties, in addition to a pleural fluid C-reactive protein (CRP) level >100mg/L. Large radiological effusions and a pleural fluid pH ≤7.15 were the best predictors for chest drainage in patients with PPE. In the subgroup of patients with non-purulent effusions, pleural fluid CRP also contributed to CPPE identification. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  7. Streptococcus milleri infections of the pleural space: operative management predominates.

    Science.gov (United States)

    Ripley, R Taylor; Cothren, C Clay; Moore, Ernest E; Long, Jeffrey; Johnson, Jeffrey L; Haenel, James B

    2006-12-01

    Management of patients with thoracic empyema ranges from tube thoracostomy drainage, with or without fibrinolytics, to operative intervention, with the optimal intervention remaining uncertain. Streptococcus milleri, typically a benign bacterium colonizing the oropharynx, has recently been reported as a potential pathogen in pneumonia and pleural space disease. Our initial experience indicated this infection, when in the pleural space, was particularly tenacious and often required major operative intervention to eradicate. Therefore, we hypothesized that patients with S milleri pleural space infections often require operative intervention as definitive treatment. We reviewed all patients from June 17, 1999 to April 15, 2005 with S milleri infections at our level I academic trauma/acute care surgery department at a safety-net hospital. S milleri infections were diagnosed by thoracentesis, bronchoalveolar lavage, tube thoracostomy fluid, or intraoperative culture. Over the 70-month period evaluated, of 697 patients with S milleri infections, 39 patients had S milleri infections of the pleural space; 26 (67%) patients underwent operative intervention. The majority (72%) were men with a mean age of 46 (range 22 to 63); the underlying etiology in those patients requiring operation was pneumonia (26 patients; 67%), trauma (9 patients; 23%), postoperative infection (2 patients), foreign body ingestion (1 patient), and malignancy (1 patient). The vast majority of patients in the operative group were treated preoperatively with tube thoracostomy (88%) and antibiotics (96%). The average duration of chest tube drainage prior to operation was 4.4 days (95% confidence interval [CI] 2.6 to 6.2) and antibiotic treatment was 6.0 days (95% CI 3.8 to 8.2). Thirteen patients (50%) underwent video-assisted thoracoscopic surgery (VATS) and 13 patients required thoracotomy. VATS was performed more often when operative intervention occurred early (average hospital day 6.2) compared to

  8. Charcot-Leyden crystals in pleural fluids.

    Science.gov (United States)

    Naylor, B; Novak, P M

    1985-01-01

    Charcot-Leyden crystals have rarely been reported in serous fluids. We present eight examples of Charcot-Leyden crystals, all found in eosinophilic pleural effusions. The crystals were found in toluidine blue-stained wet films of pleural fluid after either the fluid or the wet film had stood for at least 24 hours at 4 C.

  9. Differential diagnosis of pleural mesothelioma using Logic Learning Machine.

    Science.gov (United States)

    Parodi, Stefano; Filiberti, Rosa; Marroni, Paola; Libener, Roberta; Ivaldi, Giovanni Paolo; Mussap, Michele; Ferrari, Enrico; Manneschi, Chiara; Montani, Erika; Muselli, Marco

    2015-01-01

    Tumour markers are standard tools for the differential diagnosis of cancer. However, the occurrence of nonspecific symptoms and different malignancies involving the same cancer site may lead to a high proportion of misclassifications. Classification accuracy can be improved by combining information from different markers using standard data mining techniques, like Decision Tree (DT), Artificial Neural Network (ANN), and k-Nearest Neighbour (KNN) classifier. Unfortunately, each method suffers from some unavoidable limitations. DT, in general, tends to show a low classification performance, whereas ANN and KNN produce a "black-box" classification that does not provide biological information useful for clinical purposes. Logic Learning Machine (LLM) is an innovative method of supervised data analysis capable of building classifiers described by a set of intelligible rules including simple conditions in their antecedent part. It is essentially an efficient implementation of the Switching Neural Network model and reaches excellent classification accuracy while keeping low the computational demand. LLM was applied to data from a consecutive cohort of 169 patients admitted for diagnosis to two pulmonary departments in Northern Italy from 2009 to 2011. Patients included 52 malignant pleural mesotheliomas (MPM), 62 pleural metastases (MTX) from other tumours and 55 benign diseases (BD) associated with pleurisies. Concentration of three tumour markers (CEA, CYFRA 21-1 and SMRP) was measured in the pleural fluid of each patient and a cytological examination was also carried out. The performance of LLM and that of three competing methods (DT, KNN and ANN) was assessed by leave-one-out cross-validation. LLM outperformed all other considered methods. Global accuracy was 77.5% for LLM, 72.8% for DT, 54.4% for KNN, and 63.9% for ANN, respectively. In more details, LLM correctly classified 79% of MPM, 66% of MTX and 89% of BD. The corresponding figures for DT were: MPM = 83%, MTX

  10. Asbestos-related pleural disease

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2013-06-01

    Full Text Available The image shows asbestos plaques on the right parietal pleura of a 58-year-old former shipyard worker who died of acute suppurative bronchitis. He also had cor pulmonale and congestive heart failure. Histologically, pulmonary interstitial fibrosis with asbestos bodies was demonstrated. The pleural plaques consist predominantly of dense collagen. This photograph was taken after removal of the lung with the camera held in the lower right thorax, at approximately the level of the diaphragm, looking up toward the apex of the chest cavity.

  11. Derrame pleural causado por Tiamazol

    OpenAIRE

    Silva, Filipa Castanheira Dinis Duarte

    2016-01-01

    Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016 Os fármacos anti-tiroideus estão associados a um número significativo de reacções adversas, nomeadamente febre, rash, artralgias, agranulocitose e hepatite. As complicações pleurais são muito raras. Na literatura estão descritos cinco casos de derrame pleural induzido por estes fármacos, dois associados ao propiltiouracilo e três casos induzidos pelo carbimazol. Apresenta-se o ...

  12. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01