WorldWideScience

Sample records for pleural mesothelioma heparanase-assisted

  1. Malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Wentz, K.U.; Irngartinger, G.; Georgi, P.; Kaick, G. van; Kleckow, M.; Vollhaber, H.H.; Deutsches Krebsforschungszentrum, Heidelberg; Krankenhaus Rohrbach

    1986-01-01

    In 34 patients with suspected malignant pleural mesothelioma the results of computed tomography are compared with the findings of 67 Ga-scintigraphy. The differential diagnosis of 14 pleural mesotheliomas, 7 pleural carcinoses, 10 inflammatory and 3 other pleural diseases is performed more accurately by CT than by scintigraphy. 67 Ga uptake depends on the thickness of inflammatory as well as malignant lesions. Thus, numerous pleural processes that can be localised by CT escape scintigraphic detection, CT is indicated if there is clinical and radiological suspicion of pleural mesothelioma; in that case, there is hardly any indication for 67 Ga scintigraphy. (orig.)

  2. Pleural mesothelioma - case report.

    Science.gov (United States)

    Klawiter, Anna; Damaszke, Tomasz

    2010-10-01

    Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Although no neoplastic cells were found in the thoracoscopic specimen from the supradiaphragmatic tumor, we assumed that to be a case of a diffuse, primarily local form of mesothelioma. Diagnostics of pleural mesothelioma is very difficult. CT and thoracoscopy seem to be very valuable diagnostic methods. It is worth remembering that pleural mesothelioma can have a local form which may transform into a diffuse one.

  3. Clinical diagnosis of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Nishi, Hideyuki; Washio, Kazuhiro; Mano, Masayuki

    2008-01-01

    We evaluated clinical and thoracoscopic findings of cases that underwent thoracoscopic biopsy for the diagnosis of malignant pleural mesothelioma. We reviewed 32 cases suspected of having malignant pleural mesothelioma from 2003 to 2006. We made a diagnosis of malignant pleural mesothelioma via thoracoscopic biopsy (19 cases). The cut-off level of hyaluronic acid in malignant effusions, selected on the basis of the best diagnostic efficacy, was 100 μg/ml. We can decrease the incidence of false negative cases by the combination of CT findings and the presence of hyaluronic acid in pleural effusion. In the pleural thickening type of thoracoscopic appearance, the parietal pleurae were thickened, and small nodules were rare. As for this type, tumor cells were histologically absent or confined to the submesothelial tissue. We considered that determinations of specific sites were difficult. Adequate tissue samples obtained via video-assisted thoracoscopy were necessary for diagnosis. We can decrease the incidence of false negative cases by the combination of the presence of hyaluronic acid in pleural effusion and thoracoscopic biopsy. (author)

  4. Pleural mesothelioma – case report

    International Nuclear Information System (INIS)

    Klawiter, Anna; Damaszke, Tomasz

    2010-01-01

    Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Although no neoplastic cells were found in the thoracoscopic specimen from the supradiaphragmatic tumor, we assumed that to be a case of a diffuse, primarily local form of mesothelioma. Diagnostics of pleural mesothelioma is very difficult. CT and thoracoscopy seem to be very valuable diagnostic methods. It is worth remembering that pleural mesothelioma can have a local form which may transform into a diffuse one

  5. Radiologic diagnosis of pleural mesothelioma

    International Nuclear Information System (INIS)

    Fujimoto, Toshifumi; Hayashi, Kuniaki; Matsunaga, Naofumi

    1989-01-01

    Five cases of pleural mesothelioma (3 benign and 2 malignant) were evaluated with chest radiograph and CT. A case of benign localized mesothelioma growing within the major fissure, and a case of diffuse malignant mesothelioma encircling the descending thoracic aorta are included among the five cases. Pleural mesotheliomas present a variety of roentgenographic manifestations depending upon the histologic type, the site of origin, and the direction of the extension, and can easily be misdiagnosed as lung tumor, aortic aneurysm, or mediastinal tumor. It is emphasized that pleural mesothelioma should be considered as a differential diagnosis when a mass lesion is found in the mediastinum, hilar region, interlobar fissure, or near the chest wall. (author)

  6. 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.

  7. Computed tomography findings of malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Shiota, Yutaro; Sato, Toshio; Yamaguchi, Kazuo; Ono, Tetsuya; Kaji, Masaro; Niiya, Harutaka (Kure Kyosai Hospital, Hiroshima (Japan))

    1994-04-01

    Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleural into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions in malignant mesothelioma. (author).

  8. Computed tomography findings of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Shiota, Yutaro; Sato, Toshio; Yamaguchi, Kazuo; Ono, Tetsuya; Kaji, Masaro; Niiya, Harutaka

    1994-01-01

    Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleural into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions in malignant mesothelioma. (author)

  9. Radiation therapy for pleural mesothelioma

    International Nuclear Information System (INIS)

    Seydel, H.G.

    1986-01-01

    There is clear evidence that both pleural and peritoneal malignant mesothelioma are increasing in incidence in the United States. There is a recognized long period of latency from asbestos exposure to the emergence and diagnosis of tumor. Considering the levels of asbestos utilization in the mid-20th century, we must expect that the number of cases will continue to increase until the end of this century. Evaluation of treatment options is thus a critical issue in determining treatment approaches for this disease. Recognized only recently, mesothelioma has no effective treatment, and patients are reported only anecdotally as cured. Pleural mesothelioma is the more common presentation, but even here the reports are from small, uncontrolled series. Only one study is available in which a concomitant comparison of treatment methods was carried out. Randomized clinical studies regarding treatment of pleural mesothelioma have only recently been initiated by the clinical cooperative groups. There is thus a paucity of information on treatment in general and radiation therapy specifically for malignant mesothelioma. This chapter reviews the reported experience using radiation therapy alone and combined with other modalities for the treatment of malignant pleural mesothelioma and considers the potential for improvement of the results of current methods of radiation therapy

  10. Pleural mesothelioma – case report

    OpenAIRE

    Klawiter, Anna; Damaszke, Tomasz

    2010-01-01

    Summary Background: Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. Case Report: We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Althoug...

  11. Localized malignant pleural mesothelioma: report of two cases.

    Science.gov (United States)

    Tanzi, Silvia; Tiseo, Marcello; Internullo, Eveline; Cacciani, Giancarlo; Capra, Roberto; Carbognani, Paolo; Rusca, Michele; Rindi, Guido; Ardizzoni, Andrea

    2009-08-01

    Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.

  12. [Molecular heterogeneity of malignant pleural mesotheliomas].

    Science.gov (United States)

    Tranchant, Robin; Montagne, François; Jaurand, Marie-Claude; Jean, Didier

    2018-01-01

    Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2 LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2 LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Compensation of pleural mesothelioma in France: data from the French National Mesothelioma Surveillance Programme.

    Science.gov (United States)

    Chamming's, Soizick; Clin, Bénédicte; Brochard, Patrick; Astoul, Philippe; Ducamp, Stéphane; Galateau-Salle, Fançoise; Ilg, Annabelle Gilg Soit; Goldberg, Marcel; Gramond, Céline; Imbernon, Ellen; Rolland, Patrick; Pairon, Jean-Claude

    2013-02-01

    The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France. The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed. Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease. Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France. Copyright © 2012 Wiley Periodicals, Inc.

  14. Pleural mesothelioma in Costa Rica

    International Nuclear Information System (INIS)

    Maineri-Hidalgo, Jose Alberto; Putvinsky, Vladimir; Mainieri-Breedy, Giovanna

    2006-01-01

    The mesothelioma is a neoplasia originated in the serous membranes that drape the cellomic cavities and there cover the visceras that they contain, whose development has related to the exhibition to the asbestos. The present study describes the characteristics of the cases of mesothelioma pleural diagnosed in 3 adults hospitals in Costa Rica. 29 cases of pleural mesothelioma were found between 1972 and 2002 after reviewing the pathology service archives of the 3 national general hospitals of the Costa Rican social security health system. The incidence rate in 2002 was 1 case per 2 million; there were 15 females and 14 males, with a mean age of 54 years. Twenty cases presented with pleural effusion being dyspnea, chest pain, cough, fever and weight loss the most frequent symptoms. The disease was detected in all the cases because of an abnormal chest X-ray. The method used to obtain tissue for histological diagnosis was thoracotomy for 15 cases, pleural biopsy in 8, thoracoscopy in 4 and autopsy in 2. The histological diagnosis in 16 cases was fibrous mesothelioma, 10 malignant and 6 benign, 11 were epithelial (all malignant) and 2 were malignant mixed mesothelioma. The treatment in all the benign cases was surgical resection and none recurred. Two of the malignant lesions were resected, 1 had an extrapleural pneumonectomy along with pericardial and diaphragmatic resection, but the survival was not better than the rest of the malignant cases, with an average survival rate for all of them of only 6 months. Chemotherapy and radiotherapy showed no additional benefit. (author) [es

  15. Video-assisted thoracoscopic PlasmaJet ablation for malignant pleural mesothelioma.

    Science.gov (United States)

    Perikleous, Periklis; Asadi, Nizar; Anikin, Vladimir

    2018-01-01

    The role of surgery in malignant pleural mesothelioma (MPM) remains debatable; nonetheless the relative advantages of different surgical approaches are frequently reassessed and reconsidered. While extensive operations and longer recovery periods can be justified for a group of carefully selected patients, many will present at an advanced stage of their disease or with associated co-morbidities which will exclude them from selection criteria for radical treatment. For these patients, minimally invasive video-assisted procedures may be considered, for purposes of cytoreduction and/or symptomatic relief. Even though there is currently not enough clinical evidence to suggest an improvement in overall survival with limited debulking procedures, it has been suggested that they can improve quality of life over drainage and pleurodesis alone. We consider video-assisted PlasmaJet ablation to potentially have a role in mesothelioma surgery, as it may be used for effective cytoreduction while minimising the risk for complications often associated with extensive pleurectomy procedures, and we report on the use of the PlasmaJet Surgical System in our centre for surgical management of a patient with MPM. After demonstrating safety and absence of major adverse events with this approach, we feel justified in offering the procedure to more of our patients as we aim to collect additional data.

  16. Malignant pleural mesothelioma in a 13-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, M.; Konez, O.; Patel, D. [Department of Radiology, Children' s Hospital Medical Center of Akron, OH (United States); Department of Radiology, Aultman Hospital, Canton, OH (United States); Swanson, K.F.; Vyas, P.K. [Department of Radiology, Children' s Hospital Medical Center of Akron, OH (United States)

    2000-11-01

    Pleural mesothelioma is an uncommon tumor in all age groups, but is especially rare in childhood. We describe the clinical and radiological features of malignant pleural mesothelioma in a 13-year-old girl. The chest radiograph showed nearly complete opacification and loss of volume in the left hemithorax. Computed tomography demonstrated a large pleural effusion centrally surrounded by a thick enhancing rind of soft tissue. The radiological features of childhood pleural mesothelioma in our case were similar to those described in adults with this disease. (orig.)

  17. Malignant pleural mesothelioma in a 13-year-old girl

    International Nuclear Information System (INIS)

    Goyal, M.; Konez, O.; Patel, D.; Swanson, K.F.; Vyas, P.K.

    2000-01-01

    Pleural mesothelioma is an uncommon tumor in all age groups, but is especially rare in childhood. We describe the clinical and radiological features of malignant pleural mesothelioma in a 13-year-old girl. The chest radiograph showed nearly complete opacification and loss of volume in the left hemithorax. Computed tomography demonstrated a large pleural effusion centrally surrounded by a thick enhancing rind of soft tissue. The radiological features of childhood pleural mesothelioma in our case were similar to those described in adults with this disease. (orig.)

  18. Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Tanaka, Toshiki; Tao, Hiroyuki; Hayashi, Tatsuro; Yoshiyama, Koichi; Furukawa, Masashi; Yoshida, Kumiko; Okabe, Kazunori

    2015-12-01

    A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. CT diagnosis and differential diagnosis of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Xiong Juxin; Yang Zenian; Luo Zhongyao

    2008-01-01

    Objective: To study the CT features of malignant pleural mesothelioma and improve diagnostic accuracy. Methods: The CT findings of 14 patients with malignant pleural mesothelioma proven by surgery or histopathology were analyzed retrospectively. CT plain scan was performed in all cases, 9 cases received both CT plain scan and contrast CT scan. Results: All the cases demonstrated various pleural thickening including diffuse pleural thickening (n=10). Among all the cases, there were nodular pleural thickening (n=4), lumpy pleural thickening (n=7), ring-like pleural thickening (n=3). Pleural thickness which was more than 1.0 cm was found in 12 cases. Pleural effusion (n=10), mediastinum immobilization (n=10) and thoracic cavity stricture in the trouble side (n=10) were also revealed. Conclusion: Obvious characteristics in cases with malignant pleural mesothelioma was showed in CT examination, which plays an important role in the diagnosis and differential diagnosis of this disease. (authors)

  20. Malignant pleural mesothelioma in a nuclear engineer

    International Nuclear Information System (INIS)

    Huncharek, M.

    1988-01-01

    Malignant pleural mesothelioma accounts for a large proportion of deaths among occupational cohorts exposed to asbestos. Of particular interest are recent reports of a high risk of mesothelioma among occupational groups previously thought to be at low risk for developing this neoplasm. In the present report we present a case of pleural mesothelioma associated with bystander exposure to asbestos in a nuclear engineer. To our knowledge, this is the first report of the disease occurring in a member of this occupational group after work related exposure to asbestos. (author)

  1. Novel therapies for malignant pleural mesothelioma.

    Science.gov (United States)

    Scherpereel, Arnaud; Wallyn, Frederic; Albelda, Steven M; Munck, Camille

    2018-03-01

    Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. [Malignant pleural mesothelioma].

    Science.gov (United States)

    Sritharan, Sajitha Sophia; Frandsen, Jens Lundby; Omland, Øyvind; Bruun, Jens Meldgaard

    2018-04-09

    Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.

  3. External radiotherapy in a pleural mesothelioma tumor

    International Nuclear Information System (INIS)

    Fernandez, M.C.; Garcia, J.L.; Gomez, A.; Simon, J.L.; Maillo, M.; Jimenez Torres, M. J.

    1994-01-01

    Pleural mesothelioma is an uncommon tumor compared with other thoracic malignancies and a 80% of the cases have asbestos exposure. From 1983 to 1992 we have examined patients suffering from malignant pleural mesothelioma treated with external radiotherapy. We treated 11 patients of which 9 were males and 2 were females. The most frequent symptom was the chest pain and all these patients underwent a torascoscopy followed by a pleasured. Of the 11 cases: 10 were malignant epithelial mesothelioma and 1 was a mixed pleural case. Afterwards, they were treated with external radiotherapy between 30 and 55 Gy, with few complications. At the moment, 5 patients are still alive and there is a survival rate of 50% at 24 and 60 months and of 25% at 120 months. We think that external radiotherapy is a good palliative treatment with few complications. (Author) 28 refs

  4. Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion.

    Science.gov (United States)

    Tsuji, S; Tsuura, Y; Morohoshi, T; Shinohara, T; Oshita, F; Yamada, K; Kameda, Y; Ohtsu, T; Nakamura, Y; Miyagi, Y

    2010-08-10

    Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.

  5. Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Il; Ryu, Young Hoon; Lee, Kwang Hun; Choe, Kyu Ok; Kim, Sang Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    2000-01-01

    To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: (1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), (2) the presence of pleural effusion, (3) chest wall or rib invasion, (4) the involvement of a major fissure, (5) extra-pleural fat proliferation, (6) calcified plaque, (7) metastatic lymph nodes, (8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic

  6. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    International Nuclear Information System (INIS)

    Rosenzweig, Kenneth E.; Zauderer, Marjorie G.; Laser, Benjamin; Krug, Lee M.; Yorke, Ellen; Sima, Camelia S.; Rimner, Andreas; Flores, Raja; Rusch, Valerie

    2012-01-01

    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

  7. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    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

  8. Evaluation of pleural disease using MR and CT: With special reference to malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Knuuttila, A.; Kivisaari, L.; Kivisaari, A.; Palomaeki, M.; Tervahartiala, P.; Mattson, K.

    2001-01-01

    Purpose: To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease. Material and Methods: Thirty-four patients (18 pleural mesothelioma, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods. Results: The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of inter lobar fissures. In mesothelioma, enhancement of inter lobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences. Conclusion: MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of inter lobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases

  9. Evaluation of pleural disease using MR and CT: With special reference to malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Knuuttila, A. [Helsinki Univ. Central Hospital (Finland). Dept. of Medicine; Kivisaari, L.; Kivisaari, A.; Palomaeki, M.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept. of Radiology; Mattson, K. [Helsinki Univ. Central Hospital (Finland). Dept. of Medicine

    2001-09-01

    Purpose: To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease. Material and Methods: Thirty-four patients (18 pleural mesothelioma, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods. Results: The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of inter lobar fissures. In mesothelioma, enhancement of inter lobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences. Conclusion: MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of inter lobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases.

  10. Limbic Encephalitis Driven by a Pleural Mesothelioma: A Paraneoplastic Complication

    Directory of Open Access Journals (Sweden)

    Jacob O. Day

    2016-10-01

    Full Text Available Paraneoplastic neurological syndromes have only been described with pleural mesothelioma in five cases. We have described a 72-year-old man who developed anterograde amnesia 27 months after diagnosis of epithelioid pleural mesothelioma. Investigations revealed a limbic encephalitis with no alternative causes identified. Limbic encephalitis is a classical paraneoplastic syndrome and presentation within five years of a cancer with no other causes identified is sufficient to diagnose a paraneoplastic etiology. This is the first case of isolated paraneoplastic limbic encephalitis driven by a pleural mesothelioma.

  11. Multimodal treatment for resectable epithelial type malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  12. Duodenal Metastasis of Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  13. Diffuse malignant pleural mesothelioma in an urban hospital: Clinical spectrum and trend in incidence over time

    International Nuclear Information System (INIS)

    Shepherd, K.E.; Oliver, L.C.; Kazemi, H.

    1989-01-01

    This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over the study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected

  14. Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion.

    Science.gov (United States)

    Kato, Katsuya; Gemba, Kenichi; Fujimoto, Nobukazu; Aoe, Keisuke; Takeshima, Yukio; Inai, Kouki; Kishimoto, Takumi

    2016-09-01

    To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT. Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics. Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients. Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (ppleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%. This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Pleural Mesothelioma Surveillance: Validity of Cases from a Tumour Registry

    Directory of Open Access Journals (Sweden)

    France Labrèche

    2012-01-01

    Full Text Available BACKGROUND: Pleural mesothelioma is a rare tumour associated with exposure to asbestos fibres. Fewer than than one-quarter of cases registered in the Quebec Tumour Registry (QTR have been compensated as work-related. While establishing a surveillance system, this led to questioning as to whether there has been over-registration of cases that are not authentic pleural mesotheliomas in the QTR.

  16. 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

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

    International Nuclear Information System (INIS)

    Seely, Jean M.; Nguyen, Elsie T.; Churg, Andrew M.; Mueller, Nestor L.

    2009-01-01

    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

  18. The role of CT in the differential diagnosis of malignant pleural mesothelioma and diffuse metastatic pleural involvement

    International Nuclear Information System (INIS)

    Kirova, G.; Beeva, M.; Sergieva, S.; Tsenkov, Kh.; Tsonev, P.

    1997-01-01

    The purpose of the study was to establish the presence of similarities and differences in the CT finding of patients presenting histologically proved diffuse pleural metastases and malignant pleural mesothelioma. Twenty-six patients with diffuse metastatic involvement of the pleura divided in two groups according to histological diagnosis, made on basis of findings at examination of the specimens obtained by pneumonectomy and pleural biopsy, are subjected to retrospective investigation. Group one is of ten patients with malignant pleural mesothelioma, and group two - sixteen patients presenting diffuse metastatic changes in the pleural membranes. All scanograms are separately evaluated in terms of state of the pulmonary parenchyma and that of of the pleurae, chest wall and mediastinum. As shown by the summed up data, the CT image of the pleura in malignant pleural mesothelioma and diffuse metastatic pleural disease lacks clearcut distinction, and its roentgenological characterization does not warrant a specific morphological diagnosis. There is difference in the degree of manifestation of so-called additional signs such as enlarged hilum and mediastinal lymph nodes, metastatic lesions to the pulmonary parenchyma and destruction of adjacent bone structures

  19. Malignant pleural mesothelioma: a phase II trial with docetaxel.

    Science.gov (United States)

    Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

    2002-03-01

    Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

  20. [Prevalence of pleural malignant mesothelioma in Poland in 1980-1993].

    Science.gov (United States)

    Szeszenia-Dabrowska, N; Szymczak, W; Wilczyńska, U

    1996-01-01

    Malignant pleural mesothelioma is subject of special interest for environmental epidemiologists due to its proven cause-effect relationship with the exposure to asbestos dust, particularly crocidolite. The paper discusses the prevalence trends and geographical distribution of pleural mesothelioma in Poland based on the death rate analysis. In 1993 the crude death rate for that neoplasm was found to be 4.48 per 1 million for men and 3.14 per 1 million for women. While interpreting the numerical data, such aspects were considered as the problems with histopathological diagnosis of pleural mesothelioma; the long latency period of 30-40 years; and consequently, the possibility that for the male population the results may have been affected by other causes of death owing to its relatively short average lifespan. The volume and types of asbestos used in Poland were also taken into account.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas

    International Nuclear Information System (INIS)

    Sriram, Krishna B; Courtney, Deborah; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M; Relan, Vandana; Clarke, Belinda E; Duhig, Edwina E; Windsor, Morgan N; Matar, Kevin S; Naidoo, Rishendran; Passmore, Linda; McCaul, Elizabeth

    2012-01-01

    The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE. We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA. Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively). Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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.

  4. 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.

  5. Pleural mesothelioma in differential diagnostics of a tubercular exudative pleuritis

    Directory of Open Access Journals (Sweden)

    O.M. Raznatovskaya

    2017-02-01

    Rivalta’s test, a lymphocytosis of 93–100 %, a proliferation of mesothelium with dystrophia signs in cytoplasma, groups of cells with enlarged nucleoluses in cell cores; aspirate of epithelial lining fluid (even in the absence of pathology of a tracheobronchial tree is presented by alveolus cells and bronchial epithelium, glandular groups of cells with hyperplasia signs; typical signs of pleura mesothelioma of pleural cavity at ultrasound examination were: identification of formations of rounded shape, various echogenicity, the sizes and quantity (depending on a form: nodular or diffusive, with accurate contours of masses which intimately adjoins to visceral pleura and the structure often contains from single to numerous small hyperechogenic inclusions against the background of liquid; in all cases video-assisted thoracoscopy data of visceral pleura was confirmed by pathohistological examination. Conclusions. All applied diagnostic methods were high-informative that allowed quickly diagnose and prescribe the correct treatment. On their basis the algorithm of differential diagnostics of specific exudative pleuritis and caused pleura mesotheliomas were roentgenography of thoracic organs (if possible computer tomography, an ultrasonic examination of thoracic organs, cytologic research of pleural liquid, video thoracoscopy with biopsy of parietal pleura, research of pleura smear and pathohistological examination of biopsy material.

  6. Treatment of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Yusa, Toshikazu

    2007-01-01

    In Japan, it is predicted that mesothelioma will rapidly increase in the future. Malignant pleural mesothelioma that accounts for approximately 90% of mesothelioma as a whole has a median survival time of approximately nine months which is considered a poor prognosis. As for the treatment of this disease, extrapleural pneumonectomy or pleurectomy/decortication are available for those patients who can be surgically operated on. However, since a complete cure rate is low when only surgical treatment is performed, generally a multimodality treatment is performed wherein chemotherapy and/or radiotherapy are combined. For chemotherapy, a large-scale randomized phase III study demonstrated that a treatment using two agents: pemetrexed, which is a new multitargeted antifolate, and cisplatin is effective. Pemetrexed will be the drug of first choice for mesothelioma in the future. As other treatment methods, chemohyperthermia, treatments using various kinds of cytokines and angiogenesis inhibitors, genetic treatment and photodynamic therapy have been attempted. The current treatment results for this disease are very poor, and there has been a strong demand for establishing an effective treatment method. (author)

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

    International Nuclear Information System (INIS)

    Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C.; Garcia Garc'ia, T.; Azagra Ros, P.; Maruenda Paulino, J.I.; Ferrer Albiach, C.

    1999-01-01

    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.) [de

  8. 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.)

  9. Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.

    Science.gov (United States)

    Finley, Brent L; Benson, Stacey M; Marsh, Gary M

    2017-03-01

    Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc. We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years. There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma. We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.

  10. Pleural mesothelioma: management updates and nursing initiatives to improve patient care

    Directory of Open Access Journals (Sweden)

    Lehto RH

    2014-05-01

    Full Text Available Rebecca H LehtoCollege of Nursing, Michigan State University, East Lansing, MI, USAAbstract: Malignant pleural mesothelioma is a relatively rare but aggressive malignancy that is primarily associated with occupational asbestos exposure. While treatment options for mesothelioma have expanded, the disease carries a poor prognosis, with a median of 8 months to 1 year of survival postdiagnosis. This article synthesizes current disease-management practices, including the diagnostic workup, treatment modalities, emerging therapies, and symptom management, and identifies comprehensive nursing strategies that result in the best care based on updated evidence. Multidisciplinary coordination, palliative care initiation, survivorship, and end-of-life care are discussed. Findings may be applied in clinical environments as a resource to help nurses better understand treatment options and care for patients facing malignant pleural mesothelioma. Recommendations for future research are made to move nursing science forward and to improve patient well-being and health-related quality-of-life outcomes for patients and their family members.Keywords: pleural mesothelioma, cancer, symptom management, evidence-based care

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Primary pleural angiosarcoma as a mimicker of mesothelioma: a case report **VS**

    Directory of Open Access Journals (Sweden)

    Kao Yu-Chien

    2011-12-01

    Full Text Available Abstract Primary pleural angiosarcoma is a rare and clinically aggressive tumor. Patients usually present with chest pain, dyspnea, hemoptysis and/or cough. Radiologic studies reveal diffuse pleural thickening and pleural effusion with or without mass lesion. The clinical and radiological features both resemble those of mesothelioma, and its definite diagnosis requires careful histologic examination. However, frequent epithelioid feature and immunoreactivity to cytokeratin in primary pleural angiosarcoma further complicate the pathologic diagnosis. The use of proper immunohistochemical stains is often needed to support endothelial differentiation in the tumor cells and to exclude metastatic carcinoma and mesothelioma. We report the case of a 49-year-old male patient with primary pleural angiosarcoma, who presented with initial hemothorax, followed by a rapid progress to an inoperable status.

  13. Mesothelioma with non-pleural malignancy: a red herring or just an uncommon pairing?

    Directory of Open Access Journals (Sweden)

    Shah Amit K

    2006-11-01

    Full Text Available Abstract Malignant pleural mesothelioma (MPM is a highly aggressive cancer of the pleura with a well-established male predominance and causative link with asbestos exposure. We report four cases of female patients with MPM referred for palliation of symptoms thought to be due to previous non-pleural malignancy. With emerging novel treatments for MPM, this article discusses four unusual cases of MPM occurring in the setting of other malignancy, highlights the importance of considering a primary diagnosis of MPM even in patients with other malignancy, and reinforces the benefits of video-assisted surgical biopsy which allows simultaneous diagnosis and treatment.

  14. Mesothelioma with non-pleural malignancy: a red herring or just an uncommon pairing?

    Science.gov (United States)

    Drain, Andrew J; Saeb-Parsy, Kourosh; Shah, Amit K; Rassl, D; Ritchie, Andrew J

    2006-01-01

    Malignant pleural mesothelioma (MPM) is a highly aggressive cancer of the pleura with a well-established male predominance and causative link with asbestos exposure. We report four cases of female patients with MPM referred for palliation of symptoms thought to be due to previous non-pleural malignancy. With emerging novel treatments for MPM, this article discusses four unusual cases of MPM occurring in the setting of other malignancy, highlights the importance of considering a primary diagnosis of MPM even in patients with other malignancy, and reinforces the benefits of video-assisted surgical biopsy which allows simultaneous diagnosis and treatment. PMID:17078889

  15. 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.

  16. Glycosaminoglycan, computed tomography and gallium-67 scanning in malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Nakano, Takashi; Fujii, Junji; Yamakawa, Kiyohiro; Tamura, Shinsuke; Amuro, Yoshiki; Nabeshima, Kenji; Hada, Toshikazu; Higashino, Kazuya; Horai, Takeshi.

    1985-01-01

    Malignant pleural mesothelioma is an unusual disease, often difficult to diagnose. This paper describes the results of quantitative studies on glycosaminoglycan (GAG) in tumor tissues and the findings of chest computed tomography (CT) and gallium-67 scanning in 5 malignant pleural mesotheliomas. The total amount of GAG in tumor tissue was 2.3 to 17.0 times as high as that in adenocarcinoma of the lung. The amount of hyaluronic acid was 3.5 to 170 times higher than that in adenocarcinoma. Also, the amount of chondroitin sulfate increased 2.6 to 10.0 times, but there were no changes in dermatan sulfate and heparan sulfate contents in this neoplasm when compared with adenocarcinoma. The present study suggests that a marked increase of the total amount of GAG and elevation of either hyaluronic acid and chondroitin sulfate content or both is a characteristic abnormality in this neoplasm. In most cases, CT scan of the chest showed pleural effusion, irregular pleural tumorous thickening surrounding the whole lung surface and extension into the fissure. In 3 cases, tumorous lesions extending into the chest wall at the site of pleural biopsy could be visualized on CT. In the terminal stage, the thoracic cavity was occupied by tumor tissues. Gallium-67 scanning showed a diffusely increased radionuclide accumulation over the involved hemithorax with or without particular intensity in the periphery. Conversely, identification of these characteristic findings of CT and gallium-67 scanning indicates the possibility of malignant pleural mesothelioma. (author)

  17. Use of imaging in the management of malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Benamore, R.E. [Department of Radiology, University Hospitals of Leicester, Leicester (United Kingdom); O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospital, London (United Kingdom); Entwisle, J.J. [Department of Radiology, University Hospitals of Leicester, Leicester (United Kingdom)]. E-mail: james.entwisle@uhl-tr.nhs.uk

    2005-12-15

    Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The death rate associated with MPM is predicted to peak in the next 10 years, although radiologists and clinicians will be encountering cases for the next few decades. Contrast-enhanced CT is an established technique for evaluating suspected malignant pleural disease, but MPM can be reliably diagnosed only by histological sampling. However, even with adequate sampling and the use of immunocytochemistry, histological diagnosis is known to be difficult; definitive diagnosis may involve a combination of clinical presentation, radiological and histological appearances. Percutaneous biopsy is a promising technique for sampling the pleura. In view of its pattern of growth, MPM is a challenging disease to image by any method, and it behaves quite differently from lung cancer. This review aims to highlight the practical aspects of assessing malignant pleural mesothelioma.

  18. Dysphagia as an unusual complication of pleural mesothelioma

    International Nuclear Information System (INIS)

    Khan, S.; But, N.; Bajwa, F.

    2008-01-01

    Dysphagia is an unusual presentation of pleural mesothelioma and carries a grim prognosis. A case of an elderly patient is presented herein, in whom the diagnosis was confirmed histologically, and the patient was still surviving 6 months after palliation. (author)

  19. 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...

  20. Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma.

    Science.gov (United States)

    Sato, Tadashi; Suzuki, Yohei; Mori, Takanori; Maeda, Masahiro; Abe, Masaaki; Hino, Okio; Takahashi, Kazuhisa

    2014-10-01

    Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Pleural malignant mesothelioma causing cord infiltration through the nerve root. Case report.

    Science.gov (United States)

    Okura, Hidehiro; Suga, Yasuo; Akiyama, Osamu; Kudo, Kentaro; Tsutsumi, Satoshi; Abe, Yusuke; Yasumoto, Yukimasa; Ito, Masanori; Izumi, Hiroshi; Shiomi, Kazu

    2009-04-01

    A 61-year-old man presented with a rare pleural malignant mesothelioma of the spine manifesting as progressive weakness of the bilateral lower extremities, numbness in the body and both legs, and dysfunction of the bladder and bowel. He had previous occupational exposure to asbestos while working at a car repair shop and had undergone right panpleuropneumonectomy under a diagnosis of sarcomatous type mesothelioma in the right pleural space. Magnetic resonance imaging of the spine with gadolinium showed an enhanced intramedullary tumor at the T4 level. Operative findings disclosed the clouded and swollen right posterior nerve root, and the pial surface was covered by clouded arachnoid-like membrane. The removed part of the T4 posterior nerve root and intramedullary tumor revealed malignant mesothelioma with invasion spreading along the posterior nerve root. He died of respiratory failure 3 months after the diagnosis. This case shows that spinal metastasis must be considered if a patient with pleural malignant mesothelioma shows neurological worsening and neuroimaging shows an abnormal lesion in the thoracic spinal cord. However, the patient's neurological condition is very difficult to improve in the presence of spinal cord infiltration.

  2. 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

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

    African Journals Online (AJOL)

    This article is a review of a series of three studies that proved the involvement of osteopontin as a prognostic marker in malignant pleural mesothelioma (MPM) cancers. The approach used involved synthesizing and analysing the three articles. The first proves the utilization of osteopontin and mesothelin for diagnostic and ...

  4. Pleural mesothelioma: epidemiological and public health issues. Report from the Second Italian Consensus Conference on Pleural Mesothelioma.

    Science.gov (United States)

    Magnani, Corrado; Fubini, Bice; Mirabelli, Dario; Bertazzi, Pier Alberto; Bianchi, Claudio; Chellini, Elisabetta; Gennaro, Valerio; Marinaccio, Alessandro; Menegozzo, Massimo; Merler, Enzo; Merletti, Franco; Musti, Marina; Pira, Enrico; Romanelli, Antonio; Terracini, Benedetto; Zona, Amerigo

    2013-01-01

    Malignant mesothelioma is closely connected to asbestos exposure, with epidemiological patterns closely reshaping the geography and history of asbestos exposure. Mechanisms of causation and of interaction of asbestos fibres with pleura are complex and currently not yet completely understood. Curative efforts so far provided little results. Italy shows one of the highest incidence of MM and developed a network of specialized cancer registries in order to monitor disease occurrence and describe its epidemiology in details. The second Italian Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th-25th, 2011. Besides the main consensus report summarizing the contribution of the different expertises, that was published elsewhere, the participants in 'Public Health and Epidemiology' section decided to report in major details the evidence and the conclusions regarding epidemiology, causative mechanisms and the public health impact of the disease.

  5. 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

  6. Predictors of trimodality therapy and trends in therapy for malignant pleural mesothelioma.

    Science.gov (United States)

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

    2018-05-01

    Malignant pleural mesothelioma is an aggressive and rare malignancy that frequently recurs despite aggressive therapy. We evaluated the frequency of treatment with surgery, radiation or chemotherapy, changes in therapy and survival over time and factors associated with the receipt of trimodality therapy. The National Cancer Database (NCDB) was used to query patients with histologically proven malignant pleural mesothelioma (2004-14). Treatment over time was evaluated using the Armitage trend test. Factors associated with the receipt of trimodality therapy were analysed using logistic regression. Among 20 561 patients, only 4028 (20%) underwent cancer-directed surgery; 533 (2.6%) of whom received trimodality therapy. From 2004 to 2014, the use of surgery with chemotherapy increased 87% (P 26 miles for treatment were more likely to undergo trimodality therapy. Additional factors associated with the receipt of trimodality therapy include age less than 70, Charlson comorbidity score of 0 and presence of private insurance. Many malignant pleural mesothelioma patients are not treated with trimodality therapy, with significant variation in treatment patterns. Referrals to high-volume and specialized centres may help offer more therapeutic options and trial or registry enrolment.

  7. Gallium-67 scanning in patients with malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Nakano, Takashi; Maeda, Juichiro; Iwahashi, Noriaki; Tamura, Shinsuke; Hada, Toshikazu; Higashino, Kazuya

    1990-01-01

    The findings of gallium-67 scans in eleven patients with malignant pleural mesothelioma were reviewed and compared to those of chest CT findings. All patients had an abnormal thoracic Ga-67 accumulation. Six out of 11 showed a diffuse accumulation over the entire involved hemithorax and a localized uptake was shown in 5. A marked diffuse thickening of pleura in the absence of adequate gallium accumulation was observed in one patient. Two out of 11 had a reduction of gallium uptake after having combination chemotherapy. These results suggest that a diffusely increased uptake over the entire involved hemithorax is the most characteristic finding of Ga-67 scan in malignant pleural mesothelioma, and that Ga-67 scans may be helpful as a valuable indicator of the proper therapy. However, the superiority of Ga-67 scan to thoracic CT as a means of determining the extent of disease process could not be verified. (author)

  8. 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

  9. Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Bölükbas, Servet; Biancosino, Christian; Redwan, Bassam; Eberlein, Michael

    2017-06-01

    Surgical resection represents one of the essential cornerstones in multimodal treatment of malignant pleural mesothelioma. In cases of tumor infiltration of the lung, lung-scarifying procedures such as lobectomies or pneumonectomies might be necessary to achieve macroscopic complete resection. However, this increases the morbidity of the patients because it leads to possible delay of the planned chemotherapy or radiotherapy. Innovative surgical techniques are therefore required to enable salvage of the lung parenchyma and optimization of surgical treatment. Here we report our first experience with a diode-pumped neodymium-doped yttrium aluminium garnet laser for parenchyma-sparing lung resection during surgery for malignant pleural mesothelioma. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. 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...

  11. BTS guideline for the investigation and management of malignant pleural mesothelioma.

    Science.gov (United States)

    Woolhouse, Ian; Bishop, Lesley; Darlison, Liz; de Fonseka, Duneesha; Edey, Anthony; Edwards, John; Faivre-Finn, Corinne; Fennell, Dean A; Holmes, Steve; Kerr, Keith M; Nakas, Apostolos; Peel, Tim; Rahman, Najib M; Slade, Mark; Steele, Jeremy; Tsim, Selina; Maskell, Nick A

    2018-01-01

    The full guideline for the investigation and management of malignant pleural mesothelioma is published in Thorax . The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.

  12. 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).

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

    International Nuclear Information System (INIS)

    Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi

    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)

  14. Update of predictions of mortality from pleural mesothelioma in the Netherlands

    NARCIS (Netherlands)

    O. Segura; A. Burdorf (Alex); C.W.N. Looman (Caspar)

    2003-01-01

    textabstractAIMS: To predict the expected number of pleural mesothelioma deaths in the Netherlands from 2000 to 2028 and to study the effect of main uncertainties in the modelling technique. METHODS: Through an age-period-cohort modelling technique, age specific mortality rates

  15. 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...

  16. 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.

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

    International Nuclear Information System (INIS)

    Park, Hwi Ryong; Chong, Se Min; Kim, Mi Kyung

    2017-01-01

    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. 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.

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

    International Nuclear Information System (INIS)

    Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon; Choi, Sang Bong

    2008-01-01

    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

  20. 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.

  1. Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

    OpenAIRE

    Ayako Tsuchiya; Yoshiko Kaku; Takashi Nakano; Tomoyuki Nishizaki

    2015-01-01

    1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species ...

  2. A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    O'Rourke, Noelle; Garcia, Jose Curto; Paul, Jim; Lawless, Claire; McMenemin, Rhona; Hill, Jennifer

    2007-01-01

    Background and purpose: To assess the effectiveness of radiotherapy in preventing tumour seeding after chest drain or pleural biopsy in patients with malignant mesothelioma and to determine, if tract metastases appear, whether they are tender or troublesome to patients. Patients and methods: Patients with a histological diagnosis of pleural mesothelioma and an invasive procedure within the preceding 21 days were stratified by age, performance status and treatment centre. Randomisation was performed between immediate drain site radiotherapy 21 Gy in three fractions (XRT arm) or best supportive care (BSC) with follow-up to 12 months. Patients were asked to complete questionnaires on treatment toxicity and on symptoms from any tract metastases detected. Results: Sixty-one patients were recruited from two centres between 1998 and 2004; 56 men, 5 women, median age 70. 31 were allocated to drain site radiotherapy. Seven patients developed tract metastases associated with the drain site (four XRT arm, three BSC) and four developed metastases associated with subsequent procedures at other sites (three XRT, one BSC). Two patients each developed two tract metastases. Of the 12 metastases, nine overlay the previous drain site but three were adjacent to the site. No statistically significant difference was found in the risk of tract metastasis associated with the drain site between the arms (p = 0.748). Conclusions: Prophylactic drain site radiotherapy in malignant pleural mesothelioma does not reduce the incidence of tumour seeding by the margin indicated by previous studies

  3. Malignant mesothelioma

    OpenAIRE

    Parker Robert J; Moore Alastair J; Wiggins John

    2008-01-01

    Abstract Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting featu...

  4. 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.

  5. 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

    International Nuclear Information System (INIS)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G.; Akira, Masanori; Itoh, Harumi

    2013-01-01

    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

  6. [Relationship between asbestos exposure and malignant pleural mesothelioma: occurrence near the old Japanese naval shipyard].

    Science.gov (United States)

    Kishimoto, T

    1994-12-01

    Kure City, Hiroshima Prefecture, was the site of a Japanese naval shipyard before World War II, and commercial ships were built there after the War. Large amounts of asbestos were used in this area primarily for shipbuilding, from before the war to around 1975. Probably due to exposure to asbestos, the incidence of malignant pleural mesothelioma is high in this city. Of the 31 patients with this disease, 27 were men. Patients over 60 years of age constituted a high percentage of the total and 28 had a history of asbestos exposure: 12 in the Japanese naval shipyard and 12 in the commercial shipyards. The average period of asbestos exposure for these 28 patients was 20 years. Malignant pleural mesothelioma developed more than 40 years after the first exposure to asbestos. Many asbestos particles and fibers were detected in the lungs and tumors of these patients. Most of the asbestos fibers detected were crocidolites or amosites. Considering that the amount of asbestos used in Japanese has been higher than in any other country, the incidence of malignant pleural mesothelioma may be expected to increase in this country. Countermeasures are now advisable.

  7. Pleural malignant mesothelioma and non occupational exposure to asbestos in Casale Monferrato, Italy; Mesotheliome pleural malin et exposition environnementale l'amiante a Casale Monferrato, Italy

    Energy Technology Data Exchange (ETDEWEB)

    Magnani, C.; Terracini, B.; Ivaldi, C.; Botta, M.; Mancini, A.; Andrion, A.

    1998-03-01

    The objective is to study the possibility of the risk of a pleural malignant mesothelioma associated to an environmental exposure to asbestos coming from industry, by estimating the incidence of mesotheliomas in a population without professional exposure but living near a asbestos-cement factory.

  8. 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...

  9. Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure.

    Science.gov (United States)

    Tsuzuki, Toyonori; Ninomiya, Hironori; Natori, Yuji; Ishikawa, Yuichi

    2008-07-01

    Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.

  10. 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...

  11. 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...

  12. 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...

  13. MRI, CT, and sonography in the preoperative evaluation of primary tumor extension in malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Layer, G.; Steudel, A.; Schild, H.H.; Schmitteckert, H.; Tuengerthal, S.; Schirren, J.; Kaick, G. van

    1999-01-01

    Purpose: Evaluation of the diagnostic value of the imaging modalities computed tomography (CT), magnetic resonance imaging (MRI), and thoracic sonography in the preoperative staging of malignant pleural mesothelioma. Results: The accuracy rates for CT were 85%, 98%, 83%, 73%, 71%, and 83%. MRI had an accuracy of 71%, 92%, 71%, 83%, 71%, and 96%, the thoracic ultrasound examinations of 76%, 63%, 51%, 60%, 71% and 89%. Conclusions: According to these results CT remains the method of choice in the preoperative assessment of T-stage of malignant pleural mesothelioma. MRI is of nearly the same value, but is not a must. Sonography may be supplementary method for operation planning. (orig./AJ) [de

  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. CT findings of intrathoracic mesothelioma

    International Nuclear Information System (INIS)

    Kim, Yeong Hwa; Choi, Kyu Ok; Lee, Jong Doo

    1989-01-01

    8 patients with pathologically proven pleural mesothelioma (5 localized type, 3 diffuse type), and 1 patient with malignant pericardial mesothelioma, were examined by computed tomography (CT), and obtained some results as follows: 1. Pleural Mesothelioma a. Localized pleural mesothelioma 4 cases were benign and 1 case was malignant in microscopic examination. CT showed invariably sharply marginated pleura-based soft tissue mass and the density of the mass was variable, homogenous in small tumor but inhomogenous with low density area in larger ones, and even calcification was seen in one of them. The angle of pleura-mass interface was obtuse in only one small tumor and acute with smooth taping end in four lager tumor. b. Diffuse pleural mesothelioma (DPM) Multiple nodular pleural masses encompassing nearly entire lung were seen with associated multiple subpleural parenchymal nodule and localized axial interstitial thickening in two case. Protruding chest wall mass with destruction of rib was seen in previous pneumonectomized thorax. Minimal pleural effusion/thickening was also seen in all. 2. Pericardial mesothelioma Pericardial fluid and multiple nodular masses, which occupied pericardial sac up to superior sinus were well delineated on CT. It had been misinterpreted as pericardial effusion for years on echocardiogram

  16. Malignant pleural mesothelioma in a child

    Directory of Open Access Journals (Sweden)

    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. Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline.

    Science.gov (United States)

    Kindler, Hedy L; Ismaila, Nofisat; Armato, Samuel G; Bueno, Raphael; Hesdorffer, Mary; Jahan, Thierry; Jones, Clyde Michael; Miettinen, Markku; Pass, Harvey; Rimner, Andreas; Rusch, Valerie; Sterman, Daniel; Thomas, Anish; Hassan, Raffit

    2018-05-01

    Purpose To provide evidence-based recommendations to practicing physicians and others on the management of malignant pleural mesothelioma. Methods ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, pathology, imaging, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2017. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 222 relevant studies to inform the evidence base for this guideline. Recommendations Evidence-based recommendations were developed for diagnosis, staging, chemotherapy, surgical cytoreduction, radiation therapy, and multimodality therapy in patients with malignant pleural mesothelioma. Additional information is available at www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

  18. CT of pleural abnormalities

    International Nuclear Information System (INIS)

    Webb, W.R.

    1995-01-01

    Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.)

  19. CT of pleural abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Webb, W R [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.).

  20. Pleural mesothelioma: Case-report of uncommon occupational asbestos exposure in a small furniture industry.

    Science.gov (United States)

    Oddone, Enrico; Imbriani, Marcello

    2016-01-01

    The relationship between asbestos exposure and malignant mesothelioma is no longer disputed, although it is not always easy to trace past occupational exposure. This report describes a case of uncommon asbestos exposure of a small furniture industry worker, who subsequently died of pleural malignant mesothelioma, to stress the crucial importance of a full reconstruction of the occupational history, both for legal and compensation purposes. Sarcomatoid pleural mesothelioma was diagnosed in a 70-year-old man, who was previously employed as a carpenter in a small furniture industry. He worked for about 6 years in the small factory, was exposed to asbestos during the assembly of the furniture inspired by classical architecture, in which asbestos cement tubes were used to reproduce classical columns. During this production process no specific work safety measures were applied, nor masks or local aspirators. No extra-professional exposure to asbestos was identified. This mesothelioma case was investigated by the Public Prosecutor's assignment that commissioned expert evidence on the legal accountability for the disease. Despite its uncommon expositive circumstance, the length of latency (about 30 years), the duration of exposure, the clinical and histochemical features are all consistent with literature evidence, accounting for the occupational origin of this malignancy. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    Energy Technology Data Exchange (ETDEWEB)

    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. Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

    Science.gov (United States)

    Berzenji, Lawek; Van Schil, Paul E; Snoeckx, Annemie; Hertoghs, Marjan; Carp, Laurens

    2018-05-01

    A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

    Science.gov (United States)

    Rosen, Lauren E; Karrison, Theodore; Ananthanarayanan, Vijayalakshmi; Gallan, Alexander J; Adusumilli, Prasad S; Alchami, Fouad S; Attanoos, Richard; Brcic, Luka; Butnor, Kelly J; Galateau-Sallé, Françoise; Hiroshima, Kenzo; Kadota, Kyuichi; Klampatsa, Astero; Stang, Nolween Le; Lindenmann, Joerg; Litzky, Leslie A; Marchevsky, Alberto; Medeiros, Filomena; Montero, M Angeles; Moore, David A; Nabeshima, Kazuki; Pavlisko, Elizabeth N; Roggli, Victor L; Sauter, Jennifer L; Sharma, Anupama; Sheaff, Michael; Travis, William D; Vigneswaran, Wickii T; Vrugt, Bart; Walts, Ann E; Tjota, Melissa Y; Krausz, Thomas; Husain, Aliya N

    2018-04-01

    A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple

  5. Analysis about X-ray and CT images of pleural mesothelioma case of death. Examination about 2003 mesothelioma case of death 878 examples

    International Nuclear Information System (INIS)

    Kato, Katsuya; Kanazawa, Susumu; Kishimoto, Takumi; Genba, Kenichi; Aoe, Keisuke; Takeshima, Yukio; Inai, Kouki

    2008-01-01

    We investigated a clinical record and images for 212 examples in 878 examples diagnosed as mesothelioma in the death votes of 2003. CT images demonstrated pleural plaque to be obtained 42.0%, but in chest X-ray films only 9.8% demonstrated pleural plaque. For examination of CT findings of 117 examples, cases to present extensive irregular findings of pleura were 81.2%. Cases we made the ''no irregularity'' and ''slightness irregularity'' were 18.8%. (author)

  6. Malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Suzanne Alkul

    2016-04-01

    Full Text Available Seventy percent of patients with malignant mesothelioma have had exposure to asbestos fibers. Other patients without this exposure have had chronic pleural inflammation or received radiation to the thorax. Occasionally patients present with no obvious exposure history relevant to the development of malignant mesothelioma. This diagnosis needs to be in the differential diagnosis of all patients with unexplained pleural disease.

  7. 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. Keywords: malignant pleural mesothelioma, microRNA-31, chemoresistance, cisplatin, ABCB9

  8. 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...

  9. Malignant pleural mesothelioma: an update on biomarkers and treatment.

    Science.gov (United States)

    Ray, Mandira; Kindler, Hedy Lee

    2009-09-01

    Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.

  10. 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.

  11. 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.

  12. Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

    International Nuclear Information System (INIS)

    Mould, Richard F; Lahanas, Michael; Asselain, Bernard; Brewster, David; Burgers, Sjaak A; Damhuis, Ronald A M; Rycke, Yann De; Gennaro, Valerio; Szeszenia-Dabrowska, Neonila

    2004-01-01

    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

  13. CT Scan-Guided Abrams' Needle Pleural Biopsy versus Ultrasound-Assisted Cutting Needle Pleural Biopsy for Diagnosis in Patients with Pleural Effusion: A Randomized, Controlled Trial.

    Science.gov (United States)

    Metintas, Muzaffer; Yildirim, Huseyin; Kaya, Tamer; Ak, Guntulu; Dundar, Emine; Ozkan, Ragip; Metintas, Selma

    2016-01-01

    Image-guided pleural biopsies, both using ultrasound (US) or computed tomography (CT), are important in the diagnosis of pleural disease. However, no consensus exists regarding which biopsy needles are appropriate for specific procedures. In this randomized, prospective study, we aimed to compare CT scan-guided pleural biopsy using an Abrams' needle (CT-ANPB) with US-assisted pleural biopsy using a cutting needle (US-CNPB) with respect to both diagnostic yield and safety. Between February 2009 and April 2013, 150 patients with exudative pleural effusion who could not be diagnosed by cytological analysis were included in the study. The patients were randomized into either the US-CNPB group or the CT-ANPB group. The two groups were compared in terms of diagnostic sensitivity and complications. Of the 150 patients enrolled in this study, 45 were diagnosed with malignant mesothelioma, 46 were diagnosed with metastatic pleural disease, 18 were diagnosed with pleural tuberculosis, 34 were diagnosed with benign pleural disease, and 7 were lost to follow-up. In the US-CNPB group, the diagnostic sensitivity was 66.7%, compared with 82.4% in the CT-ANPB group; the difference between the two groups was statistically significant (p = 0.029). The sensitivity of CT-ANPB increased to 93.7% for patients with a pleural thickness ≥1 cm. The complication rates were low and acceptable. The first diagnostic intervention that should be preferred in patients with pleural effusion and associated pleural thickening on a CT scan is CT-ANPB. US-CNPB should be used primarily in cases for which only pleural thickening but no pleural effusion is noted. © 2016 S. Karger AG, Basel.

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

    International Nuclear Information System (INIS)

    Botticella, A.; Defraene, G.; Nackaerts, K.; Deroose, C.; Coolen, J.; Nafteux, P.; Vanstraelen, B.; Joosten, S.; Michiels, L.A.W.; Peeters, S.; Ruysscher, D. de

    2017-01-01

    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.) [de

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  16. Intensity-modulated photon arc therapy for treatment of pleural mesothelioma

    International Nuclear Information System (INIS)

    Tobler, Matt; Watson, Gordon; Leavitt, Dennis

    2002-01-01

    Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We have developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord

  17. 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.

  18. Malignant pleural mesothelioma in bakers and pastry cooks.

    Science.gov (United States)

    Ascoli, V; Calisti, R; Carnovale-Scalzo, C; Nardi, F

    2001-10-01

    The occurrence of malignant pleural mesothelioma (MPM) among bakers and pastry cooks has never been documented. We detected eight cases of MPM in bakers, pastry cooks, and biscuit cooks engaged in making, baking/cooking, and selling pastry/bread in two hospital-based series (Rome and Orbassano/Turin, Italy; period 1990-1997; 222 cases). Field-investigations revealed asbestos-containing material (ACM) in ovens for baking bread, that were manufactured prior to the 1980s. It is suggested that there is a possible new association of the risk of having worked as a baker or pastry cook and MPM. Presumptive source of exposure to asbestos was the use of asbestos-insulated ovens. Copyright 2001 Wiley-Liss, Inc.

  19. Identification of pleural effusion with low levels of adenosine deaminase but without signs of acute inflammation or pleural thickening to diagnose early malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Moriyama, Satoru; Tanahashi, Masayuki; Suzuki, Eriko

    2012-01-01

    We reviewed the clinical findings and diagnostic methods used in the diagnosis of malignant pleural mesothelioma (MPM) in patients with pleural effusion with low levels of adenosine deaminase (ADA), but without signs of acute inflammation or pleural thickening. The hospital records of 40 patients with pleural effusion of unknown origin or pleural thickening were retrospectively investigated. In all of those studies, pleural effusion was exudative, lymphocyte-dominant, no mycobacteria or other bacteria, and low levels of ADA. There were 30 men and 10 women with an average age of 62.8 years old. The diagnosis of MPM was obtained by cytology of the pleural effusion in 3 patients and by core-needle biopsy of the thickened pleura in 3. Thoracoscopic pleural biopsy under general anesthesia was performed for the other 34 patients. The pathologic diagnosis of pleural biopsy was MPM in 20 patients, inflammatory change in 12, and pleural dissemination of cancer in 2. All of the 7 patients with more than 100 μg/ml of hyaluronic acid in their pleural effusion received a diagnosis of MPM. A total of 20 of 23 patients with irregular or nodular pleural thickening on computed tomography findings were confirmed to have MPM. Moreover, 6 of 17 patients with smooth pleural thickening were confirmed to have MPM. In patients with nodular pleural thickening it was easy to make the diagnosis. However, in those with smooth thickening, careful observation was required to select the appropriate biopsy site and resection margins of full-thickness pleura. As the rate of MPM in the patients with pleural effusion with low levels of ADA, but without signs of acute inflammation or pleural thickening is high (65%), an early thoracoscopic pleural biopsy is strongly recommended. (author)

  20. Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

    Science.gov (United States)

    Klebanov, Nikolai; Reddy, Bobby Y; Husain, Sameera; Silvers, David N; Grossman, Marc E; Tsao, Hensin

    2018-05-01

    Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation.

  1. Morphologic and functional imaging of malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Imaging in pleural mesothelioma: a review of the 11th International Conference of the International Mesothelioma Interest Group.

    Science.gov (United States)

    Armato, Samuel G; Labby, Zacariah E; Coolen, Johan; Klabatsa, Astero; Feigen, Malcolm; Persigehl, Thorsten; Gill, Ritu R

    2013-11-01

    Imaging of malignant pleural mesothelioma (MPM) is essential to the diagnosis, assessment, and monitoring of this disease. The complex morphology and growth pattern of MPM, however, create unique challenges for image acquisition and interpretation. These challenges have captured the attention of investigators around the world, some of whom presented their work at the 2012 International Conference of the International Mesothelioma Interest Group (iMig 2012) in Boston, Massachusetts, USA, September 2012. The measurement of tumor thickness on computed tomography (CT) scans is the current standard of care in the assessment of MPM tumor response to therapy; in this context, variability among observers in the measurement task and in the tumor response classification categories derived from such measurements was reported. Alternate CT-based tumor response criteria, specifically direct measurement of tumor volume change and change in lung volume as a surrogate for tumor response, were presented. Dynamic contrast-enhanced CT has a role in other settings, but investigation into its potential use for imaging mesothelioma tumor perfusion only recently has been initiated. Magnetic resonance imaging (MRI) and positron-emission tomography (PET) are important imaging modalities in MPM and complement the information provided by CT. The pointillism sign in diffusion-weighted MRI was reported as a potential parameter for the classification of pleural lesions as benign or malignant, and PET parameters that measure tumor activity and functional tumor volume were presented as indicators of patient prognosis. Also reported was the use of PET/CT in the management of patients who undergo high-dose radiation therapy. Imaging for MPM impacts everything from initial patient diagnosis to the outcomes of clinical trials; iMig 2012 captured this broad range of imaging applications as investigators exploit technology and implement multidisciplinary approaches toward the benefit of MPM patients

  3. 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.

  4. Analysis of "dry" mesothelioma with ultrasound guided biopsies

    NARCIS (Netherlands)

    Stigt, Jos A.; Boers, James E.; Groen, Harry J. M.

    2012-01-01

    Background: Image-guided sampling of the thickened pleura is a sensitive approach in patients with malignant pleural mesothelioma with pleural effusion. Malignant pleural mesothelioma presenting without effusion however is more of a diagnostic challenge. In this study we report the diagnostic yield

  5. Guidelines of the French Speaking Society for Chest Medicine for management of malignant pleural mesothelioma.

    Science.gov (United States)

    Scherpereel, Arnaud

    2007-06-01

    Previously considered as a rare tumor, malignant pleural mesothelioma (MPM) has become a very important public health issue. In fact, MPM is a tumor with a poor survival, and its incidence is expected to continue to increase for at least the next 10 years. Asbestos exposure is the main factor involved in MPM pathogenesis. The diagnosis of MPM may be difficult because of differential diagnosis such as pleural benign disease induced by asbestos exposure or pleural metastasis of adenocarcinoma. Management of patients with MPM also remains complicated because they are often referred for evaluation late in the evolution of the disease. Moreover, MPM exhibits a high resistance to radiotherapy and chemotherapy; only few patients are candidates for radical surgery. New therapeutic strategies such as gene or cell therapy are still on clinical trial. Therefore, an optimal treatment of MPM is not clearly defined yet, despite the introduction of recent drugs. Between April 2005 and January 2006, the French Speaking Society for Chest Medicine (SPLF), in collaboration with other French scientific societies, brought together experts on mesothelioma to draw up recommendations in order to provide clinicians with clear, concise, up-to-date guidelines on management of MPM, presented in this report.

  6. 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.

  7. Malignant Pleural Mesothelioma: Are There Imaging Characteristics Associated With Different Histologic Subtypes on Computed Tomography?

    Science.gov (United States)

    Escalon, Joanna G; Harrington, Kate A; Plodkowski, Andrew J; Zheng, Junting; Capanu, Marinela; Zauderer, Marjorie G; Rusch, Valerie W; Ginsberg, Michelle S

    2018-04-02

    Determine imaging characteristics specific to epithelioid (eMPM), sarcomatoid (sMPM), and biphasic (bMPM) subtypes of malignant pleural mesothelioma (MPM) on computed tomography. Preoperative computed tomography scans of patients with MPM were retrospectively assessed for numerous features including primary affected side, volume loss, pleural thickness, pleural calcifications, pleural effusion, and lymphadenopathy. One hundred twenty-five patients with MPM were included. Histologic subdivision was 97 eMPM (77%), 17 bMPM (14%), and 11 sMPM (9%). Nonepithelioid MPM (bMPM and sMPM) was more likely than eMPM to have calcified pleural plaques (P = 0.035). Analyzed separately, bMPM and sMPM each demonstrated calcified plaques more frequently than eMPM, and sMPM more often had internal mammary nodes; however, P values did not reach significance (P = 0.075 and 0.071, respectively). Calcified plaques are significantly more common in nonepithelioid subtypes compared with eMPM. Given the different prognoses and management of MPM subtypes, accurate noninvasive subtype classification is clinically vital.

  8. 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...

  9. 18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma

    OpenAIRE

    Hall, D. O.; Hooper, C. E.; Searle, J.; Darby, M.; White, P.; Harvey, J. E.; Braybrooke, J. P.; Maskell, N. A.; Masani, V.; Lyburn, I. D.

    2018-01-01

    Purpose\\ud \\ud The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma.\\ud \\ud Patients and methods\\ud \\ud 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two...

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

    International Nuclear Information System (INIS)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G.; Akira, Masanori; Itoh, Harumi

    2012-01-01

    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.

  11. 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.

  12. Malignant pleural mesothelioma: diagnostic value of medical thoracoscopy and long-term prognostic analysis.

    Science.gov (United States)

    Xu, Li-Li; Yang, Yuan; Wang, Zhen; Wang, Xiao-Juan; Tong, Zhao-Hui; Shi, Huan-Zhong

    2018-04-03

    Malignant pleural mesothelioma (MPM) is marked by its difficult diagnosis and poor prognosis. Medical thoracoscopy (MT) is an effective and safe procedure for the diagnosis of exudative pleural effusions and many factors associated with poor prognosis of MPM. We conducted this study to investigate the value of MT for diagnosing of MPM and to identify prognostic factors for MPM patients. From July 2005 through June 2014, a total of 833 patients with undiagnosed pleural effusions underwent MT and pleural biopsies were taken. Clinical data of all patients with MPM were retrospectively analyzed, and those with complete follow-up data were analyzed for prognostic factors. Eventually, MPM was the final diagnosis in 40 patients. Diagnostic efficiency of MT for MPM was 87.5%, since diagnosis of MPM failed to be established in 5 patients during the initial MT. Median survival was 17.1 mo (95% confidence interval: 13.6-20.7 mo). MT findings of pleural adhesion and plaques were adverse prognostic factors for MPM. In addition, old age, male gender, smoking history, histological type, poor staging, no treatment, low total protein level in pleural fluid, and computed tomographic findings such as pulmonary consolidation or infiltration, mediastinal lymphopathy, pulmonary mass or nodules, and pleural nodularity were also poor prognostic factors for MPM. MT is safe with a high positive rate in the diagnosis of MPM, and pleural adhesion and plaques seen under MT may be the adverse prognostic factors for MPM. Multiple clinical characteristics can affect the survival of MPM patients.

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

    International Nuclear Information System (INIS)

    Metz-Flamant, C; Guseva Canu, I; Laurier, D

    2011-01-01

    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)

  14. 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)

  15. Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

    Science.gov (United States)

    Lee, Hyun-Sung; Jang, Hee-Jin; Choi, Jong Min; Zhang, Jun; de Rosen, Veronica Lenge; Wheeler, Thomas M; Lee, Ju-Seog; Tu, Thuydung; Jindra, Peter T; Kerman, Ronald H; Jung, Sung Yun; Kheradmand, Farrah; Sugarbaker, David J; Burt, Bryan M

    2018-04-05

    We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes. This molecular signature, representative of a favorable intratumoral cell network, was independently associated with improved survival in MPM and predicted response to immune checkpoint inhibitors in patients with MPM and melanoma. These data additionally suggest a potentially novel mechanism of response to checkpoint blockade: requirement for high measured abundance of neopeptides in the presence of high expression of MHC proteins specific for these neopeptides.

  16. Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Minnema-Luiting, Jorien; Vroman, Heleen; Aerts, Joachim; Cornelissen, Robin

    2018-03-30

    Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited therapy options and dismal prognosis. In recent years, the role of immune cells within the tumor microenvironment (TME) has become a major area of interest. In this review, we discuss the current knowledge of heterogeneity in immune cell content and checkpoint expression in MPM in relation to prognosis and prediction of treatment efficacy. Generally, immune-suppressive cells such as M2 macrophages, myeloid-derived suppressor cells and regulatory T cells are present within the TME, with extensive heterogeneity in cell numbers. Infiltration of effector cells such as cytotoxic T cells, natural killer cells and T helper cells is commonly found, also with substantial patient to patient heterogeneity. PD-L1 expression also varied greatly (16-65%). The infiltration of immune cells in tumor and associated stroma holds key prognostic and predictive implications. As such, there is a strong rationale for thoroughly mapping the TME to better target therapy in mesothelioma. Researchers should be aware of the extensive possibilities that exist for a tumor to evade the cytotoxic killing from the immune system. Therefore, no "one size fits all" treatment is likely to be found and focus should lie on the heterogeneity of the tumors and TME.

  17. Malignant pleural mesothelioma segmentation for photodynamic therapy planning.

    Science.gov (United States)

    Brahim, Wael; Mestiri, Makram; Betrouni, Nacim; Hamrouni, Kamel

    2018-04-01

    Medical imaging modalities such as computed tomography (CT) combined with computer-aided diagnostic processing have already become important part of clinical routine specially for pleural diseases. The segmentation of the thoracic cavity represents an extremely important task in medical imaging for different reasons. Multiple features can be extracted by analyzing the thoracic cavity space and these features are signs of pleural diseases including the malignant pleural mesothelioma (MPM) which is the main focus of our research. This paper presents a method that detects the MPM in the thoracic cavity and plans the photodynamic therapy in the preoperative phase. This is achieved by using a texture analysis of the MPM region combined with a thoracic cavity segmentation method. The algorithm to segment the thoracic cavity consists of multiple stages. First, the rib cage structure is segmented using various image processing techniques. We used the segmented rib cage to detect feature points which represent the thoracic cavity boundaries. Next, the proposed method segments the structures of the inner thoracic cage and fits 2D closed curves to the detected pleural cavity features in each slice. The missing bone structures are interpolated using a prior knowledge from manual segmentation performed by an expert. Next, the tumor region is segmented inside the thoracic cavity using a texture analysis approach. Finally, the contact surface between the tumor region and the thoracic cavity curves is reconstructed in order to plan the photodynamic therapy. Using the adjusted output of the thoracic cavity segmentation method and the MPM segmentation method, we evaluated the contact surface generated from these two steps by comparing it to the ground truth. For this evaluation, we used 10 CT scans with pathologically confirmed MPM at stages 1 and 2. We obtained a high similarity rate between the manually planned surface and our proposed method. The average value of Jaccard index

  18. Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden

    Science.gov (United States)

    Gilham, Clare; Rake, Christine; Burdett, Garry; Nicholson, Andrew G; Davison, Leslie; Franchini, Angelo; Carpenter, James; Hodgson, John; Darnton, Andrew; Peto, Julian

    2016-01-01

    Background We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens. Methods Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks. Results Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%). Conclusions The approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women. PMID:26715106

  19. Canine pleural mesothelioma as an indicator of environmental exposure to asbestos; Il mesotelioma pleurico del cane come indicatore di esposizione ambientale ad amianto

    Energy Technology Data Exchange (ETDEWEB)

    De Nardo, P. [Istituto Superiore di Sanita`, Rome (Italy). Lab. di Medicina Veterinaria

    1996-12-01

    Canine pleural mesothelioma represents a `sentinel health event` because of the role of asbestos exposure in its etiology and pathogenesis. The observation of such event may thus trigger prevention-oriented remedial actions. This is especially due to the relatively short induction-latency time of canine mesothelioma, i.e. eight-nine years, versus the corresponding induction-latency time in humans (on average about thirty years). The observation of cases of canine mesothelioma may concur to the detection of previously unrecognized hazardous exposures to asbestos. On this ground, the epidemiologic surveillance of canine mesothelioma in Italy is suggested.

  20. The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma

    NARCIS (Netherlands)

    Schouwink, J. Hugo; Kool, Leo Schultze; Rutgers, Emiel J.; Zoetmulder, Frans A. N.; van Zandwijk, Nico; v d Vijver, Marc J.; Baas, Paul

    2003-01-01

    BACKGROUND: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is

  1. Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective netherlands cohort study

    NARCIS (Netherlands)

    Offermans, N.S.M.; Vermeulen, R.; Burdorf, A.; Goldbohm, R.A.; Kauppinen, T.; Kromhout, H.; Brandt, P.A. van den

    2014-01-01

    OBJECTIVE:: To study the association between occupational asbestos exposure and pleural mesothelioma, lung cancer, and laryngeal cancer, specifically addressing risk associated with the lower end of the exposure distribution, risk of cancer subtypes, and the interaction between asbestos and smoking.

  2. Value of a new inflammatory parameter in malignant pleural mesothelioma prognosis

    Directory of Open Access Journals (Sweden)

    Özlem Abakay

    2013-01-01

    Full Text Available Malignant Pleural Mesothelioma (MPM generallyassociated with asbestos exposure is a tumor withpoor prognosis. Modified Glasgow Prognostic Score(GPS which may be a prognostic parameter in patientswith MPM is a designed based score including increasedC-reactive protein (CRP levels and decreased albumin.In this study we aimed to investigate the effect of GPSscore on the prognosis of MPM and the role of other potentialfactors.Methods: In this retrospective planned study 140 histologicaldiagnosed MPM patients were included.Results: Mean age of 140 MPM patients were 52.92years (83 male and 57 female. A total of 91 patients hadenvironmental asbestos exposure and exposure timewas the 31 years. Symptoms of the patients started approximately4.8 months before the application. The mostfrequently seen symptoms were in 125 patients dyspnea,in 94 patients chest pain and in 22 patients weight loss.GPS score of the patients were as follows; 64 patientstwo, 14 patients one, 22 patients zero. Of the patients,112 died and 28 were alive. Mean survival time was 14months. Patients with GPS score 2 lived for 10 months,GPS score 1 lived for 15 and GPS score 0 lived for 18months. This difference was statistically significant. Furthermore,the male sex and age older than 65 years werefound as poor prognostic parameters on the survival.Conclusion: A simple and inexpensive parameter able tobe used to estimate the prognosis of MPM patients couldnot be developed .GPS score increases in inflammatoryconditions. GPS is a simple and inexpensive parameterthat can be used for detecting the severity of patients withMPM.Key words: Modified Glasgow Prognostic Score, MalignantPleural Mesothelioma, Prognosis

  3. Updates in the diagnosis and treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Katzman, Daniel; Sterman, Daniel H

    2018-03-16

    This review article describes current diagnostic and treatment modalities for malignant pleural mesothelioma (MPM). Few randomized trials in MPM have demonstrated improved survival with current therapies. A randomized trial of first-line chemotherapy with and without bevacizumab in unresectable MPM is the only randomized trial of a new treatment regimen to demonstrate a survival benefit since cisplatin with pemetrexed became the standard of care for unresectable MPM in 2003. Unfortunately, in unresectable MPM, first-line chemotherapy alone or in combination with bevacizumab has demonstrated only limited improvements in overall survival. Recently, in nonrandomized observational studies, multimodality treatments with chemotherapy, surgery, radiation, and novel therapies have been associated with prolonged survival in select patients. Currently, there are no FDA approved second-line therapies, and clinical trial enrollment is recommended for second-line treatment. MPM remains difficult to treat and has an overall poor prognosis despite current multimodality treatment. Thoracoscopy with multiple pleural biopsies can provide adequate tissue specimens for diagnostic testing to distinguish histologic MPM subtypes and perform molecular profiling, which influence prognosis and treatment options. In early clinical trials, immunotherapies and therapies directed against cancer-associated antigens and oncogenic alterations are emerging as promising future treatments.

  4. New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Marika Rossini

    2018-04-01

    Full Text Available Malignant pleural mesothelioma (MPM is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.

  5. New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Rossini, Marika; Rizzo, Paola; Bononi, Ilaria; Clementz, Anthony; Ferrari, Roberto; Martini, Fernanda; Tognon, Mauro G

    2018-01-01

    Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.

  6. New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

    Science.gov (United States)

    Rossini, Marika; Rizzo, Paola; Bononi, Ilaria; Clementz, Anthony; Ferrari, Roberto; Martini, Fernanda; Tognon, Mauro G.

    2018-01-01

    Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches. PMID:29666782

  7. Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

    Science.gov (United States)

    Boyer, Arnaud; Pasquier, Eddy; Tomasini, Pascale; Ciccolini, Joseph; Greillier, Laurent; Andre, Nicolas; Barlesi, Fabrice; Mascaux, Celine

    2018-03-31

    Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-income countries where access to expensive drugs is limited. This review assesses the published preclinical and clinical data about drug repurposing in MPM.In this review, we identified 11 therapeutic classes that could be repositioned in mesothelioma. Most of these treatments have been evaluated in vitro , half have been evaluated in vivo in animal models of MPM and only three ( i.e. valproate, thalidomide and zoledronic acid) have been investigated in clinical trials, with limited benefits so far. Efforts could be coordinated to pursue further investigations and test promising drugs identified in preclinical experiments in appropriately designed clinical trials. Copyright ©ERS 2018.

  8. 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.

  9. Malignant pleural mesothelioma due to environmental mineral fiber exposure in Turkey. Analysis of 135 cases

    Energy Technology Data Exchange (ETDEWEB)

    Selcuk, Z.T.; Coeplue, L.Em.; Emri, S.; Kalyoncu, A.F.; Sahin, A.A.; Baris, Y.I. (Department of Chest Diseases, Hacettepe University School of Medicine, Ankara (Turkey))

    1992-09-01

    We reviewed data from 135 patients with environment-associated malignant pleural mesothelioma (MPM) from the Central Anatolian region of Turkey. The most significant factors suggesting the diagnosis of MPM were the village where the patient resided and the typical presenting symptoms and signs of unilateral exudative pleural effusion associated with nonpleuritic chest pain. Computed tomography and ultrasonography were very useful for evaluating the extension of the tumor in the thoracic and abdominal cavities and chest wall. The tissue diagnosis was established by either thoracoscopy (39 percent) or pleural biopsy (39 percent) in the majority of the cases. The median survival after diagnosis was 13.52 months for erionite-associated MPM and 21.56 months for asbestos-associated MPM. The actuarial survival curves for the fibrous minerals were significantly different for survival computed both from onset of the symptoms and after diagnosis. Medical or surgical treatment or both did not change the outcome of the disease.

  10. The state of the art in the technical performance of lung-sparing operations for malignant pleural mesothelioma.

    Science.gov (United States)

    Friedberg, Joseph S

    2013-01-01

    Malignant pleural mesothelioma remains an incurable disease for which the role of surgery remains controversial. Though not yet clearly defined there does appear to be a subset of patients who benefit from a surgery-based multimodal treatment plan, beyond what would be expected with current nonoperative therapies. As with other pleural cancers it is probably not possible to achieve a microscopic complete resection with any operation. The goal of surgery in this setting, therefore, is to remove all visible and palpable disease - a macroscopic complete resection. There are basically two surgical approaches to achieve a macroscopic complete resection, lung-sacrificing and lung-sparing. Lung-sacrificing surgery, which likely leaves behind the least amount of microscopic disease, is accomplished as an extrapleural pneumonectomy. This is a well established and standardized operation. Lung-sparing surgery for malignant pleural mesothelioma, on the other hand, does not currently enjoy any degree of consistency. Not only are the reported variations on the operation widely disparate, but even the nomenclature to describe the operation is highly variable. Often the selection of a lung-sparing approach is reported as an intraoperative decision that hinges on the bulk of the cancer and/or the degree of extension into the pulmonary fissures. This article describes the current evolution of a lung-sparing procedure, radical pleurectomy, which has been used to achieve a macroscopic complete resection in over a hundred patients. Many of these cases involved bulky cancers, some exceeding two liters in volume, and often with extensive invasion of the pulmonary fissures. With the described technique there has not yet been an instance where conversion to extrapleural pneumonectomy would have contributed to the ability to achieve a macroscopic complete resection. Whether or not radical pleurectomy is the optimal approach for any or all patients undergoing surgery-based multimodal

  11. Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma.

    Science.gov (United States)

    Di Marzo, Domenico; Forte, Iris Maria; Indovina, Paola; Di Gennaro, Elena; Rizzo, Valeria; Giorgi, Francesca; Mattioli, Eliseo; Iannuzzi, Carmelina Antonella; Budillon, Alfredo; Giordano, Antonio; Pentimalli, Francesca

    2014-01-01

    Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT.   Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.

  12. Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog.

    Science.gov (United States)

    Di Tommaso, Morena; Rocconi, Francesca; Marruchella, Giuseppe; D'Angelo, Anna Rita; Masci, Stefano; Santori, Domenico; Civitella, Carla; Luciani, Alessia; Boari, Andrea

    2015-12-02

    A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed.

  13. Pathways for the direct extension of malignant pleural mesothelioma into peritoneal cavity. Assessment using computed tomography (CT) and magnetic resonance imaging (MRI)

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Takashi; Inoue, Yasushi; Iida, Shinichiro; Tonomura, Atsushi; Miyake, Mitsutomi; Togawa, Naoki; Hada, Toshikazu [Hyogo Coll. of Medicine, Nishinomiya (Japan); Chahinian, A.P.

    2000-01-01

    We investigated pathways for the direct extension of malignant pleural mesothelioma into peritoneal cavity using CT and MRI, and compared the radiographic findings with the corresponding gross pathologic features at thoracotomy or autopsy to make sure an accurate radiologic assessment. Three different pathways could be recognized ; direct invasion of diaphragmatic muscle to penetrate into peritoneal cavity, direct contiguous extension along the descending aorta into retroperitoneum through the aortic hiatus, and extension from the medial and lateral arcuate ligaments into retroperitoneum along the psoas major muscle and quadratus lumbrum muscle. MRI could evaluate a diaphragmatic muscle invasion and differentiate it from transdiaphragmatic extension. Irregularity of the infradiaphragmatic fat tissue in T1-weighted image was a reliable indicator of transdiaphragmatic extension. MRI is of value in assessing diaphragmatic involvement in patients with malignant pleural mesothelioma. (author)

  14. Gallium scanning in differentiating malignant from benign asbestos-related pleural disease

    International Nuclear Information System (INIS)

    Teirstein, A.S.; Chahinian, P.; Goldsmith, S.J.; Sorek, M.

    1986-01-01

    In order to assess the utility of 67gallium citrate in delineating malignant pleural mesothelioma from benign asbestos-related pleural disease, 49 patients with malignant mesothelioma and 16 with benign asbestos-related pleural disease were studied. Seven patients with malignant mesothelioma had no history of asbestos exposure, while the remaining 58 patients were exposed. Forty-three of the 49 patients (88%) with malignant mesothelioma had a positive 67gallium scan including 36 of the 42 (86%) patients with asbestos exposure and all 7 patients without a history of asbestos exposure. Three of 16 patients (19%) with benign asbestos-related pleural disease had a positive scan. 67Gallium radionuclide imaging is nonspecific but may be valuable in noninvasive monitoring of asbestos-exposed populations, which have a high risk for the late development of benign and/or malignant pleural disease

  15. Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy

    Directory of Open Access Journals (Sweden)

    Caterina Bruno

    2014-06-01

    Full Text Available INTRODUCTION. Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite. MATERIALS AND METHODS. Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. RESULTS. The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50. DISCUSSION AND CONCLUSIONS. Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.

  16. Content validity and electronic PRO (ePRO) usability of the Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso) in mesothelioma patients.

    Science.gov (United States)

    Gelhorn, Heather L; Skalicky, Anne M; Balantac, Zaneta; Eremenco, Sonya; Cimms, Tricia; Halling, Katarina; Hollen, Patricia J; Gralla, Richard J; Mahoney, Martin C; Sexton, Chris

    2018-02-01

    Obtaining qualitative data directly from the patient perspective enhances the content validity of patient-reported outcome (PRO) instruments. The objective of this qualitative study was to evaluate the content validity of the Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso) and its usability on an electronic device. A cross-sectional methodological study, using a qualitative approach, was conducted among patients recruited from four clinical sites. The primary target population included patients with pleural mesothelioma; data were also collected from patients with peritoneal mesothelioma on an exploratory basis. Semi-structured interviews were conducted consisting of concept elicitation, cognitive interviewing, and evaluation of electronic patient-reported outcome (ePRO) usability. Participants (n = 21) were interviewed in person (n = 9) or by telephone (n = 12); 71% were male with a mean age of 69 years (SD = 14). The most common signs and symptoms experienced by participants with pleural mesothelioma (n = 18) were shortness of breath, fluid build-up, pain, fatigue, coughing, and appetite loss. The most commonly described symptoms for those with peritoneal mesothelioma (n = 4) were bloating, changes in appetite, fatigue, fluid build-up, shortness of breath, and pain. Participants with pleural mesothelioma commonly described symptoms assessed by the LCSS-Meso in language consistent with the questionnaire and a majority understood and easily completed each of the items. The ePRO version was easy to use, and there was no evidence that the electronic formatting changed the way participants responded to the questions. Results support the content validity of the LCSS-Meso and the usability of the electronic format for use in assessing symptoms among patients with pleural mesothelioma.

  17. 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 miR...

  18. Diffuse malignant mesothelioma. Prospective evaluation of 69 patients

    International Nuclear Information System (INIS)

    Chahinian, A.P.; Pajak, T.F.; Holland, J.F.; Norton, L.; Ambinder, R.M.; Mandel, E.M.

    1982-01-01

    From 1974 to 1980, 69 patients with ith diffuse malignant mesothelioma were prospectively evaluated. The initial site of involvement was the pleura in 57 patients and the peritoneum in 12. Previous asbestos exposure was found in 53 patients (77%), with a shorter period of latency for peritoneal (mean, 28 years) than for ith pleural mesothelioma (mean, 35 years) than for pleural mesothelioma (mean, 35 years). Other associated exposure or diseases included talc, mica, familial Mediterranean fever, and diffuse lymphocytic lymphoma (one patient each). Thrombocytosis was common, as were thromboembolic episodes. Survival was significantly better for patients with an epithelial subtype, with pleural versus peritoneal mesothelioma, and for those under 65 years of age. Surgery was never curative, but its extent was correlated with survival and earlier diagnosis. Results of chemotherapy with doxorubicin and 5-azacytidine yielded a somewhat better survival rate than a combined program with doxorubicin and radiotherapy. Survival after chemotherapy was correlated with performance status, response to chemotherapy, and extent of previous surgery

  19. What is the best way to diagnose and stage malignant pleural mesothelioma?

    Science.gov (United States)

    Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco

    2011-02-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was which diagnostic modality [computed tomography (CT), positron emission tomography (PET), combination PET/CT and magnetic resonance imaging (MRI)] provides the best diagnostic and staging information in patients with malignant pleural mesothelioma (MPM). Overall, 61 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that fluorodeoxyglucose (FDG)-PET is superior to MRI and CT but inferior to PET-CT, in terms of diagnostic specificity, sensitivity and staging of MPM. Four studies reported outcomes using FDG-PET to diagnose MPM. PET diagnosed MPM with high sensitivity (92%) and specificity (87.9%). Mean standardised uptake value (SUV) was higher in malignant than benign disease (4.91 vs. 1.41, Pone biopsy (100% vs. 9%) much more often than a 'blind' approach. CT had a lower success rate (92% vs. 100%) than thoracoscopic pleural biopsy but was equivalent to MRI in terms of detection of lymph node metastases (P=0.85) and visceral pleural tumour (P=0.64). CT had a lower specificity for stage II (77% vs. 100%, P<0.01) and stage III (75% vs. 100%, P<0.01) disease compared to PET-CT. Overall, the high specificity and sensitivity rates seen with open pleural biopsy make it a superior diagnostic modality to CT, MRI or PET for diagnosing patients with MPM.

  20. 18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

    Science.gov (United States)

    Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

    2018-02-01

    The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

  1. Clinical appearance and treatment of malignant pleural mesothelioma; Klinik und Therapie des malignen Pleuramesothelioms

    Energy Technology Data Exchange (ETDEWEB)

    Schiebe, M. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Hoffmann, W. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Kortmann, R.D. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Bamberg, M. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie

    1994-11-01

    We report about 7 of our own cases, treated with surgery and radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy (3) and discuss the clinical aspects, diagnosis and the different ways of treatment of malignant pleural mesothelioma and its influence on survival. (orig.) [Deutsch] Wir berichten ueber sieben Patienten, die operiert und bestrahlt (vier) oder durch eine Kombination von operativen Massnahmen, Strahlen- und Chemotherapie behandelt wurden (drei). Klinische und diagnostische Aspekte sowie verschiedene Therapiemodalitaeten in der Behandlung des malignen Pleuramesothelioms werden im Ueberblick dargestellt. (orig.)

  2. Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.

    Science.gov (United States)

    Bobek, Vladimir; Kacprzak, Grzegorz; Rzechonek, Adam; Kolostova, Katarina

    2014-05-01

    Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients. Patients with diagnosed MPM were enrolled into this study. A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope. The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

  3. 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.

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

    Science.gov (United States)

    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.

  5. Malignant Mesothelioma Versus Metastatic Carcinoma of the Pleura: A CT Challenge

    International Nuclear Information System (INIS)

    Bakhshayesh Karam, Mehrdad; Karimi, Shirin; Mosadegh, Leila; Chaibakhsh, Samira

    2016-01-01

    Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm of the pleura that typically affects individuals occupationally exposed to asbestos through a variety of industries. MPM presents with several CT features similar to more common pleural diseases such as metastatic pleural malignancy. The aim of this study is to differentiate malignant pleural mesothelioma from metastatic carcinoma of the pleura by pathological and radiological assessment in order to investigate accuracy of CT scan in this regard and to compare CT features of these two malignancies. Chest CT scans of 55 pleural malignancy patients including MPM and metastatic pleural malignancy were evaluated in this retrospective study. The pathologist made the definite diagnosis based on immunohistochemistry. A chest radiologist unaware of the pathology diagnosis observed all CT scans. Several parameters including pleural thickening, pleural effusion, thickening of inter lobar fissure, contralateral extension, contraction of involved hemithorax, parenchymal involvement (infiltration, nodules, fibrosis), pleural mediastinal involvement, lymphadenopathy, extrapleural invasion (hepatic, chest wall, diaphragm, intraperitoneal), and pericardial involvement were checked. Data analysis was carried out using SPSS version 16, and the ability of CT scan to differentiate malignant pleural mesothelioma and metastatic pleural diseases was investigated. Totally 29 males and 26 females were assessed in this study. Based on pathology, 17 MPM and 38 metastatic pleural malignancies were diagnosed. According to CT study, about 82% of the patients with MPM and about 79% of the patients with metastatic pleural diseases were correctly diagnosed by a radiologist. The most common findings suggestive of MPM were pleural thickening (88.2%), loculated effusion (58.8%), and thickening of the interlobar fissure (47.1%). Whereas free pleural effusion (71.7%), parenchymal infiltration (65.8%) and pleural thickening (63.2%) were

  6. Changing Pattern in Malignant Mesothelioma Survival

    Directory of Open Access Journals (Sweden)

    Jennifer Faig

    2015-02-01

    Full Text Available Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal. Data are conflicting regarding the effect of asbestos exposure on mesothelioma location. OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure. METHODS: Data were analyzed from cases (n = 380 diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record. RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001 after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1 diagnosed with peritoneal mesothelioma, 2 female, 3 exposed, and 4 diagnosed at a younger age and to have a 5 shorter latency compared to occupational cases (P < .001. CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.

  7. Mesotheliomas of the pleura and the peritoneum

    International Nuclear Information System (INIS)

    Engelhard, K.; Roedl, W.

    1985-01-01

    From 1972 and 1982 we observed 6 cases of diffuse pleural mesothelioma and 3 cses of peritoneal mesothelioma in the Department of Internal Medicine of the University of Erlangen-Nuernberg. In 5 of 6 cases one sided noncharacteristic relapsing pleural effusion was the only sign of the pleural tumor process. Only in one case a pleural tumor constallation was diagnosed. Tomography of the lung showed a normal free central bronchial system and peripheral bronchial infiltration or displacement. In all cases CT scans were able to localize the tumor furthermor to demonstrate the exact extension and the infiltration of the mediastinum or of the diaphragm into the abdomen. Beside conventional X-rays such as double contrast examination of the colon and mesenterial angiography CT scans played the major role in diagnosing this rare peritoneal mesothelioma. Massive ascites, mesenterial infiltration, thickening of the mesentherial radix, and tumor embedding of bowel and vessels is of diagnostic significance. To ensure the diagnosis one has to do a thoraco- or laparoscopy. (orig.) [de

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

    International Nuclear Information System (INIS)

    Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H

    2015-01-01

    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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

    Science.gov (United States)

    Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

    2018-02-01

    There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

  12. Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

    Directory of Open Access Journals (Sweden)

    Ayako Tsuchiya

    2015-11-01

    Full Text Available 1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX. DAPE generated reactive oxygen species (ROS and inhibited activity of thioredoxin (Trx reductase (TrxR. DAPE decreased an association of apoptosis signal-regulating kinase 1 (ASK1 with thioredoxin (Trx, thereby releasing ASK1. DAPE activated p38 mitogen-activated protein kinase (MAPK, which was inhibited by an antioxidant or knocking-down ASK1. In addition, DAPE-induced NCI-H28 cell death was also prevented by knocking-down ASK1. Taken together, the results of the present study indicate that DAPE stimulates NOX-mediated ROS production and suppresses TrxR activity, resulting in the decrease of reduced Trx and the dissociation of ASK1 from a complex with Trx, allowing sequential activation of ASK1 and p38 MAPK, to induce apoptosis of NCI-H28 MPM cells.

  13. Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway.

    Science.gov (United States)

    Tsuchiya, Ayako; Kaku, Yoshiko; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-11-01

    1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species (ROS) and inhibited activity of thioredoxin (Trx) reductase (TrxR). DAPE decreased an association of apoptosis signal-regulating kinase 1 (ASK1) with thioredoxin (Trx), thereby releasing ASK1. DAPE activated p38 mitogen-activated protein kinase (MAPK), which was inhibited by an antioxidant or knocking-down ASK1. In addition, DAPE-induced NCI-H28 cell death was also prevented by knocking-down ASK1. Taken together, the results of the present study indicate that DAPE stimulates NOX-mediated ROS production and suppresses TrxR activity, resulting in the decrease of reduced Trx and the dissociation of ASK1 from a complex with Trx, allowing sequential activation of ASK1 and p38 MAPK, to induce apoptosis of NCI-H28 MPM cells. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. 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.

  15. Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

    2014-03-01

    Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

  16. 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

  17. Comparative study of mesothelioma and asbestosis using computed tomography and conventional chest radiography

    International Nuclear Information System (INIS)

    Rabinowitz, T.G.; Efremidis, S.C.; Cohen, B.; Dan, S.; Efremidis, A.; Chahinian, A.P.; Teirstein, A.S.

    1982-01-01

    A comparative study using computed tomography and conventional posteroanterior radiography was performed on 27 patients with mesothelioma and 13 patients with advanced asbestosis. The major pathologic features of both asbestosis and mesothelioma were well demonstrated by both modalities; computed tomography demonstrated the findings more frequently and in greater detail. No distinguishing features could be established based on configuration and size of the lesion. Many pleural plaques associated with advanced asbestosis were large and irregular and resembled those associated with mesothelioma. However, nodular involvement of the pleural fissures, pleural effusion, and ipsilateral volume loss with a fixed mediastinum were features predominating in mesothelioma. Growth determination of the plaques associated with asbestosis may be of minimal value since such plaques also undergo growth due to active inflammatory changes

  18. Peritoneal mesothelioma: CT and MRI findings

    International Nuclear Information System (INIS)

    Puvaneswary, M.; Chen, S.; Proietto, T.

    2002-01-01

    Two patients with histologically proven diagnosis of peritoneal mesothelioma are presented. Both patients had CT scans of the abdomen. The second patient was also examined with MRI. Although imaging findings are striking, they are non-specific and diagnosing peritoneal mesothelioma in the absence of pleural calcification or pleural plaque on chest radiograph or CT is difficult. However, it is possible to suggest the correct diagnosis in a patient with the presence of non-calcified omental and peritoneal infiltration or masses without liver secondaries or lymphadenopathy. Magnetic resonance imaging with its multi-planar capabilities is a highly sensitive non-invasive modality in the evaluation of malignant peritoneal mesothelioma and can demonstrate the exact site and clarify whether the mass is arising from the peritoneal surface or within a visceral organ. Copyright (2002) Blackwell Science Pty Ltd

  19. Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.

    Science.gov (United States)

    Matboli, Marwa; Shafei, Ayman E; Azazy, Ahmed Em; Reda, Maged; El-Khazragy, Nashwa; Nagy, Ahmed Aly; Ali, Mahmoud A; Sobhi, Mohamed; Abdel-Rahman, Omar

    2018-02-01

    miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum  miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]). Serum miR-548a-3p and  miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR. The expression of serum miR-548a-3p and  miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM. The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.

  20. Radiological Findings in a case of Advance staged Mesothelioma

    Science.gov (United States)

    Aziz, Fahad

    2009-01-01

    Chest X Ray is the initial screening test for the mesothelioma like all other the chest diseases. But computed tomography (CT) is the imaging technique of choice for charactering pleural masses. CT also gives important information regarding invasion of the chest wall and surrounding structures. Certain CT features help differentiate benign from malignant processes. This short article highlights the salient CT appearance of mesothelioma; the most common pleural tumor. PMID:22263002

  1. Mesotheliomas in Lebanon: Witnessing a Change in Epidemiology.

    Science.gov (United States)

    Kattan, Joseph; Eid, Roland; Kourie, Hampig Raphael; Farhat, Fadi; Ghosn, Marwan; Ghorra, Claude; Tomb, Roland

    2016-01-01

    Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001. Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families. A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care. Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.

  2. Investigational Approaches for Mesothelioma

    International Nuclear Information System (INIS)

    Surmont, Veerle F.; Thiel, Eric R. E. van; Vermaelen, Karim; Meerbeeck, Jan P. van

    2011-01-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000–2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA), NIH database (USA), International Pleural Mesothelioma Program – WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  3. 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.

  4. 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

  5. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

    Science.gov (United States)

    Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Metastases skin of a mesothelioma. Report case

    International Nuclear Information System (INIS)

    Aguero, M.; Gauna, C.; Plans, J.; Pereira, R.; Caballero, C.

    2010-01-01

    Introduction: Malignant mesothelioma derived from mesothelium cells. On his pleural location is frequently associated with stroke and that is the first manifestation, presenting low rates performing diagnostic cytology of the spill, with only a third positivity, and even conducting blind pleural biopsy. In early stages of thoracoscopy disease expands the diagnostic possibilities. The age of neoplasia presentation is between 50 and 70 years, with a predominance in men than matters women, probably because the most common occupational exposure to asbestos in it, main risk factor. The main sites of metastases occurring in a patient with malignant mesothelioma in lung, liver and central nervous system. The incidence of skin metastases (visceral primary) are between 1.2% and 4.4% and the ranks occurs in all types of tumours. There is one report of cutaneous metastasis of mesothelioma as a diagnostic event. Case report: Patient 63, who consulted for chest pain of one month evolution by which it prompted Chest X-ray being verified the left pleural effusion which is drained and analyzed to meet the biochemical criteria of an exudate, with crops negative. pleural biopsy, and thoracentesis was performed which resulted in negative cells neoplastic. It was decided to perform VATS where multiple pleural nodules notes occupying the entire pleural cavity which biopsy; the pathology report Undifferentiated Malignant Tumour reported. IHC: Cytokeratin AE1 / AE3 weak positive, cytokeratin 8/18 Vimentin Positive Positive and thus favors the diagnosis of Mesothelioma. It was made 6 cycles of cisplatin + pemetrexed completed in February / 2010 with good response. Six months have chest pain again so PET-CT is performed where finds local relapse, and likely adrenal marrow MTS MTS and contralateral lung. Eight Study days after skin nodules are detected in respecting scalp and face neck which supports 1rio biopsy is taken. known. Conclusion: The Mesothelioma is a rare entity in our

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal.

    Science.gov (United States)

    Schelch, Karin; Wagner, Christina; Hager, Sonja; Pirker, Christine; Siess, Katharina; Lang, Elisabeth; Lin, Ruby; Kirschner, Michaela B; Mohr, Thomas; Brcic, Luka; Marian, Brigitte; Holzmann, Klaus; Grasl-Kraupp, Bettina; Krupitza, Georg; Laszlo, Viktoria; Klikovits, Thomas; Dome, Balazs; Hegedus, Balazs; Garay, Tamas; Reid, Glen; van Zandwijk, Nico; Klepetko, Walter; Berger, Walter; Grusch, Michael; Hoda, Mir Alireza

    2018-04-05

    Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers the worst prognosis, but the signals and pathways controlling EMT in MPM are not well understood. We demonstrate that treatment with FGF2 or EGF induced a fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by scattering, decreased cell adhesion and increased invasiveness. This depended on the MAP-kinase pathway but was independent of TGFβ or PI3-kinase signaling. In addition to changes in known EMT markers, microarray analysis demonstrated differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1 prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more epithelioid morphology and gene expression pattern. Our findings suggest a critical role of the MAP-kinase axis in the morphological and behavioral plasticity of mesothelioma.

  11. Calcification in a pleural mesothelioma

    International Nuclear Information System (INIS)

    Nichols, D.M.; Johnson, M.A.

    1983-01-01

    Extensive calcification in a rapidly growing malignant mixed mesothelioma of the pleura was observed on plain radiography and computed tomography of the chest in a patient with a long history of asbestos exposure and chronic renal failure

  12. Unilateral brown fat on [18F]-F.D.G. PET/CT in the follow-up of a pleural mesothelioma

    International Nuclear Information System (INIS)

    Waele, A. de; Deroose, C.M.; Nafteux, P.; Nackaerts, K.

    2009-01-01

    The fixation of the fluorodeoxyglucose (F.D.G.) in the brown fat is generally characterized by a strongly symmetric setting in some areas of predilection.Is reported here the case of a patient that after having undergone a multi modal treatment for a pleural mesothelioma presents a unilateral F.D.G. fixation in the brown fat, this fixation can be inhibited by the administering of a beta adrenergic blocking agent. (N.C.)

  13. Asymmetrically increased rib cage uptake on bone scintigraphy: Incidental detection of pleural mesothelioma on single photon emission computed tomography/computed tomography

    International Nuclear Information System (INIS)

    Dhull, Varun Singh; Sharma, Punit; Durgapal, Prashant; Karunanithi, Sellam; Tripathi, Madhavi; Kumar, Rakesh

    2014-01-01

    Follow-up bone scintigraphy (BS) in a patient of carcinoma left breast, who was treated with surgery followed by radiotherapy 12 years back, revealed asymmetrically increased radiotracer uptake in left-sided ribs. Since, this pattern was atypical for metastatic rib involvement, single photon emission computed tomography/computed tomography (SPECT/CT) of thorax was done in the same setting which revealed circumferential nodular left-sided pleural thickening. Biopsy confirmed it to be pleural mesothelioma. Left-sided ribs showed no abnormality on CT, thus suggesting the rib uptake as reactive in nature. This pattern of asymmetric rib uptake on BS should be kept in mind and warrants further investigation for determining underlying pathology

  14. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Krug, Lee M.; Kindler, Hedy L.; Calvert, Hilary; Manegold, Christian; Tsao, Anne S.; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E. E.; Fukuoka, Kazuya; Gaafar, Rabab M.; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A.; Lubiniecki, Gregory M.; Sun, Xing; Smith, Margaret; Baas, Paul

    2015-01-01

    Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat

  15. Different imaging methods in the assessment of radiation-induced lung injury following hemithorax irradiation for pleural mesothelioma

    International Nuclear Information System (INIS)

    Maasilta, P.; Kivisaari, L.; Mattson, K.

    1990-01-01

    The authors have characterized the radiation-induced lung-injury on serial chest X-rays, CTs and ultralow field MRs and evaluated the clinical value and cost/benefit ratio of the different imaging methods in 30 patients receiving high-dose hemithorax irradiation for pleural mesothelioma. Lung injury was severe in all patients, but non-specific and essentially as described in text-books. CT provided no clinically relevant, cost effective diagnostic advantage over conventional X-rays in the detection of early or late radiation-induced lung injury, but it was necessary for the evaluation of the disease status of the mesothelioma. The possible advantage of MR over CT could not be evaluated and needs further studies. Optimal time-points for imaging CTs or MRs to detect early radiation-induced lung injury following high dose hemithorax irradiation were during the latter part of the treatment or very shortly after the end of the irradiation. Late injury or irreversible fibrosis develop rapidly after 6 months and was clearly documented by chest X-rays. The authors recommend serial chest X-rays at 1-2, 6 and 12 months following radiotherapy as a cost-effective method for the detection of radiation-induced lung injury with additional CTs to document the stage of mesothelioma, when needed. (author). 31 refs.; 4 figs

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

    International Nuclear Information System (INIS)

    Di Salvo, Maurizio; Gambaro, Giuseppina; Pagella, Simonetta; Manfredda, Iren e; Casadio, Caterina; Krengli, Marco

    2008-01-01

    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

  17. 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.

  18. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma

    International Nuclear Information System (INIS)

    Maasilta, P.

    1991-01-01

    Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy

  19. Radiofrequency Ablation Effectively Treated Focal Recurrence of Mesothelioma.

    Science.gov (United States)

    Nakamura, Akifumi; Takuwa, Teruhisa; Hashimoto, Masaki; Kondo, Nobuyuki; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Hasegawa, Seiki

    2018-02-01

    A 55-year-old man with malignant pleural mesothelioma underwent multimodality treatment comprising induction chemotherapy followed by extrapleural pneumonectomy and radiation therapy. After 2.5 years, focal recurrence occurred, with computed tomography revealing a tumor in the left cardiophrenic angle. Surgery was considered a problem for the patient because of the previous extrapleural pneumonectomy and difficult tumor location. Radiofrequency ablation was thus performed; the course was uneventful, and there was no recurrence. Radiofrequency ablation should be considered an option to treat recurrence of malignant pleural mesothelioma. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Mesothelioma: treatment and survival of a patient population and review of the literature.

    Science.gov (United States)

    Stathopoulos, John; Antoniou, Dimosthenis; Stathopoulos, George P; Rigatos, Sotiris K; Dimitroulis, John; Koutandos, John; Michalopoulou, Pinelopi; Athanasiades, Athanasios; Veslemes, Marinos

    2005-01-01

    Our purpose was to evaluate the survival of patients with pleural and intraperitoneal malignant mesothelioma and, particularly, to estimate the efficacy of chemotherapy as well as radiotherapy and surgery. A review of the literature with respect to these parameters is included. Thirty-five patients with malignant mesothelioma (28 with pleural and 7 with intraperitoneal) were enrolled. Twenty-eight patients underwent chemotherapy, 7/35 radiation and 9/35 surgery (2 with pleural and 7 with abdominal disease). Combination chemotherapy included cisplatin-gemcitabine, cisplatin (or carboplatin) with premetrexed and doxorubicin-cyclophosphamide. In 2/28 patients with pleural mesothelioma the tumor was excised and in 7 with intraperitoneal disease, surgical therapy was palliative and there was survival prolongation. Radiotherapy was only palliative. Chemotherapy produced a very low response: 2/28 (7.14%) patients achieved a partial response. The median survival was 17 months, 4-year survival, 24.4% and 5-year survival, 12.12%. No serious toxicity was observed. Malignant mesothelioma of the pleura and intraperitoneum is a slow-growing disease which is indicated by the long survival, despite the failure of chemotherapy, radiation therapy and surgery.

  1. Expression analysis of HMGB1 in histological samples of malignant pleural mesothelioma.

    Science.gov (United States)

    Rrapaj, Eltjona; Trisolini, Elena; Bertero, Luca; Salvo, Michela; Indellicato, Rossella; Andorno, Silvano; Garcia-Manteiga, Jose M; Rena, Ottavio; Boldorini, Renzo L

    2018-05-01

    High mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear. Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0-3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔC t method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS. These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma. © 2018 John Wiley & Sons Ltd.

  2. Radiation-induced mesotheliomas in rats

    International Nuclear Information System (INIS)

    Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

    1990-01-01

    Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of 239 PuO 2 , mixed uranium-plutonium oxide, or 144 CeO 2 . Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs

  3. The role of ultrasonography in the management of lung and pleural diseases.

    Science.gov (United States)

    Rumende, C Martin

    2012-04-01

    Ultrasonographic examination in pulmonology provides a revolutionary advance because it is very helpful in the diagnosis and management of various pleural and peripheral pulmonary defects. Lung ultrasonography allows the clinicians to diagnose some pulmonary abnormalities more rapidly, including the diagnosis of pleural effusion. Ultrasound examination also provides great assistance for the clinicians to perform invasive techniques in the field of pulmonology, which may increase the success rate and reduce the likelihood of complications. In addition to pleural effusion, other lung disorders can be diagnosed by ultrasound such as peripheral lung tumors and other pleural abnormalities caused by pleural fibrosis and tumor metastasis as well as the primary pleural tumor (mesothelioma). Ultrasound-guided invasive procedures include aspiration of minimal effusion, Transthoracal Needle Aspiration, Transthoracal biopsies and chest tube insertion. Lung ultrasound also offers other advantages, i.e. free from radiation hazards, portable, non-invasive and relatively inexpensive. Ultrasonography in the thorax also has its limitations, especially in detecting mediastinal abnormalities.

  4. 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.

  5. Use of Computed Tomography and Positron Emission Tomography/Computed Tomography for Staging of Local Extent in Patients With Malignant Pleural Mesothelioma

    OpenAIRE

    Frauenfelder, Thomas; Kestenholz, Peter; Hunziker, Roger; Nguyen, Thi Dan Linh; Fries, Martina; Veit-Haibach, Patrick; Husmann, Lars; Stahel, Rolf; Weder, Walter; Opitz, Isabelle

    2015-01-01

    PURPOSE The objective of this study was to determine the diagnostic value of computed tomography (CT) and positron emission tomography (PET)/CT for staging of malignant pleural mesothelioma (MPM) in patients undergoing induction chemotherapy. METHODS Sixty-two patients (median age, 61 years; female: n = 9) with proven MPM underwent CT after induction chemotherapy. Of these, 28 underwent additional PET/CT. Extrapleural pneumonectomy was performed for pathological TNM staging. Clinical TNM s...

  6. Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for malignant pleural mesothelioma: A 10-year experience.

    Science.gov (United States)

    Ambrogi, Marcello Carlo; Bertoglio, Pietro; Aprile, Vittorio; Chella, Antonio; Korasidis, Stylianos; Fontanini, Gabriella; Fanucchi, Olivia; Lucchi, Marco; Mussi, Alfredo

    2018-04-01

    The best surgical treatment for malignant pleural mesothelioma is still under a debate, but recent evidence points toward a less-invasive approach to reduce morbidity and mortality. We reported our 10-year experience of a limited surgical approach associated with hyperthermic intrathoracic chemotherapy (HITHOC). Between 2005 and 2014, patients with epithelioid or biphasic malignant pleural mesothelioma were treated with lung-diaphragm-pericardium-sparing pleurectomy associated with double-drug HITHOC; at least 3 cycles of adjuvant chemotherapy were then administered. The primary outcome examined was the feasibility of the procedure, whereas secondary outcomes were overall survival and disease-free interval. Among 49 patients, 41 were male. Median age was 68 years (35-76 years). Histology was epithelioid in 43 cases. Pathologic stage I, II, III, and IV occurred in 12, 14, 20, and 3 cases, respectively. No intraoperative complications or postoperative mortality occurred, whereas morbidity rate was 46.9%. Median hospital stay was 8 days (5-45 days). Actuarial median overall survival was 22 months and a 1-, 2-, and 5-year survival accounted for 79.6%, 45.7%, and 9.9%, respectively. Disease-free survival after surgery was 62%, 37.5%, and 18.5% at 1, 2, and 5 years, respectively. Risk factors analysis for overall survival confirmed a significant role for early stages, epithelioid histology, and fibrinogen serum levels. Cytoreductive surgery associated with HITHOC and adjuvant chemotherapy appears feasible and safe, with no mortality and low morbidity. Preserving lung and diaphragmatic function might warrant an acceptable long-term outcome. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma.

    Science.gov (United States)

    Shigeeda, Wataru; Shibazaki, Masahiko; Yasuhira, Shinji; Masuda, Tomoyuki; Tanita, Tatsuo; Kaneko, Yuka; Sato, Tatsuhiro; Sekido, Yoshitaka; Maesawa, Chihaya

    2017-11-07

    Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA treatment increased cell motility and invasion, and this was abolished by RHAMM knockdown, suggesting that HA may augment local progression of MPM cells via RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM transcription by modulating YAP1/TAZ activity, decreased the motility and invasion of MPM cells. Collectively, these data suggest that HA is an "unfavorable" factor because it promotes malignancy in mesothelioma and that the YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for inhibition of disease progression in MPM.

  8. Radiation-induced mesotheliomas in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

    1990-01-01

    Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of {sup 239}PuO{sub 2}, mixed uranium-plutonium oxide, or {sup 144}CeO{sub 2}. Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs. (MHB)

  9. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Nilsonne, Gustav; Arslan, Sertaç; Csürös, Karola; Hillerdal, Gunnar; Yildirim, Huseyin; Metintas, Muzaffer; Dobra, Katalin; Hjerpe, Anders

    2013-01-01

    Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  10. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Directory of Open Access Journals (Sweden)

    Filip Mundt

    Full Text Available PURPOSE: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. PATIENTS AND METHODS: Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. RESULTS: Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39, N-ERC/mesothelin (4.81, 3.19-7.93, CERC/mesothelin (3.58, 2.43-5.59 and syndecan-1 (1.34, 1.03-1.77. A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00 in the model generation dataset and 0.83 (0.74-0.91 in the validation dataset, respectively. CONCLUSIONS: A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  11. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  12. 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.

  13. Malignant peritoneal mesothelioma presenting with respiratory symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Daskalogiannaki, M.; Prassopoulos, P.; Raissaki, M.; Gourtsoyiannis, N. [Dept. of Radiology, University Hospital of Heraklion (Greece); Tsardi, M. [Dept. of Pathology, University Hospital of Heraklion (Greece)

    2000-05-01

    Malignant peritoneal mesothelioma is a rare disease associated with mild, nonspecific abdominal symptoms and a wide spectrum of imaging findings, with thickened mesentery and peritoneum being the most common ones. A case of a malignant peritoneal mesothelioma presenting with manifestations of pulmonary disease is reported. Imaging evaluation revealed pleural, lung and pericardial involvement together with retroperitoneal lymphadenopathy, little ascites and extensive omental, but only subtle, mesenteric thickening. (orig.)

  14. 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.)

  15. 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

  16. Heparanase expression in periapical granulomas and radicular cysts.

    Science.gov (United States)

    Elad, S; Sherman, Y; Palmon, A; Vlodavsky, I; Or, R

    2013-01-01

    Heparanase is an endo-β-D-glucuronidase enzyme which degrades heparan sulfate glycosaminoglycan side chains of proteoglycans in the extracellular matrix and in basement membranes. The aim of this study was to evaluate the expression of heparanase in periapical granulomas (PGs) and radicular cysts (RCs). Immunohistochemistry was used to assess heparanase expression in PGs and RCs. Parameters including stain intensity, location and cell type were used to characterize heparanase expression in the periapical lesions. Ordered categories (from weak to strong) were used to compare the level of heparanase staining in the PG and RC groups. Both epithelial cells and inflammatory cells were positive for heparanase. The relative staining of the epithelial cells was strong, whereas the relative staining of the inflammatory cells was weak. Significant differences in immunohistochemical staining of epithelial cells were observed between RCs and PGs (p = 0.002). The relative expression of heparanase in epithelial cells in RCs was strong. In PGs, lesions with few or no epithelial cells, heparanase was predominantly expressed weakly by inflammatory cells. PGs and RCs have the same infectious origin. Therefore, the different cellular sources of heparanase in these periapical lesions may imply that this enzyme has specific pathogenetic functions in RCs and PGs.

  17. Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Cristobal Ramirez Sevilla

    2017-01-01

    Full Text Available Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.

  18. In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

    International Nuclear Information System (INIS)

    Melotti, Alice; Daga, Antonio; Marubbi, Daniela; Zunino, Annalisa; Mutti, Luciano; Corte, Giorgio

    2010-01-01

    Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties. The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated. The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor. These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma

  19. Mesothelioma in Two Nondomestic Felids: North American Cougar (Felis concolor and Cheetah (Acinonyx jubatus

    Directory of Open Access Journals (Sweden)

    Amanda Whiton

    2013-01-01

    Full Text Available A 15-year-old male North American cougar (Felis concolor presented with a 2-day history of anorexia, restlessness, and dyspnea. White blood cell count ( cells/μL and absolute segmented neutrophil count ( cells/μL were increased, and BUN (143 mg/dL, creatinine (6.3 mg/dL, and phosphorus (8.5 mg/dL concentrations indicated chronic renal disease. Thoracic radiographs showed severe pleural and pericardial effusion. During attempts to remove the fluid, cardiac tamponade developed and the cat died. At necropsy, nodular masses decorated the pericardium at the level of the base of the heart. The final microscopic diagnosis was mesothelioma of the pericardium, tunica adventitia of the main pulmonary artery, left auricle epicardium, and left ventricular epicardium. A 15-year-old female cheetah (Acinonyx jubatus was evaluated for acute respiratory distress. The white blood cell count ( cells/μL and absolute segmented neutrophil count ( cells/μL were increased. Radiographically pleural effusion and a cranial thoracic mass were seen. The cheetah was euthanized, and a gross diagnosis of disseminated pleural mesothelioma with thoracic effusion was made. Histologically, pleural mesothelioma was confirmed with local invasion of the lung and pulmonary arterial emboli and infarction. In both cases, a diagnosis of mesothelioma was made based on cellular morphology, microscopic architecture, and neoplastic cell coexpression of cytokeratin and vimentin.

  20. Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, S. [Medical Clinic II, Univ. Hospital, Ulm (Germany); Medical Clinic I, Univ. Hospital RWTH, Aachen (Germany); Pauls, S. [Dept. of Diagnostic and Interventional Radiology, Univ. Hospital, Ulm (Germany); Mottaghy, F.M.; Buck, A.K.; Reske, S.N. [Dept. of Nuclear Medicine, Univ. Hospital, Ulm (Germany); Schelzig, H. [Dept. of Thoracic and Vascular Surgery, Univ. Hospital, Ulm (Germany); Hombach, V. [Medical Clinic II, Univ. Hospital, Ulm (Germany)

    2007-07-01

    Aim of this study was to investigate, how often TNM staging is changed in patients with malignant pleural mesothelioma (MPM) by the application of integrated PET-CT compared to computed tomography alone and how often these changes are clinically relevant. Patients, methods: We studied 17 patients (68 {+-} 6 years, 8 women) with MPM. Integrated PET-CT scan and histological confirmation were performed in all patients. Results: Final histological diagnosis confirmed 9 epithelial type, 2 sarcomatoid type and 6 biphasic type MPM. Mean standardized uptake value (SUV) was 5.9 {+-} 1.9 in epithelial MPM and 15.1 {+-} 10.2 in sarcomatoid MPM. CT and PET-CT revealed discordances in 8/17 (47%) patients in TNM classification with 4/8 (50%) being clinically relevant. PET-CT led to downstaging in 5 (29%) and upstaging in 3 (18%) patients. Mean survival time tended to be higher in the subgroup of patients with lower mean SUV. Conclusions: PET-CT seems to be a valuable tool in staging of MPM and leads to discordant findings in almost every second patient compared to CT alone. In many cases these differences are clinically relevant and have therapeutic consequences. (orig.)

  1. Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

    Science.gov (United States)

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-09-01

    The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells. DAPE-induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1. DAPE generated reactive oxygen species (ROS) followed by disruption of mitochondrial membrane potentials in NCI-H28 cells. DAPE-induced mitochondrial damage was attenuated by cyclosporin A, an inhibitor of cyclophilin D (CypD). DAPE did not affect expression and mitochondrial localization of p53 protein in NCI-H28 cells. DAPE significantly decreased intracellular ATP concentrations in NCI-H28 cells. Overall, the results of the present study indicate that DAPE induces necroptosis and necrosis of MPM cells; the former is mediated by RIP1 kinase and the latter is caused by generating ROS and opening CypD-dependent mitochondrial permeability transition pore, to reduce intracellular ATP concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study

    NARCIS (Netherlands)

    Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Vincent, Andrew D.; Korse, Catharina M.; van Klaveren, Rob J.; Schramel, Franz M. N. H.; Pavlakis, Nick; Nowak, Anna K.; Custers, Frank L. J.; Schouwink, J. Hugo; Gans, Steven J. M.; Groen, Harry J. M.; Strankinga, Wim F. M.; Baas, Paul

    2013-01-01

    Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic

  3. The peritoneal mesothelioma: 4 cases reports

    International Nuclear Information System (INIS)

    Park, Youn Kyeung; Sung, Kyu Bo; Park, Hae Won; Lee, Young Rae

    1990-01-01

    Mesothelioma are infrequently encountered tumors that aries from the surface of any mesothelial lined body cavity. They are found most often in the pleural cavity, less frequently in the peritoneal cavity, and much less frequently in the pericardial cavity or arising from the tunica vaginalis. Tumors are most malignant and usually are detected late in their course when they begin to interfere with organ function. Most noninvasive diagnostic efforts are not helpful. The radiographic appearance is nonspecific and so, diagnosis is commonly made by laparoscopy and laparotomy. We experienced 4 cases of 2 malignant and 2 benign peritoneal mesothelioma which were no evidence of asbestose exposure. And, we believe that one case of malignant mesothelioma may be a consequence of prior radiation therapy

  4. Pleuroperitoneal Mesothelioma: A Rare Entity on 18F-FDG PET/CT

    Science.gov (United States)

    Sahoo, Manas Kumar; Mukherjee, Anirban; Girish; Parida, Kumar; Agarwal, Krishan Kant; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

    2017-01-01

    Pleuroperitoneal mesothelioma is an extremely rare entity. Only few cases are reported worldwide. We hereby represent a case of pleural mesothelioma referred for F-18-Fluorodeoxyglucose positron emission tomography/computed tomography for response evaluation. Diffuse F-18-Fluorodeoxyglucose avid peritoneal and omental thickening noted which subsequently turned out to be mesothelial involvement on peritoneal biopsy. This case demonstrates the role of F-18-Fluorodeoxyglucose positron emission tomography/computed tomography in detecting other sites of involvement in case of malignant mesothelioma. PMID:28242997

  5. 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

  6. Case-control study of pleural mesothelioma in workers with social security in Mexico.

    Science.gov (United States)

    Aguilar-Madrid, Guadalupe; Robles-Pérez, Eduardo; Juárez-Pérez, Cuauhtémoc Arturo; Alvarado-Cabrero, Isabel; Rico-Méndez, Flavio Gerardo; Javier, Kelly-García

    2010-03-01

    Environmental and occupational exposure to asbestos in Mexico in the past has been a cause of deaths and health damages. Its magnitude is unknown to date. Our objective was to identify the proportion of cases of malignant pleural mesothelioma (MPM) that can be attributed to and occupational exposure to asbestos. We carried out a case-control study of MPM in 472 workers insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases and 353 controls. Cases were histologically confirmed. Participants were questioned concerning their occupational history and sociodemographic data. Assignment to one of the four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and attributable risks (ARs) were calculated using a non-conditional logistic regression model. A total of 80.6% of cases and 31.5% of controls had occupational exposure to asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an increase with probability of exposure as follows: 3.7(95% CI 1.3-10.4) for the likely category and 14.3(95% CI 8-26) for the certain category; AR in the group occupationally exposed to asbestos was 83.2%, and the population AR was 44%. Our results show that the relationship between industrial uses of all forms of asbestos is generating an increase in mesothelioma-related diseases and deaths among Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in all production processes with the aim of controlling the epidemic and preventing the occurrence of new cases of MPM. 2009 Wiley-Liss, Inc.

  7. Stereotactic intensity-modulated radiation therapy (IMRT) and inverse treatment planning for advanced pleural mesothelioma. Feasibility and initial results

    Energy Technology Data Exchange (ETDEWEB)

    Muenter, M.W.; Thilmann, C.; Hof, H.; Debus, J. [Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (dkfz), Heidelberg (Germany); Nill, S.; Hoess, A.; Partridge, M. [Dept. of Medical Physics, German Cancer Research Center (dkfz), Heidelberg (Germany); Haering, P. [Dept. of Central Dosimetry, German Cancer Research Center (dkfz), Heidelberg (Germany); Manegold, C. [Dept. of Medical Oncology/Internal Medicine, Thoraxklinik Heidelberg gGmbH, Heidelberg (Germany); Wannenmacher, M. [Dept. of Clinical Radiology, Univ. of Heidelberg, Heidelberg (Germany)

    2003-08-01

    Background and Purpose: Complex-shaped malignant pleural mesotheliomas (MPMs) with challenging volumes are extremely difficult to treat by conventional radiotherapy due to tolerance doses of the surrounding normal tissue. In a feasibility study, we evaluated if inversely planned stereotactic intensity-modulated radiation therapy (IMRT) could be applied in the treatment of MPM. Patients and Methods: Eight patients with unresectable lesions were treated after failure of chemotherapy. All patients were positioned using noninvasive patient fixation techniques which can be attached to the applied extracranial stereotactic system. Due to craniocaudal extension of the tumor, it was necessary to develop a special software attached to the inverse planning program KonRad, which can connect two inverse treatment plans and consider the applied dose of the first treatment plan in the area of the matchline of the second treatment plan. Results: Except for one patient, in whom radiotherapy was canceled due to abdominal metastasis, treatment could be completed in all patients and was well tolerated. Median survival after diagnosis was 20 months and after IMRT 6.5 months. Therefore, both the 1-year actuarial overall survival from the start of radiotherapy and the 2-year actuarial overall survival since diagnosis were 28%. IMRT did not result in clinically significant acute side effects. By using the described inverse planning software, over- or underdosage in the region of the field matchline could be prevented. Pure treatment time ranged between 10 and 21 min. Conclusion: This study showed that IMRT is feasible in advanced unresectable MPM. The presented possibilities of stereotactic IMRT in the treatment of MPM will justify the evaluation of IMRT in early-stage pleural mesothelioma combined with chemotherapy in a study protocol, in order to improve the outcome of these patients. Furthermore, dose escalation should be possible by using IMRT. (orig.)

  8. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Gupta, Vishal; Mychalczak, Borys; Krug, Lee; Flores, Raja; Bains, Manjit; Rusch, Valerie W.; Rosenzweig, Kenneth E.

    2005-01-01

    Purpose: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). Methods and Materials: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. Results: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. Conclusions: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival

  9. Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma.

    Science.gov (United States)

    Kanteti, Rajani; Mirzapoiazova, Tamara; Riehm, Jacob J; Dhanasingh, Immanuel; Mambetsariev, Bolot; Wang, Jiale; Kulkarni, Prakash; Kaushik, Garima; Seshacharyulu, Parthasarathy; Ponnusamy, Moorthy P; Kindler, Hedy L; Nasser, Mohd W; Batra, Surinder K; Salgia, Ravi

    2018-04-03

    The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.

  10. MESOTHELIOMA PRESENTING WITH PNEUMOTHORAX AND INTERLOBAR TUMOR

    NARCIS (Netherlands)

    MANNES, GPM; GOUW, ASH; BERENDSEN, HH; VERHOEFF, AJ; POSTMUS, PE

    A patient presented with a pneumothorax, a parahilar mass and a pleural effusion on the left side. Histology proved that this was caused by a malignant mesothelioma, epithelial type. The pneumothorax persisted, even after chest drainage and pleurodesis with talc powder and tetracycline.

  11. A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma.

    Science.gov (United States)

    Kinoshita, Yoshiaki; Hida, Tomoyuki; Hamasaki, Makoto; Matsumoto, Shinji; Sato, Ayuko; Tsujimura, Tohru; Kawahara, Kunimitsu; Hiroshima, Kenzo; Oda, Yoshinao; Nabeshima, Kazuki

    2018-01-01

    Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions. The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH. MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks. A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. © 2017 American Cancer Society. © 2017 American Cancer Society.

  12. SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features.

    Science.gov (United States)

    Kimura, Noriko; Hasegawa, Masaru; Hiroshima, Kenzo

    2018-02-01

    Malignant mesothelioma (MM) with rhabdoid features is an MM variant. Fifteen cases have been reported previously, all of which were combined with other types of MM. Herein, we report an autopsy case of pleural MM with monomorphic rhabdoid features. The patient was a 62-year-old male without a history of asbestos exposure. An autopsy revealed a soft, granular tumor that replaced the entire left pleura and had invaded to the diaphragm and lower lobe of the lung. The tumor cells, which had eosinophilic plump cytoplasm and eccentric nuclei, were loosely cohesive. Immunohistochemistry showed that the cells were diffusely positive for calretinin, D2-40, vimentin, CAM5.2, and AE1/AE3; and negative for WT-1, TTF-1, CK7, CEA, desmin, CD34, BCL-2, S100 protein, and p40. Neither homozygous deletion of p16 nor BAP-1 protein loss was observed. Loss of INI1/BAF47 protein, an indicator of malignant rhabdoid tumor, was observed. Therefore, MM with rhabdoid features was confirmed. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  13. The role of radiation therapy in malignant pleural mesothelioma: A systematic review

    International Nuclear Information System (INIS)

    Ung, Yee C.; Yu, Edward; Falkson, Conrad; Haynes, Adam E.; Stys-Norman, Denise; Evans, William K.

    2006-01-01

    Introduction: Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM. Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed. Results: Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis found no significant reduction in the frequency of procedure tract metastases. Four non-comparative studies have shown that hemithoracic irradiation alone resulted in significant toxicity, including radiation-induced pulmonary fibrosis, radiation pneumonitis, and bronchopleural fistula, without any survival benefit. Few of the identified studies reported on symptom control, and no studies included formal measures of quality of life. Conclusion: There is limited evidence for the role of radiotherapy in the management of patients with MPM. Future studies including radiotherapy for the treatment of such patients should include formal measures of quality of life and symptom control

  14. Proton Therapy for Malignant Pleural Mesothelioma After Extrapleural Pleuropneumonectomy

    International Nuclear Information System (INIS)

    Krayenbuehl, Jerome; Hartmann, Matthias; Lomax, Anthony J.

    2010-01-01

    Purpose: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. Methods and Materials: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. Results: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The mean dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm 3 ), decreasing from 0 to 18.5 cm 3 /day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. Conclusion: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.

  15. Diagnostic yield of pleural biopsy in exudative pleural effusion.

    Science.gov (United States)

    Devkota, K C; Chokhani, R; Gautam, S

    2014-09-01

    To know the diagnostic role of pleural biopsy in determining underlying etiological causes of exudative pleural effusion. A total of 47 patients, aged 16-104 years with mean age of 47.36 years, of either sex, with exudative pleural effusion underwent closed pleural biopsy with Abram's needle in standard way. Average 4-6 biopsy specimens were obtained from each patient, which were sent for histopathological examination. In this study, 47 cases of exudative pleural effusion were included, among them 26 (55.31%) cases were male and 21 (44.69%) were female with mean age 47.36 years. Cough was reported by 42 (89.36%) cases, expectoration 28 (59.57%), hemoptysis 3 (6.38%), breathlessness 27 (57.44%), wheezing 3 (6.38%), chest pain 38 (80.85%) and fever by 30 (63.82%) cases. Out of 47 cases, 28 (59.57%) cases had a positive yield, whereas in 19 (40.43%) cases the result was nonspecific inflammation. Out of 28 (59.57%) cases with positive yield 21 (44.68%) were found to have granulomatous inflammation and 10 (21.28%) cases were malignant. Among malignant pleural effusion, 4 cases were squamous cell carcinoma; 3 small cell carcinoma; 1 case adenocarcinoma and 1 case found to have mesothelioma. Tuberculosis and malignancy are the two most common causes of exudative pleural effusion in our set up. Pleural biopsy is a safe, simple and well validated diagnostic tool that helps us to differentiate between malignancy and tuberculosis.

  16. Optimal gross tumor volume definition in lung-sparing intensity modulated radiotherapy for pleural mesothelioma: an in silico study.

    Science.gov (United States)

    Botticella, Angela; Defraene, Gilles; Nackaerts, Kristiaan; Deroose, Christophe M; Coolen, Johan; Nafteux, Philippe; Peeters, Stephanie; Ricardi, Umberto; De Ruysscher, Dirk

    2016-12-01

    The gross tumor volume (GTV) definition for malignant pleural mesothelioma (MPM) is ill-defined. We therefore investigated which imaging modality is optimal: computed tomography (CT) with intravenous contrast (IVC), positron emission tomography-CT (PET/CT) or magnetic resonance imaging (MRI). Sixteen consecutive patients with untreated stage I-IV MPM were included. Patients with prior pleurodesis were excluded. CT with IVC, 18FDG-PET/CT and MRI (T2 and contrast-enhanced T1) were obtained. CT was rigidly co-registered with PET/CT and with MRI. Three sets of pleural GTVs were defined: GTV CT , GTV CT+PET/CT and GTV CT+MRI . Quantitative and qualitative evaluations of the contoured GTVs were performed. Compared to CT-based GTV definition, PET/CT identified additional tumor sites (defined as either separate nodules or greater extent of a known tumor) in 12/16 patients. Compared to either CT or PET/CT, MRI identified additional tumor sites in 15/16 patients (p = .7). The mean GTV CT , GTV CT+PET/CT and GTV CT+MRI [±standard deviation (SD)] were 630.1 cm 3 (±302.81), 640.23 cm 3 (±302.83) and 660.8 cm 3 (±290.8), respectively. Differences in mean volumes were not significant. The mean Jaccard Index was significantly lower in MRI-based contours versus all the others. As MRI identified additional pleural disease sites in the majority of patients, it may play a role in optimal target volume definition.

  17. Measurement of mesothelioma on thoracic CT scans: A comparison of manual and computer-assisted techniques

    International Nuclear Information System (INIS)

    Armato, Samuel G. III; Oxnard, Geoffrey R.; MacMahon, Heber; Vogelzang, Nicholas J.; Kindler, Hedy L.; Kocherginsky, Masha; Starkey, Adam

    2004-01-01

    Our purpose in this study was to evaluate the variability of manual mesothelioma tumor thickness measurements in computed tomography (CT) scans and to assess the relative performance of six computerized measurement algorithms. The CT scans of 22 patients with malignant pleural mesothelioma were collected. In each scan, an initial observer identified up to three sites in each of three CT sections at which tumor thickness measurements were to be made. At each site, five observers manually measured tumor thickness through a computer interface. Three observers repeated these measurements during three separate sessions. Inter- and intra-observer variability in the manual measurement of tumor thickness was assessed. Six automated measurement algorithms were developed based on the geometric relationship between a specified measurement site and the automatically extracted lung regions. Computer-generated measurements were compared with manual measurements. The tumor thickness measurements of different observers were highly correlated (r≥0.99); however, the 95% limits of agreement for relative inter-observer difference spanned a range of 30%. Tumor thickness measurements generated by the computer algorithms also correlated highly with the average of observer measurements (r≥0.93). We have developed computerized techniques for the measurement of mesothelioma tumor thickness in CT scans. These techniques achieved varying levels of agreement with measurements made by human observers

  18. Porcelain Factory Worker With Asbestos-related Mesothelioma

    Directory of Open Access Journals (Sweden)

    Meng-Ting Tsou

    2009-10-01

    Full Text Available Malignant mesothelioma is a rare tumor among the general population, but for people exposed to asbestos, the lifetime risk is high. A 58-year old man presented with suffering from chest pain, upper back pain, shortness of breath, and coughing that had continued for several months. A chest X-ray revealed right-side pleural effusion; however, pleural biopsy from drainage treatment confirmed a diagnosis of malignant mesothelioma. According to his occupational and environmental history, the patient had worked continuously in a porcelain factory for 30 years. The specific characteristics of his work, making asbestos wallboards and gaskets, entailed working in high-temperature conditions with a high fine-particle content in the atmosphere. The high working temperature caused asbestos debris and dust to fall down regularly from the wallboards, however, it was not until recently that the patient had started to wear personal protection. Asbestos is a significant source of hazardous exposure in old buildings, and this case serves as a reminder of the importance of asbestos-related exposure history, which facilitated the correct diagnosis of pulmonary malignant mesothelioma. Asbestos-containing materials that are now banned or regulated are still present in older buildings and remain an exposure hazard; they continue to be a serious health concern in many countries.

  19. Altered fractionation of hemithorax irradiation for pleural mesothelioma and failure patterns after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Holsti, L.R. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Pyrhoenen, S. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Kajanti, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Maentylae, M. [Dept. of Radiotherapy and Oncology, Helsinki University Central Hospital (Finland); Mattson, K. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Maasilta, P. [Dept. of Internal Medicine, Div. of Pulmonary Medicine, Helsinki University Central Hospital (Finland); Kivisaari, L. [Dept. of Diagnostic Radiology, Helsinki University Central Hospital (Finland)

    1997-09-01

    Malignant pleural mesothelioma is a rare malignancy with a bleak prognosis. The role of radiotherapy has not yet been clarified. Our aim was to study the effect of altered fractionation on mesothelioma. We have treated 57 patients, 41 males and 16 females, with hemithorax irradiation with six different fractionation schedules. All the patients have been included in a combined modality program consisting of surgery followed by chemotherapy and finally by hemithorax irradiation. The radiotherapy schedules used were: I. Conventional fractionation of 20 Gy in 10 fractions over 12 days. II, Split-course radiotherapy 55 Gy in 25 fractions of 2.2 Gy over 7 weeks (a two weeks rest halfways) followed by a boost dose of 15 Gy over 8 days to the major tumour area. III. Hyperfractionation of 70 Gy over 7 weeks, 1.25 Gy BID with a 6-h interval and a 10-day rest halfways. IV. Combined hyperfractionation and hypofractionation, 35 Gy hyperfractionation in 28 fractions (1.25 Gy BID with a 6-h interval) over three weeks followed by 36 Gy hypofractionation 9 fractions of 4 Gy given every other day over 3 weeks to the major tumour areas only. V. Hypofractionation of 38.5 Gy over 15 days (9x3.5 Gy). VI. Combined conventional radiotherapy and hypofractionation with 20 Gy given conventionally in 10 fractions followed by 10 fractions of 3 Gy over two weeks, overall time 4 weeks. The 2-year survival rate of all patients was 21% and the 5-year survival rate 9%. Two patients are still alive more than 6 and 9 years after radiotherapy. Progression occurred after surgery in four patients, during and after chemotherapy in 22 patients and after completed radiotherapy in 29 patients. The pattern of progression was similar in each treatment group. (orig.).

  20. Soluble Mesothelin-Related Protein in Malignant Pleural Mesothelioma

    International Nuclear Information System (INIS)

    AZIM, H.A.; GAAFAR, R.; KHORSHID, O.; ABDEL SALAM, I.; ASHMAWY, A.; EL-GUINDY, S.; ELATTAR, I.

    2008-01-01

    Background and Purpose: Building-up evidence suggests that soluble mesothelinrelated protein (SMRP) carries a diagnostic and a prognostic value in malignant pleural mesothelioma (MPM). Egypt suffers endemic asbestosis and thus this study was conducted to evaluate the sensitivity and specificity of SMRP in patients with MPM and to correlate this marker with known clinico pathological prognostic factors. Material and Methods: During the period from January 2006 till March 2008, Serum samples were obtained from MPM patients presenting to the Egyptian National Cancer Institute, Cairo University. Serum samples were provided from patients with breast cancer and from healthy individuals to function as controls. The SMRP was assayed using the ELISA technique and correlations were made with different clinico-pathological prognostic parameters. Results: 83 patients (50 MPM and 33 breast cancer) as well as 22 healthy individuals were enrolled in this study. Serum SMRP levels were not different between patients with breast cancer and healthy controls (p>0.05). However, there was a significant difference between MPM patients and the other two groups (p<0.0001). ROC analysis showed an AUC=0.765 for differentiating between the controls and MPM with a best statistical cut-off of 7.22 nM/L (sensitivity=66%, specificity=70.9%). The mean SMRP concentrations were significantly higher in patients with advanced disease (p=0.038), poor performance status (p=0.017) and high alkaline phosphatase (p=0.015). The mean SMRP concentrations were also higher in males, elderly patients, asbestos-exposed patients, epithelioid subtypes and patients with high platelet and leucocytic counts. However, these differences did not reach statistical significance. 224 Conclusions: This study confirms that SMRP is of considerable sensitivity and specificity in Egyptian patients with MPM. Higher levels are frequently seen in patients with high tumor burden, which could be helpful in monitoring response to

  1. Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

    Science.gov (United States)

    Stewart, Duncan; Waller, David; Edwards, John; Jeyapalan, Kanagaratnam; Entwisle, James

    2003-12-01

    To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

  2. Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma

    International Nuclear Information System (INIS)

    Federico, Rea; Matteo, Ceccarelli; Gbenga, Kazeem; Paolo, Marchi; Francesco, Facciolo; Adolfo, Favaretto; Giuseppe, Marulli; Lorenzo, Spaggiari; Martino, DePas Tommaso; Anna, Ceribelli; Adriano, Paccagnella; Gino, Crivellari; Francesca, Russo

    2013-01-01

    Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results. Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m 2 +cisplatin 75 mg/m 2 IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3–8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4–8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation. Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%). Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended. The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation. Clinicaltrial.com registrationID #NCT00087698

  3. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Krug, Lee M; Kindler, Hedy L; Calvert, Hilary; Manegold, Christian; Tsao, Anne S; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E E; Fukuoka, Kazuya; Gaafar, Rabab M; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A; Lubiniecki, Gregory M; Sun, Xing; Smith, Margaret; Baas, Paul

    2015-04-01

    Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). In this randomised trial, vorinostat given as a second-line or third

  4. Peritoneal mesothelioma

    International Nuclear Information System (INIS)

    Raptopoulos, V.

    1985-01-01

    The definitive diagnosis of peritoneal mesothelioma and its differentiation from metastatic peritoneal carcinomatosis may be difficult because of the clinical, macroscopic, and microscopic variability of the tumor. To this purpose, a combination of criteria, including the clinical picture, the gross pathologic findings, the exclusion of other primary neoplasms, and the microscopic findings, must be taken into consideration. Conventionally, these criteria may be established only after surgical exploration and extensive sampling. Experience with patients with peritoneal mesothelioma and metastatic peritoneal carcinomatosis, as well as a review of the recent imaging literature, shows excellent correlation between computed tomography or ultrasound and the operative or autopsy findings. These imaging modalities showed soft-tissue masses or nodules; thickened omentum (omental cake), peritoneum, mesentery, and bowel wall; pleural plaques; and usually disproportionally small, if any, ascites. The latter two observations may be useful in differentiating mesothelioma from carcinomatosis macroscopically. Furthermore, fine-needle aspiration biopsy, after performing wide sampling of the tumors in different locations under ultrasonic or computed tomographic guidance, produced diagnostic cytologic specimens. Thus, the need for exploratory surgery may be alleviated, and the diagnosis of peritoneal mesothelioma may be made prospectively and relatively noninvasively with the use of computed tomography or ultrasound and fine-needle aspiration biopsy. Since epidemiologic studies predict increasing incidence of this neoplasm, especially among asbestos workers, it is suggested that these techniques be seriously considered as screening methods for high-risk populations.67 references

  5. Contribution of positron emission tomography in pleural disease.

    Science.gov (United States)

    Duysinx, B; Corhay, J-L; Larock, M-P; Withofs, N; Bury, T; Hustinx, R; Louis, R

    2010-10-01

    Positron emission tomography (PET) now plays a clear role in oncology, especially in chest tumours. We discuss the value of metabolic imaging in characterising pleural pathology in the light of our own experience and review the literature. PET is particularly useful in characterising malignant pleural pathologies and is a factor of prognosis in mesothelioma. Metabolic imaging also provides clinical information for staging lung cancer, in researching the primary tumour in metastatic pleurisy and in monitoring chronic or recurrent pleural pathologies. PET should therefore be considered as a useful tool in the diagnosis of liquid or solid pleural pathologies. Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  6. 4EGI-1 represses cap-dependent translation and regulates genome-wide translation in malignant pleural mesothelioma.

    Science.gov (United States)

    De, Arpita; Jacobson, Blake A; Peterson, Mark S; Jay-Dixon, Joe; Kratzke, Marian G; Sadiq, Ahad A; Patel, Manish R; Kratzke, Robert A

    2018-04-01

    Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells. This effect was associated with hypophosphorylation of 4E-binding protein 1 (4E-BP1) and decreased protein levels of the cancer-related genes, c-myc and osteopontin. 4EGI-1 showed enhanced cytotoxicity in combination with pemetrexed or gemcitabine. Translatome-wide polysome microarray analysis revealed a large cohort of genes that were translationally regulated upon treatment with 4EGI-1. The 4EGI-1-regulated translatome was negatively correlated to a previously published translatome regulated by eIF4E overexpression in human mammary epithelial cells, which is in agreement with the notion that 4EGI-1 inhibits the eIF4F complex. These data indicate that inhibition of the eIF4F complex by 4EGI-1 or similar translation inhibitors could be a strategy for treating mesothelioma. Genome wide translational profiling identified a large cohort of promising target genes that should be further evaluated for their potential significance in the treatment of MPM.

  7. Primary Malignant Peritoneal Mesothelioma Mimicking Peritoneal Carcinomatosis on F-18 FDG PET/CT

    International Nuclear Information System (INIS)

    Kim, Jin Suk; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee

    2009-01-01

    Malignant mesothelioma of the peritoneum is a rare neoplasm with a rapidly fatal course. The tumour arises from the mesothelial cells lining the pleura and peritoneum or, rarely, in the pericardium or tunica vaginalis. This neoplasm is characterized by being difficult to diagnose, having a rapid evolution and a poor response to therapy. Mesothelioma is very glucose avid, and malignant pleural mesothelioma has been reported concerning the utility of F-18 FDG PET or PET/CT. But little has been known about the imaging finding of malignant peritoneal mesothelioma on F-18 FDG PET/CT. We report a case of malignant peritoneal mesothelioma mimicking peritoneal carcinomatosis of F-18 FDG PET/CT

  8. Primary Malignant Peritoneal Mesothelioma Mimicking Peritoneal Carcinomatosis on F-18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Suk; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-08-15

    Malignant mesothelioma of the peritoneum is a rare neoplasm with a rapidly fatal course. The tumour arises from the mesothelial cells lining the pleura and peritoneum or, rarely, in the pericardium or tunica vaginalis. This neoplasm is characterized by being difficult to diagnose, having a rapid evolution and a poor response to therapy. Mesothelioma is very glucose avid, and malignant pleural mesothelioma has been reported concerning the utility of F-18 FDG PET or PET/CT. But little has been known about the imaging finding of malignant peritoneal mesothelioma on F-18 FDG PET/CT. We report a case of malignant peritoneal mesothelioma mimicking peritoneal carcinomatosis of F-18 FDG PET/CT.

  9. Contribution of positron emission tomography in pleural disease.

    OpenAIRE

    Duysinx, Bernard; Corhay, Jean-Louis; Larock, Marie-Paule; Withofs, Nadia; Bury, Thierry; Hustinx, Roland; Louis, Renaud

    2010-01-01

    INTRODUCTION: Positron emission tomography (PET) now plays a clear role in oncology, especially in chest tumours. We discuss the value of metabolic imaging in characterising pleural pathology in the light of our own experience and review the literature. BACKGROUND: PET is particularly useful in characterising malignant pleural pathologies and is a factor of prognosis in mesothelioma. Metabolic imaging also provides clinical information for staging lung cancer, in researching the primary tumou...

  10. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

    2016-01-01

    Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  11. Unilateral brown fat on [{sup 18}F]-F.D.G. PET/CT in the follow-up of a pleural mesothelioma; Detection unilaterale de graisse brune en [{sup 18}F]-FDG TEP/TDM dans le suivi d'un mesotheliome pleural

    Energy Technology Data Exchange (ETDEWEB)

    Waele, A. de; Deroose, C.M. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, UZ Leuven, Dept. de Medecine Nucleaire, Leuven (Belgium); Nafteux, P. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, Dept. de Chirurgie Thoracique, Leuven (Belgium); Nackaerts, K. [Katholieke Universiteit Leuven, Hopitaux Universitaires de Leuven, Dept. de Pneumologie, Leuven (Belgium)

    2009-10-15

    The fixation of the fluorodeoxyglucose (F.D.G.) in the brown fat is generally characterized by a strongly symmetric setting in some areas of predilection.Is reported here the case of a patient that after having undergone a multi modal treatment for a pleural mesothelioma presents a unilateral F.D.G. fixation in the brown fat, this fixation can be inhibited by the administering of a beta adrenergic blocking agent. (N.C.)

  12. The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Pignochino, Ymera; Dell’Aglio, Carmine; Inghilleri, Simona; Zorzetto, Michele; Basiricò, Marco; Capozzi, Federica; Canta, Marta; Piloni, Davide; Cemmi, Francesca; Sangiolo, Dario; Gammaitoni, Loretta; Soster, Marco; Marchiò, Serena; Pozzi, Ernesto; Morbini, Patrizia; Luisetti, Maurizio; Aglietta, Massimo; Grignani, Giovanni; Stella, Giulia M

    2015-01-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify ‘druggable’ pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in ‘hot spot’ regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA). Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice. ERM and mTOR pathways are activated in MPM and ‘druggable’ by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM. The online version of this article (doi:10.1186/s12885-015-1363-1) contains supplementary material, which is available to authorized users

  13. Heparanase augments insulin receptor signaling in breast carcinoma

    Science.gov (United States)

    Goldberg, Rachel; Sonnenblick, Amir; Hermano, Esther; Hamburger, Tamar; Meirovitz, Amichay; Peretz, Tamar; Elkin, Michael

    2017-01-01

    Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer. In the present study we analyzed clinical samples of breast carcinoma derived from diabetic/non-diabetic patients, and investigated effects of heparanase on insulin signaling in breast carcinoma cell lines, as well as insulin-driven growth of breast tumor cells. We demonstrate that heparanase activity leads to enhanced insulin signaling and activation of downstream tumor-promoting pathways in breast carcinoma cells. In agreement, heparanase enhances insulin-induced proliferation of breast tumor cells in vitro. Moreover, analyzing clinical data from diabetic breast carcinoma patients, we found that concurrent presence of both diabetic state and heparanase in tumor tissue (as opposed to either condition alone) was associated with more aggressive phenotype of breast tumors in the patient cohort analyzed in our study (two-sided Fisher's exact test; p=0.04). Our findings highlight the emerging role of heparanase in powering effect of hyperinsulinemic state on breast tumorigenesis and imply that heparanase targeting, which is now under intensive development/clinical testing, could be particularly efficient in a growing fraction of breast carcinoma patients suffering from metabolic disorders. PMID:28038446

  14. Nephroprotective effect of heparanase in experimental nephrotic syndrome.

    Directory of Open Access Journals (Sweden)

    Suheir Assady

    Full Text Available Heparanase, an endoglycosidase that cleaves heparan sulfate (HS, is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS in a mouse model.BALB/c wild-type (wt mice and heparanase overexpressing transgenic mice (hpa-TG were tail-vein injected with either Adriamycin (ADR, 10 mg/kg or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.Our results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

  15. 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

  16. Investigational approaches for mesothelioma

    Directory of Open Access Journals (Sweden)

    Veerle F Surmont

    2011-08-01

    Full Text Available MPM is a rare, aggressive tumour with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the aetiology, epidemiology, natural history and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics and provide perspective on where the clinical research in mesothelioma is moving.The evidence was collected by a systematic analysis of the literature (2000–2011 using the databases Medline (National Library of Medicine, USA, Embase (Elsevier, Netherlands, Cochrane Library (Great Britain, National Guideline Clearinghouse (USA, HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA, NIH database (USA, International Pleural Mesothelioma Program – WHOLIS (WHO Database , with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugsCurrently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  17. 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....

  18. Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

    International Nuclear Information System (INIS)

    Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion

    2005-01-01

    Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RARα and PLZF-RARα fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RARα from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells

  19. In Vitro and In Vivo Antitumor Activity of [Pt(O,O'-acac)(γ-acac)(DMS)] in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Muscella, Antonella; Vetrugno, Carla; Cossa, Luca Giulio; Antonaci, Giovanna; De Nuccio, Francesco; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Marsigliante, Santo

    2016-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy. There is an urgent need for effective therapy inasmuch as resistance, intrinsic and acquired, to conventional therapies is common. Among Pt(II) antitumor drugs, [Pt(O,O'-acac)(γ-acac)(DMS)] (Ptac2S) has recently attracted considerable attention due to its strong in vitro and in vivo antiproliferative activity and reduced toxicity. The purpose of this study was to examine the efficacy of Ptac2S treatment in MPM. We employed the ZL55 human mesothelioma cell line in vitro and in a murine xenograft model in vivo, to test the antitumor activity of Ptac2S. Cytotoxicity assays and Western blottings of different apoptosis and survival proteins were thus performed. Ptac2S increases MPM cell death in vitro and in vivo compared with cisplatin. Ptac2S was more efficacious than cisplatin also in inducing apoptosis characterized by: (a) mitochondria depolarization, (b) increase of bax expression and its cytosol-to-mitochondria translocation and decrease of Bcl-2 expression, (c) activation of caspase-7 and -9. Ptac2S activated full-length PKC-δ and generated a PKC-δ fragment. Full-length PKC-δ translocated to the nucleus and membrane, whilst PKC-δ fragment concentrated to mitochondria. Ptac2S was also responsible for the PKC-ε activation that provoked phosphorylation of p38. Both PKC-δ and PKC-ε inhibition (by PKC-siRNA) reduced the apoptotic death of ZL55 cells. Altogether, our results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, providing a solid starting point for its validation as a suitable candidate for further pharmacological testing.

  20. P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.

    Science.gov (United States)

    Hostettler, Nina; Naggi, Annamaria; Torri, Giangiacomo; Ishai-Michaeli, Riva; Casu, Benito; Vlodavsky, Israel; Borsig, Lubor

    2007-11-01

    Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we identified modified, nonanticoagulant species of heparin that specifically inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity, or both. We show that selective inhibition of selectin interactions or heparanase with specific heparin derivatives in mouse models of MC-38 colon carcinoma and B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had no effect, in accordance with the virtual absence of heparanase activity in these cells. Heparin derivatives had no further effect on metastasis in mice deficient in P- and L-selectin, indicating that selectins are the primary targets of heparin antimetastatic activity. Selectin-specific and heparanase-specific derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When mice were injected with a derivative containing both heparanase and selectin inhibitory activity, no additional attenuation of metastasis could be observed. Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of both tumor cell types whereas inhibition of heparanase led to reduction of metastasis only in tumor cells producing heparanase.

  1. Prognostic Impact of Inflammation-related Biomarkers on Overall Survival of Patients with Inoperable Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Otoshi, Takehiro; Kataoka, Yuki; Kaku, Sawako; Iki, Reika; Hirabayashi, Masataka

    2018-01-01

    The aim of the present study was to assess the prognostic utility of the pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein-to-albumin ratio (CAR) in patients with inoperable malignant pleural mesothelioma (MPM). The medical records of consecutive patients with histologically confirmed MPM from our hospital between January 2007 and August 2017 were retrospectively reviewed. The primary outcome was overall survival (OS). Univariate and multivariate analyses for the prognostic factors were performed using a Cox proportional hazards model. A total of 143 patients with inoperable MPM were included. On multivariate analysis, pretreatment CAR was an independent factor associated with worse OS (hazard ratio(HR)=1.72; 95% confidence interval(CI)=1.11-2.67; p=0.016). However, NLR was not associated with OS in any of the analyses. CAR appears to be a prognostic factor in patients with inoperable MPM. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Comparison of the Diagnostic Accuracy of the MSLN Gene Products, Mesothelin and Megakaryocyte Potentiating Factor, as Biomarkers for Mesothelioma in Pleural Effusions and Serum

    Directory of Open Access Journals (Sweden)

    Jenette Creaney

    2013-01-01

    Full Text Available The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF, are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM. Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC for MPF (0.945±0.02 and mesothelin (0.928±0.03 when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of 0.813±0.04 and 0.829±0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.

  3. Emergence of nuclear heparanase induces differentiation of human mammary cancer cells

    International Nuclear Information System (INIS)

    Nobuhisa, Tetsuji; Naomoto, Yoshio; Takaoka, Munenori; Tabuchi, Yoko; Ookawa, Keizou; Kitamoto, Dai; Gunduz, Esra; Gunduz, Mehmet; Nagatsuka, Hitoshi; Haisa, Minoru; Matsuoka, Junji; Nakajima, Motowo; Tanaka, Noriaki

    2005-01-01

    The study of epithelial differentiation touches upon many modern aspects of biology. The epithelium is in constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. Recently we reported that heparanase is expressed in nucleus as well as in the cytoplasm and that nuclear heparanase seems to be related to cell differentiation. In this study, we investigated the role of nuclear heparanase in differentiation by transducing human mammary epithelial cancer cells with heparanase which was delivered specifically into nucleus. We observed that expression of nuclear heparanase allowed the cells to differentiate with the appearance of lipid droplets. This finding supports the idea that heparanase plays a novel role in epithelial cell differentiation apart from its known enzymatic function

  4. Elevated urine heparanase levels are associated with proteinuria and decreased renal allograft function.

    Directory of Open Access Journals (Sweden)

    Itay Shafat

    Full Text Available Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD, and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR, suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome.

  5. Ga-67 tumor scan in malignant diffuse mesothelioma. Comparison with CT and pathological findings

    International Nuclear Information System (INIS)

    Yoshida, Shoji; Fukumoto, Mitsutaka; Motohara, Tomofumi; Oobayashi, Kayoko; Takada, Yoshiki; Tsubota, Noriaki; Sashikata, Terumasa

    1999-01-01

    Malignant diffuse mesothelioma is characterized by more difficult diagnosis and worse prognosis than other pleural tumors. In the Department of Thoracic Surgery, Hyogo Medical Center for Adults, 11 patients underwent panpleuropneumonectomy for this disease between January, 1988 and March, 1993. In 7 of these cases, Ga-67 scans were obtained before the operation. To clarify the factors affecting Ga-67 uptake in the pleural tumor, we compared Ga-67 uptake on the involved side of the thorax with CT and the pathological findings of the tumor. Regarding the use of Ga-67 scan imaging for the diagnosis of this disease, a number of related findings must be considered, such as an encircled wide Ga-67 uptake in the thickened pleural involvement and a diffuse slight Ga-67 uptake on the affected side with very slight involvement of the pleura. When the involved pleural thickness was over 6 mm, a definite correlation was found between the degree of Ga-67 uptake and the macroscopic thickness of mesothelioma in resected specimens. Thickness of the pleura on CT images demonstrates the real tumor thickness in the case of thickened involvement but in the case of thin involvement the real thickness of active mesothelioma could not be identified. No definite correlation was found between the degree of Ga-67 uptake and the histological type, or among microscopic findings, such as the extent of tumor parenchyma, interstitial volume and tumor vascularity. Our results suggest that the Ga-67 scan is very useful for revealing the extent of pleural involvement, especially when this involvement is more than 6 mm thick. (author)

  6. Ga-67 tumor scan in malignant diffuse mesothelioma. Comparison with CT and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Shoji; Fukumoto, Mitsutaka [Kochi Medical School, Nankoku (Japan); Motohara, Tomofumi; Oobayashi, Kayoko; Takada, Yoshiki; Tsubota, Noriaki; Sashikata, Terumasa

    1999-02-01

    Malignant diffuse mesothelioma is characterized by more difficult diagnosis and worse prognosis than other pleural tumors. In the Department of Thoracic Surgery, Hyogo Medical Center for Adults, 11 patients underwent panpleuropneumonectomy for this disease between January, 1988 and March, 1993. In 7 of these cases, Ga-67 scans were obtained before the operation. To clarify the factors affecting Ga-67 uptake in the pleural tumor, we compared Ga-67 uptake on the involved side of the thorax with CT and the pathological findings of the tumor. Regarding the use of Ga-67 scan imaging for the diagnosis of this disease, a number of related findings must be considered, such as an encircled wide Ga-67 uptake in the thickened pleural involvement and a diffuse slight Ga-67 uptake on the affected side with very slight involvement of the pleura. When the involved pleural thickness was over 6 mm, a definite correlation was found between the degree of Ga-67 uptake and the macroscopic thickness of mesothelioma in resected specimens. Thickness of the pleura on CT images demonstrates the real tumor thickness in the case of thickened involvement but in the case of thin involvement the real thickness of active mesothelioma could not be identified. No definite correlation was found between the degree of Ga-67 uptake and the histological type, or among microscopic findings, such as the extent of tumor parenchyma, interstitial volume and tumor vascularity. Our results suggest that the Ga-67 scan is very useful for revealing the extent of pleural involvement, especially when this involvement is more than 6 mm thick. (author)

  7. Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

    Science.gov (United States)

    Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

    2016-09-01

    Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  8. Poor Prognostic Factors in Patients with Malignant Pleural Mesothelioma Classified as Pathological Stage IB According to the Eighth Edition TNM Classification.

    Science.gov (United States)

    Takuwa, Teruhisa; Hashimoto, Masaki; Kuroda, Ayumi; Nakamura, Akifumi; Nakamichi, Toru; Fukuda, Akihiro; Matsumoto, Seiji; Kondo, Nobuyuki; Hasegawa, Seiki

    2018-04-03

    The change in TNM classification of malignant pleural mesothelioma (MPM) between the seventh and eighth edition classifications has resulted in the downstaging of many advanced-stage patients into pathological stage IB. Many mesotheliomas without lymph node metastasis have been classified as stage IB in the eighth edition classification. Stage IB mesotheliomas comprised a heterogeneous group with different prognosis. It is necessary to clarify the prognostic factors in this group. Between September 2009 and August 2016, a total of 89 patients with MPM underwent curative intent surgery [pleurectomy decortication n = 57 (64.1%), extrapleural pneumonectomy n = 32 (35.9%)] at our institution. Of these, 40 were reclassified as stage IB according to the eighth edition TNM classification. Independent unfavorable prognostic factors were identified by univariate analyses using the log-rank test and Cox proportional hazards regression models. Three independent significant factors were identified that indicated an unfavorable prognosis: a nonepithelioid subtype, lymphovascular invasion, and preoperative forced expiratory volume in 1 s (FEV1) < 2000 ml. Patients with no, one, and two of these risk factors showed 3-year overall survival probabilities of 94.7, 62.5, and 0%, respectively. The 3-year survival of patients with one factor did not differ significantly from that of patients with stage III MPM, whereas that of patients with two factors was significantly shorter (p = 0.015). Independent poor prognostic factors for patients with stage IB MPM patients, allowing subgroups with poorer and more favorable prognoses to be identified. This should help personalize decisions on adjuvant chemotherapy.

  9. Paraneoplastic Encephalitis Associated with Anti-Ma2 Antibodies and Mesothelioma-Like Poorly Differentiated Lung Cancer

    Directory of Open Access Journals (Sweden)

    Can Ebru Bekircan

    2009-06-01

    Full Text Available We report a case of paraneoplastic encephalitis associated with anti-Ma2 antibodies. Medical history and thorax computed tomog- raphy findings suggested malignant mesothelioma. Pleural biopsy results were compatible with high-grade neoplastic infiltration. Alt- hough the biopsy could not differentiate the type of neoplasm, mesothelioma was considered a strong possibility in this poorly dif- ferentiated lung carcinoma. To the best of our knowledge this is the first case report of paraneoplastic encephalitis associated with anti-Ma2 antibodies and mesothelioma

  10. Heparanase Expression in Malignant Salivary Gl, Tumors Inversely Correlates with Long-Term Survival

    Directory of Open Access Journals (Sweden)

    Ofer Ben-Izhak

    2006-10-01

    Full Text Available BACKGROUND: Upregulation of the endo-b-Dglucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local, distant metastatic spread, increased vascular density, reduced postoperative survival. PATIENTS, METHODS: We analyzed heparanase expression in 60 patients (aged 59 ± 17 years with malignant salivary tumors (39 males, 21 females using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS: Heparanase staining was positive (> 0 in 70% of tumors (42 of 60 patients, was negative (0 in the remaining 30% (18 patients. The cumulative survival of patients diagnosed as heparanase-negative (n = 18 at 300 months was 70% (95% confidence interval = 35-88. In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42 at 300 months was 0% (statistically significant difference, P = .035. CONCLUSIONS: Heparanase expression levels inversely correlate with the survival rates of salivary gl, cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, an attractive target for anticancer drug development.

  11. Non-resolving pleural effusion in a patient with HIV infection

    African Journals Online (AJOL)

    night sweats, cough and shortness of breath. The results of ... treatment,but he then developed a pleural effusion that ... lymphoma, mesothelioma and lung cancer seemed unlikely ... that two active antibiotics are used, which should have good.

  12. Malignant peritoneal mesothelioma associated with deep vein thrombosis following radiotherapy for seminoma of the testis

    International Nuclear Information System (INIS)

    Sato, Fuminori; Yamazaki, Hajime; Ataka, Ken; Mashima, Ichiro; Suzuki, Kenta; Takahashi, Toru; Umezu, Hajime; Gejyo, Fumitake

    2000-01-01

    A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy. (author)

  13. Malignant peritoneal mesothelioma associated with deep vein thrombosis following radiotherapy for seminoma of the testis

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Fuminori; Yamazaki, Hajime; Ataka, Ken; Mashima, Ichiro; Suzuki, Kenta; Takahashi, Toru; Umezu, Hajime; Gejyo, Fumitake [Niigata Univ. (Japan). School of Medicine

    2000-11-01

    A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy. (author)

  14. 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.

  15. A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Jamil MO

    2017-06-01

    Full Text Available Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Malignant pleural mesothelioma (MPM is a rare malignancy with a dismal median survival of <12 months with current therapy. Single and combination chemotherapy regimens have shown only modest clinical benefit. In preclinical studies, nitrogen-containing bisphosphonates (zoledronic acid inhibit growth of mesothelioma cells by different mechanisms: inhibition of mevalonate pathway, inhibition of angiogenesis, activation of apoptosis through caspase activation, and alteration in activity of matrix metalloproteinases, thereby affecting invasiveness of cancer cells.Patients and methods: We investigated the role of zoledronic acid in a pilot, single-arm trial of MPM patients with Eastern Cooperative Oncology Group (ECOG performance status (PS 0–2 who had progressed on prior treatments or had not received systemic therapy due to poor PS. Primary end point was composite response rate by modified response evaluation criteria in solid tumors and/or metabolic response by 2-deoxy-2-[fluorine-18]fluoro-d-glucose (18F-FDG positron emission tomography criteria. Secondary end points were progression-free survival (PFS and overall survival (OS. Exploratory end points include the effect of zoledronic acid therapy on vascular endothelial growth factor (VEGF, basic fibroblast growth factor, interleukin 8, transforming growth factor beta, mesothelin, and osteopontin levels.Results: Eight male patients (median age of 62 years with the following clinical characteristics were treated; ECOG PS was 0–2, 75% with epithelioid type, and 62% had prior chemotherapy. Overall composite response rate was 12.5% and the clinical benefit rate (response + stable disease was 37.5%. Median PFS was 2 months (0.5–21 months and median OS was

  16. Role of CT in management of mesothelioma

    International Nuclear Information System (INIS)

    Godwin, J.D.; Rusch, V.W.; Shuman, W.P.

    1987-01-01

    The authors examined the accuracy of CT in determining the extent of disease and its role in the follow-up of patients with malignant pleural mesothelioma. Twenty patients underwent complex CT-anatomic correlation. CT was unable to demonstrate small tumor implants in the chest wall (four cases), upper abdomen (two cases), or contralateral hemidiaphragm (one case). Occasionally there was difficulty distinguishing tumor invasion of soft tissues from simple contiguity, benign from malignant nodes, and recurrent tumor from surgical changes. In six of eight treated patients, CT demonstrated recurrence -8 months before signs or symptoms appeared. Despite its limitations, CT is essential in the initial evaluation and follow-up of patients with mesothelioma

  17. 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

  18. MRI, CT, and sonography in the preoperative evaluation of primary tumor extension in malignant pleural mesothelioma; MRT, CT und Sonographie in der praeoperativen Beurteilung der Primaertumorausdehnung beim malignen Pleuramesotheliom

    Energy Technology Data Exchange (ETDEWEB)

    Layer, G.; Steudel, A.; Schild, H.H. [Radiologische Universitaetsklinik Bonn (Germany); Schmitteckert, H.; Tuengerthal, S.; Schirren, J. [Thoraxklinik Heidelberg-Rohrbach (Germany); Kaick, G. van [Deutsches Krebsforschungszentrum Heidelberg (Germany). Schwerpunkt fuer Onkologische Diagnostik und Therapie

    1999-04-01

    Purpose: Evaluation of the diagnostic value of the imaging modalities computed tomography (CT), magnetic resonance imaging (MRI), and thoracic sonography in the preoperative staging of malignant pleural mesothelioma. Results: The accuracy rates for CT were 85%, 98%, 83%, 73%, 71%, and 83%. MRI had an accuracy of 71%, 92%, 71%, 83%, 71%, and 96%, the thoracic ultrasound examinations of 76%, 63%, 51%, 60%, 71% and 89%. Conclusions: According to these results CT remains the method of choice in the preoperative assessment of T-stage of malignant pleural mesothelioma. MRI is of nearly the same value, but is not a must. Sonography may be supplementary method for operation planning. (orig./AJ) [Deutsch] Ziel: Evaluation der diagnostischen Wertigkeit der Schnittbildverfahren MRT, CT und Sonographie in der praeoperativen Diagnostik des Pleuramesothelioms. Ergebisse: Die Treffsicherheiten betrugen fuer die genannten anatomischen Regionen im CT 85%, 98%, 83%, 73%, 71%, und 83%, im MRT 71%, 92%, 71%, 83%, 71% bzw. 96%, waehrend sich fuer die thorakale Ultraschalluntersuchung Treffsicherheiten von 76%, 63%, 51%, 60%, 71% und 89% errechneten. Schlussfolgerungen: Die CT bleibt damit das Verfahren erster Wahl in der praeoperativen Diagnostik des malignen Pleuramesothelioms. Eine unbedingte Forderung nach praeoperativer Durchfuehrung einer MRT-Untersuchung ergibt sich nach der vorliegenden Studie nicht. Die Sonographie des Thorax und oberen Abdomens liefert einen wichtigen ergaenzenden Beitrag bei der Planung der Operation des malignen Pleuramesothelioms. (orig./AJ)

  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. Establishment of an induced rat model of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Han Dan; Wu Beihai; Yang Hongsheng; Song Guangyi

    2004-01-01

    Objective: To establish a convenient and practical malignant pleural mesothelioma (MPM) model induced by crocidolite in Da Yao, which has a high induction rate and can be used for imaging and multiple experimental studies and is similar to human MPM. Methods 40 mg of crocidolite suspension was injected into the right chest cavity in 100 Wistar rats in the test group, while same amount of sterilized saline water was injected in 20 rats in the control group. The animals were observed daily , and weighted once a month. CT scanning was performed regularly. When the rats were dead or dying, they were dissected immediately and pathological changes were recorded after CT examination. The experiment lasted for 2 years. Results: The overall induction rate was 71.6%. The survival time of the first MPM rat was 285 days. The mean living span of rats with MPM was (469 ± 21) days. The pathological features of the induced MPMs were multiple morphologically and there were some CT features in different periods. CT imaging could show some MPM features and find the tumour earlier. Conclusion: The cause, positions, tissues and clinical condition of induced tumors were the same as humans. The model had a higher similarity with human MPM in differentiation degree and histological type, and the model can be used to study the mechanism of MPM, to discuss the measures of prevention, and to guide clinical diagnosis and treatment. Multi-morphology of the history from the induced tumors could make up the shortage, which was the difficulty in getting all periods of tissue samples in clinical research and being used in imaging and many kinds of researches. It was a valuable animal model to study MPM. (authors)

  1. 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.

  2. Heparanase-1 activities in the development of laser induced choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Bao-Ke Hou

    2013-04-01

    Full Text Available AIM:To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV.METHODS:Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis.RESULTS:The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photocoagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P<0.01. Immunostaining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space.CONCLUSION:Heparanase-1 is closely involved in the development of laser induced CNV.

  3. A multiwell format assay for heparanase.

    Science.gov (United States)

    Behzad, Farhad; Brenchley, Paul E C

    2003-09-15

    This assay employs a biotinylated heparan sulfate glycosaminoglycan (HSGAG) substrate that is covalently linked to the surface of 96-well immunoassay plates. The ratio of biotin:HSGAG and the coating concentration of substrate bound to the wells have been optimized and allow removal of biotin HSGAG within 60 min of incubation at 37 degrees C in assay buffer with a standard dilution of bacterial heparitinase or platelet heparanase. Loss of biotin signal from the well surface is detected on incubation with peroxidase-streptavidin followed by color development using 3,3',5,5'-tetramethylbenzidine as the peroxidase substrate. The new assay allows specific detection of heparanase activity in multiple samples in a total time of 3 h including a 1-h substrate digestion step and is a significant improvement with regard to sensitivity, specificity, and ease of handling of multiple samples compared to other described assays. Heparanase specifically degrades the biotinylated HSGAG substrate, when used with an optimized assay buffer. A range of enzymes including collagenase, trypsin, plasmin, pepsin, chondroitinases, hyaluronidase, and neuraminidase show no effect on the substrate under optimized assay conditions. The covalent linkage of the substrate to the well prevents leaching of substrate and allows preparation and long-term storage of substrate-coated plates. The assay can be used to detect heparanase levels in clinical samples and cell culture supernatants and is ideal as a screening method for antagonists of enzyme activity.

  4. 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.

  5. Detection of circulating tumour cells in peripheral blood of patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Raphael, Jacques; Massard, Christophe; Gong, Inna Y; Farace, Françoise; Margery, Jacques; Billiot, Fanny; Hollebecque, Antoine; Besse, Benjamin; Soria, Jean-Charles; Planchard, David

    2015-01-01

    The independent prognostic value of Circulating Tumour Cells (CTC) level has been demonstrated in several solid tumours. There is currently few data on Malignant Pleural Mesothelioma (MPM) and CTC. We investigated whether the presence of CTC was correlated with prognosis factors and treatment efficacy. MPM patients (pts) were enrolled in a prospective monocentric study. CTC detection was made using the "CellSearch" assay. The correlation between the presence of CTC and worse prognosis factors was assessed using the X(2) test. Comparison of Overall Survival (OS) and Progression Free Survival (PFS) according to CTC detection was performed using the log-rank test. Twenty-seven MPM pts with a median follow-up of 4.2 months were included. CTC were detected in 44% of pts with a median level of 1.5. No significant correlation was observed between the presence of CTC and worse prognosis factors. Moreover, CTC detection was not a significant predictor of OS or PFS (p=0.155 and p=0.32 respectively). CTC were detected in a small cohort of MPM patients. We couldn't demonstrate a significant prognostic value or a difference in OS/PFS between CTC levels. Further analyses, validation studies and detection techniques are needed to establish their real clinical value in MPM.

  6. The incidence of mesothelioma has not decreased for the last twenty ...

    African Journals Online (AJOL)

    Background: Malignant pleural Mesothelioma (MPM) is a very rarely encountered tumor in the normal population. Objectives: To investigate the variations in incidence of MPM in Southeast region of Turkey. Methods: We retrospectively investigated the data of 161 MPM patients who were diagnosed from January 2000 to ...

  7. Protumorigenic role of HAPLN1 and its IgV domain in malignant pleural mesothelioma.

    Science.gov (United States)

    Ivanova, Alla V; Goparaju, Chandra M V; Ivanov, Sergey V; Nonaka, Daisuke; Cruz, Christina; Beck, Amanda; Lonardo, Fulvio; Wali, Anil; Pass, Harvey I

    2009-04-15

    Tumor extracellular matrix (ECM) plays a crucial role in cancer progression mediating and transforming host-tumor interactions. Targeting the ECM is becoming an increasingly promising therapeutic approach in cancer treatment. We find that one of the ECM proteins, HAPLN1, is overexpressed in the majority of mesotheliomas. This study was designed to characterize the protumorigenic role of HAPLN1 in mesothelioma. Overexpression of HAPLN1 was assessed and validated on a large set of normal/mesothelioma specimens on the RNA and protein levels. We also analyzed DNA copy number alterations in the HAPLN1 genomic locus using the array-based comparative genomic hybridization representational oligonucleotide microarray analysis tool. Tumorigenic activities of the HAPLN1 domains were evaluated in vitro on mesothelioma cells transfected with HAPLN1-expressing constructs. We found that HAPLN1 is 23-fold overexpressed in stage I mesothelioma and confirmed it for 76% samples (n = 53) on RNA and 97% (n = 40) on protein levels. The majority of lung cancers showed no differential expression of HAPLN1. Analysis of DNA copy number alterations identified recurrent gain in the 5q14.3 HAPLN1 locus in approximately 27% of tumors. Noteworthy, high expression of HAPLN1 negatively correlated with time to progression (P = 0.05, log-rank test) and overall survival (P = 0.006). Proliferation, motility, invasion, and soft-agar colony formation assays on mesothelioma cells overexpressing full-length HAPLN1 or its functional domains strongly supported the protumorigenic role of HAPLN1 and its SP-IgV domain. Overexpression of HAPLN1 and its SP-IgV domain increases tumorigenic properties of mesothelioma. Thus, targeting the SP-IgV domain may be one of the therapeutic approaches in cancer treatment.

  8. Radiation induces invasiveness of pancreatic cancer via up-regulation of heparanase

    International Nuclear Information System (INIS)

    Lerner, I.; Bensoussan, E.; Meirovitz, A.; Elkin, M.; Vlodavsky, I.

    2013-01-01

    The full text of the publication follows. Pancreatic cancer is one of the most aggressive neoplasms with an extremely low survival rate. Because most pancreatic carcinoma patients miss the opportunity for complete surgical resection at the time of diagnosis, radiotherapy remains a major component of treatment modalities. However, pancreatic cancer often shows resistance to radiation therapy. Ionizing radiation (IR)-induced aggressiveness is emerging as one of the important mechanisms responsible for the limited benefit of radiation therapy in pancreatic cancer, but the identity of downstream effectors responsible for this effect remains poorly investigated. Here we report that IR promotes pancreatic cancer aggressiveness through up-regulation of the heparanase. Heparanase is a predominant mammalian enzyme capable of degrading heparan sulfate (HS), the main polysaccharide component of the basement membrane and other types of extracellular matrix (ECM). Cleavage of HS by heparanase leads to disassembly of ECM, enables cell invasion, releases HS-bound angiogenic and growth factors from the ECM depots, and generates bioactive HS fragments. We found that clinically relevant doses of IR augment invasive ability of pancreatic cells in vitro and in vivo via induction of heparanase. Our results indicate that the effect of IR on heparanase expression is mediated by Egr1 transcription factor. Moreover, specific inhibitor of heparanase enzymatic activity abolished IR-induced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with IR and the heparanase inhibitor, but not IR alone, attenuated ortho-topic pancreatic tumor progression in vivo. The proposed up-regulation of heparanase by IR represents a new molecular pathway through which IR may promote pancreatic tumor aggressiveness, providing explanation for the limited benefit from radiation therapy in pancreatic cancer. Our research is expected to offer a new approach to improve the efficacy of

  9. Medical thoracoscopy: a useful diagnostic tool for undiagnosed pleural effusion.

    Science.gov (United States)

    Agarwal, Abhishek; Prasad, Rajendra; Garg, Rajiv; Verma, S K; Singh, Abhijeet; Husain, N

    2014-01-01

    We aimed to assess the role of medical thoracoscopy in patients with undiagnosed pleural effusion. Patiens presenting with pleural effusion underwent three pleural aspirations. Patients in whom pleural fluid analysis was inconclusive underwent closed pleural biopsy for diagnostic confirmation. Patients in whom closed pleural biopsy was incolcusive underwent medical thoracoscopy using a rigid thoracoscope with a viewing angle of zero degrees was done under local anaesthesia and sedation with the patient lying in lateral decubitus position with the affected side up. Biopsy specimens from parietal pleura were obtained under direct vision and were sent for histopathological examination. Of the 128 patients with pleural effusion who were studied, pleural fluid examination established the diagnosis in 81 (malignancy 33, tuberculosis 33, pyogenic 14 and fungal 1); 47 patients underwent closed pleural biopsy and a diagnosis was made in 28 patients (malignancy 24, tuberculosis 4). The remaining 19 patients underwent medical thoracoscopy and pleural biopsy and the aetiological diagnosis could be confirmed in 13 of the 19 patients (69%) (adenocarcinoma 10, poorly differentiated carcinoma 2 and mesothelioma 1). Medical thoracoscopy is a useful tool for the diagnosis of pleural diseases. The procedure is safe with minimal complications.

  10. Radiation?induced mesothelioma among long?term solid cancer survivors: a longitudinal analysis of SEER database

    OpenAIRE

    Farioli, Andrea; Ottone, Marta; Morganti, Alessio G.; Compagnone, Gaetano; Romani, Fabrizio; Cammelli, Silvia; Mattioli, Stefano; Violante, Francesco S.

    2016-01-01

    Abstract We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long?term (>5?years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973?2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with re...

  11. Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a french population-based case-control study; Mesotheliome pleural: relation dose-reponse a faibles niveaux d'exposition a l'amiante dans une etude cas-temoins au sein d'une polulation francaise

    Energy Technology Data Exchange (ETDEWEB)

    Iwatsubo, Y.; Pairo, J.C.; Boutin, C.; Menard, O.; Massin, N.; Caillaud, D.; Orlowski, E.; Galateau-Salle, F.; Bignon, J.; Brochard, P.

    1998-03-01

    The objectives of this study were to study the dose-response relationship between professional exposure to asbestos and the supervening of the pleural mesothelioma in general population. This work notes an excess of death by pulmonary cancer among the asbestos-cement workers but one can regret the weakness of the exposure estimation (only one source of exposure is considered) and that some others risk factors have not been taken into account (tobacco, for example). (N.C.)

  12. Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report.

    Science.gov (United States)

    Naeini, Yalda B; Arcega, Ramir; Hirschowitz, Sharon; Rao, Nagesh; Xu, Haodong

    2018-02-01

    Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.

  13. Malignant Mesothelioma Presenting as a Giant Chest, Abdominal and Pelvic Wall Mass

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Zhi Hong; Gao, Xiao Long; Yi, Xiang Hua; Wang, Pei Jun [Tongji Hospital of Tongji University, Shanghai (China)

    2011-11-15

    Malignant mesothelioma (MM) is a relatively rare carcinoma of the mesothelial cells, and it is usually located in the pleural or peritoneal cavity. Here we report on a unique case of MM that developed in the chest, abdominal and pelvic walls in a 77-year-old female patient. CT and MRI revealed mesothelioma that manifested as a giant mass in the right flank and bilateral pelvic walls. The diagnosis was confirmed by the pathology and immunohistochemistry. Though rare, accurate investigation of the radiological features of a body wall MM may help make an exact diagnosis.

  14. Malignant Mesothelioma Presenting as a Giant Chest, Abdominal and Pelvic Wall Mass

    International Nuclear Information System (INIS)

    Shao, Zhi Hong; Gao, Xiao Long; Yi, Xiang Hua; Wang, Pei Jun

    2011-01-01

    Malignant mesothelioma (MM) is a relatively rare carcinoma of the mesothelial cells, and it is usually located in the pleural or peritoneal cavity. Here we report on a unique case of MM that developed in the chest, abdominal and pelvic walls in a 77-year-old female patient. CT and MRI revealed mesothelioma that manifested as a giant mass in the right flank and bilateral pelvic walls. The diagnosis was confirmed by the pathology and immunohistochemistry. Though rare, accurate investigation of the radiological features of a body wall MM may help make an exact diagnosis.

  15. Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.

    Science.gov (United States)

    Paliogiannis, Panagiotis; Putzu, Carlo; Ginesu, Giorgio Carlo; Cossu, Maria Laura; Feo, Claudio Francesco; Attene, Federico; Scognamillo, Fabrizio; Nonnis, Rita; Cossu, Antonio; Palmieri, Giuseppe; Pirina, Pietro; Fois, Alessandro

    2018-03-01

    Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available. English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database. The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma." Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail. The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme. © 2017 John Wiley & Sons Ltd.

  16. An emerging indication of FDG-PET: pleural tumours

    International Nuclear Information System (INIS)

    Balogova, S.; Kerrou, K.; Montravers, F.; Grahek, D.; Aide, N.; Jacob, T.; Younsi, N.; Cailleux, N.; Talbot, J.N.

    2003-01-01

    The diagnosis and staging of malignant pleural tumours is difficult by means of radiology and also histology. Nevertheless an early diagnose, in particular in those people exposed to asbestos, and an accurate staging are key factors for a better survival. There is thus a potential role for FD G imaging in these relatively rare cancers. In our series, were are currently able to evaluate 22 FD G examinations performed in 16 patients referred for apparently isolated pleural lesions. Twelve FD G examinations were performed with a dedicated PET machine (C-PET, Adac) and ten with a coincidence detection gamma camera (Irix, Picker). The precise clinical settings were the following: characterisation of pleural masses or search for the unknown primary tumour in case of adenocarcinoma (6 cases), staging of a mesothelioma (5 cases), suspicion of recurrence and/or residual lesions (11 cases). The pleural lesions took-up FD G in all cases. By adding our results to data of the five previously published studies, the sensitivity for detecting malignant pleural lesions that are not yet characterised as primary pleural cancer is 99% and the specificity 79%. There was in our series one false positive result due to an inflammatory lesion. False negative results for the detection of lymph node invasion occurred in three patients and were in relation with an infra-centimetric size and the difficulty to distinguish, on FD G images, mediastinal lymph nodes from a widespread pleural and pulmonary extension of cancer. A change in patient management was induced by the FD G examination in 4 patients (25%) and the evolution confirmed that the choice was appropriate. Unknown lesions that could have modified the management were discovered in two other patients. This study highlights the fact that FD G imaging has an impact on the management of patients with solitary pleural lesions and can detect recurrences, in some cases even more accurately than invasive procedures with histology. From our

  17. Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma

    Science.gov (United States)

    Rohloff, J; Zinke, J; Schoppmeyer, K; Tannapfel, A; Witzigmann, H; Mössner, J; Wittekind, C; Caca, K

    2002-01-01

    Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients. British Journal of Cancer (2002) 86, 1270–1275. DOI: 10.1038/sj/bjc/6600232 www.bjcancer.com © 2002 Cancer Research UK PMID:11953884

  18. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  19. Heparanase facilitates cell adhesion and spreading by clustering of cell surface heparan sulfate proteoglycans.

    Directory of Open Access Journals (Sweden)

    Flonia Levy-Adam

    2008-06-01

    Full Text Available Heparanase is a heparan sulfate (HS degrading endoglycosidase participating in extracellular matrix degradation and remodeling. Apart of its well characterized enzymatic activity, heparanase was noted to exert also enzymatic-independent functions. Non-enzymatic activities of heparanase include enhanced adhesion of tumor-derived cells and primary T-cells. Attempting to identify functional domains of heparanase that would serve as targets for drug development, we have identified heparin binding domains of heparanase. A corresponding peptide (residues Lys(158-Asp(171, termed KKDC was demonstrated to physically associate with heparin and HS, and to inhibit heparanase enzymatic activity. We hypothesized that the pro-adhesive properties of heparanase are mediated by its interaction with cell surface HS proteoglycans, and utilized the KKDC peptide to examine this possibility. We provide evidence that the KKDC peptide interacts with cell membrane HS, resulting in clustering of syndecan-1 and syndecan-4. We applied classical analysis of cell morphology, fluorescent and time-lapse microscopy and demonstrated that the KKDC peptide efficiently stimulates the adhesion and spreading of various cell types, mediated by PKC, Src, and the small GTPase Rac1. These results support, and further substantiate the notion that heparanase function is not limited to its enzymatic activity.

  20. 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.

  1. International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision

    Directory of Open Access Journals (Sweden)

    Paolo Boffetta

    2017-08-01

    Full Text Available Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates. Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.

  2. Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells

    International Nuclear Information System (INIS)

    Savion, N.; Disatnik, M.H.; Nevo, Z.

    1987-01-01

    Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the [ 35 S]O 4 - -labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of [ 35 S]O 4 - -labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10μg/ml), arteparon (10μg/ml), and heparin at a concentration of 3 μg/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis

  3. Production of heparanase constructs suitable for nuclear magnetic resonance and drug discovery studies.

    Science.gov (United States)

    Mosulén, Silvia; Ortí, Leticia; Bas, Esperanza; Carbajo, Rodrigo J; Pineda-Lucena, Antonio

    2011-02-01

    Heparanase is an endo-β-D-glucosidase capable of specifically degrading heparan sulphate, one of the main components of the extracellular matrix. This 65 kDa polypeptide is implicated in cancer processes such as tumour formation, angiogenesis and metastasis, making it a very attractive target in antitumour treatments. Structure-based approaches to find inhibitors of heparanase have been historically hampered by the lack of success in crystallizing the protein. With the aim to undertake the NMR structural characterisation of heparanase, we have designed and produced, using recombinant methods, smaller constructs of heparanase containing the catalytically active glutamic acids and the two binding sites for heparan sulphate. An extensive range of expression and purification conditions were evaluated to alleviate the intrinsic low solubility and aggregation propensity of heparanase, allowing the obtention of the enzyme in milligram quantities, both unlabelled and ¹⁵N-labelled for NMR studies. Using the smallest of the designed constructs and applying NMR and SPR methodologies, we have demonstrated that known inhibitors of heparanase bind to this construct specifically and selectively with K(D) values in the range of those reported for human heparanase, validating it for future drug discovery projects focused on the identification of novel inhibitors of this enzyme. © 2010 Wiley Periodicals, Inc.

  4. The N-ERC index is a novel monitoring and prognostic marker for advanced malignant pleural mesothelioma.

    Science.gov (United States)

    Mori, Takanori; Tajima, Ken; Hirama, Michihiro; Sato, Tadashi; Kido, Kenji; Iwakami, Shin-Ichiro; Sasaki, Shinichi; Iwase, Akihiko; Shiomi, Kazu; Maeda, Masahiro; Hino, Okio; Takahashi, Kazuhisa

    2013-04-01

    Although N-ERC/mesothelin (N-ERC) is an attractive diagnostic and treatment monitoring biomarker for malignant pleural mesothelioma (MPM), its clinical utility for predicting the prognosis has not yet been clarified. The aim of this study is to investigate whether the serum N-ERC level can accurately predict the outcome in patients with MPM. Twenty-six patients with MPM were enrolled. Serum N-ERC level was measured before and after chemotherapy. The N-ERC index was determined by the logarithm of the division of the N-ERC level after two courses of chemotherapy by the prior level. The median N-ERC index in the partial response (PR) group was significantly lower than that in patients with the stable disease (SD) plus the progressive disease (PD) group. The overall survival in the group whose median N-ERC index was lower than its median value was significantly longer than the group whose median N-ERC index was higher than its median value. The N-ERC index is therefore considered to be a useful biomarker for predicting not only the chemotherapeutic response, but also the prognosis in patients with advanced MPM.

  5. Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

    Directory of Open Access Journals (Sweden)

    Angélica M. Gomes

    2013-01-01

    Full Text Available Breast cancer is defined as a cancer originating in tissues of the breast, frequently in ducts and lobules. During the last 30 years, studies to understand the biology and to treat breast tumor improved patients’ survival rates. These studies have focused on genetic components involved in tumor progression and on tumor microenvironment. Heparan sulfate proteoglycans (HSPGs are involved in cell signaling, adhesion, extracellular matrix assembly, and growth factors storage. As a central molecule, HSPG regulates cell behavior and tumor progression. HS accompanied by its glycosaminoglycan counterparts regulates tissue homeostasis and cancer development. These molecules present opposite effects according to tumor type or cancer model. Studies in this area may contribute to unveil glycosaminoglycan activities on cell dynamics during breast cancer exploring these polysaccharides as antitumor agents. Heparanase is a potent tumor modulator due to its protumorigenic, proangiogenic, and prometastatic activities. Several lines of evidence indicate that heparanase is upregulated in all human sarcomas and carcinomas. Heparanase seems to be related to several aspects regulating the potential of breast cancer metastasis. Due to its multiple roles, heparanase is seen as a target in cancer treatment. We will describe recent findings on the function of HSPGs and heparanase in breast cancer behavior and progression.

  6. Aminopeptidase N/CD13 as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Otsuki, Takahiko; Nakashima, Taku; Hamada, Hironobu; Takayama, Yusuke; Akita, Shin; Masuda, Takeshi; Horimasu, Yasushi; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Miyata, Yoshihiro; Miyake, Masayuki; Kohno, Nobuoki; Okada, Morihito; Hattori, Noboru

    2018-03-08

    Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM), and antiangiogenic strategies might be effective against MPM. Aminopeptidase N/CD13 (APN/CD13) promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanized anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells.High tumour APN/CD13 expression was associated with poor prognosis in MPM patients ( P =0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10, but not MSTO-211H, cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together these results suggested that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression. Copyright ©ERS 2018.

  7. [The diagnostic value of medical thoracoscopy for unexplained pleural effusion].

    Science.gov (United States)

    Jiang, Shu-juan; Mu, Xiao-yan; Zhang, Song; Su, Li-li; Ma, Wei-xia

    2013-05-01

    To explore the endoscopic features of patients with unexplained pleural effusion, and to evaluate the diagnostic value of medical thoracoscopy. A retrospective analysis of 2380 patients with unexplained pleural effusion (1320 males and 1060 females; age 15-94 years) in Shandong Provincial Hospital from 1992 to 2011 were performed .The diagnosis was confirmed by medical thoracoscopy. The endoscopic findings of malignant pleural effusion mostly showed nodules of varying sizes. The nodules could be grape-like, cauliflower-like, fused into masses, or diffused small nodules . The appearance of cancerous nodules was more diversified compared to tuberculous nodules. Tuberculous pleurisy was manifested as diffuse pleural congestion and miliary changes, multiple small gray-white nodules, fibrin deposition and adhesion in the pleural cavity, pleural thickening and loculation . The pathological diagnosis was as follows: pleural metastases in 899 (37.8%), primary pleural mesothelioma in 439 (18.4%), tuberculous pleurisy in 514 (21.6%), non-specific inflammation in 226 (9.5%), empyema in 190 (8.0%), hepatic pleural effusion in 36 (1.5%) and pleural effusion of unknown causes in 76 (3.2%) cases. The diagnostic positive rate of medical thoracoscopy was 96.8%. No serious complications were observed. Medical thoracoscopy is a relatively safe procedure and has an important application value in the diagnosis of unexplained pleural effusion.

  8. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

    International Nuclear Information System (INIS)

    Kalra, Neetu; Zhang, Jingli; Thomas, Anish; Xi, Liqiang; Cheung, Mitchell; Talarchek, Jacqueline; Burkett, Sandra; Tsokos, Maria G; Chen, Yuanbin; Raffeld, Mark; Miettinen, Markku; Pastan, Ira; Testa, Joseph R; Hassan, Raffit

    2015-01-01

    The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient derived xenografts were generated by injecting the cells in nude or SCID mice, and malignant potential of the cells was analyzed by soft agar colony assay. Molecular profiles of the primary patient tumors, early passage cell cultures, and patient derived xenografts were assessed using mutational analysis, fluorescence in situ hybridization (FISH) analysis and IHC. Primary cultures from all five tumors exhibited morphologic and IHC features consistent to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected in four tumors. BAP1 mutation was associated with the lack of expression of BAP1 protein. Three cell cultures, all of which were derived from BAP1 mutant primary tumors, exhibited anchorage independent growth and also formed tumors in mice, suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A deletions identical to those found in the corresponding primary patient tumors. The mesothelioma patient derived tumor xenografts with mutational alterations that mimic those observed in patient tumors which we established can be used for preclinical development of novel drug regimens and for studying the functional aspects of BAP1 biology in mesothelioma. The online version of this article (doi:10.1186/s12885-015-1362-2) contains supplementary material, which is available to authorized users

  9. In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM).

    Science.gov (United States)

    Singh, Anand S; Heery, Richard; Gray, Steven G

    2018-04-26

    Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70⁻90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial⁻mesenchymal transition (EMT), a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (200 nucleotides). A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs) in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

  10. In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM

    Directory of Open Access Journals (Sweden)

    Anand S. Singh

    2018-04-01

    Full Text Available Malignant pleural mesothelioma (MPM is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70–90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial–mesenchymal transition (EMT, a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (<200 nucleotides or long (>200 nucleotides. A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

  11. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

    Science.gov (United States)

    Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

    2010-11-01

    Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

  12. Clinical Investigation of Benign Asbestos Pleural Effusion

    Directory of Open Access Journals (Sweden)

    Nobukazu Fujimoto

    2015-01-01

    Full Text Available There is no detailed information about benign asbestos pleural effusion (BAPE. The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1 history of asbestos exposure; (2 presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3 the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%. Asbestosis was present in 6 (5.5% cases, rounded atelectasis was detected in 41 (37.3% cases, and diffuse pleural thickening (DPT was detected in 30 (27.3% cases. One case developed lung cancer (LC before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM during the follow-up.

  13. Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2017-02-01

    Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

  14. Mesothelioma Cells Escape Heat Stress by Upregulating Hsp40/Hsp70 Expression via Mitogen-Activated Protein Kinases

    Directory of Open Access Journals (Sweden)

    Michael Roth

    2009-01-01

    Full Text Available Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP, which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39–42°C induced the phosphorylation of two mitogen activated kinases (MAPK Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down-regulated heat stress-induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy.

  15. Aggressive malignant abdominal mesothelioma: Clinical report

    International Nuclear Information System (INIS)

    Al-Hassan, Ahmad M.; Al-Saigh, Abdulrehman A.

    2004-01-01

    A 32-year-old Filipino female, working as an x-ray technician, presented to the Emergency Room (ER) with acute abdominal pain for one day. The pain was mainly on the left side and left hypochondrium. She had recurring abdominal pain before but not significant to worry her. She also complained of abdominal distension, which she noticed one week ago. Abdominal examination revealed fullness in the left hypochondrium with marked tenderness but negative rebound. Abdominal ultrasound (US) showed a huge mass mainly in the left hypochondrium. The origin of the mass cannot be identified by US. A computerized tomography scan showed a mass in the left side of the abdomen crossing the midline with a necrotic centre. The hospital course of the patient runs smoothly, and she was discharged after 7-days and referred to an Oncology Center. Abdominal mesothelioma is a neoplasm arising from the mesothelial surface lining the abdominal cavity. It is less frequent than that of the pleura. It is a rapidly growing and fatal malignancy with a median survival of less than 1-year. The relation between pleural malignant mesothelioma and asbestos is well recognized since it was described in 19602 but implication of asbestos exposure in the etiology of the peritoneal type is less obvious. This patient history is giving no obvious exposure to asbestos but as she is working in the Radiology Department as an x-ray technician she is well exposed to x-ray, but the effect of radioactivity on induction of mesothelioma is still disputed.4 There are several reports linking malignant mesothelioma to radioactivity due to radiation therapy.The fibrous mesothelioma (sarcomatous), as in this case, which is difficult to diagnose microscopically, looks like a fibroma, unless helped by tissue culture. The treatment options of malignant mesothelioma include surgery, intraperitoneal chemotherapy and whole abdominal radiation or multimodality therapy, which were suggested that might prolong the survival in

  16. Ambulatory intercostal drainage for the management of malignant pleural effusion: a single center experience.

    Science.gov (United States)

    Bazerbashi, Samer; Villaquiran, Jaime; Awan, Mohammad Yousaf; Unsworth-White, Michael Jonathan; Rahamim, Joe; Marchbank, Adrian

    2009-12-01

    Malignant pleural effusions are common and can be difficult to manage. We have reviewed our use of ambulatory drains (Pleurex drains) in this regard with particular reference to hospital stay, duration of drainage, and incidence of complications. Of 125 patients with malignant pleural effusion with trapped lung or failed previous pleurodesis who underwent insertion of ambulatory pleural drain, 41 patients were under local anesthesia and 84 patients were under general anesthesia. Mean age was 66.5 years with male:female = 80:45. Data were collected retrospectively from the clinical notes, and the family doctors' clinics were contacted to enquire about the patients' survival. When data collection concluded, 48 patients (38.4%) had died, giving mean survival following drain insertion of 84.1 days. There were no in-hospital deaths related to the procedure. One procedure was converted to a mini-thoracotomy to control bleeding from a lung tear. Mean duration of catheter placement was 87.01 days (5-434). Video-assisted thoracoscopic surgery was used in 77 patients (61.6%), and Seldinger's technique was used in 48 patients (38.4%). Mesothelioma was the most common malignant cause. Minor complications were encountered in 15 patients (12%), and they were managed as outpatients. The use of ambulatory pleural catheters for managing malignant pleural effusion is a safe and effective strategy. It has only minor complications that are related to prolonged drainage. We feel that this strategy should be considered the first choice option for these patients.

  17. Genes Associated With Prognosis After Surgery For Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

    International Nuclear Information System (INIS)

    Gordon, Gavin J; Bueno, Raphael; Sugarbaker, David J

    2011-01-01

    Mesothelioma is an aggressive neoplasm with few effective treatments, one being cytoreductive surgery. We previously described a test, based on differential expression levels of four genes, to predict clinical outcome in prospectively consented mesothelioma patients after surgery. In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype. We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1) in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. Successful knockdown was confirmed using quantitative RT-PCR. Detection of statistically significant changes in apoptosis and mitosis was performed using immunological assays and quantified using video-assisted microscopy at a single time-point. Changes in nuclear shape, size, and numbers were used to provide additional support of initial findings. Each experiment was conducted in triplicate. Specificity was assured by requiring that at least 2 different siRNAs produced the observed change in each cell line/time-point/gene/assay combination. Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only) and tumor cells (all three genes). No statistically significant changes were observed in apoptosis after knockdown of PKM2 or for mitosis after knockdown of any gene. We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma

  18. Malignant mesothelioma in situ.

    Science.gov (United States)

    Churg, Andrew; Hwang, Harry; Tan, Larry; Qing, Gefei; Taher, Altaf; Tong, Amy; Bilawich, Ana M; Dacic, Sanja

    2018-05-01

    The existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis. Here we report two cases that appear to be true MIS on the basis of in-situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost BRCA1-associated protein 1 (BAP1) and showed loss of cyclin-dependent kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in-situ hybridisation (FISH). NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1 immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH. These cases show that morphologically bland single-layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant MIS. More cases are need to understand the frequency of such changes and the time-course over which invasive tumour develops. © 2018 John Wiley & Sons Ltd.

  19. Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents

    Czech Academy of Sciences Publication Activity Database

    Pasdar, E.A.; Smits, M.; Stapelberg, M.; Bajziková, Martina; Stantic, M.; Goodwin, J.; Yan, B.; Štursa, J.; Kovářová, Jaromíra; Sachaphibulkij, K.; Bezawork-Geleta, A.; Sobol, Margaryta; Philimonenko, Anatoly; Tomasetti, M.; Zobalová, Renata; Hozák, Pavel; Dong, L.F.; Neužil, Jiří

    2015-01-01

    Roč. 10, č. 5 (2015), e0119549 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : MALIGNANT PLEURAL MESOTHELIOMA * EMBRYONIC STEM-CELLS * ALPHA-TOCOPHERYL SUCCINATE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  20. Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

    Science.gov (United States)

    2014-07-01

    malignant pleural mesothelioma. Expert Rev Anticancer Ther Feb;8(2):293-303, 2008. Korchagina, E.Y., Pochechueva, T.V., Obukhova, P.S., Formanovsky...over tract  3. Stomach membrane highly porforated +  liquid  release upon pressure 4. Meso contained within perionteum  5. Ascitic Fluid: 17mLs 6. GI...Used to be in cage  788 170.4 1. Horizontal incision to show natural colors of control  animal organs and natural  pleural  cavity architecture  X X 47

  1. Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and 18F-FDG PET/CT scan correlation

    International Nuclear Information System (INIS)

    Feigen, Malcolm; Lawford, Catherine; Churcher, Katheryn; Zupan, Eddy; Hamilton, Chris; Lee, Sze Ting; Scott, Andrew M.

    2011-01-01

    The management of malignant pleural mesothelioma represents one of the most challenging issues in oncology, as there is no proven long-term benefit from surgery, radiotherapy or chemotherapy alone or in combination. Locoregional progression remains the major cause of death, but radical surgical resection may produce major postoperative morbidity. While radical or postoperative radiotherapy using conventional techniques has resulted in severe toxicity with no impact on survival, recent advances in radiotherapy delivery may be more effective. We treated patients with locally advanced mesothelioma whose tumours had been sub optimally resected with high-dose three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) to large volumes of one hemithorax, using CT and positron emission tomography (PET) scan-based treatment planning. Clinical outcomes were assessed by determining patterns of failure and metabolic changes in total glycolytic volume (TGV) between pre- and post-irradiation 18 F-FDG PET/CT scans and by recording acute and late toxicity grades. Fourteen patients were analysed with 40 PET scans performed before and up to 4.5 years after radiotherapy. Eleven patients had pleurectomy/decortications, one had an extrapleural pneumonectomy and two had no surgery. Four patients who received chemotherapy had all progressed prior to radiotherapy. After radiotherapy, the in-field local control rate was 71%. No progression occurred in two patients, one was salvaged with further radiotherapy to a new site, four recurred inside the irradiated volume all with concurrent distant metastases and the other seven had distant metastases only. The TGVs were reduced by an average of 67% (range 12–100%) after doses of 45 to 60 Gy to part or all of one hemithorax. There were no serious treatment-related toxicities. Median survival was 25 months from diagnosis and 17 months after starting radiotherapy. We have established that mesothelioma can be

  2. Use of F-18 fluoro deoxyglucose (FDG) positron emission tomography (PET) in the assessment of malignant mesothelioma

    International Nuclear Information System (INIS)

    Brown, F.M.M.; Pathmaraj, K.; Berlangieri, S.U.; Knight, S.; Clarke, C.P.; Scott, A.M.

    2002-01-01

    Full text: Australia has the highest mesothelioma incidence rate in the world and the incidence of Mesothelioma is increasing. Therapy for Mesothelioma involves surgery (including phototherapy), radiotherapy and chemotherapy. Computed tomography (CT) is frequently used to stage the extent of Mesothelioma. This study aimed to evaluate the utility of FDG PET in staging Mesothelioma and monitoring response to therapy. Nineteen F-18 FDG PET was performed at the A and RMC Centre for PET in 14 patients (13M: 1F, age range 39-77 years, mean age 58 years) with biopsy proven malignant pleural Mesothelioma. Patients were referred for staging (5 patients) or evaluation of patients post surgery or phototherapy (9 patients). 3 patients had more than 1 PET scan. FDG scans were reviewed with full access to the CT report. Standardised Uptake Values (SUV) were performed in all scans in regions of maximal FDG uptake corresponding to CT abnormality. Normal lung SUVs were also calculated. Follow-up was possible in all patients to the time of death or December 2001 (Follow-up 4 - 45 months, mean 16 months; 3 patients still alive). All FDG PET scans were positive for FDG-avid pleural tissue. No surgery was deferred due to FDG PET findings. In 3 patients mediastinal nodes were identified pre-surgery. Post surgical therapy assessment by FDG PET (9 patients) guided therapy by confirming disease progression or further characterising post-operative changes when CT findings were uncertain. FDG PET was able to more accurately distinguish between collapse/consolidation and recurrent disease than CT scan. Almost all post-surgical scans were performed in patients who received phototherapy. Different Mesothelioma histological subtypes could not be differentiated by SUV criteria. False positive FDG PET studies were seen in 3 patients, all of whom had post-surgical empyemas. In conclusion, FDG PET has a potential role in the management of malignant mesothelioma patients, particularly in the post

  3. 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.

  4. Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Staffolani, S.; Nocchi, L.; Neužil, Jiří; Strafella, E.; Manzella, N.; Mariotti, L.; Bracci, M.; Matteo, V.A.; Amati, M.; Santarelli, L.

    2012-01-01

    Roč. 45, 7-8 (2012), s. 575-581 ISSN 0009-9120 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Circulating miRNA markers * relative qRT-PCR * pleural mesothelioma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.450, year: 2012

  5. An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Pasello, G; Ceresoli, G L; Favaretto, A

    2013-02-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 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

  7. Analysis of heparanase isoforms and cathepsin B in the plasma of patients with gastrointestinal carcinomas: analytical cross-sectional study

    Directory of Open Access Journals (Sweden)

    Carina Mucciolo Melo

    Full Text Available CONTEXT AND OBJECTIVE: Heparanase-1 degrades heparan sulfate and has been correlated with tumor progression. Although the isoform heparanase-2 has no catalytic activity, it seems to be important for modulating heparanase-1 activity. Cathepsin B is a proteinase involved in tumor metastasis. The aim of this study was to analyze heparanase isoform expression and cathepsin B activity in plasma samples from patients with gastrointestinal carcinomas, compared with healthy individuals (control group. DESIGN AND SETTING: This was an analytical cross-sectional study. Peripheral blood samples were collected at a Brazilian public hospital, from 21 patients with histopathological diagnoses of gastrointestinal carcinomas and from 43 healthy individuals. The analyses were performed in two Brazilian medical schools. METHODS: Heparanase isoforms were identified and quantified in plasma samples by means of Western blot. The enzymatic activities of heparanase-1 and cathepsin B were also measured. RESULTS: The results demonstrated that the expression of both heparanase isoforms was significantly greater in plasma samples from gastrointestinal carcinoma patients, compared with the control group. Logistic regression analysis showed that increased heparanase-1 and heparanase-2 expression was exclusively dependent on the tumor. There was a significant increase in heparanase-1 and cathepsin B activity in the patients' plasma. CONCLUSION: Overexpression of heparanase-1 and heparanase-2, along with increased heparanase-1 and cathepsin B activity in plasma, is associated with the diagnosis of gastrointestinal carcinoma. These findings provide support for using non-invasive assays (plasma samples as an auxiliary method for diagnosing gastrointestinal tumors.

  8. Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists

    Science.gov (United States)

    Urso, Loredana; Biasini, Lorena; Zago, Giulia; Calabrese, Fiorella; Conte, Pier Franco; Ciminale, Vincenzo; Pasello, Giulia

    2017-01-01

    Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL. In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs. In vivo studies were conducted on a sarcomatoid MPM mouse model. In all the cell lines tested (with the exception of ZL55, which carries a biallelic loss-of-function mutation of p53), Nutlin 3a enhanced p21, MDM2 and DR5 expression, and decreased survivin expression. These changes were associated to cell cycle arrest but not to a significant induction of apoptosis. A synergistic pro-apoptotic effect was obtained through the association of rhTRAIL in all the cell lines harboring functional p53. This synergistic interaction of MDM2 inhibitor and TRAIL agonist was confirmed using a mouse preclinical model. Our results suggest that the combined targeting of MDM2 and TRAIL might provide a novel therapeutic option for treatment of MPM patients, particularly in the case of sarcomatoid MPM with MDM2 overexpression and functional inactivation of wild-type p53. PMID:28562336

  9. Efficacy of fluorescence diagnosis for pleural tumors with alasens

    Directory of Open Access Journals (Sweden)

    O. V. Pikin

    2013-01-01

    Full Text Available The study of efficacy of thoracoscopy-assisted fluorescence diagnosis with Alasens is described in the article. The results of fluorescence diagnosis in 27 patients with suspicion on pleral tumor are represented. Before thoracoscopy-assisted fluorescence diagnosis in 21 patients according to radiological studies there was a fluid in pleural ca, in 19 patients of them tumor cells were found by cytological study of pleural fluid, in 10 patients differential diagnosis was performed between mesothelioma and adenogenic cancer. For fluorescence diagnosis fluorescence system by company Кarl Storz and xenon lamp with set of light filters was used: fluorescence study was performed by excitation at wavelength 380–460 nm. 3 h before investigation the patient received alasens per os in dose of 30 mg/kg body weight in 100 ml of water. For routine thoracoscopy tumor lesions were determined in 20 (87.0% patients, other 3 (13.0% patients had no tumors. In the group of patients with tumor lesions determined by routine thoracoscopy the fluorescence during fluorescence study was registered in all lesions determined in white light, besides this 24 additional foci of fluorescence were noticed, according to morphological study 21 of them had tumor nature, 3 lesions were inflammatory. In 1 of 3 patients with no lesion in white light there was one focus of fluorescence, morphological study proved the metastasis of adenocarcinoma in this area. According to morphological study of pleural biopsy specimens the true-positive results for fluorescence thoracoscopy accounted for 82, false-negative – 10, true-negative – 23, false-positive – 3. The sensitivity of the method was 89,1%, the specificity – 88,4%, the diagnostic accuracy – 88,9%. 

  10. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  11. Genes Associated With Prognosis After Surgery For Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

    Directory of Open Access Journals (Sweden)

    Sugarbaker David J

    2011-05-01

    Full Text Available Abstract Background Mesothelioma is an aggressive neoplasm with few effective treatments, one being cytoreductive surgery. We previously described a test, based on differential expression levels of four genes, to predict clinical outcome in prospectively consented mesothelioma patients after surgery. In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype. Methods We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1 in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. Successful knockdown was confirmed using quantitative RT-PCR. Detection of statistically significant changes in apoptosis and mitosis was performed using immunological assays and quantified using video-assisted microscopy at a single time-point. Changes in nuclear shape, size, and numbers were used to provide additional support of initial findings. Each experiment was conducted in triplicate. Specificity was assured by requiring that at least 2 different siRNAs produced the observed change in each cell line/time-point/gene/assay combination. Results Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only and tumor cells (all three genes. No statistically significant changes were observed in apoptosis after knockdown of PKM2 or for mitosis after knockdown of any gene. Conclusions We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma.

  12. Dual roles of heparanase in vascular calcification associated with human carotid atherosclerosis

    DEFF Research Database (Denmark)

    Aldi, S.; Eriksson, L.; Kronqvist, M.

    2017-01-01

    Vascular intimal calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of heparanase in osteogenesis and bone remodeling...

  13. Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study.

    Science.gov (United States)

    Xing, Deyin; Banet, Natalie; Sharma, Rajni; Vang, Russell; Ronnett, Brigitte M; Illei, Peter B

    2018-02-01

    Serous ovarian neoplasms can overlap morphologically with peritoneal mesothelial proliferations, including well-differentiated papillary mesothelioma (WDPM) and malignant epithelioid mesothelioma (MM). Accurate histologic classification of these neoplasms is important for clinical management. The Pax-8 protein is commonly used for differentiating peritoneal MM from serous carcinoma, but the diagnostic value of Pax-8 for distinguishing WDPM from borderline or low-grade serous tumors is unknown. We used immunohistochemistry staining to assess Pax-8 expression in 33 WDPMs, 34 peritoneal MMs, 48 pleural MMs, 11 adenomatoid tumors, 5 peritoneal inclusion cysts, and 51 benign/reactive mesothelium specimens. Staining was noted in 20 WDPMs (61%), with 17 showing strong and diffuse nuclear staining and 3 patchy/focal staining. Calretinin was expressed in 33 cases (100%), whereas focal BerEP4 staining was noted in 2 of 29 cases (7%). In contrast, 4 peritoneal MM (12%) were Pax-8 positive (3 diffuse and 1 focal staining). All adenomatoid tumors and peritoneal inclusion cysts were negative for Pax-8. Of the 48 pleural MM cases, 2 (4%) showed focal weak to moderate nuclear labeling for Pax-8, and 2 cases (4%) of reactive mesothelium demonstrated focal and scattered Pax-8 staining. Pax-8 appears to be a useful marker for distinguishing MM from gynecologic malignancies but is not reliable for distinguishing WDPM from borderline or low-grade gynecologic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-11-01

    The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

  15. EphB4 as a therapeutic target in mesothelioma

    International Nuclear Information System (INIS)

    Liu, Ren; Ferguson, Benjamin D; Zhou, Yue; Naga, Kranthi; Salgia, Ravi; Gill, Parkash S; Krasnoperov, Valery

    2013-01-01

    Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted

  16. Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase

    Directory of Open Access Journals (Sweden)

    Lubor Borsig

    2011-05-01

    Full Text Available Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation.

  17. Novel computer-aided diagnosis of mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens

    Science.gov (United States)

    Tosun, Akif Burak; Yergiyev, Oleksandr; Kolouri, Soheil; Silverman, Jan F.; Rohde, Gustavo K.

    2014-03-01

    diagnostic standard is a pleural biopsy with subsequent histologic examination of the tissue demonstrating invasion by the tumor. The diagnostic tissue is obtained through thoracoscopy or open thoracotomy, both being highly invasive procedures. Thoracocenthesis, or removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. However, it is insufficient to definitively confirm or exclude the diagnosis of malignant mesothelioma, since tissue invasion cannot be determined. In this study, we present a computerized method to detect and classify malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Our method aims at determining whether a set of nuclei belonging to a patient, obtained from effusion fluid images using image segmentation, is benign or malignant, and has a potential to eliminate the need for tissue biopsy. This method is performed by quantifying chromatin morphology of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the modified Fisher discriminant analysis, a k-nearest neighborhood classification, and a simple voting strategy. Our results show that we can classify the data of 10 different human cases with 100% accuracy after blind cross validation. We conclude that nuclear structure alone contains enough information to classify the malignant mesothelioma. We also conclude that the distribution of chromatin seems to be a discriminating feature between nuclei of benign and malignant mesothelioma cells.

  18. Primary Pericardial Mesothelioma: Report of a Patient and Literature Review

    Directory of Open Access Journals (Sweden)

    Åse Nilsson

    2009-07-01

    Full Text Available Primary mesothelioma of the pericardium is a rare tumor and carries a dismal prognosis. This case report presents a 38-year-old man who suffered from recurrent pericardial fluid. Initial symptoms were unspecific, with dry cough and progressing fatigue. Pericardiocentesis was performed, but analyses for malignant cells and tuberculosis were negative. After recurrence a pericardiectomy was planned. At operation, partial resection of tumor tissue surrounding the heart was performed. Histopathologic examination including immunohistochemical staining for calretinin showed a biphasic mesothelioma. During the postoperative period the patient’s condition ameliorated, but symptoms recurred and the patient died 3 months after diagnosis and 15 months after the first symptoms. At autopsy, the pericardium was transformed by the tumor that also expanded into the mediastinum and had set metastases to the liver. A review of 29 cases presented in the recent literature indicates a higher incidence of malignant pericardial mesothelioma among men than women. Median age was 46 (range, 19–76 years. In pleural mesotheliomas, exposure to asbestos is a known risk factor. However, in primary pericardial mesotheliomas the evidence for asbestos as an etiologic factor seems to be less convincing (3 exposed among 14 cases. Symptoms are often unspecific and cytologic examination of pericardial fluid is seldom conclusive (malignant cells demonstrated in 4/17 cases. Partial resection of the tumor can give a period of symptom reduction. Only a few patients have been treated with chemotherapy. Median survival of patients with pericardial mesotheliomas is approximately 6 months.

  19. Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation.

    Science.gov (United States)

    Takeuchi, Shinji; Fukuda, Koji; Yamada, Tadaaki; Arai, Sachiko; Takagi, Satoshi; Ishii, Genichiro; Ochiai, Atsushi; Iwakiri, Shotaro; Itoi, Kazumi; Uehara, Hisanori; Nishihara, Hiroshi; Fujita, Naoya; Yano, Seiji

    2017-04-01

    Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility. In contrast, overexpression of PDPN in PDPN-low expressing MPM cells enhanced cell motility. PDPN stimulated motility was mediated by activation of the RhoA/ROCK pathway. Moreover, knocking down PDPN with short hairpin (sh) RNA in PDPN-high expressing MPM cells resulted in decreased development of a thoracic tumor in mice with severe combined immune deficiency (SCID). In sharp contrast, transfection of PDPN in PDPN-low expressing MPM cells resulted in an increase in the number of Ki-67-positive proliferating tumor cells and it promoted progression of a thoracic tumor in SCID mice. Interestingly, PDPN promoted focus formation in vitro, and a low level of E-cadherin expression and YAP1 activation was observed in PDPN-high MPM tumors. These findings indicate that PDPN is a diagnostic marker as well as a pathogenetic regulator that promotes MPM progression by increasing cell motility and inducing focus formation. Therefore, PDPN might be a pathogenetic determinant of MPM dissemination and aggressive growth and may thus be an ideal therapeutic target. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan Sulfate in Murine and Human Sepsis.

    Directory of Open Access Journals (Sweden)

    Lukas Martin

    Full Text Available Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.

  1. 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.

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

    International Nuclear Information System (INIS)

    Duan, J

    2016-01-01

    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.

  3. 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.

  4. Impact of an asbestos cement factory on mesothelioma incidence: global assessment of effects of occupational, familial, and environmental exposure.

    Science.gov (United States)

    Mensi, Carolina; Riboldi, Luciano; De Matteis, Sara; Bertazzi, Pier Alberto; Consonni, Dario

    2015-01-01

    Few studies have examined the incidence of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure (occupational, familial, or environmental). We assessed the impact of asbestos exposure-global and by source-on the incidence of MM in Broni, an Italian town in which an asbestos cement factory once operated (1932-1993). Based on data collected by the Lombardy Mesothelioma Registry, we calculated the number of observed and expected MM cases among workers, their cohabitants, and people living in the area in 2000-2011. We identified 147 MM cases (17.45 expected), 138 pleural and nine peritoneal, attributable to exposure to asbestos from the factory. Thirty-eight cases had past occupational exposure at the factory (2.33 expected), numbering 32 men (26 pleural, six peritoneal) and six women (four pleural, two peritoneal). In the families of the workers, there were 37 MM cases (4.23 expected), numbering five men (all pleural) and 32 women (31 pleural, one peritoneal). Among residents in Broni or in the adjacent/surrounding towns, there were 72 cases of pleural MM (10.89 expected), numbering 23 men and 49 women. The largest MM excess was found in the towns of Broni (48 observed, 3.68 expected) and Stradella (16 observed, 1.85 expected). This study documents the large impact of the asbestos cement factory, with about 130 excess MM cases in a 12-year period. The largest MM burden was among women, from non-occupational exposure. Almost half of the MM cases were attributable to environmental exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Parakeratotic-like cells in effusions - A clue to diagnosis of malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Ling Gao

    2012-01-01

    Full Text Available Background : Malignant mesothelioma (MM is an aggressive neoplasm with a poor prognosis. Its incidence has been increasing worldwide. Cytological examination of an effusion is often the first opportunity to diagnose MM. However, the cytological diagnosis of MM can be difficult. We have noticed that parakeratotic-like cells, with orange cytoplasm and pyknotic nuclei, are present in many cases of mesothelioma on Papanicolaou-stained cytology slides. Although this cytological finding has been described previously, to our knowledge, there has been no systematic study of this finding. Our study is to determine whether the presence of small parakeratotic / orangeophilic cells (PK-like cells is specific for the cytodiagnosis of mesothelioma. Materials and Methods: A total of 90 body fluid cases were selected from our archived specimens in the Cytology Section at the University of Chicago Hospital accessioned between January 2000 to November 2011. They included 30 cases of mesothelioma, 30 cases of adenocarcinoma, and 30 cases of reactive mesothelial cells. Results: PK-like cells were present in 83% of the mesothelioma cases, 13% of the adenocarcinoma cases, and 7% of the reactive cases. Our data showed that the presence of PK-like cells has a specificity of 90%, sensitivity of 83%, positive predictive value of 81%, and negative predictive value of 84% for the diagnosis of malignant mesothelioma in body cavity fluids. Conclusion: The presence of PK-like cells in the effusion specimen, especially in pleural effusions, is a highly specific and moderately sensitive cytological feature for diagnosis of mesothelioma.

  6. The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression

    Directory of Open Access Journals (Sweden)

    Preeti Singh

    2017-03-01

    Full Text Available Heparanase activity is highly implicated in cellular invasion and tumor metastasis, a consequence of cleavage of heparan sulfate and remodeling of the extracellular matrix underlying epithelial and endothelial cells. Heparanase expression is rare in normal epithelia, but is often induced in tumors, associated with increased tumor metastasis and poor prognosis. In addition, heparanase induction promotes tumor growth, but the molecular mechanism that underlines tumor expansion by heparanase is still incompletely understood. Here, we provide evidence that heparanase down regulates the expression of p21 (WAF1/CIP1, a cyclin-dependent kinase inhibitor that attenuates the cell cycle. Notably, a reciprocal effect was noted for PG545, a potent heparanase inhibitor. This compound efficiently reduced cell proliferation, colony formation, and tumor xenograft growth, associating with a marked increase in p21 expression. Utilizing the APC Min+/− mouse model, we show that heparanase expression and activity are increased in small bowel polyps, whereas polyp initiation and growth were significantly inhibited by PG545, again accompanied by a prominent induction of p21 levels. Down-regulation of p21 expression adds a novel feature for the emerging pro-tumorigenic properties of heparanase, while the potent p21 induction and anti-tumor effect of PG545 lends optimism that it would prove an efficacious therapeutic in colon carcinoma patients.

  7. Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40

    Directory of Open Access Journals (Sweden)

    Rehak Peter

    2006-11-01

    Full Text Available Abstract Background It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40 in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries. Methods We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status. Results Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 – 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates nor in females. Conclusion Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated.

  8. Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase1

    Science.gov (United States)

    Borsig, Lubor; Vlodavsky, Israel; Ishai-Michaeli, Rivka; Torri, Giangiacomo; Vismara, Elena

    2011-01-01

    Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation. PMID:21532885

  9. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    Directory of Open Access Journals (Sweden)

    Abigail Morris

    Full Text Available Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/- mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  10. Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

    Czech Academy of Sciences Publication Activity Database

    Santarelli, L.; Strafella, E.; Staffolani, S.; Amati, M.; Emanuelli, M.; Sartini, D.; Pozzi, V.; Carbonari, D.; Bracci, M.; Pignotti, E.; Mazzanti, P.; Sabbatini, A.; Ranaldi, R.; Gasparini, S.; Neužil, Jiří; Tomasetti, M.

    2011-01-01

    Roč. 6, č. 4 (2011), e18232 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Malignant pleural mesothelioma * microRNAs * soluble mesothelin-related peptides Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.092, year: 2011

  11. Pleuroscopic punch biopsy using insulated-tip diathermic knife-2 for the diagnosis of desmoplastic malignant mesothelioma.

    Science.gov (United States)

    Masai, Kyohei; Sasada, Shinji; Izumo, Takehiro; Taniyama, Tomoko; Nakamura, Yukiko; Chavez, Christine; Sakurai, Hiroyuki; Tsuta, Koji; Tsuchida, Takaaki

    2013-10-01

    Desmoplastic malignant mesothelioma (DMM) is a rare subtype of malignant pleural mesothelioma (MPM) and is often difficult to distinguish from pleural fibrosis and reactive mesothelial hyperplasia, especially if the biopsy samples are small. We performed full-thickness pleural biopsy on a lesion suspected to be DMM using an insulated-tip diathermic knife-2 (IT knife-2) during flex-rigid pleuroscopy. IT knife-2 is a novel electrosurgical device for endoscopic submucosal dissection in the early gastrointestinal cancer. It consists of a needle knife with 3 short blades at the distal end attached to an insulated ceramic tip. A 54-year-old man presenting with chest wall mass and thickened pleura, in whom a computed tomography-guided percutaneous needle aspiration had remained negative, underwent flex-rigid pleuroscopy for definitive diagnosis. While applying electric current, we used the IT knife-2 to incise the pleura in a circular shape just above the endothoracic fascia. The incised pleura was removed by forceps and examined pathologically. The microscopic examination was compatible with DMM. We discovered that pleuroscopic punch biopsy using IT knife-2 can diagnose DMM. Use of IT knife-2 during flex-rigid pleuroscopy can obtain sufficient samples from densely thickened pleura, which is difficult to diagnose with small biopsies.

  12. 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

  13. 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

  14. Is Pleurectomy/Decortication Superior to Extrapleural Pneumonectomy for Patients with Malignant Pleural Mesothelioma? A Single-Institutional Experience.

    Science.gov (United States)

    Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kamohara, Ryotaro; Hatachi, Go; Nagayasu, Takeshi

    2018-04-20

    This study was performed to compare the outcome of pleurectomy/decortication (P/D) with that of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma (MPM). Patients with MPM underwent either P/D or EPP from August 2008 to December 2014. Various clinicopathological factors were analyzed to identify differences between the two procedures. P/D was performed in nine patients and EPP in 30 patients. Most of the patients' background characteristics were not significantly different between the groups. The surgery time (680 vs. 586 min, p = 0.0034) and bleeding volume (4050 vs. 2110 mL, p = 0.002) were significantly greater in P/D than in EPP; however, grade ≥3 complications (44% vs. 33%, p = 0.54) and length of postoperative hospital stay (29 vs. 37 days, p = 0.26) were not significantly different. The median survival time and 2- and 3-year survival rates in all patients were 16.7 months, 28.5%, and 15.3%, respectively. The median survival time and 2- and 3-year survival in the P/D and EPP groups were 22.5 months, 43.8%, and 43.8% and 16.5 months, 24.0%, and 14.4%, respectively (p = 0.13). Survival of patients with MPM remains poor despite multidisciplinary treatment. P/D is comparable with EPP and could be a safe and another surgical treatment for patients with MPM.

  15. 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.

  16. p53-Induced Apoptosis Occurs in the Absence of p14ARF in Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Sally Hopkins-Donaldson

    2006-07-01

    Full Text Available Malignant pleural mesotheliomas (MPMs are usually wild type for the p53 gene but contain homozygous deletions in the INK4A locus that encodes p14ARF, an inhibitor of p53-MDM2 interaction. Previous findings suggest that lack of p14ARF expression and the presence of SV40 large T antigen (L-Tag result in p53 inactivation in MPM. We did not detect SV40 L-Tag mRNA in either MPM cell lines or primary cultures, treatment of p14ARF-deficient cells with cisplatin (CDDP increased both total and phosphorylated p53 and enhanced p53 DNA-binding activity. On incubation with CDDP, levels of positively regulated p53 transcriptional targets p21WAF, PIG3, MDM2, Bax, PUMA increased in p14ARF-deficient cells, whereas negatively regulated survivin decreased. Significantly, p53-induced apoptosis was activated by CDDP in p14ARF-deficient cells, treatment with p53-specific siRNA rendered them more CDDP-resistant. p53 was also activated by: 1 inhibition of MDM2 (using nutlin-3; 2 transient overexpression of p14ARF; and 3 targeting of survivin using antisense oligonucleotides. However, it is noteworthy that only survivin downregulation sensitized cells to CDDP-induced apoptosis. These results suggest that p53 is functional in the absence of p14ARF in MPM and that targeting of the downstream apoptosis inhibitor survivin can sensitize to CDDP-induced apoptosis.

  17. Use of computed tomography and positron emission tomography/computed tomography for staging of local extent in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Frauenfelder, Thomas; Kestenholz, Peter; Hunziker, Roger; Nguyen, Thi Dan Linh; Fries, Martina; Veit-Haibach, Patrick; Husmann, Lars; Stahel, Rolf; Weder, Walter; Opitz, Isabelle

    2015-01-01

    The objective of this study was to determine the diagnostic value of computed tomography (CT) and positron emission tomography (PET)/CT for staging of malignant pleural mesothelioma (MPM) in patients undergoing induction chemotherapy. Sixty-two patients (median age, 61 years; female: n = 9) with proven MPM underwent CT after induction chemotherapy. Of these, 28 underwent additional PET/CT. Extrapleural pneumonectomy was performed for pathological TNM staging. Clinical TNM stage was assessed by 3 independent readers. Relative and absolute underestimation and overestimation were compared with pathological tumor stage. Sensitivity, specificity, and accuracy for differentiation between stages T2 and T3 were assessed. Interobserver agreement between the readers was analyzed (κ). Positron emission tomography/CT and CT underestimated T stage in up to 30% of the cases. Positron emission tomography/CT had a higher accuracy for tumor extent compared with CT (PET/CT: 0.92; CT: 0.84). The accuracy for nodal staging was higher for CT than for PET/CT (PET/CT: 0.78; CT: 0.87). Concerning International Mesothelioma Interest Group classification, PET/CT improved the accuracy of preoperative staging compared with CT (PET/CT: 0.91; CT: 0.82). Interobserver agreement was moderate for CT (0.48-0.62) and good for PET/CT (0.64-0.83) for T staging. For nodal staging, interobserver agreement was fair to moderate for CT and good for PET/CT (CT: 0.37-0.51; PET/CT: 0.73-0.76). Positron emission tomography/CT is more accurate and has a lower interobserver variability for clinical intrathoracic staging of MPM compared with CT. Nevertheless PET/CT underestimated tumor stage in a substantial number of cases, showing the need for a more accurate imaging technology or approach.

  18. Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses.

    Science.gov (United States)

    Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Kim, Yongsoo; Alifrangis, Constantine; Zwart, Wilbert; Baas, Paul; Neefjes, Jacques

    2018-04-01

    Purpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor. Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment. Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway. Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761-70. ©2017 AACR See related commentary by John and Chia, p. 1513 . ©2017 American Association for Cancer Research.

  19. Radiosensitivity of mesothelioma cell lines

    International Nuclear Information System (INIS)

    Haekkinen, A.M.; Laasonen, A.; Linnainmaa, K.; Mattson, K.; Pyrhoenen, S.

    1996-01-01

    The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters α and β of the linear quadratic model (LQ-model) and mean inactivation dose (D MID ) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean α value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The α/β ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.)

  20. Radiosensitivity of mesothelioma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, A.M. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland); Laasonen, A. [Dept. of Pathology, Central Hospital of Etelae-Pohjanmaa, Seinaejoki (Finland); Linnainmaa, K. [Dept. of Industrial Hygiene and Toxicology, Inst. of Occupational Health, Helsinki (Finland); Mattson, K. [Dept. Pulmonary Medicine, Univ. Central Hospital, Helsinki (Finland); Pyrhoenen, S. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland)

    1996-10-01

    The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters {alpha} and {beta} of the linear quadratic model (LQ-model) and mean inactivation dose (D{sub MID}) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean {alpha} value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The {alpha}/{beta} ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.).

  1. Mesothelioma with superior vena cava obstruction in young female following short latency of asbestos exposure

    Directory of Open Access Journals (Sweden)

    Anupam Patra

    2015-01-01

    Full Text Available An 18 years female was admitted with right-sided chest pain, dry cough, and low-grade fever and weight loss for last 1 month. On examination, patient had features of superior vena cava (SVC syndrome with right-sided pleural effusion. Chest X-ray showed mediastinal widening with nonhomogenous opacity mainly in the periphery of right upper and mid zone with right-sided pleural effusion. Ultrasonography thorax confirmed mild pleural effusion. Pleural fluid analysis showed lymphocytic, exudative, low adenosine deaminase with negative for Pap smear. Contrast-enhanced computed tomography (CT thorax revealed large extensive nodular soft tissue lesion along right mediastinum as well as costal pleura, with enlarged pretracheal lymphadenopathy and SVC obstruction. CT guided Tru-cut biopsy report came as malignant epithelial tumor with polygonal shape, abundant eosinophilic cytoplasm and nuclei with prominent nucleoli suggestive of mesothelioma of epithelioid type. The tumor cell expressed calretinin, WT-1, and immunonegative for thyroid transcription factor-1.

  2. Minimally invasive vacuum-assisted closure therapy in the management of complex pleural empyema.

    Science.gov (United States)

    Sziklavari, Zsolt; Grosser, Christian; Neu, Reiner; Schemm, Rudolf; Szöke, Tamas; Ried, Michael; Hofmann, Hans-Stefan

    2013-07-01

    The pool of potential candidates for pleural empyema is expanding. In a previous technical report, we tested the feasibility of the minimally invasive insertion of a vacuum-assisted closure (Mini-VAC) system without the insertion of an open-window thoracostomy (OWT). In this study, we describe a consecutive case series of complex pleural empyemas that were managed by this Mini-VAC therapy. In this retrospective study, we investigated 6 patients with multimorbidity (Karnofsky index ≤ 50%) who were consecutively treated with Mini-VAC for a primary, postoperative or recurrent pleural empyema between January 2011 and February 2012. Local control of the infection and control of sepsis were satisfactory in all 6 of the patients treated by Mini-VAC therapy. The suction used did not create any air leaks or bleeding from the lung or mediastinal structures. Mini-VAC therapy allowed a reduction of the empyema cavity and improved the re-expansion of the residual lung. Mini-VAC therapy resulted in a rapid eradication of the empyema. The chest wall was closed in all patients during the first hospital stay. All patients left the hospital in good health (Karnofsky index >70%) and with a non-infected pleural cavity at a mean of 22 ± 11 days after Mini-VAC installation. Pleural empyema was not detected in any of the 6 patients at the 3-month follow-up appointment. The Mini-VAC procedure with the abdication of an OWT offers a rapid treatment for complex pleural empyema with minimal surgical effort and the opportunity for a primary closure of the empyema cavity.

  3. Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review.

    Science.gov (United States)

    Bruno, Rossella; Alì, Greta; Fontanini, Gabriella

    2018-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in

  4. Desmoplastic malignant mesothelioma of the pericardium: Description of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Antonello Nicolini

    2011-01-01

    Full Text Available Desmoplastic mesothelioma (DMM is a rare and highly lethal subtype of diffuse malignant mesothelioma and is often difficult to distinguish from reactive pleural fibrosis. The term "desmoplastic" refers to the growth of fibrous or connective tissue. We report the clinical, radiological, and pathological features of a primary DMM of the pericardium and a short review of the literature. A 72-year-old man was admitted presenting shortness of breath, cough, and asthenia. Computed tomography scan showed thickenings and effusions both in the pleura and in the pericardium. Histopathological diagnosis was performed by surgical pericardial biopsy and confirmed by autopsy. The patient had a history of asbestos exposure. Primary mesothelioma of the pericardium is a rare tumor occurring in the fourth to seventh decades with nonspecific symptoms and a rapid clinical course. The diagnosis is difficult and often needing a surgical pericardial biopsy. The prognosis is poor although newer antiblastic drugs seem to prolong survival times.

  5. Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case report

    Directory of Open Access Journals (Sweden)

    Rais Ghizlane

    2012-04-01

    Full Text Available Abstract Introduction Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult. Case presentation A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. Conclusions Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified.

  6. A phase Ia/Ib clinical trial of metronomic chemotherapy based on a mathematical model of oral vinorelbine in metastatic non-small cell lung cancer and malignant pleural mesothelioma: rationale and study protocol

    International Nuclear Information System (INIS)

    Elharrar, Xavier; Barbolosi, Dominique; Ciccolini, Joseph; Meille, Christophe; Faivre, Christian; Lacarelle, Bruno; André, Nicolas; Barlesi, Fabrice

    2016-01-01

    Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile. This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patients with metastatic NSCLC or malignant pleural mesothelioma in whom standard treatments failed and who exhibited ECOG performance status 0–2 and adequate organ function will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 schedule (named Vinorelbine Theoretical Protocol) with a respective dose of 60, 30 and 60 mg. Trial recruitment will be two-staged, as 12 patients are planned to participate in phase Ia to confirm safety and consolidate the calibration of the model parameters. Depending on the phase Ia results and after a favourable decision from a consultative committee, the extension phase (phase Ib) will be an efficacy study including 20 patients who will receive the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for phase Ib. An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial. This ongoing trial is the first to prospectively test a mathematically optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer

  7. Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Stephens, R J; Whiting, C; Cowan, K

    2015-08-01

    In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma. Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting. Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10. The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be

  8. Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

    Directory of Open Access Journals (Sweden)

    Shinya Okamoto

    Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

  9. Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site

    Directory of Open Access Journals (Sweden)

    Lucia Fazzo

    2014-12-01

    Full Text Available BACKGROUND: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated. METHODS: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR between the two subareas was computed. RESULTS: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02. The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88; 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40. The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17 in the age-classes below 55 years. CONCLUSIONS: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.

  10. Quantitative structure - mesothelioma potency model ...

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  11. Pulmonary asbestos body counts and electron probe analysis of asbestos body cores in patients with mesothelioma: a study of 25 cases

    International Nuclear Information System (INIS)

    Roggli, V.L.; McGavran, M.H.; Subach, J.; Sybers, H.D.; Greenberg, S.D.

    1982-01-01

    Malignant mesotheliomas of the pleura and peritoneum are well-recognized risks of asbestos exposure. We determined the asbestos body content of the lungs from 24 cases of malignant mesothelioma (19 pleural, five peritoneal) and compared such to the content of lungs from 50 consecutive adult autopsies and four cases of overt asbestosis using a Clorox-digestion concentration technique. The cores of 90 asbestos bodies were examined by energy dispersive x-ray analysis and compared with similar data from 120 standard asbestos fibers and 20 fiberglass fibers. The malignant mesothelioma patients had asbestos body counts intermediate between those of the general population and those of patients with asbestosis, although some of the mesothelioma cases overlapped with the general population. These latter cases often lacked an identifiable occupational exposure to asbestos. EDXA studies demonstrated an amphibole core in 88 of the 90 asbestos bodies (amosite or crocidolite in 80 of 88, anthophyllite or tremolite in eight of 88), and chrysotile in two instances

  12. Evaluation of glycosaminoglycans and heparanase in placentas of women with preeclampsia.

    Science.gov (United States)

    Famá, Eduardo Augusto Brosco; Souza, Renan Salvioni; Melo, Carina Mucciolo; Melo Pompei, Luciano; Pinhal, Maria Aparecida Silva

    2014-11-01

    Preeclampsia is a multisystem disorder whose etiology remains unclear. It is already known that circulation of soluble fms-like tyrosine kinase-1 (sFlt-1) is directly involved in pre-eclampsia development. However, the molecular mechanisms involved with sFlt-1 shedding are still unidentified. We identified, quantified glycosaminoglycans and determined the enzymatic activity of heparanase in placentas of women with preeclampsia, in order to possibly explain if these compounds could be related to cellular processes involved with preeclampsia. A total of 45 samples collected from placentas, 15 samples from placentas of preeclampsia women and 30 samples from non-affected women. Heparan sulfate and dermatan sulfate were identified and quantified by agarose gel electrophoresis, whilst hyaluronic acid was quantified by an ELISA like assay. Heparanase activity was determined using biotynilated heparan sulfate as substrate. The results showed that dermatan sulfate (P=0.019), heparan sulfate levels (P=0.015) and heparanase activity (P=0.006) in preeclampsia were significantly higher than in the control group. There was no significant difference between the groups for hyaluronic acid expression in placentas (P=0.110). The present study is the first to demonstrate directly the increase of heparan sulfate in human placentas from patients with preeclampsia, suggesting that endogenous heparan sulfate could be involved in the release of sFlt-1 from placenta, increasing the level of circulating sFlt-1. Alterations of extracellular matrix components in placentas with preeclampsia raise the possibility that heparan sulfate released by heparanase is involved in mechanisms of preeclampsia development. Published by Elsevier B.V.

  13. MicroRNA-126 Suppresses Mesothelioma Malignancy by Targeting IRS1 and Interfering with the Mitochondrial Function

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Nocchi, L.; Staffolani, S.; Manzella, N.; Amati, M.; Goodwin, J.; Klučková, Katarína; Nguyen, M.; Strafella, E.; Bajziková, Martina; Peterka, Martin; Lettlová, Sandra; Truksa, Jaroslav; Lee, W.; Dong, L.-F.; Santarelli, L.; Neužil, Jiří

    2014-01-01

    Roč. 21, č. 15 (2014), s. 2109-2125 ISSN 1523-0864 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : ATP CITRATE LYASE * OXIDATIVE STRESS * PLEURAL MESOTHELIOMA * CANCER- CELL S Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.407, year: 2014

  14. MicroRNA-126 Suppresses Mesothelioma Malignancy by Targeting IRS1 and Interfering with the Mitochondrial Function

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Nocchi, L.; Staffolani, S.; Manzella, N.; Amati, M.; Goodwin, J.; Klučková, Katarína; Nguyen, M.; Strafella, E.; Bajziková, Martina; Peterka, Martin; Lettlová, Sandra; Truksa, Jaroslav; Lee, W.; Dong, L.-F.; Santarelli, L.; Neužil, Jiří

    2014-01-01

    Roč. 21, č. 15 (2014), s. 2109-2125 ISSN 1523-0864 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : ATP CITRATE LYASE * OXIDATIVE STRESS * PLEURAL MESOTHELIOMA * CANCER-CELLS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.407, year: 2014

  15. 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.

  16. A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis.

    Science.gov (United States)

    Brims, Fraser J H; Meniawy, Tarek M; Duffus, Ian; de Fonseka, Duneesha; Segal, Amanda; Creaney, Jenette; Maskell, Nicholas; Lake, Richard A; de Klerk, Nick; Nowak, Anna K

    2016-04-01

    Malignant pleural mesothelioma (MPM) is a rare cancer with a heterogeneous prognosis. Prognostic models are not widely utilized clinically. Classification and regression tree (CART) analysis examines the interaction of multiple variables with a given outcome. Between 2005 and 2014, all cases with pathologically confirmed MPM had routinely available histological, clinical, and laboratory characteristics recorded. Classification and regression tree analysis was performed using 29 variables with 18-month survival as the dependent variable. Risk groups were refined according to survival and clinical characteristics. The model was then tested on an external international cohort. A total of 482 cases were included in the derivation cohort; the median survival was 12.6 months, and the median age was 69 years. The model defined four risk groups with clear survival differences (p loss. The group with the best survival at 18 months (86.7% alive, median survival 34.0 months, termed risk group 1) had no weight loss, a hemoglobin level greater than 153 g/L, and a serum albumin level greater than 43 g/L. The group with the worst survival (0% alive, median survival 7.5 months, termed risk group 4d) had weight loss, a performance score of 0 or 1, and sarcomatoid histological characteristics. The C-statistic for the model was 0.761, and the sensitivity was 94.5%. Validation on 174 external cases confirmed the model's ability to discriminate between risk groups in an alternative data set with fair performance (C-statistic 0.68). We have developed and validated a simple, clinically relevant model to reliably discriminate patients at high and lower risk of death using routinely available variables from the time of diagnosis in unselected populations of patients with MPM. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  17. Combined doxorubicin and radiation therapy in malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Sinoff, C.; Falkson, G.; Sandison, A.G.; De Muelenaere, G.

    1982-01-01

    Ten patients with histologically confirmed inoperable malignant mesothelioma of the pleura were treated with doxorubicin and fractionated radiotherapy courses. Three patients derived significant clinical benefit from this treatment, although only one of the three had measureable tumor shrinkage that could be defined as partial response. Two of the ten patients showed only progressive disease, while the remaining five showed disease stabilization for 30--100 weeks. The treatment was subjectively well-tolerated and hematopoietic toxicity was acceptable. Radiation pneumonitis did not occur. Two of the four patients who lived greater than or equal to 94 weeks developed fibrosis of the irradiated hemithorax. The median survival time for all patients was 46 weeks. Although the combined treatment could be given with acceptable toxic effects and although four patients benefited from it, the best objective assessment, namely, survival time, did not appear to be adequately influenced to justify an extension of this series

  18. Mesothelioma mortality surveillance and asbestos exposure tracking in Italy

    Directory of Open Access Journals (Sweden)

    Lucia Fazzo

    2012-01-01

    Full Text Available INTRODUCTION: Spatial distribution of mortality from pleural mesothelioma (which in the ICD-10 Revision has a specific code: C45.0 in Italy for the period 2003-2009 is described. Previous mortality studies at national level employed the topographic code "Malignant neoplasms of pleura", because of unavailability of a specific code in ICD-9 Revision for pleural mesothelioma. METHODS: Standardized mortality ratios were computed for all municipalities, using each regional population as reference; for municipalities in Regions with rate higher than the national rate, the latter has been used as reference. SMRs were computed specifically also for each Italian Polluted Sites "of national concern for environmental remediation" (IPS with asbestos exposure sources, composed by one or more municipalities, using regional rate as reference. Spatial Scan Statistics procedure, using SatScan software, was applied in cluster analysis: the country was divided into geographic macro-areas and the relative risks (RR express the ratio of risk within the cluster to the risk of the macro-area outside the cluster. Clusters with p-value < 0.10 were selected. RESULTS: The national standardized annual mortality rate was 1.7 cases per 100 000. Several areas with evident burden of asbestos-related disease were detected. Significant clusters were found in correspondence to asbestos-cement industries (e.g. Casale Monferrato, women: RR = 28.7, shipyards (e.g. Trieste, men: RR = 4.8, petrochemical industries (e.g. Priolo, men: RR = 6.9 and a stone quarry contaminated by fluoro-edenite fibres (Biancavilla, women: RR = 25.9. Some of the increased clusters correspond to IPS. CONCLUSIONS: The results may contribute to detect asbestos exposure and to set priorites for environmental remediation.

  19. 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.

    Science.gov (United States)

    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.

  20. Idiopathic pleural panniculitis with recurrent pleural effusion not associated with Weber-Christian disease

    Directory of Open Access Journals (Sweden)

    Laperuta Paolo

    2016-01-01

    Full Text Available A 82-year-old patient with dyspnea and a recurrent history of pleural effusion was admitted into our unit. He performed a Chest computed tomography showing right pleural effusion. Video-assisted thoracoscopy (VATS exploratory showed parietal pleural thickening of adipose tissue. The surgical procedure consisted, therefore, in the execution of multiple biopsies of the parietal pleura which appeared covered, on the whole surface, by islands of adipose tissue, without macroscopic pathological aspects. After the procedure was performed pleurodesis with talc. The definitive histological examination consisted of normal mesothelial cells surrounded by fatty tissue infiltrated by small lymphocytes in a patient without skin lesions or visceral or systemic signs of inflammatory involvement of the adipose tissue. We reported a rare case of idiopathic pleural panniculitis with recurrent pleural effusion not associated with Weber-Christian disease.

  1. Mesothelioma

    Science.gov (United States)

    ... stomach, heart, and other organs is called mesothelium. Mesothelioma is a tumor of that tissue. It usually ... be benign (not cancer) or malignant (cancer.) Malignant mesothelioma is a rare but serious type of cancer. ...

  2. Microcystic variant malignant mesothelioma presenting as a localized paraspinal mass

    Directory of Open Access Journals (Sweden)

    Hyang Mi Ko

    2014-01-01

    Full Text Available A 58-year-old man presented with productive cough and fever. Computed tomography (CT scan of the chest showed an upper right paraspinal mass. CT-guided fine-needle aspiration biopsy showed lobules of vacuolated cells against a background of myxoid material. The cells demonstrated moderate to severe nuclear atypia and occasional mitoses. Immunohistochemistry revealed tumor cells to be immunoreactive for calretinin, WT-1, D2-40, cytokeratin (CK 7, AE1/AE3, high molecular weight keratin, vimentin and epithelial membrane antigen, and negative for thyroid transcription factor-1, Ber-EP4, carcinoembryonic antigen, S100 protein, CK20, and CDX2. The combined morphologic and immunohistochemical findings confirmed the diagnosis of microcystic variant of localized malignant mesothelioma. The subsequent lung resection showed a pleural-based mass in the right upper lobe and confirmed the diagnosis. Awareness of the existence of unusual morphologic variants and localized forms of mesothelioma are necessary to avoid misdiagnosis of fine needle biopsy samples. Recognition of characteristic cytomorphologic features along with optimal use of panel of immunohistochemistry studies is crucial for making a specific diagnosis.

  3. Polymeric films loaded with cisplatin for malignant pleural mesothelioma: a pharmacokinetic study in an ovine model

    Science.gov (United States)

    Barocelli, Elisabetta; Cavazzoni, Andrea; Petronini, Piergiorgio; Mucchino, Claudio; Cantoni, Anna Maria; Leonardi, Fabio; Ventura, Luigi; Barbieri, Stefano; Colombo, Paolo; Fusari, Antonella; Carbognani, Paolo; Rusca, Michele; Sonvico, Fabio

    2018-01-01

    Background Malignant pleural mesothelioma (MPM) continues to be a distressing tumor due to its aggressive biologic behavior and scanty prognosis. Several therapeutic approaches have been tested both in clinical and preclinical settings, being intrapleural chemotherapy one of the most promising. Some years ago, our interest focused on polymeric films loaded with cisplatin for the adjuvant intrapleural treatment of surgical patients. After in vitro and in vivo studies in a rat recurrence model of MPM, the aim of this study was to evaluate the pharmacokinetics of the polymeric films in a sheep model in view of further studies in a clinical setting. Methods An ovine model was used. Animals were divided into four groups according to pharmacologic treatment: control group (three animals undergoing left pneumonectomy and saline-NaCl solution); intrapleural hyaluronate cisplatin films (HYALCIS) group (six animals undergoing left pneumonectomy and intrapleural application of polymeric films loaded with cisplatin); intrapleural cisplatin solution (six animals undergoing left pneumonectomy and intrapleural application of cisplatin solution); intravenous cisplatin (five animals undergoing left pneumonectomy and intravenous administration of cisplatin solution). The primary objective was the plasmatic and pleural concentration of cisplatin in the treatment groups. The secondary objective was the treatment-related toxicity evaluated by plasmatic analysis performed at prearranged time intervals and histological examinations of tissue samples collected during animal autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Results Twenty female Sardinian sheep with a mean weight of 45.1 kg were studied. All animals survived the surgical procedures. The whole surgical procedure had a mean duration of 113 minutes. Cisplatin blood levels obtained from polymeric films application were low during the

  4. The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.

    Science.gov (United States)

    Marinaccio, Alessandro; Corfiati, Marisa; Binazzi, Alessandra; Di Marzio, Davide; Scarselli, Alberto; Ferrante, Pierpaolo; Bonafede, Michela; Verardo, Marina; Mirabelli, Dario; Gennaro, Valerio; Mensi, Carolina; Schallemberg, Gert; Mazzoleni, Guido; Merler, Enzo; Girardi, Paolo; Negro, Corrado; D'Agostin, Flavia; Romanelli, Antonio; Chellini, Elisabetta; Silvestri, Stefano; Pascucci, Cristiana; Calisti, Roberto; Stracci, Fabrizio; Romeo, Elisa; Ascoli, Valeria; Trafficante, Luana; Carrozza, Francesco; Angelillo, Italo Francesco; Cavone, Domenica; Cauzillo, Gabriella; Tallarigo, Federico; Tumino, Rosario; Melis, Massimo; Iavicoli, Sergio

    2018-04-01

    The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register. Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated. In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries. The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis

    OpenAIRE

    Wang, Ying; Rishi, Arun K.; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I.; Wali, Anil

    2011-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has...

  6. 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.

  7. Mesotelioma pleural com metástase renal em gato Pleural mesothelioma with renal metastasis in a cat

    Directory of Open Access Journals (Sweden)

    A.M. Piacenti

    2004-08-01

    Full Text Available It has been described the anatomopathological and immunohistochemical characteristics of a multinodular neoplasm distributed in the parietal and visceral pleurae, pericardium, thoracic portion of the diaphragm and renal cortex of an eight year-old, female, mixed breed, cat. Based on the anatomopathological and immunohistochemical findings it was firmed the diagnosis of biphasic pleural mesotelioma with renal metastasis.

  8. Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos.

    Science.gov (United States)

    Merler, Enzo; Somigliana, Anna; Girardi, Paolo; Barbieri, Pietro Gino

    2017-03-01

    To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed. The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either 'definite' or 'probable' or 'possible'. The participants had finished working in asbestos exposure conditions more than 20 years ago (on average 26.1±11.0 years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in industry, in chemical or textile industry and among those performing brake repair activities. The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. 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.)

  10. Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

    Science.gov (United States)

    Chouaid, Christos; Assié, Jean Baptiste; Andujar, Pascal; Blein, Cecile; Tournier, Charlène; Vainchtock, Alexandre; Scherpereel, Arnaud; Monnet, Isabelle; Pairon, Jean Claude

    2018-04-01

    This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1- and 2-year survival according to sex, age, co-morbidities, management, population-density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co-morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One- and 2-year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7-15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co-morbidities, living in rural/semi-rural area was associated with better 2-year survival (HR: 0.83 [95% CI: 0.73-0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co-morbidities, sex, age, and living place appear to be significant factors of prognosis. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Crovella, S; Moura, R R; Cappellani, S; Celsi, F; Trevisan, E; Schneider, M; Brollo, A; Nicastro, E M; Vita, F; Finotto, L; Zabucchi, G; Borelli, V

    2018-01-01

    The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Early pleural fluid dynamics following video-assisted thoracoscopic lobectomy has limited clinical value

    DEFF Research Database (Denmark)

    Holbek, Bo Laksáfoss; Petersen, René Horsleben; Kehlet, Henrik

    2017-01-01

    The objective of this study was to evaluate the potential of predicting the pleural fluid output in patients after video-assisted thoracoscopic lobectomy of the lung. Detailed measurements of continuous fluid output were obtained prospectively using an electronic thoracic drainage device (Thopaz...... and 48 hours. Assessment of initial fluid production may predict high 24-hour fluid output (≥500 mL) but seems to lack clinical value in drain removal criteria....

  14. Influence of Pleurectomy and Decortication in Health-Related Quality of Life Among Patients with Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Vigneswaran, Wickii T; Kircheva, Diana Y; Rodrigues, Adrian E; Watson, Sydeaka; Celauro, Amy Durkin; Rose, Berkley; Kindler, Hedy L; Husain, Aliya N

    2018-04-01

    Complete macroscopic resection surgery, pleurectomy and decortication (PD) improve survival in selected patients with malignant pleural mesothelioma (MPM). Yet its value has been questioned because of concern that this extensive surgical procedure may disrupt health-related quality of life (HRQoL). HRQoL was studied in patients undergoing PD surgery for MPM using EORTC QLQ-C30 instrument at baseline (prior to surgery), 1, 4-5, 7-8, and 10-11 months following surgery. Global health and variables in function and symptom domains were investigated. Sub-groups analyses were performed for ECOG performance status (PS), histological sub-types and pathological tumor volume (pTV). Within-patient comparisons to baseline scores were made using Wilcoxon signed-rank test. Trends over time were evaluated using Cuzick's nonparametric test. There were 114 patients with median age of 70 years (range: 50-88) and PS 0: 35 (30.7%), epithelioid histology: 61 (53.5%) and volume <600 ml: 58 (50.9%). Patients with good PS (PS 0), epithelioid histology and small pTV had greater level of functioning and were less symptomatic at baseline. Overall global health worsened at the first postoperative month (p = 0.0005) with subsequent improvement. Non-epithelioid histology and patients with large pTV demonstrated greater improvement in global health, function and symptoms domains following a PD. At baseline, the overall health-related quality of life, function and symptom domains were adversely affected in non-epithelioid histology and patients with large pTV. However, greatest improvement in global health, symptom and function domains were observed first month after PD and during the follow-up in these sub-groups.

  15. Peritoneal mesothelioma

    International Nuclear Information System (INIS)

    Ros, P.R.; Yuschok, T.J.; Buck, J.L.; Shekitka, K.M.; Kaude, J.V.; Armed Forces Inst. of Pathology, Washington, DC

    1991-01-01

    Previous imaging reports of peritoneal mesothelioma have described a variety of radiologic appearances, but have not included its pathologic classification. We retrospectively reviewed 10 cases of peritoneal mesothelioma representing the following histologic categories: 7 epithelial, 2 sarcomatoid, and one biphasic. By imaging, epithelial mesotheliomas demonstrated diffuse thickening of the peritoneum and mesentery and/or multiple small nodules. The sarcomatoid-type appeared as a mass and the biphasic-type had radiologic and gross pathologic features of both sarcomatoid and epithelial types. We conclude that peritoneal mesothelioma presents with a wide spectrum of radiographic appearances and should therefore be included in the differential diagnoses of diffuse as well as localized peritoneal processes. (orig.)

  16. Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies.

    Science.gov (United States)

    Icard, Philippe; Philippe, Icard; Zhang, Xiao-Dong; Xiao-Dong, Zhang; Lemoisson, Edwige; Edwige, Lemoisson; Louis, Marie-Hélène; Marie-Hélène, Louis; Allouche, Stéphane; Stéphane, Allouche; Lincet, Hubert; Hubert, Lincet; Poulain, Laurent; Laurent, Poulain

    2012-02-01

    Over many years we have taken advantage of the special metabolism of cancer cells involving an increased consumption of glucose associated with lactic acid production even in the presence of oxygen, a phenomenon referred to as the "Warburg effect", to counteract cancer cell growth. We have tested 3-bromopyruvate (3-BrPA), an inhibitor of pyruvate-associated reactions. Firstly, we tested this agent, in vitro, in two mesothelioma cell lines. Cellular response would appear to depend on the mode of administration (immediately or 24 h after seeding). Depending on the line, 3-BrPA induced a cytostatic or cytotoxic effect. This effect was accompanied by cell death induction even in cells highly refractory to cisplatin. Mitochondrial apoptotic death appeared to involve both lines; however, a different death pathway such as necrosis cannot be excluded. Interestingly, 3-BrPA leads to a diminution of the expression of the anti-apotptoic protein Mcl-1. We then tested 3-BrPA in vivo. Survival of nude mice bearing human mesothelioma was significantly prolonged (p < 0.0001). Toxicity and clinical studies should be performed to test 3- BrPA as local therapy for patients suffering from pleural or peritoneal mesothelioma. Association with cisplatin should be particularly considered.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. CT findings and serum ca 125 levels in malignant peritoneal mesothelioma: report of 11 new cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kebapci, Mahmut; Adapinar, Baki [Department of Radiology, Osmangazi University School of Medicine, 26480, Meselik, Eskisehir (Turkey); Vardareli, Eser [Department of Gastroenterology, Osmangazi University School of Medicine, 26480, Meselik, Eskisehir (Turkey); Acikalin, Mustafa [Department of Pathology, Osmangazi University School of Medicine, 26480, Meselik, Eskisehir (Turkey)

    2003-12-01

    The aim of this study was to review and reappraise the clinical and CT features of malignant peritoneal mesothelioma (MPM), and to discuss differential diagnosis. The history, clinical, and laboratory data, and imaging studies of 11 patients with a histologically proven diagnosis of MPM, were retrospectively reviewed. Our patients consisted of 7 women and 4 men, with a median age of 48 years (age range 40-55 years). There was a definite history of significant asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was 230 U/ml (range 19-1000 U/ml). The most common radiological findings were extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9 of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper abdominal masses. Computed tomography findings of MPM are nonspecific and inadequate to pinpoint specific diagnosis. The diagnosis requires histological demonstration which is commonly made by an image or laparoscopic-guided biopsy. Pleural changes suggesting asbestosis combined with CT findings and high CA-125 levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the diagnosis of MPM is important because histological and immunohistochemical tests are needed for diagnostic accuracy. (orig.)

  19. CT findings and serum ca 125 levels in malignant peritoneal mesothelioma: report of 11 new cases and review of the literature

    International Nuclear Information System (INIS)

    Kebapci, Mahmut; Adapinar, Baki; Vardareli, Eser; Acikalin, Mustafa

    2003-01-01

    The aim of this study was to review and reappraise the clinical and CT features of malignant peritoneal mesothelioma (MPM), and to discuss differential diagnosis. The history, clinical, and laboratory data, and imaging studies of 11 patients with a histologically proven diagnosis of MPM, were retrospectively reviewed. Our patients consisted of 7 women and 4 men, with a median age of 48 years (age range 40-55 years). There was a definite history of significant asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was 230 U/ml (range 19-1000 U/ml). The most common radiological findings were extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9 of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper abdominal masses. Computed tomography findings of MPM are nonspecific and inadequate to pinpoint specific diagnosis. The diagnosis requires histological demonstration which is commonly made by an image or laparoscopic-guided biopsy. Pleural changes suggesting asbestosis combined with CT findings and high CA-125 levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the diagnosis of MPM is important because histological and immunohistochemical tests are needed for diagnostic accuracy. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    Goricar, Katja; Kovac, Viljem; Dolzan, Vita

    2014-01-01

    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

  2. Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Arzt, Lisa; Halbwedl, Iris; Gogg-Kamerer, Margit; Popper, Helmut H

    2017-07-01

    Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

  3. The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.

    Science.gov (United States)

    Khella, Mina S; Salem, Ahmed M; Abdel-Rahman, Omar; Saad, Amr S

    2018-02-01

    Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk. FTO rs9939609 (T >A) genotypes were screened using a TaqMan ® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design. In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025). The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.

  4. Peritoneal mesothelioma.

    OpenAIRE

    Anderson, J. H.; Stewart, C. J.; Hansell, D. T.; Anderson, J. R.

    1990-01-01

    We report two patients who presented with small bowel obstruction secondary to peritoneal mesothelioma. The difficulties in establishing this diagnosis at an early stage are illustrated. Recent advances in the management of peritoneal mesothelioma are reviewed.

  5. Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT activation

    Science.gov (United States)

    Cioce, M; Canino, C; Goparaju, C; Yang, H; Carbone, M; Pass, H I

    2014-01-01

    Clinical management of malignant pleural mesothelioma (MPM) is very challenging because of the uncommon resistance of this tumor to chemotherapy. We report here increased expression of macrophage colony-stimulating-factor-1-receptor (M-CSF/CSF-1R) mRNA in mesothelioma versus normal tissue specimens and demonstrate that CSF-1R expression identifies chemoresistant cells of mesothelial nature in both primary cultures and mesothelioma cell lines. By using RNAi or ligand trapping, we demonstrate that the chemoresistance properties of those cells depend on autocrine CSF-1R signaling. At the single-cell level, the isolated CSF-1Rpos cells exhibit a complex repertoire of pluripotency, epithelial–mesenchymal transition and detoxifying factors, which define a clonogenic, chemoresistant, precursor-like cell sub-population. The simple activation of CSF-1R in untransformed mesothelial cells is sufficient to confer clonogenicity and resistance to pemetrexed, hallmarks of mesothelioma. In addition, this induced a gene expression profile highly mimicking that observed in the MPM cells endogenously expressing the receptor and the ligands, suggesting that CSF-1R expression is mainly responsible for the phenotype of the identified cell sub-populations. The survival of CSF1Rpos cells requires active AKT (v-akt murine thymoma viral oncogene homolog 1) signaling, which contributed to increased levels of nuclear, transcriptionally competent β-catenin. Inhibition of AKT reduced the transcriptional activity of β-catenin-dependent reporters and sensitized the cells to senescence-induced clonogenic death after pemetrexed treatment. This work expands what is known on the non-macrophage functions of CSF-1R and its role in solid tumors, and suggests that CSF-1R signaling may have a critical pathogenic role in a prototypical, inflammation-related cancer such as MPM and therefore may represent a promising target for therapeutic intervention. PMID:24722292

  6. TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages

    International Nuclear Information System (INIS)

    Yuan, Bao-Zhu; Chapman, Joshua; Ding, Min; Wang, Junzhi; Jiang, Binghua; Rojanasakul, Yon; Reynolds, Steven H

    2013-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignancy closely associated with asbestos exposure and extremely resistant to current treatments. It exhibits a steady increase in incidence, thus necessitating an urgent development of effective new treatments. Proteasome inhibitors (PIs) and TNFα-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents. To develop effective new treatments, the proapoptotic effects of PIs, MG132 or Bortezomib, and TRAIL were investigated in MPM cell lines NCI-H2052, NCI-H2452 and NCI-H28, which represent three major histological types of human MPM. Treatment with 0.5-1 μM MG132 alone or 30 ng/mL Bortezomib alone induced a limited apoptosis in MPM cells associated with the elevated Mcl-1 protein level and hyperactive PI3K/Akt signaling. However, whereas 10–20 ng/ml TRAIL alone induced a limited apoptosis as well, TRAIL and PI combination triggered a robust apoptosis in all three MPM cell lines. The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells. The combinatorial treatment using TRAIL and PI may represent an effective new treatment for MPMs

  7. Gender differences in asbestos exposure and disease location in 327 patients with mesothelioma

    DEFF Research Database (Denmark)

    Panou, Vasiliki; Weinreich, Ulla Moller; Bak, Jens

    2017-01-01

    Introduction: The Region of North Denmark has a high incidence of malignant mesothelioma (MM) of 6.2/100.000 for men and 1/100.000 for women mainly due to large-scale use of chrysotile asbestos.Aims: The aim of the study is to investigate gender differences in asbestos exposure and disease location...... workers; domestic, referring to patients living with an asbestos worker; environmental, defined as living or working within 10.000 meters from asbestos emitting location; unknown, where no source of asbestos exposure could be identified. MM location was classified as pleural (MPM) or peritoneal (MAM...

  8. Study of the interaction of enzyme Heparanase 1 (HPSE1) active with deoxyribonucleic acids; Estudo de interacao da enzima Heparanase 1 (HPSE 1) ativa com acido desoxirribonucleicos

    Energy Technology Data Exchange (ETDEWEB)

    Cid, Gisele da Silva

    2016-07-01

    The human heparanase 1 (HPSE 1) is a protein with multiple functions and has emerged as a promising therapeutic target in the context of antitumor therapy. This fact is due to its clinical relevance in the tumor development and progression, as determined by their enzymatic ability to degrade heparan sulfate (HS), the main constituent of the extracellular matrix, providing a tumor microenvironment to tumor dissemination. In addition, this protein plays a significant role in the increase of tumor cells migration ionizing radiation dose delivery in radiotherapy from the increase in the expression levels of HPSE1. In order to evaluate in more detail the functions of active HPSE1, it has been proposed to characterize the interaction of human heparanase protein 1 with deoxyribonucleic acids. Our results are original and point to a new function of HPSE1 of the endonuclease type. (author)

  9. Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis.

    Directory of Open Access Journals (Sweden)

    Svenja Thies

    Full Text Available The epithelioid and sarcomatoid histologic variants of malignant pleural mesothelioma (MPM can be considered as E- and M-parts of the epithelial-mesenchymal transition (EMT axis; the biphasic being an intermediate. EMT is associated with an increase of stem cell (SC traits. We correlated the neural crest SC marker nestin and the EMT marker periostin with histology, type of neo-adjuvant chemotherapy (CT and overall survival (OS of MPM patients.Tumor tissues of a historic cohort 1 (320 patients and an intended induction chemotherapy followed by extrapleural pneumonectomy (EPP cohort 2 (145 patients were immunohistochemically H-scored (intensity of immunoreactivity multiplied by frequency of stained cells. Paired chemo-naïve biopsies and -treated surgical specimens were available for 105/145 patients. CT included platinum/gemcitabine (Pla/Gem or platinum/pemetrexed (Pla/Pem.Expression of any cytosolic nestin progressively increased from epithelioid to biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the expression level of nestin in comparison to Pla/Gem, whereas the opposite was found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid. In addition to non-epithelioid histology, any expression of nestin in chemo-naïve biopsies (median overall survival: 22 vs. 17 months and chemo-treated surgical specimens (18 vs. 12 months as well as high periostin in biopsies (23 vs. 15 months were associated with poor prognosis. In the multivariate survival analysis, any nestin expression in chemo-naïve biopsies proved to be an independent prognosticator against histology. In both pre- and post-CT situations, the combination of nestin or periostin expression with non-epithelioid histology was particularly/ dismal (all p-values <0.05.The SC marker nestin and the EMT marker periostin allow for further prognostic

  10. A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

    Directory of Open Access Journals (Sweden)

    Sarah Hackman

    2016-01-01

    Full Text Available Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22(p13;q12 translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22(p13;q12 translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

  11. Malignant mesothelioma following radiation exposure

    International Nuclear Information System (INIS)

    Antman, K.H.; Corson, J.M.; Li, F.P.; Greenberger, J.; Sytkowski, A.; Henson, D.E.; Weinstein, L.

    1983-01-01

    Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered

  12. National Mesothelioma Virtual Bank: A Platform for Collaborative Research and Mesothelioma Biobanking Resource to Support Translational Research.

    Science.gov (United States)

    Amin, Waqas; Parwani, Anil V; Melamed, Jonathan; Flores, Raja; Pennathur, Arjun; Valdivieso, Federico; Whelan, Nancy B; Landreneau, Rodeny; Luketich, James; Feldman, Michael; Pass, Harvey I; Becich, Michael J

    2013-01-01

    The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New York University, University of Pennsylvania, University of Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).

  13. 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

  14. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.

    Science.gov (United States)

    Boffetta, P; Righi, L; Ciocan, C; Pelucchi, C; La Vecchia, C; Romano, C; Papotti, M; Pira, E

    2018-02-01

    Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene. We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression. The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival. We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure. © The Author 2017. Published by Oxford University Press on behalf of the European Society for

  15. Micro-pleural Metastasis Without Effusion: CT and US Findings

    International Nuclear Information System (INIS)

    Na, Hyoung Il; Yoo, Seung Min; Kim, Yang Soo; Lee, Hwa Yeon; Song, In Sup; Shim, Hyung Jin; Kwak, Byung Kook; Shin, Jong Wook

    2004-01-01

    Pleural metastasis from malignancy is commonly combined with effusion. We report the ultrasonographic and CT findings in a rare case of micro-pleural metastasis without effusion. A 34-year-old male patient with lung cancer underwent video-assisted thoracoscopic surgery (VATS), prior to open thoracotomy. VATS revealed multiple metastatic micronodules on the pleura, which were overlooked on the preoperative CT scan. The HRCT images and chest ultrasonograms showed clear evidence of pleural micro-nodules

  16. Micro-pleural Metastasis Without Effusion: CT and US Findings

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hyoung Il; Yoo, Seung Min; Kim, Yang Soo; Lee, Hwa Yeon; Song, In Sup; Shim, Hyung Jin; Kwak, Byung Kook; Shin, Jong Wook [Chung-Ang University College of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Pleural metastasis from malignancy is commonly combined with effusion. We report the ultrasonographic and CT findings in a rare case of micro-pleural metastasis without effusion. A 34-year-old male patient with lung cancer underwent video-assisted thoracoscopic surgery (VATS), prior to open thoracotomy. VATS revealed multiple metastatic micronodules on the pleura, which were overlooked on the preoperative CT scan. The HRCT images and chest ultrasonograms showed clear evidence of pleural micro-nodules

  17. Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial).

    Science.gov (United States)

    Hasegawa, Seiki; Okada, Morihito; Tanaka, Fumihiro; Yamanaka, Takeharu; Soejima, Toshinori; Kamikonya, Norihiko; Tsujimura, Tohru; Fukuoka, Kazuya; Yokoi, Kohei; Nakano, Takashi

    2016-06-01

    We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM). Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0-3, N0-2, M0 disease; no prior treatment for the disease; age 20-75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m(2)) plus cisplatin (60 mg/m(2)) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT. Forty-two eligible patients were enrolled: median age 64.5 (range 43-74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %. This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.

  18. Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.

    Science.gov (United States)

    Linton, Anthony; Soeberg, Matthew; Broome, Richard; Kao, Steven; van Zandwijk, Nico

    2017-07-01

    Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM. We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed. We identified 910 patients (67% residing in major cities; 92% 70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001). This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW. © 2017 Asian Pacific Society of Respirology.

  19. Prognostic value of pretreatment volume-based quantitative 18F-FDG PET/CT parameters in patients with malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Kitajima, Kazuhiro; Doi, Hiroshi; Kuribayashi, Kozo; Hashimoto, Masaki; Tsuchitani, Tatsuya; Tanooka, Masao; Fukushima, Kazuhito; Nakano, Takashi; Hasegawa, Seiki; Hirota, Shozo

    2017-01-01

    Purpose: To investigate the relationships between pretreatment volume-based quantitative 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM). Materials and methods: We retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment 18 F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test. Results: The median follow-up was 15 months (range, 1–96 months; median, 17 months). In a univariate analysis of all patients, older age (p < 0.05), high EORTC score (p < 0.001), non-epithelioid histological subtype (p < 0.001), high T stage (p < 0.001), positive N/M status (p < 0.05, p < 0.001), advanced TNM stage (p < 0.001), non-surgical treatment (p < 0.001), and high SUVmax (p < 0.001), MTV (p < 0.001), or TLG (p < 0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14–2.48; p < 0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34–0.95; p < 0.05), and high TLG (HR: 1.97, 95% CI: 1.14–3.44; p < 0.05) as independent negative predictors. Conclusions: Pretreatment volume-based quantitative 18 F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.

  20. The Controlling Nutritional Status Score Is a Significant Independent Predictor of Poor Prognosis in Patients With Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Takamori, Shinkichi; Toyokawa, Gouji; Taguchi, Kenichi; Edagawa, Makoto; Shimamatsu, Shinichiro; Toyozawa, Ryo; Nosaki, Kaname; Seto, Takashi; Hirai, Fumihiko; Yamaguchi, Masafumi; Shoji, Fumihiro; Okamoto, Tatsuro; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2017-07-01

    Malignant pleural mesothelioma (MPM) is a devastating neoplasm; however, some patients exhibit a good response to chemotherapy or multidisciplinary therapy, including surgery and chemotherapy. It is therefore important to discover the factors that can be used to select patients who will benefit from such treatment. Although the Controlling Nutritional Status (CONUT) score has been used to predict the prognosis in other types of malignancy, its utility in patients with MPM is unknown. The aim of this study was to clarify the clinical significance of the CONUT in patients with MPM. The data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy, were analyzed in the present study. A cut-off CONUT score of 2 was used to classify all of the patients into low or high CONUT groups. Fifty-two of the 83 patients were classified into the low CONUT group. A high CONUT score was significantly correlated with chemotherapy alone (P = .011). The high CONUT group had significantly poorer overall survival (OS) (P clinical stage and the CONUT score were found to be independent predictive factors for the OS: clinical stage, I/II and III/IV; P = .001 and CONUT score, ≥ 3 and ≤ 2; P = .011, respectively. The clinical stage and the CONUT score were also independent predictive factors for DFS/PFS: clinical stage, I/II and III/IV; P = .006 and CONUT score, ≥ 3 and ≤ 2; P = .013, respectively. The CONUT score was an independent predictor of a poor prognosis in the patients with MPM. This score provides useful information for selecting patients who will benefit from the treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

    Science.gov (United States)

    Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

    2017-08-15

    Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

  2. Diagnostic imaging of small amounts of pleural fluid: pleural effusion vs. physiologic pleural fluid.

    Science.gov (United States)

    Kocijancic, Igor

    2007-12-01

    The aim of this article is to present an overview of our 10 years clinical research work and early clinical experience with small pleural effusions. Small amounts of pleural fluid are severely difficult to identify with imaging methods (chest x-rays and ultrasound). Nevertheless, it may be an important finding, sometimes leading to a definitive diagnosis of pleural carcinomatosis, infection or other pathologic condition. Chest x-rays were used for many years for the diagnosis of small pleural effusions. Lateral decubitus chest radiographs represented a gold standard for imaging of small amounts of plural fluid for more than 80 years. In the last two decades, ultrasonography of pleural space became a leading real-time method for demonstrating small pleural effusions. Furthermore, the advent of sonographic technology actually enables detection of physiologic pleural fluid in some otherwise healthy individuals. In conclusion, new definitions of the key terms in the field of diagnostic imaging of small amounts of pleural fluid seem to be justified. We suggest that the term pleural fluid should determine physiologic pleural space condition while the term pleural effusion should only be used in the cases of pleural involvement or pleural illness.

  3. BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

    Science.gov (United States)

    Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

    2004-02-01

    The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

  4. Apoptosis by [Pt(O,O'-acac)(γ-acac)(DMS)] requires PKC-δ mediated p53 activation in malignant pleural mesothelioma.

    Science.gov (United States)

    Muscella, Antonella; Vetrugno, Carla; Cossa, Luca Giulio; Antonaci, Giovanna; Barca, Amilcare; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Marsigliante, Santo

    2017-01-01

    Mesothelioma cancer cells have epithelioid or sarcomatoid morphology. The worst prognosis is associated with sarcomatoid phenotype and resistance to therapy is affected by cells heterogeneity. We recently showed that in ZL55 mesothelioma cell line of epithelioid origin [Pt(O,O'-acac)(γ-acac)(DMS)] (Ptac2S) has an antiproliferative effect in vitro and in vivo. Aim of this work was to extend the study on the effects of Ptac2S on ZL34 cell line, representative of sarcomatoid mesothelioma. ZL34 cells were used to assay the antitumor activity of Ptac2S in a mouse xenograft model in vivo. Then, both ZL34 and ZL55 cells were used in order to assess the involvement of p53 protein in (a) the processes underlying the sensitivity to chemotherapy and (b) the activation of various transduction proteins involved in apoptosis/survival processes. Ptac2S increases ZL34 cell death in vivo compared with cisplatin and, in vitro, Ptac2S was more efficacious than cisplatin in inducing apoptosis. In Ptac2S-treated ZL34 and ZL55 cells, p53 regulated gene products of apoptotic BAX and anti-apoptotic Bcl-2 proteins via transcriptional activation. Ptac2S activated PKC-δ and PKC-ε; their inhibition by PKC-siRNA decreased the apoptotic death of cells. PKC-δ was responsible for JNK1/2 activation that has a role in p53 activation. In addition, PKC-ε activation provoked phosphorylation of p38MAPK, concurring to apoptosis. In ZL34 cells, Ptac2S also activated PKC-α thus provoking ERK1/2 activation; inhibition of PKC-α, or ERK1/2, increased Ptac2S cytotoxicity. Results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, giving a substantial starting point for its further validation.

  5. Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in malignant mesothelioma.

    Science.gov (United States)

    Arnold, David T; Rowen, Donna; Versteegh, Matthijs M; Morley, Anna; Hooper, Clare E; Maskell, Nicholas A

    2015-01-23

    In order to estimate utilities for cancer studies where the EQ-5D was not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping algorithms. Several mapping algorithms exist for this transformation, however, algorithms tend to lose accuracy in patients in poor health states. The aim of this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in a dataset of patients with malignant pleural mesothelioma, an invariably fatal malignancy where no previous mapping estimation has been published. Health related quality of life (HRQoL) data where both the EQ-5D and QLQ-C30 were used simultaneously was obtained from the UK-based prospective observational SWAMP (South West Area Mesothelioma and Pemetrexed) trial. In the original trial 73 patients with pleural mesothelioma were offered palliative chemotherapy and their HRQoL was assessed across five time points. This data was used to test the nine available mapping algorithms found in the literature, comparing predicted against observed EQ-5D values. The ability of algorithms to predict the mean, minimise error and detect clinically significant differences was assessed. The dataset had a total of 250 observations across 5 timepoints. The linear regression mapping algorithms tested generally performed poorly, over-estimating the predicted compared to observed EQ-5D values, especially when observed EQ-5D was below 0.5. The best performing algorithm used a response mapping method and predicted the mean EQ-5D with accuracy with an average root mean squared error of 0.17 (Standard Deviation; 0.22). This algorithm reliably discriminated between clinically distinct subgroups seen in the primary dataset. This study tested mapping algorithms in a population with poor health states, where they have been previously shown to perform poorly. Further research into EQ-5D estimation should be directed at response mapping methods given its superior performance in this study.

  6. Sphingosine kinase 1 is required for mesothelioma cell proliferation: role of histone acetylation.

    Directory of Open Access Journals (Sweden)

    Satish Kalari

    Full Text Available Malignant pleural mesothelioma (MPM is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets for the development of highly efficacious therapeutics.In this study, we report that the expression of Sphingosine Kinase 1 (SphK1 protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid compared to normal tissue (n = 13. In addition, we also observed significantly elevated levels of SphK1 and SphK2 mRNA and SphK1 protein expression in MPM cell lines such as H2691, H513 and H2461 compared to the non-malignant mesothelial Met5 cells. The underlying mechanism appears to be mediated by SphK1 induced upregulation of select gene transcription programs such as that of CBP/p300 and PCAF, two histone acetyl transferases (HAT, and the down regulation of cell cycle dependent kinase inhibitor genes such as p27Kip1 and p21Cip1. In addition, using immunoprecipitates of anti-acetylated histone antibody from SphK inhibitor, SphK-I2 treated Met5A and H2691 cell lysates, we also showed activation of other cell proliferation related genes, such as Top2A (DNA replication, AKB (chromosome remodeling and mitotic spindle formation, and suppression of p21 CIP1 and p27KIP1. The CDK2, HAT1 and MYST2 were, however, unaffected in the above study. Using SphK inhibitor and specific siRNA targeting either SphK1 or SphK2, we also unequivocally established that SphK1, but not SphK2, promotes H2691 mesothelioma cell proliferation. Using a multi-walled carbon nanotubes induced peritoneal mesothelioma mouse model, we showed that the SphK1-/- null mice exhibited significantly less inflammation and granulamatous nodules compared to their wild type counterparts.The lipid kinase SphK1 plays a positive and essential role in the growth and development of malignant mesothelioma and is therefore a likely

  7. Mesothelioma Applied Research Foundation

    Science.gov (United States)

    ... Foundation Experts Can Answer Your Questions! The Mesothelioma Applied Research Foundation's team of experts is available to answer ... a law firm. Read more about the Mesothelioma Applied Research Foundation . TO GET HELP CALL: (877) End-Meso ...

  8. Prognostic value of pretreatment volume-based quantitative {sup 18}F-FDG PET/CT parameters in patients with malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Kazuhiro, E-mail: kitajima@med.kobe-u.ac.jp [Division of Nuclear Medicine and PET Center, Department of Radiology, Hyogo College of Medicine, Hyogo (Japan); Doi, Hiroshi, E-mail: h-doi@hyo-med.ac.jp [Department of Radiology, Hyogo College of Medicine, Hyogo (Japan); Kuribayashi, Kozo, E-mail: kuririn@hyo-med.ac.jp [Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Hyogo (Japan); Hashimoto, Masaki, E-mail: kogekogemasaki@gmail.com [Department of Thoracic Surgery, Hyogo College of Medicine, Hyogo (Japan); Tsuchitani, Tatsuya, E-mail: tty-823@hyo-med.ac.jp [Department of Radiological Technology, Hyogo College of Medicine College Hospital, Hyogo (Japan); Tanooka, Masao, E-mail: masao1108@gmail.com [Department of Radiological Technology, Hyogo College of Medicine College Hospital, Hyogo (Japan); Fukushima, Kazuhito, E-mail: fukuchan00106@gmail.com [Division of Nuclear Medicine and PET Center, Department of Radiology, Hyogo College of Medicine, Hyogo (Japan); Nakano, Takashi, E-mail: t-nakano@hyo-med.ac.jp [Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Hyogo (Japan); Hasegawa, Seiki, E-mail: hasegawa@hyo-med.ac.jp [Department of Thoracic Surgery, Hyogo College of Medicine, Hyogo (Japan); Hirota, Shozo, E-mail: hirota-s@hyo-med.ac.jp [Department of Radiology, Hyogo College of Medicine, Hyogo (Japan)

    2017-01-15

    Purpose: To investigate the relationships between pretreatment volume-based quantitative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM). Materials and methods: We retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment {sup 18}F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test. Results: The median follow-up was 15 months (range, 1–96 months; median, 17 months). In a univariate analysis of all patients, older age (p < 0.05), high EORTC score (p < 0.001), non-epithelioid histological subtype (p < 0.001), high T stage (p < 0.001), positive N/M status (p < 0.05, p < 0.001), advanced TNM stage (p < 0.001), non-surgical treatment (p < 0.001), and high SUVmax (p < 0.001), MTV (p < 0.001), or TLG (p < 0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14–2.48; p < 0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34–0.95; p < 0.05), and high TLG (HR: 1.97, 95% CI: 1.14–3.44; p < 0.05) as independent negative predictors. Conclusions: Pretreatment volume-based quantitative {sup 18}F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.

  9. Identification of cancer stem cell markers in human malignant mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Ghani, Farhana Ishrat; Yamazaki, Hiroto; Iwata, Satoshi; Okamoto, Toshihiro [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Aoe, Keisuke; Okabe, Kazunori; Mimura, Yusuke [Departments of Medical Oncology, Yamaguchi-Ube Medical Center, Yamaguchi (Japan); Fujimoto, Nobukazu; Kishimoto, Takumi [Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama (Japan); Yamada, Taketo [Department of Pathology, Keio University School of Medicine, Tokyo (Japan); Xu, C. Wilson [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-01-14

    Research highlights: {yields} We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. {yields} SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. {yields} SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony. {yields} The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. In addition, CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

  10. Proteomic study of benign and malignant pleural effusion.

    Science.gov (United States)

    Li, Hongqing; Tang, Zhonghao; Zhu, Huili; Ge, Haiyan; Cui, Shilei; Jiang, Weiping

    2016-06-01

    Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. This study used proteomics technology to acquire and analyze the protein profiles of the benign and malignant pleural effusion, to seek useful protein biomarkers with diagnostic value and to establish the diagnostic model. We chose the weak cationic-exchanger magnetic bead (WCX-MB) to purify peptides in the pleural effusion, used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to obtain peptide expression profiles from the benign and malignant pleural effusion samples, established and validated the diagnostic model through a genetic algorithm (GA) and finally identified the most promising protein biomarker. A GA diagnostic model was established with spectra of 3930.9 and 2942.8 m/z in the training set including 25 malignant pleural effusion and 26 benign pleural effusion samples, yielding both 100 % sensitivity and 100 % specificity. The accuracy of diagnostic prediction was validated in the independent testing set with 58 malignant pleural effusion and 34 benign pleural effusion samples. Blind evaluation was as follows: the sensitivity was 89.6 %, specificity 88.2 %, PPV 92.8 %, NPV 83.3 % and accuracy 89.1 % in the independent testing set. The most promising peptide biomarker was identified successfully: Isoform 1 of caspase recruitment domain-containing protein 9 (CARD9), with 3930.9 m/z, was decreased in the malignant pleural effusion. This model is suitable to discriminate benign and malignant pleural effusion and CARD9 can be used as a new peptide biomarker.

  11. Study of the interaction of enzyme Heparanase 1 (HPSE1) active with deoxyribonucleic acids

    International Nuclear Information System (INIS)

    Cid, Gisele da Silva

    2016-01-01

    The human heparanase 1 (HPSE 1) is a protein with multiple functions and has emerged as a promising therapeutic target in the context of antitumor therapy. This fact is due to its clinical relevance in the tumor development and progression, as determined by their enzymatic ability to degrade heparan sulfate (HS), the main constituent of the extracellular matrix, providing a tumor microenvironment to tumor dissemination. In addition, this protein plays a significant role in the increase of tumor cells migration ionizing radiation dose delivery in radiotherapy from the increase in the expression levels of HPSE1. In order to evaluate in more detail the functions of active HPSE1, it has been proposed to characterize the interaction of human heparanase protein 1 with deoxyribonucleic acids. Our results are original and point to a new function of HPSE1 of the endonuclease type. (author)

  12. Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Pehlivan, Berrin; Topkan, Erkan; Onal, Cem; Nursal, Gul Nihal; Yuksel, Oznur; Dolek, Yemliha; Yavuz, Melek Nur; Yavuz, Ali Aydin

    2009-01-01

    When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group. Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes. In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% ± 28.4%, mean CTV decreased by 38.7% ± 24.7%, mean PTV1 decreased by 31.1% ± 23.1%, and mean PTV2 decreased by 40.0% ± 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients. This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond

  13. Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma.

    Science.gov (United States)

    Truini, Anna; Coco, Simona; Nadal, Ernest; Genova, Carlo; Mora, Marco; Dal Bello, Maria Giovanna; Vanni, Irene; Alama, Angela; Rijavec, Erika; Biello, Federica; Barletta, Giulia; Merlo, Domenico Franco; Valentino, Alessandro; Ferro, Paola; Ravetti, Gian Luigi; Stigliani, Sara; Vigani, Antonella; Fedeli, Franco; Beer, David G; Roncella, Silvio; Grossi, Francesco

    2017-09-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date no molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed using biopsies on 27 unresected MPM patients with distinct clinical outcome: 15 patients had short survival (OS36 months). Three prognostic miRNAs (mir-99a, let-7c, and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High-risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high-risk score was independently associated with shorter OS (HR=3.14; 95% CI, 1.18-8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

  14. Asbestos-related pleuropulmonary diseases: iconographic essay

    International Nuclear Information System (INIS)

    Gustavo de Souza Portes Meirelles; Rodrigues, Reynaldo Tavares; Nery, Luiz Eduardo

    2007-01-01

    The aim of this study is to illustrate the main imaging findings of asbestos-related diseases. Pleural and pulmonary asbestos-related diseases range from benign conditions, like pleural effusion and pleural plaques, to some neoplasias, such as lung cancer and malignant mesothelioma. Pleural effusion is the earliest finding after asbestos exposure, but the imaging findings are not specific. Diffuse pleural thickening involves the visceral pleura and pleural plaques are considered to be hallmarks of exposure. Asbestosis is the pulmonary fibrosis due to asbestos. Rounded atelectasis is a peripheral lung collapse in these individuals, generally related to pleural disease. Some neoplasias, like lung carcinoma and pleural mesothelioma, are more prevalent in asbestos-exposed subjects. (author)

  15. Evaluation of lymphocytic exudative pleural effusion with pleural biopsy

    International Nuclear Information System (INIS)

    Khurram, M.; Jaffery, A.H.; Khar, Hamama-tul-Bushra; Malik, M.F.; Javed, S.; Burki, U.F.; Khan, B.A.; Ali, A.

    2002-01-01

    Objective: Evaluation of lymphocytic exudative pleural effusion by histopathological examination of pleural biopsy in patients with suspected tuberculous or malignant pleural effusion. Place and Duration of Study: The study was conducted at Pulmonology Department, Pakistan Institute of Medical Sciences, Islamabad and DHQ Teaching Hospital, Rawalpindi for two years 1999-2000. Subjects and Methods: A total of 120 patients with exudative pleural effusion underwent closed pleural biopsy with Abram's needle in standard way. Average 4 biopsy specimens were obtained in each patient which were examined histopathologically. Patients in whom a definite diagnosis was not possible were further investigated with repeat pleural biopsy, sputum examinations, bronchoscopy etc. Results definite histopathological diagnosis with pleural biopsy was possible in 59 (49.16% patients, including 13 diagnosed on repeat pleural biopsy. Two commonest diagnoses made were tuberculosis and adenocarcinoma, 64.40% and 13.55% respectively. Conclusion: Histopathological evaluation of pleural biopsy specimens can lead to diagnosis in 49.16% patients with exudative lymphocytic pleural effusion. (author)

  16. [Sarcoidosis related pleural effusion: 6 case reports and literatures review].

    Science.gov (United States)

    Wang, Feng; Tong, Zhaohui; Wang, Zhen; Wang, Xiaojuan; Xu, Lili

    2015-02-01

    To summarize the clinical features and the diagnosis-treatment points of sarcoidosis related pleural effusion. Six typical sarcoidosis related pleural effusion cases with pathological evidence were reviewed, and the clinical data of these cases were retrospectively analyzed and the related literatures were reviewed. The literature review was carried out respectively with "sarcoidosis", "pleural disease" and "pleural effusion" as the keywords in CNKI and PubMed database by January 2014. Six cases, including 1 male and 5 females, with sarcoidosis related pleural effusions were reported. 3 cases had bilateral effusions, 2 cases had left effusion and 1 case had right effusion. The pleural effusion routine test had a low specificity, which demonstrated that the fluid was exudate and consisted with large number of lymphocytes. 3 of these cases were diagnosed by medical thoracoscopy. Medical thoracoscopy revealed that pleural involvement was variable with multiple nodulespresent in some cases and subtle change in others. A total of 28 literatures and 92 cases with pleural involvement in sarcoidosis were retrieved from CNKI and PubMed database (time range: 2004.1-2014.1), including 59 cases of pleural effusion, 29 cases of pleural thickening, 3 cases of pneumothorax and 1 case of nodules in pleura. Pleural involvement in sarcoidosis was often misdiagnosed or mistreated as tuberculous pleurisy because the routine tests regarding pleural effusion usually had a low specificity. Medical thoracoscopy could provide clinicians with important clues to assist differentiation of the cause for non-conclusive pleural effusion in this situation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. The impact of asbestos exposure in Swedish construction workers.

    Science.gov (United States)

    Järvholm, Bengt; Englund, Anders

    2014-01-01

    To study the occurrence of pleural mesothelioma as a measure of the impact on health from asbestos exposure in the construction industry. The occurrence of pleural mesothelioma in different occupations, time periods and birth cohorts was studied in a cohort of construction workers. They were prospectively followed after they had participated in health examinations between 1971 and 1993. The analysis was restricted to men and in total 367,568 men was included in the analysis. In total there were 419 cases of pleural mesotheliomas between 1972 and 2009. As expected the age adjusted incidence was high in insulation workers and plumbers (39 and 16 cases per 100,000 person-years, respectively). However, only 21% of the pleural mesotheliomas occurred in those occupational groups. Occupational groups with many cases of pleural mesothelioma were concrete workers (N = 56), wood workers (N = 55), painters (N = 32), electricians (N = 48), and foremen (N = 37). The highest risk was in birth cohorts born between 1935 and 1945. Between 1995 and 2009 around one-third of all male cases in the country occurred in this birth cohort. The risk seemed to decrease considerably in men born after 1955. In Sweden a considerable proportion of pleural mesotheliomas occur among construction workers; and not only in jobs traditionally associated with asbestos exposure such as insulators and plumbers but also among electricians, for example. The results shows that asbestos exposure occurs in many occupational groups, indicating that safe handling of asbestos is a very difficult or even impossible task in the construction industry. © 2013 Wiley Periodicals, Inc.

  20. Unusual contiguous soft tissue spread of advanced malignant mesothelioma detected by FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu Yang; Edwards, Jamie; Williams, Hadyn; Hao, Zhong Lin; Khleif, Samir; Pucar, Darko [Medical College of Georgia at Augusta UniversityAugusta (United States)

    2017-06-15

    Malignant pleural mesothelioma (MPM) is a tumor of mesodermal origin that arises from the serosa of the pleura, peritoneum, pericardium or tunica vaginalis. MPM is well known to have a poor prognosis with a median survival time of 12 months. Accurate diagnosis, staging and restaging of MPM are crucial with [18F] flurodeoxy-D-glucose positron emission tomography (FDG PET/CT) playing an increasingly important role. Here we report a case of MPM with unusual contiguous soft tissue spread of the tumor along the dermal and fascial planes characterized by PET/CT. Given that the loco-regional tumor in the thorax was under control on PET/CT, the death of the patient was most likely associated with physiologic or metabolic causes associated with an extra-thoracic tumor.

  1. Ultrasound guided pleural biopsy in undiagnosed exudative pleural effusion patients

    OpenAIRE

    Adel S. Ahmed; Mostafa I. Ragab; Alaa eldin M. Elgazaar; Nagwan A. Ismail

    2016-01-01

    Introduction: Pleural biopsy for pathological confirmation is the standard diagnostic procedure for pleural diseases, transthoracic ultrasonography (TUS) has evolved as an important imaging tool for diagnosing pleural and pulmonary conditions. Aim of the study: To assess the diagnostic yield of TUS guided pleural biopsy versus both CT guided and thoracoscopic pleural biopsy in the diagnosis of undiagnosed exudative pleural effusion. Patients and methods: The study was conducted at chest...

  2. Image diagnosis of malignant mesothelioma

    International Nuclear Information System (INIS)

    Niimi, Akiko; Ueno, Keiko; Isobe, Yoshinori; Hirayama, Akira

    1987-01-01

    3 cases of malignant mesothelioma confirmed by pathological examination were reported. CT showed solid mass with moderate enhancement by contrast medium. CT appears to be a very useful tool to make a diagnosis of malignant mesothelioma. (author)

  3. Angiography of omental mesothelioma

    International Nuclear Information System (INIS)

    Marini, K.; Walter, J.F.

    1984-01-01

    Angiographic features of three cases of omental mesothelioma are presented. These lesions appeared mildly or moderately hypervascular without arteriovenous shunting or arterial encasement. The predominant feeding arteries were the right and left gastroepiploics. Since arteriography may be performed in the evaluation of the often nonspecific presenting symptoms of patients with abdominal mesothelioma, radiologists should be aware of these abnormalities

  4. Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.

    Science.gov (United States)

    Marinaccio, Alessandro; Binazzi, Alessandra; Bonafede, Michela; Corfiati, Marisa; Di Marzio, Davide; Scarselli, Alberto; Verardo, Marina; Mirabelli, Dario; Gennaro, Valerio; Mensi, Carolina; Schallemberg, Gert; Merler, Enzo; Negro, Corrado; Romanelli, Antonio; Chellini, Elisabetta; Silvestri, Stefano; Cocchioni, Mario; Pascucci, Cristiana; Stracci, Fabrizio; Ascoli, Valeria; Trafficante, Luana; Angelillo, Italo; Musti, Marina; Cavone, Domenica; Cauzillo, Gabriella; Tallarigo, Federico; Tumino, Rosario; Melis, Massimo

    2015-09-01

    Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure. The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100,000) for men and 1.45 for women, respectively. Among the 15,845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12,065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. 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.

  6. Asbestos-related malignancy

    International Nuclear Information System (INIS)

    Antmann, K.; Aisner, J.

    1986-01-01

    This book contains 20 chapters. Some of the chapter titles are: The Radiology of Asbestosis and Related Neoplasms; Computed Tomography and Malignant Mesothelioma; Radiation Therapy for Pleural Mesothelioma; and Radiation Therapy of Peritoneal Mesothelioma

  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. SU-G-JeP3-10: Update On a Real-Time Treatment Guidance System Using An IR Navigation System for Pleural PDT

    International Nuclear Information System (INIS)

    Kim, M; Penjweini, R; Zhu, T

    2016-01-01

    Purpose: Photodynamic therapy (PDT) is used in conjunction with surgical debulking of tumorous tissue during treatment for pleural mesothelioma. One of the key components of effective PDT is uniform light distribution. Currently, light is monitored with 8 isotropic light detectors that are placed at specific locations inside the pleural cavity. A tracking system with real-time feedback software can be utilized to improve the uniformity of light in addition to the existing detectors. Methods: An infrared (IR) tracking camera is used to monitor the movement of the light source. The same system determines the pleural geometry of the treatment area. Software upgrades allow visualization of the pleural cavity as a two-dimensional volume. The treatment delivery wand was upgraded for ease of light delivery while incorporating the IR system. Isotropic detector locations are also displayed. Data from the tracking system is used to calculate the light fluence rate delivered. This data is also compared with in vivo data collected via the isotropic detectors. Furthermore, treatment volume information will be used to form light dose volume histograms of the pleural cavity. Results: In a phantom study, the light distribution was improved by using real-time guidance compared to the distribution when using detectors without guidance. With the tracking system, 2D data can be collected regarding light fluence rather than just the 8 discrete locations inside the pleural cavity. Light fluence distribution on the entire cavity can be calculated at every time in the treatment. Conclusion: The IR camera has been used successfully during pleural PDT patient treatment to track the motion of the light source and provide real-time display of 2D light fluence. It is possible to use the feedback system to deliver a more uniform dose of light throughout the pleural cavity.

  9. SU-G-JeP3-10: Update On a Real-Time Treatment Guidance System Using An IR Navigation System for Pleural PDT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, M; Penjweini, R; Zhu, T [University Pennsylvania, Philadelphia, PA (United States)

    2016-06-15

    Purpose: Photodynamic therapy (PDT) is used in conjunction with surgical debulking of tumorous tissue during treatment for pleural mesothelioma. One of the key components of effective PDT is uniform light distribution. Currently, light is monitored with 8 isotropic light detectors that are placed at specific locations inside the pleural cavity. A tracking system with real-time feedback software can be utilized to improve the uniformity of light in addition to the existing detectors. Methods: An infrared (IR) tracking camera is used to monitor the movement of the light source. The same system determines the pleural geometry of the treatment area. Software upgrades allow visualization of the pleural cavity as a two-dimensional volume. The treatment delivery wand was upgraded for ease of light delivery while incorporating the IR system. Isotropic detector locations are also displayed. Data from the tracking system is used to calculate the light fluence rate delivered. This data is also compared with in vivo data collected via the isotropic detectors. Furthermore, treatment volume information will be used to form light dose volume histograms of the pleural cavity. Results: In a phantom study, the light distribution was improved by using real-time guidance compared to the distribution when using detectors without guidance. With the tracking system, 2D data can be collected regarding light fluence rather than just the 8 discrete locations inside the pleural cavity. Light fluence distribution on the entire cavity can be calculated at every time in the treatment. Conclusion: The IR camera has been used successfully during pleural PDT patient treatment to track the motion of the light source and provide real-time display of 2D light fluence. It is possible to use the feedback system to deliver a more uniform dose of light throughout the pleural cavity.

  10. 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

  11. Pleural effusion

    International Nuclear Information System (INIS)

    Jimenez Q, Andres; Camacho D, Fidel

    2009-01-01

    The pleural effusion is defined as the abnormal accumulation of liquid in the pleural space that produces to itself for increase in the production or decrease of the drainage, common reasons in clinics disorders. Inside the reasons of the increase of the production we can enunciate an increase of the capillary pleural permeability, decrease of the oncotic pressure capillary and increase of the hydrostatic capillary pressure, there are less clear the reasons of the decrease of the drainage but are outlined the alteration of the lymphatic pleural contractibility , infiltration of vessels and lymphatic nodules for neoplasia diseases and alterations to pleural level that they should prevent that the this liquid touch the lymphatic pores. The objective of this review is the analysis of the physiological bases of the pleura and the production of the pleural liquid, the physiological aspects of the pleural effusion, the approach of the diagnose and the medical and surgical managing of the same one for the different reasons that produce it.

  12. Pericardial Effusion due to Primary Malignant Pericardial Mesothelioma: A Common Finding but an Uncommon Cause

    Directory of Open Access Journals (Sweden)

    Valery Istomin

    2016-01-01

    Full Text Available This case report describes a 37-year-old female who was admitted to our Emergency Department because of shortness of breath. On physical examination, she had dyspnea and tachycardia and blood pressure was 80/50 mmHg with a pulsus paradoxus of 22 mmHg. Neck veins were distended, heart sounds were distant, and dullness was found on both lung bases. Her chest X-ray revealed bilateral pleural effusion and cardiomegaly. On both computed tomography and echocardiography the heart was of normal size and a large pericardial effusion was noted. The echocardiogram showed signs of impending tamponade, so the patient underwent an emergent pericardiocentesis. No infectious etiology was found and she was assumed to have viral pericarditis and was treated accordingly. However, when the pericardial effusion recurred and empirical therapy for tuberculosis failed, a pericardial window was performed. A typical staining pattern for mesothelioma was found on her pericardial biopsy specimen. Since no other mesodermal tissue was affected, a diagnosis of primary malignant pericardial mesothelioma was made. Chemotherapy was not effective and she passed away a year after the diagnosis was made. This case highlights the difficulties in diagnosing this uncommon disease in patients that present with the common finding of pericardial effusion.

  13. 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.

  14. The β-d-Endoglucuronidase Heparanase Is a Danger Molecule That Drives Systemic Inflammation and Correlates with Clinical Course after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair: Lessons Learnt from Mice and Men

    Directory of Open Access Journals (Sweden)

    Lukas Martin

    2017-06-01

    Full Text Available Thoracoabdominal aortic aneurysm (TAAA is a highly lethal disorder requiring open or endovascular TAAA repair, both of which are rare, but extensive and complex surgical procedures associated with a significant systemic inflammatory response and high post-operative morbidity and mortality. Heparanase is a β-d-endoglucuronidase that remodels the endothelial glycocalyx by degrading heparan sulfate in many diseases/conditions associated with systemic inflammation including sepsis, trauma, and major surgery. We hypothesized that (a perioperative serum levels of heparanase and heparan sulfate are associated with the clinical course after open or endovascular TAAA repair and (b induce a systemic inflammatory response and renal injury/dysfunction in mice. Using a reverse-translational approach, we assessed (a the serum levels of heparanase, heparan sulfate, and the heparan sulfate proteoglycan syndecan-1 preoperatively as well as 6 and 72 h after intensive care unit (ICU admission in patients undergoing open or endovascular TAAA repair and (b laboratory and clinical parameters and 90-day survival, and (c the systemic inflammatory response and renal injury/dysfunction induced by heparanase and heparan sulfate in mice. When compared to preoperative values, the serum levels of heparanase, heparan sulfate, and syndecan-1 significantly transiently increased within 6 h of ICU admission and returned to normal within 72 h after ICU admission. The kinetics of any observed changes in heparanase, heparan sulfate, or syndecan-1 levels, however, did not differ between open and endovascular TAAA-repair. Postoperative heparanase levels positively correlated with noradrenalin dose at 12 h after ICU admission and showed a high predictive value of vasopressor requirements within the first 24 h. Postoperative heparan sulfate showed a strong positive correlation with interleukin-6 levels day 0, 1, and 2 post-ICU admission and a strong negative correlation with

  15. [Non-tuberculous pleural infections versus tuberculous pleural infections].

    Science.gov (United States)

    Horo, K; N'Gom, A; Ahui, B; Brou-Gode, C; Anon, J-C; Diaw, A; Bemba, P; Foutoupouo, K; Djè Bi, H; Ouattara, P; Kouassi, B; Koffi, N; Aka-Danguy, E

    2012-03-01

    In countries where tuberculosis is endemic, the main differential diagnosis for pleural infection by common bacteria is pleural tuberculosis. The purpose of our study was to determine the differences between pleural infection by common bacteria and that caused by pleural tuberculosis. Our study was a retrospective analysis and compared the characteristics of confirmed pleural infection by common bacteria (PIB) and that due to pleural tuberculosis (PT). For the PIB, the signs evolved for 2.4 ± 1.4 weeks versus 5.6 ± 2.2 weeks for the PT (P=0.01). In multivariate analysis, for PIB the onset of symptoms was more abrupt (OR=3.8 [1.5; 9.9]; P=0.01), asthenia was less frequent (OR=0.3 [0.1; 0.9]; P=0.03), pleural liquid was more purulent (OR=40.0 [15.0; 106.7]; Ppleural effusions caused by tuberculosis (TB) and those due to other bacterial infections. However, they are not sufficiently sensitive and therefore the search for the tuberculous bacillus must be systematic while waiting for implementation of new diagnostic tests for the organism. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  16. Calcified pleural scars and pleural empyema with mural calcification

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, W.G.H.; Huebener, K.H.

    1981-06-01

    The differential diagnosis between calcified pleural scars and pleural empyemas with mural calcification was studied by computer tomography, bearing in mind the patient's history. In view of the high complication rate of pleural empyemas, such as internal or external fistulae, it is desirable to elucidate every form of pleural shadowing which is more than 20 mm thick. Criteria are offered, which permit the differentiation of the pleural changes by means of conventional radiological examinations. Valuable additional information can be obtained by computer tomography. Forty-nine patients with calcification in the pleura were found among 1.900 chest x-rays which had been examined. Out of these, seven had a pleural empyema. In one case an echinococcus cyst with mural calcification was punctured under X-ray control.

  17. Calcified pleural scars and pleural empyema with mural calcification

    International Nuclear Information System (INIS)

    Schmitt, W.G.H.; Huebener, K.H.

    1981-01-01

    The differential diagnosis between calcified pleural scars and pleural empyemas with mural calcification was studied by computer tomography, bearing in mind the patient's history. In view of the high complication rate of pleural empyemas, such as internal or external fistulae, it is desirable to elucidate every form of pleural shadowing which is more than 20 mm thick. Criteria are offered, which permit the differentiation of the pleural changes by means of conventional radiological examinations. Valuable additional information can be obtained by computer tomography. Forty-nine patients with calcification in the pleura were found among 1.900 chest x-rays which had been examined. Out of these, seven had a pleural empyema. In one case an echinococcus cyst with mural calcification was punctured under X-ray control. (orig.) [de

  18. Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.

    Directory of Open Access Journals (Sweden)

    Tünde Szatmári

    Full Text Available Malignant pleural mesothelioma is a highly malignant tumor, originating from mesothelial cells of the serous cavities. In mesothelioma the expression of syndecan-1 correlates to epithelioid morphology and inhibition of growth and migration. Our previous data suggest a complex role of syndecan-1 in mesothelioma cell proliferation although the exact underlying molecular mechanisms are not completely elucidated. The aim of this study is therefore to disclose critical genes and pathways affected by syndecan-1 in mesothelioma; in order to better understand its importance for tumor cell growth and proliferation. We modulated the expression of syndecan-1 in a human mesothelioma cell line via both overexpression and silencing, and followed the transcriptomic responses with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied pathway analysis using Ingenuity Pathway Analysis (IPA and a novel method of network enrichment analysis (NEA which elucidated signaling relations between differentially expressed genes and pathways acting via various molecular mechanisms. Syndecan-1 overexpression had profound effects on genes involved in regulation of cell growth, cell cycle progression, adhesion, migration and extracellular matrix organization. In particular, expression of several growth factors, interleukins, and enzymes of importance for heparan sulfate sulfation pattern, extracellular matrix proteins and proteoglycans were significantly altered. Syndecan-1 silencing had less powerful effect on the transcriptome compared to overexpression, which can be explained by the already low initial syndecan-1 level of these cells. Nevertheless, 14 genes showed response to both up- and downregulation of syndecan-1. The "cytokine - cytokine-receptor interaction", the TGF-β, EGF, VEGF and ERK/MAPK pathways were enriched in both experimental settings. Most strikingly, nearly all analyzed pathways

  19. Pleural pressure swing and lung expansion after malignant pleural effusion drainage: the benefits of high-temporal resolution pleural manometry.

    Science.gov (United States)

    Boshuizen, Rogier C; Sinaasappel, Michiel; Vincent, Andrew D; Goldfinger, Vicky; Farag, Sheima; van den Heuvel, Michel M

    2013-07-01

    Malignant pleural effusion is a common complication in end-stage cancer patients and can cause severe dyspnea. Therapeutic thoracentesis is often limited to 1 to 1.5 L. Pleural manometry can be used to recognize a not-expanded lung. Interval pleural pressure measurements with a high temporal resolution were performed after each removal of 200 mL of fluid to observe pleural pressure swings. Pleural elastance was defined as the difference in pleural pressure divided by the change in volume. Chest x-rays were performed to evaluate lung expansion, reexpansion pulmonary edema, and fluid residue. Thirty-four procedures in 30 patients were eligible for analysis. Four patients had incomplete lung expansion after drainage. No reexpansion pulmonary edema was observed. Pleural pressure swing after 200 mL drainage was higher when the lung did not expand. Pleural elastance after removal of 500 mL was higher in the not-expanded subgroup. We demonstrated that a high pleural pressure swing after removal of only 200 mL was related to incomplete lung expansion. We confirmed the association between pleural elastance and lung expansion.

  20. Diagnostic yield and safety of closed needle pleural biopsy in exudative pleural effusion.

    Science.gov (United States)

    Rajawat, Govind Singh; Batra, Supreet; Takhar, Rajendra Prasad; Rathi, Lalit; Bhandari, Chand; Gupta, Manohar Lal

    2017-01-01

    Closed pleural biopsy was previously considered a procedure of choice in cases of undiagnosed pleural effusion with good efficacy. Currently, the closed pleural biopsy has been replaced by thoracoscopic biopsy but not easily available in resource-limited setups. The objective of this study was to analyze the diagnostic yield and safety of closed needle pleural biopsy in exudative pleural effusion and assessment of patients' characteristics with the yield of pleural biopsy. This was a cross-sectional study. This study was conducted at Institute of Respiratory Diseases, SMS Medical College, Jaipur, a tertiary care center of West India. A total of 250 cases of pleural effusion were evaluated with complete pleural fluid biochemical, microbiological, and cytological examination. Out of these 250 patients, 59 were excluded from the study as the diagnosis could be established on initial pleural fluid examination. The remaining (191) patients were considered for closed pleural biopsy with Abrams pleural biopsy needle. The main outcome measure was diagnostic yield in the form of confirming diagnosis. Out of the 191 patients with exudative lymphocytic pleural effusion, 123 (64.40%) were diagnosed on the first pleural biopsy. Among the remaining 68 patients, 22 patients had repeat pleural biopsy with a diagnostic yield of 59.9%. The overall pleural biopsy could establish the diagnosis in 136 (71.20%) patients with pleural effusion. The most common diagnosis on pleural biopsy was malignancy followed by tuberculosis. Closed pleural biopsy provides diagnostic yield nearly comparative to thoracoscopy in properly selected patients of pleural effusions. In view of good yield, low cost, easy availability, and very low complication rate, it should be used routinely in all cases of undiagnosed exudative lymphocytic pleural effusion. There was no comparison with a similar group undergoing thoracoscopic pleural biopsy.

  1. Continuing increase in mesothelioma mortality in Britain.

    Science.gov (United States)

    Peto, J; Hodgson, J T; Matthews, F E; Jones, J R

    1995-03-04

    Mesothelioma is closely related to exposure to asbestos, and mesothelioma mortality can be taken as an index of past exposure to asbestos in the population. We analysed mesothelioma mortality since 1968 to assess the current state of the mesothelioma epidemic, and to predict its future course. We found that rates of mesothelioma in men formed a clear pattern defined by age and date of birth. Rates rose steeply with age showing a very similar pattern in all five-year birth cohorts. By date of birth, rates increased from mid-1893 to mid-1948, and then fell. Relative to the 1943-48 cohort, the risk for the 1948-53 cohort is 0.79 and for the 1953-58 cohort 0.48. Despite these falls, if the age profile of rates for these cohorts follows the pattern of past cohorts, their predicted lifetime mesothelioma risks will be 1.3%, 1.0%, and 0.6%. Combining projections for all cohorts results in a peak of annual male mesothelioma deaths in about the year 2020 of between 2700 and 3300 deaths. If diagnostic trend is responsible for a 20% growth in recorded cases every 5 years--an extreme but arguable case--and if this trend has now ceased, the peak of annual male deaths will be reduced to 1300, reached around the year 2010. Analysis of occupations recorded on death certificates indicate that building workers, especially plumbers and gas fitters, carpenters and electricians are the largest high-risk group. These data indicate that mesothelioma deaths will continue to increase for at least 15 and more likely 25 years. For the worst affected cohorts--men born in the 1940s--mesothelioma may account for around 1% of all deaths. Asbestos exposure at work in construction and building maintenance will account for a large proportion of these deaths, and it is important that such workers should be aware of the risks and take appropriate precautions.

  2. Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway

    International Nuclear Information System (INIS)

    Yu, Shengjin; Lv, Huiming; Zhang, He; Jiang, Yu; Hong, Yu; Xia, Rongjun; Zhang, Qifang; Ju, Weiwei; Jiang, Lili; Ou, Geng; Zhang, Jinhui; Wang, Shujing; Zhang, Jianing

    2017-01-01

    Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERK) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis. - Highlights: • SDC-1 anchors VEGF-C via its HS chains. • Secreted HPA-1 from hepatocarcinoma cell cleaves HS chains of SDC-1. • The shedding of SDC-1 HS chains releases VEGF-C from SDC-1/VEGF-C complex. • LMWH inhibits VEGF-C secretion through stabilizing SDC-1/VEGF-C complex. • VEGF-C secretion from hepatocarcinoma cell facilitates LEC growth via ERK signaling.

  3. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

    Directory of Open Access Journals (Sweden)

    Edward Hammond

    Full Text Available PG545 is a clinically relevant heparan sulfate (HS mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis led us to examine the effect of PG545 on the progression of both primary tumor growth and the spontaneously metastasizing disease in the 4T1 syngeneic breast carcinoma model in a non-surgical and surgical (mastectomy setting. PG545 significantly inhibited primary tumor growth but importantly also inhibited lung metastasis in treated mice, an effect not observed with the tyrosine kinase inhibitor sorafenib. Importantly, PG545 significantly enhanced overall survival compared to vehicle control and the sorafenib group, suggesting PG545's inhibitory effect on heparanase is indeed a critical attribute to induce anti-metastatic activity. In addition to blocking a common angiogenic signalling pathway in tumor cells, the expression of heparanase in the primary tumor and lung was also significantly reduced by PG545 treatment. These results support the ongoing development of PG545 and highlight the potential utility in metastatic disease settings.

  4. [Recurrent benign cystic peritoneal mesothelioma].

    Science.gov (United States)

    Stroescu, C; Negulescu, Raluca; Herlea, V; David, L; Ivanov, B; Nitipir, Cornelia; Popescu, I

    2008-01-01

    The benign cystic peritoneal mesothelioma (BCPM) is a rare neoplasm affecting mainly females at reproductive age. The natural history and physiopathology of the BCPM are not entirely known. It is mainly characterized by the lack of malignant elements, no tendency to metastasis and by a pervasive tendency to generate local recurrences after surgical removal. The clinical manifestations are insidious, uncharacteristic; the benign cystic peritoneal mesothelioma is often discovered during a surgical procedure addressing another condition. Imaging tests can raise the suspicion of BCPM but the diagnostic can only be confirmed by histopathological examination corroborated with an immunohistochemical analysis. There are no long term studies dictating a single therapeutic attitude but a high risk of local recurrences and the possibility of transformation into malignant mesothelioma have lead to the current tendency towards an aggressive treatment of the tumor. We present the case of a recurrent benign cystic peritoneal mesothelioma in a 40 years old female patient, emphasizing the therapeutic approach and the role of radical surgery in the treatment of BPCM.

  5. Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Johnson, Thomas G; Schelch, Karin; Cheng, Yuen Y; Williams, Marissa; Sarun, Kadir H; Kirschner, Michaela B; Kao, Steven; Linton, Anthony; Klebe, Sonja; McCaughan, Brian C; Lin, Ruby C Y; Pirker, Christine; Berger, Walter; Lasham, Annette; van Zandwijk, Nico; Reid, Glen

    2018-02-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM. Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted. MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion. MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. Ultrasound guided pleural biopsy in undiagnosed exudative pleural effusion patients

    Directory of Open Access Journals (Sweden)

    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.

  7. Support vector machine for the diagnosis of malignant mesothelioma

    Science.gov (United States)

    Ushasukhanya, S.; Nithyakalyani, A.; Sivakumar, V.

    2018-04-01

    Harmful mesothelioma is an illness in which threatening (malignancy) cells shape in the covering of the trunk or stomach area. Being presented to asbestos can influence the danger of threatening mesothelioma. Signs and side effects of threatening mesothelioma incorporate shortness of breath and agony under the rib confine. Tests that inspect within the trunk and belly are utilized to recognize (find) and analyse harmful mesothelioma. Certain elements influence forecast (shot of recuperation) and treatment choices. In this review, Support vector machine (SVM) classifiers were utilized for Mesothelioma sickness conclusion. SVM output is contrasted by concentrating on Mesothelioma’s sickness and findings by utilizing similar information set. The support vector machine algorithm gives 92.5% precision acquired by means of 3-overlap cross-approval. The Mesothelioma illness dataset were taken from an organization reports from Turkey.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; van der Zwan, Jan Maarten; Izarzugaza, Isabel; Jaal, Jana; Treasure, Tom; Foschi, Roberto; Ricardi, Umberto; Groen, Harry; Tavilla, Andrea; Ardanaz, Eva

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  10. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; Zwan, J.M.V.D.; Izarzugaza, I.; Jaal, J.; Treasure, T.; Foschi, R.; Ricardi, U.; Groen, H.; Tavilla, A.; Ardanaz, E.

    2012-01-01

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  11. Pleural mechanics and fluid exchange.

    Science.gov (United States)

    Lai-Fook, Stephen J

    2004-04-01

    The pleural space separating the lung and chest wall of mammals contains a small amount of liquid that lubricates the pleural surfaces during breathing. Recent studies have pointed to a conceptual understanding of the pleural space that is different from the one advocated some 30 years ago in this journal. The fundamental concept is that pleural surface pressure, the result of the opposing recoils of the lung and chest wall, is the major determinant of the pressure in the pleural liquid. Pleural liquid is not in hydrostatic equilibrium because the vertical gradient in pleural liquid pressure, determined by the vertical gradient in pleural surface pressure, does not equal the hydrostatic gradient. As a result, a viscous flow of pleural liquid occurs in the pleural space. Ventilatory and cardiogenic motions serve to redistribute pleural liquid and minimize contact between the pleural surfaces. Pleural liquid is a microvascular filtrate from parietal pleural capillaries in the chest wall. Homeostasis in pleural liquid volume is achieved by an adjustment of the pleural liquid thickness to the filtration rate that is matched by an outflow via lymphatic stomata.

  12. Heparanase-2 and syndecan-1 in colon cancer: the ugly ducklings or the beautiful swans?

    Science.gov (United States)

    Giordano, Ricardo José

    2008-08-01

    Syndecan expression, or the lack thereof by tumor cells, has been associated with poor prognosis in several types of cancer, including colorectal cancer. Syndecan is a heparan sulfate proteoglycan involved in tumor adhesion, invasion, and metastasis. In addition, the expression of the enzyme heparanase by cancer cells correlates with malignant transformation and metastasis. Given the prominent role of syndecan and heparanase in physiological and pathological processes, they are promising molecular targets in the development of diagnostic methods and drugs for cancer and other diseases. A study in this issue of the European Journal of Gastroenterology & Hepatology reports the expression of syndecan-1 (Syn-1) and HPA2 in human colorectal cancer samples. These results confirm earlier observations that Syn-1 is downregulated by colorectal carcinoma cells but raise questions about its prognostic value. This study is also the first report on the upregulation of HPA2 in human cancer samples. HPA2 and Syn-1 expression by colorectal cancer tumor cells and the possible implications in disease progression are discussed.

  13. Parapneumonic pleural effusion

    Science.gov (United States)

    Pleural effusion - pneumonia ... Pneumonia, most commonly from bacteria, causes parapneumonic pleural effusion. ... Call your provider if you have symptoms of pleural effusion. Call your provider or go to the emergency ...

  14. Peritoneal Mesothelioma

    Science.gov (United States)

    ... Recognition Societies Percentage Donations Other Giving/Fundraising Opportunities Bitcoin Donation Form The Meso Foundation saves lives by ... Recognition Societies Percentage Donations Other Giving/Fundraising Opportunities Bitcoin Donation Form © 2017 Mesothelioma Applied Research Foundation, Inc. ...

  15. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

    Full Text Available Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated median survival of 40 to 90 months and 5-year survival of 30% to 60% after the combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This improvement in survival has prompted new searches into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

  16. Mesothelioma - A rare cause of dysphagia

    Directory of Open Access Journals (Sweden)

    Vishwanathan Swati

    2016-08-01

    Full Text Available A 81-year-old elderly Caucasian male presented with progressive dysphagia and unintentional weight loss over four months. His history was significant for asbestos exposure; however there was no history of asbestos related lung disease. Barium swallow showed achalasia and a subsequent CT chest showed a posterior mediastinal mass 11.8×9.1×5.8cm, compressing the distal oesophagus. Laparoscopic biopsy of the mass showed an epitheloid mesothelioma. Mass was deemed unresectable and patient was started on chemotherapy with Cisplatin/Pemetrexed. Localised mesothelioma is extremely rare, and dysphagia can be uncommon presenting feature. 7.4 per cent of cases of Pseudoachalasia are attributed to mesothelioma

  17. Yield of abrams needle pleural biopsy in exudative pleural effusion

    International Nuclear Information System (INIS)

    Khan, I.N.; Zaman, M.; Khan, N.; Jadoon, H.; Ahmed, A.

    2009-01-01

    Pleural effusion is the abnormal collection of fluid in the pleural space resulting from excessive fluid production or decreased absorption and it is one of the most common clinical conditions that we come across in pulmonology clinics and in hospitals. The objective of prospective study was to evaluate the diagnostic role of Abrams Needle Biopsy in Exudative Pleural Effusion The study was performed at the Department of Pulmonology, Ayub Teaching Hospital, Abbottabad over a period of 1 year, i.e., January 2008 to December 2008. Sixty-three patients of either sex and all ages with exudative pleural effusion, on whom Abrams Needle Biopsy was performed were included in the study. Minimum of four specimens from each patient were taken and histopathology done. Out of 63 patients, histopathology revealed the cause in 60 (95%) cases. Tuberculosis, malignancy and rheumatoid pleurisy were confirmed in 34, 24, and 2 cases respectively. Specimens of 3 patients did not reveal any result and showed non-specific inflammation and were further investigated accordingly. The diagnostic yield of Biopsy was 95%. Pleural biopsy is still a reliable and valuable investigation in diagnosing pleural effusion, provided that adequate pleural specimen is taken. (author)

  18. Challenging a dogma; AJCC 8th staging system is not sufficient to predict outcomes of patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Abdel-Rahman, Omar

    2017-11-01

    The 8th edition of malignant pleural mesothelioma (MPM) American Joint Committee on Cancer (AJCC) staging system has been published. The current analysis aims to evaluate its performance in a population-based setting among patients recorded within the surveillance, epidemiology and end results (SEER) database. SEER database (2004-2013) has been accessed through SEER*Stat program and AJCC 8th edition stage groups were reconstructed. Survival analyses (overall and cancer-specific) were conducted according to 6th and 8th editions through Kaplan-Meier analysis. Cox-regression multivariate model was also utilized for pair wise comparisons between different prognostic groups for overall and cancer-specific survival. A total of 5382 patients with MPM were identified in the period from 2004 to 2013. According to the 6th edition, significant pair wise P values for overall survival included: IA vs. III (P=0.027); IA vs. IV: P<0.0001; IB vs. IV: P<0.0001; II vs. III: P<0.0001; II vs. IV: P<0.0001; III vs. IV: P<0.0001). According to the 8th edition, significant pair wise P values for overall survival included: all stages vs. IV: P<0.0001; IA vs. II: P=0.046; IA vs. IIIA: P=0.022; IA vs. IIIB: P <0.0001; IB vs. II: P<0.0001; IB vs. IIIB: P<0.0001; II vs. IIIA: P<0.0001; IIIA vs. IIIB: P<0.0001). C-index for 6th edition was 0.539 (SE: 0.008; 95% CI: 0.524-0.555); while C-index for 8th edition was 0.540 (SE: 0.008; 95% CI: 0.525-0.556). Based on the above findings, a simplified staging system was proposed and overall and cancer-specific survivals were evaluated according to the simplified system. For overall and cancer-specific survival assessment, P values for all pair wise comparisons among different stages were significant (<0.01). The prognostic performance of both the 6th and 8th AJCC editions is unsatisfactory; there is a need for a more practical and prognostically relevant staging system for MPM. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Diagnostic Tools of Pleural Effusion

    Science.gov (United States)

    2014-01-01

    Pleural effusion is not a rare disease in Korea. The diagnosis of pleural effusion is very difficult, even though the patients often complain of typical symptoms indicating of pleural diseases. Pleural effusion is characterized by the pleural cavity filled with transudative or exudative pleural fluids, and it is developed by various etiologies. The presence of pleural effusion can be confirmed by radiological studies including simple chest radiography, ultrasonography, or computed tomography. Identifying the causes of pleural effusions by pleural fluid analysis is essential for proper treatments. This review article provides information on the diagnostic approaches of pleural effusions and further suggested ways to confirm their various etiologies, by using the most recent journals for references. PMID:24920946

  20. Diagnostic Utility of Pleural Fluid Adenosine Deaminase Level in Tuberculousis Pleural Effusion

    International Nuclear Information System (INIS)

    Suleman, A.; Abbasi, M. A.; Anwar, S. A.; Kamal, M.; Khan, H.

    2016-01-01

    Background: Early diagnosis and management of tuberculosis is essential for decreasing the disease burden. Pakistan is one of the few countries of world with a very high burden of tuberculosis. Many diagnostic tests are available for detection of tuberculosis but each is fraught with certain limitations of its own. Methods: This study was a cross sectional validation study that sought to determine the validity of pleural fluid adenosine deaminase levels for diagnosis of tuberculous pleural effusion. Results: A total of 160 patients with exudative lymphocytic pleural effusions were enrolled in this study. The mean pleural fluid ADA level was 52.18±1.98 U/L. The mean pleural fluid ADA level in patients diagnosed to have tuberculosis on pleural biopsy/histopathology was higher as compared to patients who did not have tuberculous pleural effusion 52.16±2.4 U/L vs 38.6±3.14 U/L. The difference was found to be statistically significant between the two groups (p<0.05). The sensitivity, specificity, ppv and npv of pleural fluid ADA level were 88.88 percent, 77.04 percent, 86.28 percent and 81.04 percent respectively. Conclusion: Despite wide variations in the reported sensitivity and specificity of pleural fluid ADA level, it can be used as a surrogate for pleural biopsy when the latter is not feasible. (author)

  1. Diagnostic Tools of Pleural Effusion

    OpenAIRE

    Na, Moon Jun

    2014-01-01

    Pleural effusion is not a rare disease in Korea. The diagnosis of pleural effusion is very difficult, even though the patients often complain of typical symptoms indicating of pleural diseases. Pleural effusion is characterized by the pleural cavity filled with transudative or exudative pleural fluids, and it is developed by various etiologies. The presence of pleural effusion can be confirmed by radiological studies including simple chest radiography, ultrasonography, or computed tomography....

  2. Pleural Fluid Adenosine Deaminase (ADA) Predicts Survival in Patients with Malignant Pleural Effusion.

    Science.gov (United States)

    Terra, Ricardo Mingarini; Antonangelo, Leila; Mariani, Alessandro Wasum; de Oliveira, Ricardo Lopes Moraes; Teixeira, Lisete Ribeiro; Pego-Fernandes, Paulo Manuel

    2016-08-01

    Systemic and local inflammations have been described as relevant prognostic factors in patients with cancer. However, parameters that stand for immune activity in the pleural space have not been tested as predictors of survival in patients with malignant pleural effusion. The objective of this study was to evaluate pleural lymphocytes and Adenosine Deaminase (ADA) as predictors of survival in patients with recurrent malignant pleural effusion. Retrospective cohort study includes patients who underwent pleurodesis for malignant pleural effusion in a tertiary center. Pleural fluid protein concentration, lactate dehydrogenase, glucose, oncotic cytology, cell count, and ADA were collected before pleurodesis and analyzed. Survival analysis was performed considering pleurodesis as time origin, and death as the event. Backwards stepwise Cox regression was used to find predictors of survival. 156 patients (out of 196 potentially eligible) were included in this study. Most were female (72 %) and breast cancer was the most common underlying malignancy (53 %). Pleural fluid ADA level was stratified as low (Pleural fluid cell count and lymphocytes number and percentage did not correlate with survival. Pleural fluid Adenosine Deaminase levels (pleural effusion who undergo pleurodesis.

  3. Imaging of small amounts of pleural fluid. Part one - small pleural effusions

    International Nuclear Information System (INIS)

    Kocijancic, I.

    2005-01-01

    Background. Small pleural effusions are not readily identified on conventional radiographic views of the chest, but may be an important finding, sometimes leading, via thoracocentesis, to a definitive diagnosis of pleural carcinomatosis, infection or transudate. A small meniscus sign and a medial displacement of the costophrenic angle are the only subtle signs of small accumulations of fluid on posteroanterior chest X-rays. On lateral views the finding of a small meniscus sign in the posterior costophrenic angle is the sign of small pleural effusion. Conclusions. Lateral decubitus chest radiographs were used for many years for the diagnosis of small pleural effusions. In last decades ultrasonography of pleural space becomes a leading real-time method for demonstrating small pleural effusions. (author)

  4. Discrimination between pleural thickening and minimal pleural effusion using color Doppler chest ultrasonography

    OpenAIRE

    Hasan, Ali A.; Makhlouf, Hoda A.; Mohamed, Alaa R.M.

    2013-01-01

    Background: The discrimination of pleural thickening from minimal pleural effusion may be difficult as both lesions appear as anechoic on grayscale ultrasound, hence, free of “echoes” does not confirm the presence of pleural fluid. Aim of this study: To evaluate the value of color Doppler ultrasound in differentiating minimal pleural effusion that could be aspirated from pleural thickening and to compare it with grayscale ultrasound. Patients and methods: This analytic cross-sectional s...

  5. Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and Malignant Pleural Fluid by Proteomic Methods.

    Science.gov (United States)

    Lee, Chang Youl; Hong, Ji Young; Lee, Myung Goo; Suh, In Bum

    2017-11-01

    Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. We used samples from five patients with transudative pleural effusions for internal standard, five patients with tuberculous pleurisy, and the same numbers of patients having malignant effusions were enrolled in the study. We analyzed the proteins in pleural fluid from patients using a technique that combined two-dimensional liquid-phase electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. We identified a total of 10 proteins with statistical significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1 were related with malignant pleural effusions and human ceruloplasmin, lysozyme precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3 were expressed several times or more in tuberculous pleural effusions. Highly expressed proteins in malignant pleural effusion were associated with carcinogenesis and cell growth, and proteins associated with tuberculous pleural effusion played a role in the response to inflammation and fibrosis. These findings will aid in the development of novel diagnostic tools for tuberculous pleurisy and malignant pleural effusion of lung cancer. © Copyright: Yonsei University College of Medicine 2017

  6. 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.

  7. Managing malignant pleural effusion with an indwelling pleural catheter: factors associated with spontaneous pleurodesis.

    Science.gov (United States)

    Wong, W M; Tam, T Cc; Wong, M Ky; Lui, M Ms; Ip, M Sm; Lam, D Cl

    2016-08-01

    Malignant pleural effusion can be recurrent despite active anti-cancer treatment. Significant malignant pleural effusion leads to debilitating dyspnoea and worsening quality of life in patients with advanced cancer. An indwelling pleural catheter offers a novel means to manage recurrent malignant pleural effusion and may remove the need for repeated thoracocentesis. Spontaneous pleurodesis is another unique advantage of indwelling pleural catheter placement but the factors associated with its occurrence are not clearly established. The aims of this study were to explore the safety of an indwelling pleural catheter in the management of symptomatic recurrent malignant pleural effusion, and to identify the factors associated with spontaneous pleurodesis. This case series with internal comparisons was conducted in the Division of Respiratory Medicine, Department of Medicine, Queen Mary Hospital, Hong Kong. All patients who underwent insertion of an indwelling pleural catheter from the initiation of such service from January 2010 to December 2014 were included for data analysis. Patients were monitored until December 2014, with the last catheter inserted in July 2014. Between 2010 and 2014, a total of 23 indwelling pleural catheters were inserted in 22 consecutive patients with malignant pleural effusion, including 15 (65.2%) cases with malignant pleural effusion as a result of metastatic lung cancer. Ten (43.5%) cases achieved minimal output according to defined criteria, in five of whom the pleural catheter was removed without subsequent re-accumulation of effusion (ie spontaneous pleurodesis). Factors associated with minimal output were the absence of trapped lung (P=0.036), shorter time from first appearance of malignant pleural effusion to catheter insertion (P=0.017), and longer time from catheter insertion till patient's death or end of study (P=0.007). An indwelling pleural catheter provides a safe means to manage symptomatic malignant pleural effusion

  8. A conditional mouse model for malignant mesothelioma

    NARCIS (Netherlands)

    Jongsma, Johan; van Montfort, Erwin; Vooijs, Marc; Zevenhoven, John; Krimpenfort, Paul; van der Valk, Martin; van de Vijver, Marc; Berns, Anton

    2008-01-01

    Malignant mesothelioma is a devastating disease that has been associated with loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. We introduced similar lesions in the mesothelial lining of the thoracic cavity of mice. Mesothelioma developed at high incidence in

  9. Clinical Application of {sup 18}F-FDG PET in Malignant Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jeong [Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    2008-12-15

    Malignant pleural mesothelioma (MPM) has a poor prognosis and a strong association with exposure to asbestos. Although there are not generally accepted guidelines for treatment of MPM, recent reports suggest that multimodality therapy combining chemotherapy, radiotherapy, and surgery can improve the survival of patients with MPM. Therefore exact staging is required to decide the best treatment option. However, it is well known that there are many difficulties in determining precise preoperative stage, predicting prognosis, and monitoring response to therapy with conventional imaging modalities such as CT and MRI in MPM. Recently PET with {sup 18}F-FDG comes into the spotlight as an important staging method. There is increasing evidence that PET is superior to other conventional imaging modalities in diagnosis and staging of MPM. Particularly PET/CT improves the diagnostic and staging accuracy over PET or CT alone in MPM because it provides anatomic imaging data as well as functional information. PET and PET/CT are also useful for monitoring response to therapy and SUV is reported as a prognostic factor in MPM.

  10. Evaluation of usefulness of pleural fluid adenosine deaminase in diagnosing tuberculous pleural effusion from empyema

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

    Science.gov (United States)

    Verma, Akash; Abisheganaden, John; Light, R W

    2016-02-01

    We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

  13. Pleural effusion

    Science.gov (United States)

    Complications of pleural effusion may include: Lung damage Infection that turns into an abscess, called an empyema Air in the chest cavity ( pneumothorax ) after drainage of the effusion Pleural thickening (scarring of the lining of the ...

  14. Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.

    Science.gov (United States)

    Khanna, Swati; Graef, Suzanne; Mussai, Francis; Thomas, Anish; Wali, Neha; Yenidunya, Bahar Guliz; Yuan, Constance M; Morrow, Betsy; Zhang, Jingli; Korangy, Firouzeh; Greten, Tim F; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Middleton, Gary; De Santo, Carmela; Hassan, Raffit

    2018-03-30

    The cross talk between tumour cells, myeloid cells, and T cells play a critical role in tumour pathogenesis and response to immunotherapies. Although the aetiology of mesothelioma is well understood the impact of mesothelioma on the surrounding immune microenvironment is less well studied. In this study the effect of the mesothelioma microenvironment on circulating and infiltrating granulocytes and T cells is investigated. Tumour and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T cell suppression. Co-cultures of granulocytes, mesothelioma cells, T cells were used to identify the mechanism of T cell inhibition. Analysis of tumours showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T cell proliferation and activation. Characterisation of the blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR- granulocytes at increased frequency compared to healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of Reactive Oxygen Species (ROS) from granulocytes, resulting in T cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumours express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralising antibody, or ROS inhibition, restored T cell proliferation suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients. Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. Copyright ©2018, American Association for Cancer Research.

  15. [Causation in the court: the complex case of malignant mesothelioma].

    Science.gov (United States)

    Lageard, Giovanni

    2011-01-01

    The aim of this paper is to carry out an analysis of the legal evolution in Italy of the assessment of causation i.e. cause and effect, in oncological diseases, a question taken into consideration by the High Court almost exclusively with reference to pleural mesothelioma. The most debated question when defining the causal association between asbestos exposure and mesothelioma is the possible role that any multiple potentially causative exposures could assume in the induction and development of the disease, and in particular the role of any asbestos exposure over the successive employment periods. Indeed, this is a subject on which, to date, no agreement has yet been reached in scientific doctrine: these divergences bear important practical significance from a legal point of view, since sustaining one thesis or another may constitute determining factors when ascertaining responsibility for individuals who, in the past, had decisional statuses in the workplace. Jurisprudence in the High Court took on an oscillating position on this question as from the early 2000s, which was divided into those who sustained the thesis of the relevance of any asbestos exposure over the successive employment periods and those who were of a different opinion, i.e. only the first exposure period has relevant causative effect. The point under discussion concerns, in particular, the adequacy of a probabilistic law only governing such a question. An important turning point was made in the year 2010 when two sentences were announced in the High Court, reiterating, in strict compliance with the principles affirmed by the United Sections in 2002, that a judge cannot, and must not, be satisfied with a general causation, but must rather reach a judgment on the basis of an individual causation. In particular, not only did the second of these two sentences recognise the multifactorial nature of mesothelioma, something which had almost always been denied in jurisprudence in the past, but it also

  16. Identification of proteins in a human pleural exudate using two-dimensional preparative liquid-phase electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Nilsson, C L; Puchades, M; Westman, A; Blennow, K; Davidsson, P

    1999-01-01

    Pleural effusion may occur in patients suffering from physical trauma or systemic disorders such as infection, inflammation, or cancer. In order to investigate proteins in a pleural exudate from a patient with severe pneumonia, we used a strategy that combined preparative two-dimensional liquid-phase electrophoresis (2-D LPE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Western blotting. Preparative 2-D LPE is based on the same principles as analytical 2-D gel electrophoresis, except that the proteins remain in liquid phase during the entire procedure. In the first dimension, liquid-phase isoelectric focusing allows for the enrichment of proteins in liquid fractions. In the Rotofor cell, large volumes (up to 55 mL) and protein amounts (up to 1-2 g) can be loaded. Several low abundance proteins, cystatin C, haptoglobin, transthyretin, beta2-microglobulin, and transferrin, were detected after liquid-phase isoelectric focusing, through Western blotting analysis, in a pleural exudate (by definition, >25 g/L total protein). Direct MALDI-TOF-MS analysis of proteins in a Rotofor fraction is demonstrated as well. MALDI-TOF-MS analysis of a tryptic digest of a continuous elution sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) fraction confirmed the presence of cystatin C. By applying 2-D LPE, MALDI-TOF-MS, and Western blotting to the analysis of this pleural exudate, we were able to confirm the identity of proteins of potential diagnostic value. Our findings serve to illustrate the usefulness of this combination of methods in the analysis of pathological fluids.

  17. CT findings of peritoneal mesothelioma

    International Nuclear Information System (INIS)

    Woo, Young Hoon; Oh, Yeon Hee; Kim, Hong; Kim, Jung Sik; Woo, Seong Ku; Kim, Ok Bae; Joo, Yang Goo

    1990-01-01

    The peritoneal mesothelioma is a rare neoplasm which arises from the peritoneal lining of the abdomen, tending to spread along the peritoneal cavity and to invade abdominal organs. Authors report the CT findings of 4 patients with histologically proven peritoneal mesothelioma seen at Dongsan Medical Center, School of Medicine, Keimyung University. None of them had a history of exposure to asbestos and no clear etiologic factor could be determined in any patient. CT showed peritoneal and mesenteric thickenings in all cases, omental thickenings in 3 cases, peritoneal nodules, mesenteric masses or omental masses in 2 cases each other, bowel wall involvement in 1 case, and disproportionally small ascites in 2 cases. Distant hematogenous metastases to the liver and retroperitoneal lymph nodes were seen in 1 case. Our experience with 4 peritoneal mesotheliomas as well as a review of the recent imaging literature shows excellent correlation between computed tomography and the operitoneoscopic findings

  18. Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

  19. Certified causes of death in patients with mesothelioma in South East England

    Directory of Open Access Journals (Sweden)

    Peto Julian

    2009-01-01

    Full Text Available Abstract Background Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence. Methods We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1 mesothelioma deaths, (2 deaths certified as lung cancer deaths or (3 deaths from unspecified cancer, and (4 deaths from other causes. Results 87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate. Conclusion This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.

  20. The effectiveness of single port thoracoscopic approach in pleural effusions

    Directory of Open Access Journals (Sweden)

    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.