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Sample records for american erionite-associated mesothelioma

  1. What Are the Key Statistics about Malignant Mesothelioma?

    MedlinePlus

    ... Mesothelioma About Malignant Mesothelioma What Are the Key Statistics About Malignant Mesothelioma? Mesothelioma is fairly rare in ... on survival rates can be found in Survival Statistics for Mesothelioma . Visit the American Cancer Society’s Cancer ...

  2. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    ClinicalTrials.gov

    2016-11-14

    Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma

  3. Mesothelioma - malignant

    MedlinePlus

    ... Names Mesothelioma - malignant; Malignant pleura mesothelioma (MPM) Images Respiratory system References Broaddus VC, Robinson BWS. Pleural tumors. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  4. Update on malignant mesothelioma.

    PubMed

    Antman, Karen; Hassan, Raffit; Eisner, Milton; Ries, Lynn A G; Edwards, Brenda K

    2005-09-01

    Mesotheliomas are uncommon in the United States, with an incidence of about 3,000 new cases per year (or a risk of about 11 per million Americans per year). Incidence and mortality, however, are probably underestimated. Most are associated with asbestos, although some have arisen in ports of prior radiation, and a reported association with simian virus (SV)40 remains controversial. About 85% of mesotheliomas arise in the pleura, about 91% in the peritoneum, and a small percentage in the pericardium or tunica vaginalis testis. The histology of about half of mesotheliomas is epithelial (tubular papillary), with the remainder sarcomatous or mixed. Multicystic mesotheliomas and well-differentiated papillary mesotheliomas are associated with long survival in the absence of treatment and should be excluded from clinical trials intended for the usual rapidly lethal histologic variants of the disease. The median survival is under a year, although longer median survivals for selected patients, particularly those with epithelial histology, have been reported in some combined-modality studies. Recent randomized trials have shown significant improvement in time to progression and survival for the addition of new antifolates to platinum-based chemotherapy.

  5. Heterogeneity of exposure and attribution of mesothelioma: Trends and strategies in two American counties

    NASA Astrophysics Data System (ADS)

    Case, B. W.; Abraham, J. L.

    2009-02-01

    As mesothelioma risk has begun to decline in the United States, two trends are gaining relative importance. "Legacy" exposures causing this disease are most important in locales having past asbestos industry, shipyards, and/or local distribution of asbestos amphibole-containing material as a result. "Future" exposures are of particular concern in relation to so-called "naturally occurring asbestos" (NOA) areas which include unequivocally asbestiform amphibole. In this paper, Jefferson Parish, Louisiana is used as an example of the first trend, and El Dorado County, California as an example of the second. Available tumor registry, epidemiology, historical and mineralogical data, and lung-retained fibre content are used as indicators of disease and exposure. Jefferson Parish, LA was chosen as the prototype of "legacy" exposures on the basis of historical evidence of asbestos plants with known mesotheliomas in the workforce, known shipyards in the same area, EPA records of distribution of crocidolite-containing scrap to and remediation of over 1400 properties, NIOSH published data on mesothelioma by county, and exposure data including lung-retained fibre analyses in victims, where available. El Dorado, CA was chosen as the prototype of NOA amphibole exposures on the basis of tumor registry data, activity-based EPA sampling data in one area, and lung-retained fibre analyses in area pets, and future risk assessment based on tremolite-specific modelling in Libby, Montana and elsewhere. As expected, the legacy exposure area was high in mesothelioma incidence and mortality. Lung-retained fibre content confirms crocidolite exposures in exposed plant-workers and those exposed to crocidolite-containing scrap, and amosite in shipyard workers. In contrast, to date, cancer registry data in the NOA-amphibole ("future") county does not show a clear increase in incidence or mortality, but grouped county data from the area show a shift in higher incidence rates to the NOA areas and

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

    SciTech Connect

    Selcuk, Z.T.; Coeplue, L.Em.; Emri, S.; Kalyoncu, A.F.; Sahin, A.A.; Baris, Y.I. )

    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.

  7. Peritoneal Mesothelioma

    MedlinePlus

    ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs The Meso Foundation saves lives ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs © 2017 Mesothelioma Applied Research Foundation, ...

  8. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  9. Mesothelioma Applied Research Foundation

    MedlinePlus

    ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs Mesothelioma Awareness Day: Find out ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs © 2017 Mesothelioma Applied Research Foundation, ...

  10. Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients.

    PubMed

    Kitamura, Fumihiko; Araki, Shunichi; Suzuki, Yasunosuke; Yokoyama, Kazuhito; Tanigawa, Takeshi; Iwasaki, Ryu

    2002-04-01

    In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors.

  11. Multicystic mesothelioma with endometriosis.

    PubMed

    Groisman, G M; Kerner, H

    1992-12-01

    A multicystic mesothelioma of the omentum in a 36 year old woman consisted of a multicystic mass with foci of typical endometriosis and 'necrotic pseudoxanthomatous nodules'. The presence of endometriosis within multicystic mesothelioma has never been reported. Our findings support the hypothesis that endometriosis plays a rôle in the pathogenesis of multicystic mesothelioma and that this is a reactive rather than a neoplastic lesion.

  12. Angiography of omental mesothelioma

    SciTech Connect

    Marini, K.; Walter, J.F.

    1984-11-01

    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.

  13. Multicystic peritoneal mesothelioma

    PubMed Central

    Tentes, Antonios-Apostolos; Zorbas, Georgios; Pallas, Nicolaos; Fiska, Aliki

    2012-01-01

    Summary Background: Multicystic peritoneal mesothelioma is a rare disease. It is not certain if it is a benign or a borderline tumor. Although many therapeutic approaches have been used, complete cytoreductive surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy has gained acceptance. Case Report: A case of multicystic peritoneal mesothelioma in a 16-year old patient is reported. The patient underwent complete cytoreduction and received intraoperative hyperthermic intraperitoneal chemotherapy. The patient is disease-free one year after surgery. Conclusions: Complete cytoreductive surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy appears to be a rational therapeutic approach in multicystic peritoneal mesothelioma. PMID:23569544

  14. Multicystic peritoneal mesothelioma.

    PubMed

    Tentes, Antonios-Apostolos; Zorbas, Georgios; Pallas, Nicolaos; Fiska, Aliki

    2012-01-01

    Multicystic peritoneal mesothelioma is a rare disease. It is not certain if it is a benign or a borderline tumor. Although many therapeutic approaches have been used, complete cytoreductive surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy has gained acceptance. A case of multicystic peritoneal mesothelioma in a 16-year old patient is reported. The patient underwent complete cytoreduction and received intraoperative hyperthermic intraperitoneal chemotherapy. The patient is disease-free one year after surgery. Complete cytoreductive surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy appears to be a rational therapeutic approach in multicystic peritoneal mesothelioma.

  15. Malignant peritoneal mesothelioma

    PubMed Central

    Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D

    2009-01-01

    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. The 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 a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search 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. PMID:21160794

  16. Mesothelioma - benign-fibrous

    MedlinePlus

    ... to be called localized fibrous mesothelioma. Causes The exact cause of SFT remains unknown. This type of ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

  17. What Is Malignant Mesothelioma?

    MedlinePlus

    ... you learn about the treatment options and possible side effects, and point you to information and services to help you in your cancer journey. ... free PDFs of our malignant mesothelioma information ...

  18. Peritoneal Mesothelioma: A Review

    PubMed Central

    Bridda, Alessio; Padoan, Ilaria; Mencarelli, Roberto; Frego, Mauro

    2007-01-01

    Background Malignant peritoneal mesothelioma (MPM) is a rare aggressive tumor of the peritoneum, regarded as a universally fatal disease. It is poorly described and the knowledge of its natural history is very limited. Occupational and environmental asbestos exposure still remains a public health problem around the world. The incidence has increased in the past 2 decades. Only 20% to 33% of all mesotheliomas arise from the peritoneum itself; the pleura is the most common site of origin. PMID:17955087

  19. Mesothelioma in Scotland

    PubMed Central

    McEwen, J.; Finlayson, Angela; Mair, A.; Gibson, A. A. M.

    1970-01-01

    In a retrospective study of the incidence of mesothelioma in Scotland for 1950-67 80 cases were traced from pathological reports and biopsy material of malignant tumours invading the pleura and peritoneum. These cases were matched with two sets of controls. Detailed histories of residence, occupation, and degree of exposure to asbestos confirmed that the incidence of mesothelioma in Scotland is similar to that in other parts of Britain. PMID:5485174

  20. Investigational Approaches for Mesothelioma

    PubMed Central

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

    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. PMID

  1. Mesotheliomas and chrysotile.

    PubMed

    Elmes, P

    1994-08-01

    Mesotheliomas are rare. While most are reported to be associated with exposure to durable fibres, a proportion are not caused by the inhalation of fibres at all. Reports of individual cases and studies of small groups are unreliable as evidence of cause because: (a) diagnosis is often unreliable; (b) even if chrysotile fibres are found in lung tissues, the mesothelioma may still be spontaneous. Present knowledge has not progressed much since 1964 when the absence of cases of mesothelioma in amosite and chrysotile miners in South Africa and the very low incidence in Canadian mines was known but not believed. Now we know this information was correct. The significance of low-level amphibole exposures in predominantly chrysotile mixes was not appreciated until studies of fibres in lungs using electron microscopy showed the high lung burden of amphibole fibres in the 1970s and 1980s. The effect of these findings is to make most European and U.S.A. factory cohorts inappropriate for the evaluation of chrysotile mesothelioma risk. Reviewing the current evidence published and unpublished, it seems likely that chrysotile uncontaminated by tremolite may not have caused any mesotheliomas even at high cumulative life-time exposures. Information on the mesothelioma risk among chrysotile user populations using fibres not containing tremolite is badly needed.

  2. North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study.

    PubMed

    Gill, Ritu R; Naidich, David P; Mitchell, Alan; Ginsberg, Michelle; Erasmus, Jeremy; Armato, Samuel G; Straus, Christopher; Katz, Sharyn; Patios, Demetrois; Richards, William G; Rusch, Valerie W

    2016-08-01

    Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification. Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification. Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status. The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design

  3. [Multicystic peritoneal mesothelioma].

    PubMed

    Horling, E W; Albert, C; Bassermann, R; Stiegler, H

    1996-01-01

    We report on a 31-year-old man with a 29 x 15 x 15 cm large abdominal tumor who came to surgery under suspicion of echinococcus cyst of the liver. Histologically, the neoplasm could identified as multicystic peritoneal mesothelioma (synonyma: benign cystic mesothelioma). Additionally some cysts were located in the greater omentum and mesocolon. In contrast to our case the benign cystic mesotheliomas most commonly occur in young women, localized in the pelvis and abdomen and often complicated by postoperative local recurrence. We performed a resection of the right hemicolon and the omentum. Postoperatively no further therapy was necessary because of the benign appearance of the lesion. Close follow-up is required in these patients due to the disposition for recurrences.

  4. Malignant Pleural Mesothelioma

    PubMed Central

    Tsao, Anne S.; Wistuba, Ignacio; Roth, Jack A.; Kindler, Hedy Lee

    2009-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript. PMID:19255316

  5. Benign multicystic peritoneal mesothelioma.

    PubMed

    Uzüm, Nüket; Ozçay, Necdet; Ataoğlu, Omür

    2009-06-01

    Benign multicystic peritoneal mesothelioma is a rare tumor that occurs mainly in women in their reproductive age. It is characterized by the formation of multiple, thin-walled, multilocular cysts that frequently produce large, intra-abdominal masses. The short follow-ups and possible etiologies based on the published reports make it difficult to draw any firm conclusions.

  6. Malignant mesothelioma following radiation exposure

    SciTech Connect

    Antman, K.H.; Corson, J.M.; Li, F.P.; Greenberger, J.; Sytkowski, A.; Henson, D.E.; Weinstein, L.

    1983-11-01

    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.

  7. Metastatic mesothelioma presenting with proptosis.

    PubMed

    Gibson, Andrew; Musa, Fawaz; Pearson, Andrew; Wiggins, John

    2004-05-01

    To describe the clinical presentation and histologic findings in a patient with metastatic mesothelioma presenting to the ophthalmologist with nonaxial proptosis. Case report. A 55-year-old man presented with a short history of progressive ocular discomfort and vertical diplopia. Clinical examination identified nonaxial proptosis. Subsequent computed tomography showed a large extraconal mass consistent with a malignant process. Three months earlier the patient had been diagnosed with pleural mesothelioma. Unfortunately, he died 3 months after his ophthalmic presentation. Postmortem examination confirmed metastatic mesothelioma in the orbital roof that was histologically identical to the primary pleural malignancy. Pleural mesothelioma can metastasize to the orbit, causing proptosis.

  8. Malignant mesothelioma in Hong Kong.

    PubMed

    Chang, Kwok C; Leung, Chi C; Tam, Cheuk M; Yu, Wai C; Hui, David S; Lam, Wah K

    2006-01-01

    Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by reviewing medical records. Mesothelioma patients were identified from the database of 12 out of 20 hospitals that would have admitted mesothelioma patients territory-wide. These 12 hospitals served 73% of the total hospital bed-years of the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual incidence was one per million, which was similar to the background incidence of one to two per million among Caucasians. Occupational history was available in 43 subjects. Three quarters of mesothelioma patients with available occupational history had occupational asbestos exposure. Restricting analysis to 48 patients with accessible medical records and using 67 occupational asbestosis patients for comparison, the epidemiology of mesothelioma in Hong Kong shares similarities with the literature: mean age of 63 years upon diagnosis, mean latency of 46 years, median survival of 9.5 months, male predominance, selective presentation among women, high prevalence among workers in ships and dockyards, predominantly epithelioid type, lower prevalence of asbestos bodies, and negative association with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of mesothelioma in the 2010s if effective occupational asbestos control measures are not in place.

  9. Benign cystic peritoneal mesothelioma.

    PubMed Central

    Bhandarkar, D S; Smith, V J; Evans, D A; Taylor, T V

    1993-01-01

    The well defined but rare entity of benign cystic mesothelioma is reported. The aetiology of this neoplasm remains obscure. The presenting features make a precise preoperative diagnosis difficult; information provided by computed tomography and cytology may help. A firm diagnosis can only come from electron microscopic or immunohistochemical examination of the tumour. Diagnostic accuracy and diligent follow up are essential because, although the tumour is considered benign, it does tend towards local recurrence. Images PMID:8227441

  10. Fibrous mesothelioma. Case report.

    PubMed

    Verniers, P; De Man, R; De Muynck, P; Crolla, D; Coucke, W; Dewaele, G; Tanghe, W

    1989-12-01

    A case of fibrous mesothelioma is presented. Chest films suggested an elevation of the left diaphragm and a limited pleural effusion, which was confirmed on computed tomography. Percutaneous needle biopsy showed mesothelial cells. At thoracotomy the tumor was attached to the pleura of the mediastinum by a pedicle. Complete surgical resection was possible. Clinical, radiological and histological data in literature are summarized. The radiological features of the presented case correspond to those described in the literature.

  11. The European mesothelioma epidemic

    PubMed Central

    Peto, J; Decarli, A; Vecchia, C La; Levi, F; Negri, E

    1999-01-01

    Projections for the period 1995–2029 suggest that the number of men dying from mesothelioma in Western Europe each year will almost double over the next 20 years, from 5000 in 1998 to about 9000 around 2018, and then decline, with a total of about a quarter of a million deaths over the next 35 years. The highest risk will be suffered by men born around 1945–50, of whom about 1 in 150 will die of mesothelioma. Asbestos use in Western Europe remained high until 1980, and substantial quantities are still used in several European countries. These projections are based on the fit of a simple age and birth cohort model to male pleural cancer mortality from 1970 to 1989 for six countries (Britain, France, Germany, Italy, The Netherlands and Switzerland) which together account for three-quarters of the population of Western Europe. The model was tested by comparing observed and predicted numbers of deaths for the period 1990–94. The ratio of mesothelioma to recorded pleural cancer mortality has been 1.6:1 in Britain but was assumed to be 1:1 in other countries. © 1999 Cancer Research Campaign PMID:10027347

  12. Familial mesothelioma: a report of two families

    SciTech Connect

    Hammar, S.P.; Bockus, D.; Remington, F.; Freidman, S.; LaZerte, G.

    1989-02-01

    Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from an identical histologic type of peritoneal mesothelioma. Our report, as with those previously recorded, suggests that genetic factors may be important in the genesis of some mesotheliomas.

  13. Mesothelioma in Mongolia: case report

    PubMed Central

    Damiran, Naransukh; Davaajav, Khishigtogtokh; Erdenebayar, Erdenechimeg; Gomboloi, Burmaa; Frank, Arthur L

    2015-01-01

    Background: More than 80% of cases of mesothelioma worldwide have a history of asbestos exposure. In Mongolia, workers in coal burning thermal power plants (TPP) have widely utilized asbestos as an insulation material. Methods: We describe the case of a 47-year-old woman diagnosed with a malignant pleural mesothelioma. She worked in a TPP in Ulaanbaatar, Mongolia for 28 years. Results: A computer tomography (CT) scan showed a circumferential ring around her left lung, and tissues’ samples had a biphasic variant of mesothelioma with epithelioid and sarcomatoid components. Discussion: This is the first reported case of mesothelioma in Mongolia. We expect additional cases of mesothelioma, as well as other asbestos related diseases, will be identified in the future. In order to properly track asbestos related diseases in the country, we recommend the creation of an asbestos related disease registry. PMID:25582747

  14. Pleural mesothelioma – case report

    PubMed Central

    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. 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. Conclusions: 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. PMID:22802809

  15. General Information about Malignant Mesothelioma

    MedlinePlus

    ... form in the lining of the chest or abdomen. Malignant mesothelioma is a disease in which malignant ( ... that examine the inside of the chest and abdomen are used to detect (find) and diagnose malignant ...

  16. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Cerebral metastasis from malignant pleural mesothelioma.

    PubMed

    El Molla, Mohamed; Gragnaniello, Cristian; Al-Khawaja, Darweesh; Chiribao-Negri, Concepcion; Eftekhar, Behzad

    2013-09-26

    Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis.

  18. National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research.

    PubMed

    Amin, Waqas; Parwani, Anil V; Schmandt, Linda; Mohanty, Sambit K; Farhat, Ghada; Pople, Andrew K; Winters, Sharon B; Whelan, Nancy B; Schneider, Althea M; Milnes, John T; Valdivieso, Federico A; Feldman, Michael; Pass, Harvey I; Dhir, Rajiv; Melamed, Jonathan; Becich, Michael J

    2008-08-13

    Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid (caBIG, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only

  19. What's New in Malignant Mesothelioma Research and Treatment?

    MedlinePlus

    ... and Treatment? Malignant Mesothelioma About Malignant Mesothelioma What’s New in Malignant Mesothelioma Research and Treatment? There is ... that has shown promise in some studies. Other new drugs have different targets. For example, some new ...

  20. Multicystic mesothelioma of the peritoneum.

    PubMed

    Moghe, G M; Krishnamurthy, S C

    2001-01-01

    Multicystic mesothelioma is an uncommon lesion presenting as an abdominal mass. We report a 40-year-old woman presenting with recurrent intra-abdominal lump. She had undergone abdominal surgery thrice before. The lump at this presentation was partially excised surgically; histology and immunohistochemistry confirmed the diagnosis.

  1. [Mesothelioma and familial Mediterranean fever: A relationship?].

    PubMed

    Challita, S; Guerder, A; Charpentier, M-C; Daher, M; Giraud, F; Roche, N

    2015-03-01

    The majority of pleural and peritoneal mesotheliomas are linked to asbestos exposure but, in around 20% of cases, no history of such exposure is found. Periodic disease is associated with recurrent serositis, which could favor the development of mesothelioma. We report a case of pleural mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to asbestos but suffering from periodic disease (familial Mediterranean fever) with recurrent episodes of serositis. Many cases of peritoneal mesothelioma in patients with FMF are reported in the literature. This is the second reported case of pleural mesothelioma associated with periodic disease. Because of the low incidence of both diseases, further publications are required to support the hypothesis of a causal link. It is important, therefore, that all cases of an association of periodic disease and mesothelioma are reported. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  2. Malignant peritoneal mesothelioma after remote abdominal radiation

    SciTech Connect

    Gilks, B.; Hegedus, C.; Freeman, H.; Fratkin, L.; Churg, A.

    1988-05-15

    Peritoneal mesothelioma in a 61-year-old man, occurred 26 years after abdominal radiotherapy for a testicular seminoma. The patient had no history of asbestos exposure. After asbestos, radiation is the second most frequent defined cause of mesothelioma in North America, but the number of well-documented cases is small; this case represents only the fifth example of peritoneal mesothelioma after therapeutic irradiation of the abdomen. 16 references.

  3. Diffuse Malignant Mesothelioma: A Review

    PubMed Central

    Rom, William N.; Lockey, James E.

    1982-01-01

    Diffuse malignant mesothelioma is a signal tumor of asbestos exposure. Mesothelioma incidence has been steadily rising during the past two decades, reflecting the increases in asbestos use during and following World War II. The onset of the disease follows exposure by 25 to 40 years. The dose-response relationship appears to be much lower than that for asbestosis or lung cancer—it is not known whether current levels of exposure will entail a risk for disease 30 years hence. There is no synergistic or additive interaction with smoking for this tumor. Current knowledge indicates that pleural plaques, per se, do not increase the risk for this tumor beyond that of the previous asbestos exposure alone. Durable fibers with high aspect ratios, especially amphiboles, are associated with experimental tumor induction. Treatment modalities including surgical procedures and chemotherapy with doxorubicin and 5-azacytidine offer prospects for palliation. ImagesFigure 1.Figure 2. PMID:6761970

  4. Malignant Mesothelioma: Time to Translate?

    PubMed Central

    Napolitano, Andrea; Carbone, Michele

    2016-01-01

    Malignant mesothelioma is an aggressive cancer largely associated with asbestos exposure. In this review, we will discuss the significant advancements in our understanding of its genetics and molecular biology and their translational relevance. Remarkable findings included the discovery of germline and somatic mutations of BRCA1 associated protein-1 (BAP1) in patients, and the genome-wide characterization of pathways altered in mesothelioma that could be potentially exploited to design novel therapeutic approaches. Nevertheless, the clinical translation of these molecular findings has been slow and insufficient. In order to rapidly move translation from the bench to the bedside, we believe that cooperative research efforts have to be further endorsed and promoted at all levels. PMID:28603777

  5. Multicystic mesothelioma of the pericardium.

    PubMed

    Morita, Shigeki; Goto, Akiteru; Sakatani, Takashi; Ota, Satoshi; Murakawa, Tomohiro; Nakajima, Jun; Maeda, Eriko; Fukayama, Masashi

    2011-05-01

    Multicystic mesothelioma is a well recognized but rare serosal tumor which mainly arises from the peritoneum in women and is considered as a benign lesion. This is the second case report of pericardial multicystic mesothelioma, which took a fatal clinical course. A 63-year-old man presented with pitting edema, shortness of breath, and hoarseness. Radiological investigations revealed solid and cystic tumor of the pericardium which was continuously extending into the mediastinum and the liver. Pericardial biopsy showed micro-cystic tumor lined by single layer of mesothelial cells without atypia, and the diagnosis was multicystic mesothelioma. Curative surgery could not be performed, and three years and four months later, the patient died because of the direct compression of the heart by the tumor. At autopsy, the tumor was found to be directly extending into the right pleural cavity and the right lung, besides the mediastinum and the liver. Neither malignant transformation nor metastatic tumor was identified. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  6. Malignant peritoneal mesothelioma: a review

    PubMed Central

    Bhagwandin, Shanel; Labow, Daniel M.

    2017-01-01

    Mesothelioma is a malignancy of serosal membranes. It is most commonly encountered in the visceral pleura with the second most common location in the peritoneum. The diagnosis is very rare and has been linked to toxic exposure to industrial pollutants, especially asbestos. Malignant peritoneal mesothelioma (MPM) commonly presents with diffuse, extensive spread throughout the abdomen with rare metastatic spread beyond the abdominal cavity. Due to its rarity and nonspecific symptoms, it is usually diagnosed late when the disease burden is extensive. Because pleural mesothelioma is more common than MPM, most research has been on the pleural variant and extrapolated for MPM. While treatment advances have been made for MPM, the disease is universally fatal from either abdominal complications secondary to the spread of disease or starvation. Untreated, the life expectancy is less than a year. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has become the mainstay of therapy with systemic therapies still being developed. We will review the epidemiology of MPM and discuss diagnostic and treatment strategies. PMID:28706904

  7. Pleural mesothelioma in a couple of brothers

    PubMed Central

    Bianchi, Claudio; Bianchi, Tommaso

    2013-01-01

    Malignant mesotheliomas of the pleura, epithelial type, were observed in two brothers. Both the patients had histories of severe exposure to asbestos, having worked as insulators. The latency periods in the two cases were 26 and 38 years, respectively. Available literature data suggest that mesothelioma occurrence among blood-related people is favored by a genetic predisposition. PMID:24872671

  8. Survival of asbestos insulation workers with mesothelioma.

    PubMed Central

    Ribak, J; Selikoff, I J

    1992-01-01

    Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available. PMID:1419863

  9. Peritoneal mesothelioma: current understanding and management

    PubMed Central

    Chua, Terence C.; Yan, Tristan D.; Morris, David L.

    2009-01-01

    Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as “preterminal.” We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition. PMID:19234654

  10. Multicystic Benign Mesothelioma Complicating Pregnancy.

    PubMed

    Tamhankar, V A

    2015-01-01

    Multicystic benign mesothelioma (MBM) is a rare peritoneal pathology typically affecting women in reproductive age. Though MBM is considered benign, these lesions are prone to recurrence and their growth could be modulated by the presence of oestrogen receptors. Acute presentation of MBM is still very rare in pregnancy and management options are not established. We describe a case of MBM presenting in early pregnancy with acute pain. This was successfully treated with surgical resection. Pregnancy continued uneventfully to term and no evidence of recurrent MBM was found at Caesarean section.

  11. Multicystic Benign Mesothelioma Complicating Pregnancy

    PubMed Central

    Tamhankar, V. A.

    2015-01-01

    Multicystic benign mesothelioma (MBM) is a rare peritoneal pathology typically affecting women in reproductive age. Though MBM is considered benign, these lesions are prone to recurrence and their growth could be modulated by the presence of oestrogen receptors. Acute presentation of MBM is still very rare in pregnancy and management options are not established. We describe a case of MBM presenting in early pregnancy with acute pain. This was successfully treated with surgical resection. Pregnancy continued uneventfully to term and no evidence of recurrent MBM was found at Caesarean section. PMID:26345310

  12. Telomerase activity in human pleural mesothelioma

    PubMed Central

    Dhaene, K.; Hubner, R.; Kumar-Singh, S.; Weyn, B.; Van Marck, E.

    1998-01-01

    BACKGROUND—Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.
METHODS—Telomerase activity was semi-quantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.
RESULTS—Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.
CONCLUSIONS—Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.

 PMID:10193387

  13. Multicystic peritoneal mesothelioma: report of three cases.

    PubMed

    Charfi, S; Chetaille, B; Marcy, M; Turrini, O; Chaise De Maison, C; Delpero, J R; Viret, F; Xerri, L; Monges, G

    2008-10-01

    Multicystic peritoneal mesothelioma is a rare lesion occurring mainly in women in a reproductive age. Its pathogenesis is unclear. We report three cases of multicystic peritoneal mesothelioma in patients that were 28, 38 and 47 years of age (one male, two females). A history of abdominal surgery was reported in two cases. Explorative laparotomy was presumptive of a pseudomyxoma peritoni in two cases, and hyperthermic intraperitoneal chemotherapy was performed. Histological examination demonstrated multicystic lesions with mesothelial cells lining confirmed by immunohistochemical analysis. Unusual findings such as hyperplasia, hobnail features, cytoplasmic vacuolisation and papillary pattern were occasionally noted. The clinical presentation, pathogenesis and pathologic features including differential diagnosis of multicystic peritoneal mesothelioma are discussed.

  14. Lymph node involvement in multicystic peritoneal mesothelioma.

    PubMed

    Engohan-Aloghe, Corinne; Anaf, Vincent; Noël, Jean Christophe

    2009-11-01

    Multicystic peritoneal mesothelioma is an uncommon lesion most frequently encountered in women of reproductive age. Although the pathologic characteristics have been documented, the lymph node status associated with this pathology, the etiopathogenesis and prognosis of which remain unclear, is unknown. We report here the case of a 35-year-old woman with a 5.5 cm multicystic mesothelioma affecting the pelvic peritoneum of the rectum. Involvement by multicystic mesothelioma was observed within two lymph nodes simultaneously resected with the tumor. To the best of our knowledge, lymph node involvement has not been described in previous studies.

  15. Macroscopic, histologic, histochemical, immunohistochemical, and ultrastructural features of mesothelioma.

    PubMed

    Hammar, Samuel P

    2006-01-01

    Mesotheliomas are uncommon neoplasms that arise from the cells forming the serosal membranes of the body cavities. Approximately 90-95% of mesotheliomas arise in the pleural cavity and 5-10% in the peritoneal cavity. Rare mesotheliomas arise in the pericardium and in the tunica vaginalis. Unlike many neoplasms, mesotheliomas grow in a diffuse distribution and tend to encase the organs in the various body cavities. A combination of histochemical, immunohistochemical, and ultrastructural features are often necessary to accurately diagnose mesotheliomas. These techniques are highlighted in this review article on mesothelioma.

  16. [Environmental mesotheliomas in northeast Corsica].

    PubMed

    Rey, F; Viallat, J R; Boutin, C; Farisse, P; Billon-Galland, M A; Hereng, P; Dumortier, P; De Vuyst, P

    1993-01-01

    Since 1980, we have collected fourteen cases of mesothelioma induced by environmental exposure to asbestos, going back to childhood in patients from north-east Corsica, in a region which was remote from the asbestos mine of Canari. There were eight men and six women with a mean age of 69.5 +/- 4 years. Six patients presented with bilateral calcified pleural plaques as evidence of environmental exposure. The mineral analysis carried out on five patients (four had thoracoscopies and one an alveolar lavage), showed a moderate deposit of chrysotile (0.3 to 3.4 x 10(6) fibres per gram of dry tissue), and elevated level of tremolite (1.4 to 62 x 10(6) fibres/g). The ambient dosage of asbestos has confirmed the existence of environmental pollution by chrysotile fibres and above all by tremolite. In addition, the same type of fibres have been identified in the parietal pleural of animals subjected to the same risk. In this region, the risk is estimated, on the basis of our results, as 10 cases of mesothelioma per 100,000 inhabitants per year.

  17. [Diagnostic difficulties in primary mesothelioma].

    PubMed

    Khalil, Leila Youssef; Szturmowicz, Monika; Wawrzyńska, Liliana; Fijałkowska, Anna; Kupis, Włodzimierz; Maszkowska-Kopij, Krystyna; Szczepulska, Ewa; Burakowska, Barbara; Tomkowski, Witold; Torbicki, Adam

    2004-01-01

    A 54-year-old woman with a history of fatigue and shortness of breath was found to have a pericardial effusion and mild mediastinal lymphadenopathy. Video-assisted pericardioscopy revealed thickened pericardium studded with multiple nodules. Histologically the tumor was diagnosed as papillary adenocarcinoma. The site of the primary tumor could not be identified. As lung cancer is one of the most frequent causes of pericardial metastases the patient was treated with cisplatin and vinblastin. Following 5 courses of chemotherapy--given over a 4 month period--the amount of pericardial effusion and pericardial thickness did not change. The material from pericardial biopsy was reexamined and positive immunostaining for calretinine was found. The final diagnosis was primary pericardial mesothelioma of epithelioid type. Palliative radiotherapy of mediastinum was planned but the patient deteriorated and died due to disease progression with venous thrombosis and superior vena cava syndrome. The case illustrates the difficulties in establishing diagnosis of primary pericardial mesothelioma which is a rare tumor with poor prognosis.

  18. [Multicystic mesothelioma of the testicular tunica vaginalis].

    PubMed

    Rosales Leal, José Luis; Tallada Buñuel, Miguel; Espejo Maldonado, Eduardo; Cózar Olmo, José Manuel; Vicente Prados, Francisco Javier; Martínez Morcillo, Antonio; Buitragosivianes, Soledad; Rodríguez Herrera, Francisco; Ortiz Gorráiz, Manuel; Zilbermman Morales, Sonia; Chamorro Santos, Clara

    2003-12-01

    To report an exceptional case of multicystic mesothelioma of the testicular tunica vaginalis. A 72-year-old male was referred for study of a scrotal mass. Physical examination, blood tests, and ultrasound were performed prior to surgical excision and pathologic study of the lesion. The ultrasound study showed a multilobar cystic lesion near the spermatic cord. Pathology reported multiple 3-4 mm cystic formations, with rudimentary papillae covered by a hyperchromatic epithelium and vimentin (+), CD 34 (+) immunophenotype. Multicystic mesothelioma is a rare form of mesothelioma, easy to recognize but infrequent. This tumor generally affects the peritoneal surface of the pelvis and abdomen; although other less frequent locations have been described testicular location is exceptional. We report the case of a patient presenting with a multicystic mesothelioma of the testicular tunica vaginalis and review the diagnosis, pathology and treatment options for this type of tumor.

  19. Oral metastasis in malignant pleural mesothelioma.

    PubMed

    Sproat, C P; Brown, A E; Lindley, R P

    1993-10-01

    A case is reported of a 48-year-old man with malignant sarcomatous pleural mesothelioma, who presented with a secondary deposit in the mandibular alveolus. We believe that this is the first reported case of this nature.

  20. Dendritic cell-based immunotherapy in mesothelioma.

    PubMed

    Cornelissen, Robin; Lievense, Lysanne A; Heuvers, Marlies E; Maat, Alexander P; Hendriks, Rudi W; Hoogsteden, Henk C; Hegmans, Joost P; Aerts, Joachim G

    2012-10-01

    Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy.

  1. Global mesothelioma epidemic: Trend and features

    PubMed Central

    Bianchi, Claudio; Bianchi, Tommaso

    2014-01-01

    Background: Mesothelioma incidence has taken epidemic proportions in various countries. The trend of the epidemic remains undefined. Objective: To collect the most recent available data on mesothelioma incidence in order to determine the present trend of the epidemic. Materials and Methods: Data of the Cancer and Mesothelioma Registries have been reviewed. In addition, numerous researchers were contacted to obtain supplementary information. Results: The highest incidence rates are reported from some countries in Europe (United Kingdom, The Netherlands, Malta, Belgium), and in Oceania (Australia, New Zealand). Relatively low incidence/mortality rates are reported from Japan and from Central Europe. In many countries a trend to increase continues to be observed. Data are not available for the mostly populous countries. Conclusion: Mesothelioma epidemic does not show signs of attenuation. The lack of data for a large majority of the world does not allow that the consciousness of the risks related to asbestos exposure is reached. PMID:25568603

  2. Intra-abdominal benign multicystic peritoneal mesothelioma.

    PubMed

    Jouvin, I; Dohan, A; Gergi, P; Pocard, M

    2014-04-01

    Benign multicystic peritoneal mesotheliomas are rare: pre-operative diagnosis relies on proper imaging. The differential diagnosis includes pseudomyxoma peritonei and other peritoneal cysts. Absence of previous surgical resection offers the best chance of success when complete resection is performed in a specialized center. We report the case of a 43 year-old man with benign multicystic peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Malignant mesothelioma: Canadian perspective and research directions

    PubMed Central

    Lee, C.W.; Martin, J.; MacRae, R.; Tsao, M.S.; Nguyen, E.; Johnston, M.; Baas, P.; Laurie, S.; Feld, R.; Murray, N.; Shepherd, F.A.

    2008-01-01

    Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy.

  4. [Bilateral pleural mesothelioma--case report].

    PubMed

    Land, I; Knolle, H

    1990-08-01

    It is reported on the rare case of a 46-year-old female patient with a bilateral mesothelioma of the pleura without contact to asbest. Although the female was suspected in a malignant tumor and many diagnostic investigations were performed, diagnosis could be ensured morphologically only a short time before her death. Causes and development of mesothelioma, histological types, clinical symptoms and diagnostic procedures are described.

  5. Diffuse malignant pleural mesothelioma and asbestos exposure

    PubMed Central

    Whitwell, F.; Rawcliffe, Rachel M.

    1971-01-01

    Pleural mesothelioma has been diagnosed in 52 patients in three hospitals on Merseyside between 1955 and 1970, 60% being diagnosed from operation specimens and the rest from postmortem tissues. Necropsies eventually held on nearly half the operation cases confirmed the diagnosis, giving a necropsy rate of 70% for the series. The morbid anatomy conformed to earlier descriptions except that widespread metastases were much commoner than has usually been described. Histological findings agreed with previous accounts of the tumour, except that, in our hands, special acid mucopolysaccharide staining was less reliable than Southgate's mucicarmine, which was of value in differential diagnosis. Association with asbestos was confirmed from industrial histories in 80% of cases, the commonest industries involved being shipbuilding and repairing in men and sackware repairing in women. Lungs of industrial mesothelioma cases showed basal asbestosis in 17% and excessive asbestos bodies in almost all the rest. Quantitative comparison of asbestos bodies in lung smears from mesothelioma cases compared with lung smears from other Merseyside adults showed much higher counts in the mesothelioma cases. The interval from first exposure to asbestos until appearance of mesothelioma ranged between 13 and 63 years, with a mean of 42 years. We think the incidence of mesothelioma will continue to rise with the increased use of asbestos until about 40 years after adequate protective measures have been taken. Images PMID:5101273

  6. Cystic mesothelioma of the peritoneum.

    PubMed

    Datta, R V; Paty, P B

    1997-10-01

    A 48-year-old man presented with a 3-month history of weight loss and progressive right lower quadrant abdominal pain. His medical history was notable for appendectomy at age 17. Ultrasonography and computed tomography of the abdomen revealed a 12 cm multicystic mass in the right paracolic space. At laparotomy a large serous cyst was found arising from the lateral wall of the cecum, and four additional small cysts were found on the small bowel mesentery, greater omentum, liver capsule, and right hemi-diaphragm. Complete removal of the tumor was accomplished by right colectomy with extraperitoneal dissection of the large cyst and simple excision of the four smaller cysts. Final pathology with immunohistochemical staining confirmed cystic mesothelioma of the peritoneum. In this report we discuss the diagnostic workup and treatment of this rare disease.

  7. Malignant Mesothelioma: Development to Therapy

    PubMed Central

    Thompson, Joyce; Westbom, Catherine; Shukla, Arti

    2013-01-01

    Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM. PMID:23959774

  8. Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

    Cancer.gov

    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.

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

    DTIC Science & Technology

    2015-09-01

    mesothelial carcinogenesis occurs. Tumor development and growth during 52 weeks will also be followed in animals using high-frequency ultrasound ...line, IP synegeneic mesothelioma cell line, or intravenous Gemzar. 14 Saline SC MPM IP MPM Gemzar Saline...mesothelioma cell line, IP synegeneic mesothelioma cell line, or intravenous Gemzar. Upper panel: Complete set of the PGA 400 data. Box colors correspond

  10. Mesothelioma

    MedlinePlus

    ... a wide variety of applications, such as in insulation, brakes, shingles, flooring and many other products. When ... during the mining process or when removing asbestos insulation, dust may be created. If the dust is ...

  11. Malignant mesenterial mesothelioma in stroke patients.

    PubMed

    Budiyasa, Dewa Gde Agung; Wibawa, I Dewa Nyoman

    2008-10-01

    Mesothel is the cell lining of serosal surface of the pleura, peritoneum, pericardium, and testis. Malignant mesothelioma is a highly aggressive tumor from mesothel that has a tendency to grow rapidly and invade locally. Although the incidence of malignant mesenterial mesothelioma is not so high, the case fatality rate is very high. The aim of this case report is to report the rare and difficult case with several complications. A Balinese man, 64 years old, came with chief complaint of weakness, abdominal enlargement, and nausea, with history of previous liver disease. On physical examination were found a decrease of conciousness, subfebrile, abdominal distension, ascites, negative traube space, and paralysis of the left side of the body. Laboratory examination results showed leukocytosis, hypochromic-micrositic anemia, trombocytosis, hypoalbuminemia, increase of alkaline phosphatase, and mild hyponatremia. Abdominal USG showed intraperitoneal mass which some of them attach to abdominal wall, possibly from mesenterium and ascites, esophagogastroduodenoscopy (EGD) revealed reflux esofagitis and anthral erossive gastritis, skull CT scan showed small infarction at left parietal medulla and right basal ganglia, cytology showed spreaded and grouped mesothel with reactive lymphocyte and amorph back ground. FNAB result showed malignant mesothelioma, and normal colonoscopy. Based on the above data, the diagnoses were malignant mesenterial mesothelioma, reflux esofagitis and anthral erossive gastritis, and non hemorrhagic stroke. Malignant mesenterial mesothelioma should be considered in patient with the combination of unexplained ascites and abdominal pain. Although the result of treatment is very disappointing, the patient had to be treated optimally to increase quality of life.

  12. Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

    ClinicalTrials.gov

    2017-09-04

    Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7

  13. Non-asbestos-related malignant mesothelioma. A review

    SciTech Connect

    Peterson, J.T. Jr.; Greenberg, S.D.; Buffler, P.A.

    1984-09-01

    Malignant mesothelioma is an uncommon, but increasingly important, neoplasm. The existing English-language medical literature concerning non-asbestos-related malignant mesotheliomas was reviewed for evidence of other agents associated with the induction of malignant mesothelioma. Both animal and human data were reviewed. In most reviews of malignant mesothelioma, there are a significant proportion of cases without documented asbestos exposure (range, 0% to 87%). Furthermore, there are several fairly well-documented agents other than asbestos that induce malignant mesothelioma in animals, and strong evidence exists that such is the case in man. In reviews of malignant mesothelioma, the percentage of cases with asbestos exposure varies, but a significant number are apparently not asbestos related. It is believed that sufficient evidence exists to suggest that non-asbestos agents can induce malignant mesotheliomas in man, and additional epidemiologic studies in this area are needed.

  14. Expression of vascular endothelial growth factor in malignant mesothelioma.

    PubMed

    Aoe, Keisuke; Hiraki, Akio; Tanaka, Takehiro; Gemba, Ken-Ichi; Taguchi, Koji; Murakami, Tomoyuki; Sueoka, Naoko; Kamei, Toshiaki; Ueoka, Hiroshi; Sugi, Kazuro; Yoshino, Tadashi; Kishimoto, Takumi

    2006-01-01

    Malignant mesothelioma is the most common primary pleural neoplasm. Angiogenesis is an important component of a variety of pathological processes, including carcinogenesis and tumor metastases. Vascular endothelial growth factor (VEGF) is the most potent known endothelial, cell specific mitogen. The authors assessed the relation between VEGF expression and clinicopathological variables or overall survival, in malignant mesothelioma. We studied 37 patients with malignant pleural mesothelioma and found that 36 out of 37 (97.3%) malignant mesothelioma samples were stained positively for VEGF. An increased expression of VEGF was observed in the epithelioid type compared with the other histological types of malignant mesothelioma, including the biphasic and sarcomatoid types. No statistically significant association was observed between VEGF expression and gender, age, or clinical stage. Furthermore, the expression of VEGF did not impact on the survival of patients with malignant mesothelioma. Although VEGF expression might be important for tumor development and maintenance, it was not identified as a prognostic factor in malignant mesothelioma.

  15. Benign multicystic mesothelioma: a case report.

    PubMed

    Adolph, A J; Smith, T E; Adolph, J

    2002-03-01

    Benign multicystic mesothelioma (also known as multilocular peritoneal inclusion cyst) is a rare lesion found on any abdominal peritoneal surface that occurs most frequently in premenopausal women. We report the case of a 36-year- old woman, who presented with a history of generalized abdominal pain, intermittent abdominal bloating, and episodes of loose stools. A pelvic ultrasound revealed a complex cystic mass with fine internal septations. The patient was managed by laparotomy with removal of mass, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and multiple peritoneal biopsies. Final pathology revealed benign multicystic mesothelioma. Although mesothelioma is a rare tumour, it is important for all gynaecologists to recognize its existence, the appearance of this lesion, and its generally benign course. This is especially important as it occurs in young women where fertility considerations must be part of the discussion of any pelvic surgery.

  16. Benign multicystic peritoneal mesothelioma: a case report

    PubMed Central

    2010-01-01

    Introduction We report the case of a patient with a benign multicystic peritoneal mesothelioma and describe its appearance on computed tomography scans and ultrasonography, in correlation with gross clinical and pathological findings. Case presentation A 72-year-old Caucasian woman presented to our emergency department with acute abdomen signs and symptoms. A clinical examination revealed a painful palpable mass in her left abdomen. Abdominal ultrasonography and computed tomography demonstrated the presence of a large cystic mass in her left upper abdomen, adjacent to her left hemidiaphragm. The lower border of the mass extended to the upper margin of her pelvis. A complete resection of the lesion was performed. Pathological analysis showed a benign multicystic peritoneal mesothelioma. Conclusions Benign multicystic peritoneal mesothelioma is a rare lesion with a non-specific appearance on imaging. Its diagnosis always requires pathological analysis. PMID:21114811

  17. Benign multicystic peritoneal mesothelioma: a case report.

    PubMed

    Pitta, Xanthi; Andreadis, Efstathios; Ekonomou, Athanasios; Papachristodoulou, Athanasia; Tziouvaras, Chrisostomos; Papapaulou, Leonidas; Sapidis, Nikolaos; Chrisidis, Thomas

    2010-11-29

    We report the case of a patient with a benign multicystic peritoneal mesothelioma and describe its appearance on computed tomography scans and ultrasonography, in correlation with gross clinical and pathological findings. A 72-year-old Caucasian woman presented to our emergency department with acute abdomen signs and symptoms. A clinical examination revealed a painful palpable mass in her left abdomen. Abdominal ultrasonography and computed tomography demonstrated the presence of a large cystic mass in her left upper abdomen, adjacent to her left hemidiaphragm. The lower border of the mass extended to the upper margin of her pelvis. A complete resection of the lesion was performed. Pathological analysis showed a benign multicystic peritoneal mesothelioma. Benign multicystic peritoneal mesothelioma is a rare lesion with a non-specific appearance on imaging. Its diagnosis always requires pathological analysis.

  18. Mesothelioma in man and experimental animals.

    PubMed Central

    Kannerstein, M; Churg, J

    1980-01-01

    Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features. PMID:6993202

  19. Deciduoid peritoneal mesothelioma in a dog.

    PubMed

    Morini, M; Bettini, G; Morandi, F; Burdisso, R; Marcato, P S

    2006-03-01

    Deciduoid mesothelioma is a rare variant of epithelial mesothelioma, up to now only described in human pathology, which bears remarkable cytomorphologic resemblance to the endometrium of pregnancy, termed decidua. A case of peritoneal mesothelioma with deciduoid features in a 10-year-old, female dog is reported. Multiple whitish-gray nodules (1-5 mm in diameter) in parietal peritoneum and mesentery were histologically composed of large, proliferating, polygonal or ovoid cells with an abundant eosinophilic, glassy cytoplasm. Immunohistochemical evaluation indicated that the neoplastic cells coexpressed cytokeratin and vimentin with strong and diffuse cytoplasmic staining, and ultrastructural analysis showed long and slender mesothelial-type microvilli; these findings confirmed the mesothelial origin of the tumor.

  20. Unusual clear cell variant of epithelioid mesothelioma.

    PubMed

    Dessy, E; Falleni, M; Braidotti, P; Del Curto, B; Panigalli, T; Pietra, G G

    2001-12-01

    Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.

  1. Novel systemic therapy against malignant pleural mesothelioma.

    PubMed

    Mancuso, Michael R; Neal, Joel W

    2017-06-01

    Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy. Overall, these studies demonstrate the challenges of improving systemic therapy for MPM and highlight the need to develop therapeutic strategies to control this disease.

  2. Quantitative structure - mesothelioma potency model ...

    EPA Pesticide Factsheets

    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

  3. Advances in the management of malignant mesothelioma.

    PubMed

    Khalil, Mazen Y; Mapa, Marissa; Shin, Hyung Ju C; Shin, Dong M

    2003-07-01

    Malignant mesotheliomas are very aggressive tumors that originate from mesothelial cells, which form the serosal lining of the pleura, pericardial, and peritoneal cavities. Finding effective chemotherapeutic treatment for malignant mesothelioma is a challenge. There is no standard treatment because this tumor is relatively resistant to therapy. A resurgence of interest has been expressed in novel therapies and conventional treatments used in different ways. Several treatment modalities have been studied, including chemotherapy, radiotherapy, surgery, and immunotherapy. Chemotherapy can be administered systemically or directly into the pleura. This review presents the results of the most recent trials and highlights the most promising advances in the battle against this aggressive disease.

  4. Peritoneal mesothelioma in a jaguar (Panthera onca).

    PubMed

    Souza, Francisco de Assis Leite; de Carvalho, Ciro José Sousa; de Almeida, Hatawa M; Pires, Lidiany Viana; Silva, Lucilene dos Santos; Costa, Francisco Assis Lima; Silva, Silvana M Medeiros de Sousa

    2013-09-01

    A 21-yr-old female jaguar (Panthera onca) died in a zoo in Teresina, Piaui, Brazil, following a history of abdominal distension, ascites, anorexia, and dyspnea. At necropsy, a dark red, watery, blood-tinged serous fluid was present in the abdominal cavity. The peritoneum was thick with firm, yellow, villous projections. Histologically, the tumors were composed of a biphasic population of cells, which reacted to anti-cytokeratin and anti-vimentin antibodies, consistent with a biphasic benign mesothelioma of peritoneal origin. This is the first reported case of mesothelioma in a captive jaguar.

  5. [Malignant pleural mesothelioma with multiple nodules].

    PubMed

    Asano, Michiko; Gemba, Kenichi; Fujimoto, Nobukazu; Nishi, Hideyuki; Taguchi, Koji; Kishimoto, Takumi

    2011-12-01

    A 62-year-old man with left chest pain had left pleural effusion pointed out on a chest radiograph. Chest CT scans showed multiple nodules on the left parietal pleura and pleural effusion. He was referred to our hospital and we performed thoracoscopic examination. Malignant pleural mesothelioma (biphasic type) was diagnosed, based on the pathological findings of a parietal nodular mass, including immunohistological analysis. Chemotherapy using carboplatin and pemetrexed reduced the size of tumor and left pleural effusion. This is a rare case with atypical CT findings of malignant pleural mesothelioma.

  6. Mesothelioma following Wilms' tumor in childhood

    SciTech Connect

    Antman, K.H.; Ruxer, R.L. Jr.; Aisner, J.; Vawter, G.

    1984-07-15

    A high percentage of children with Wilms' tumor are cured with multimodal treatment. A small percentage of these children will develop second tumors, perhaps related to a genetic predisposition to neoplasia or possibly secondary to the treatment utilized for Wilms' tumor. Malignant mesothelioma has been associated with contact with asbestos but has also been reported after radiation exposure. Two patients are reported who developed malignant mesothelioma of the pleura after treatment for Wilms' tumor in childhood. Both received orthovoltage radiation; one patient also received triethylenemelamine (TEM), an alkylating agent closely related to nitrogen mustard, for 5 years. Factors in the development of second tumors are discussed.

  7. Diffuse intrapulmonary malignant mesothelioma masquerading as interstitial lung disease: a distinctive variant of mesothelioma.

    PubMed

    Larsen, Brandon T; Klein, Julianne R H; Hornychová, Helena; Nuti, Rathna; Thirumala, Seshadri; Leslie, Kevin O; Colby, Thomas V; Tazelaar, Henry D

    2013-10-01

    Malignant mesothelioma typically encases lungs as a thick rind, while relatively sparing lung parenchyma. We describe an unusual presentation of mesothelioma characterized by diffuse intrapulmonary growth, with absent or inconspicuous pleural involvement, clinically simulating interstitial lung disease (ILD). We identified 5 patients (median age 56 y, all men) with diffuse intrapulmonary malignant mesothelioma in our pathology consultation practice from 2009 to 2012. Clinical history, imaging, and pathology materials were reviewed. Symptoms included chronic dyspnea (4 cases), cough (3), and acute dyspnea with bilateral pneumothorax (1). Chest imaging showed irregular opacities (5), reticulation (4), pleural effusions (2), and subpleural nodular densities (1), without radiologic evidence of pleural disease or masses. A clinicoradiologic diagnosis of ILD was made in all cases, and wedge biopsies were performed. Histologic evaluation revealed a neoplastic proliferation of bland epithelioid or spindled cells, showing various growth patterns simulating silicotic nodules, desquamative interstitial pneumonia, organizing pneumonia, and Langerhans cell histiocytosis. Some areas mimicked adenocarcinoma, with lepidic, acinar, micropapillary, and solid patterns. Initial diagnoses by referring pathologists included reactive changes (1), hypersensitivity pneumonitis versus drug reaction (1), desquamative interstitial pneumonia versus neoplasm (1), and mesothelioma (2). Microscopic pleural involvement was identified in 4 cases. Immunohistochemistry confirmed the characteristic immunophenotype of mesothelioma in all cases. Median survival of 3 patients treated with chemotherapy was 28 months. Two patients received no therapy and survived 3 and 4 weeks, respectively. "Diffuse intrapulmonary malignant mesothelioma" is a rare variant with a distinctive presentation that clinically mimics ILD. Recognition is essential to avoid misdiagnosis.

  8. Malignant pleural mesothelioma in Italy

    PubMed Central

    Bianchi, Claudio; Bianchi, Tommaso

    2009-01-01

    This study reviews a series of 811 malignant pleural mesothelioma cases, diagnosed at hospitals in Trieste and Monfalcone districts of north eastern Italy, a narrow coastal strip with a population of about three lakh, in the period 1968-2008. The diagnosis was based on histological examination in 801 cases, and cytological findings in 10. Necropsy was performed in 610 cases. Occupational histories were obtained directly from the patients or their relatives through personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 500 cases. In 143 cases asbestos bodies were isolated and counted by chemical digestion of the lung tissue using the Smith-Naylor method. The series included 717 men and 94 women aged between 32 and 93 years (mean 69.2 years). Detailed occupational data was obtained for 732 cases. The majority of patients had marine jobs - shipbuilding (449 cases), maritime trades (56 cases), and port activities (39 cases). The nature of work of other patients included a variety of occupations, with non-shipbuilding industries being the most common. Thirty-four women cleaned the work clothes of family members occupationally exposed and hence had a history of asbestos exposure at home. Most of the patients had their first exposure to asbestos before 1960. The latency period ranged between 13 and 73 years (mean 48.2). Latency period among insulators and dock workers were shorter than other categories. Asbestos bodies were detected on routine lung sections in 343 cases (68.6%). Lung asbestos body burdens after isolation ranged between two to 10 millions bodies per gram of dried tissue. Despite some limitations in the use of asbestos in this area since the 1970s, the incidence of tumor remained high during the last years. PMID:20386624

  9. Malignant pleural mesothelioma in Italy.

    PubMed

    Bianchi, Claudio; Bianchi, Tommaso

    2009-08-01

    This study reviews a series of 811 malignant pleural mesothelioma cases, diagnosed at hospitals in Trieste and Monfalcone districts of north eastern Italy, a narrow coastal strip with a population of about three lakh, in the period 1968-2008. The diagnosis was based on histological examination in 801 cases, and cytological findings in 10. Necropsy was performed in 610 cases. Occupational histories were obtained directly from the patients or their relatives through personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 500 cases. In 143 cases asbestos bodies were isolated and counted by chemical digestion of the lung tissue using the Smith-Naylor method. The series included 717 men and 94 women aged between 32 and 93 years (mean 69.2 years). Detailed occupational data was obtained for 732 cases.The majority of patients had marine jobs - shipbuilding (449 cases), maritime trades (56 cases), and port activities (39 cases). The nature of work of other patients included a variety of occupations, with non-shipbuilding industries being the most common. Thirty-four women cleaned the work clothes of family members occupationally exposed and hence had a history of asbestos exposure at home. Most of the patients had their first exposure to asbestos before 1960. The latency period ranged between 13 and 73 years (mean 48.2). Latency period among insulators and dock workers were shorter than other categories. Asbestos bodies were detected on routine lung sections in 343 cases (68.6%). Lung asbestos body burdens after isolation ranged between two to 10 millions bodies per gram of dried tissue. Despite some limitations in the use of asbestos in this area since the 1970s, the incidence of tumor remained high during the last years.

  10. Epidemiology of Environmental Exposure and Malignant Mesothelioma.

    PubMed

    Liu, Bian; van Gerwen, Maaike; Bonassi, Stefano; Taioli, Emanuela

    2017-07-01

    Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health impact of environmental exposure (EE) to asbestos has been less studied. This review summarizes the most recent studies on the association between malignant mesothelioma and EE with asbestos to identify features associated with EE and quantify the association with malignant mesothelioma. There were 44 studies from 18 countries that met our selection criteria, with a considerable amount of heterogeneity in their study design, measures of exposure, and health outcomes. The male-to-female ratio was close to or less than 1 and generally lower than the ratio reported when both occupational and environmental exposures were considered. Although recent studies have continued to improve our understanding of environmental exposure to asbestos, challenges remain. We have highlighted a few new research directions, such as a need for reliable matrices to identify common and less recognized types of EE, asbestos biomarker studies specifically focusing on EE, and research on populations and geographic areas that have not been previously studied. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  11. The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation.

    PubMed

    Pass, Harvey; Giroux, Dorothy; Kennedy, Catherine; Ruffini, Enrico; Cangir, Ayten K; Rice, David; Asamura, Hisao; Waller, David; Edwards, John; Weder, Walter; Hoffmann, Hans; van Meerbeeck, Jan P; Nowak, Anna; Rusch, Valerie W

    2016-12-01

    For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems.

  12. Malignant mesothelioma: attributable risk of asbestos exposure.

    PubMed Central

    Spirtas, R; Heineman, E F; Bernstein, L; Beebe, G W; Keehn, R J; Stark, A; Harlow, B L; Benichou, J

    1994-01-01

    OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS--Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS--Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive. PMID:7849863

  13. Benign Cystic Mesothelioma: A Rare Cause for Scrotal Swelling

    PubMed Central

    Aber, A.; Tahir, A.; Arumuham, V.; Smith, G.; Almpanis, S.

    2012-01-01

    Benign cystic mesothelioma of the tunica vaginalis is a rare occurrence. It usually presents with painless gradual swelling in the scrotum. These types of benign mesotheliomas typically occur in the peritoneum and usually affect young to middle-aged patients. We present in this case an unusual case of benign cystic mesothelioma of the tunica vaginalis in a 77-year-old male patient. PMID:22675366

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

    DTIC Science & Technology

    2015-09-01

    as mesothelial carcinogenesis occurs. Tumor development and growth during 52 weeks will also be followed in animals using high-frequency ultrasound ...IP synegeneic mesothelioma cell line, or intravenous Gemzar. 14 Saline SC MPM IP MPM Gemzar Saline SC MPM IP MPM Gemzar Figure 9...Development of AGAs in in rodents receiving saline, SC syngeneic mesothelioma cell line, IP synegeneic mesothelioma cell line, or intravenous Gemzar

  15. CD30 is a potential therapeutic target in malignant mesothelioma

    PubMed Central

    Dabir, Snehal; Kresak, Adam; Yang, Michael; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-01-01

    CD30 is a cytokine receptor belonging to the tumor necrosis factor superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin’s disease and anaplastic large cell lymphoma. There have been sporadic reports of CD30 expression in non-lymphoid tumors, including malignant mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody-drug conjugate directed against CD30 antigen, in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma tumor specimens (N = 83) were examined for CD30 expression by immunohistochemistry. Positive CD30 expression was noted in 13 mesothelioma specimens, primarily those of epithelial histology. There was no significant correlation of CD30 positivity with either tumor grade, stage or survival. Examination of four mesothelioma cell lines (H28, H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab vedotin treatment of cultured mesothelioma cells produced a dose-dependent decrease in cell growth and viability at clinically relevant concentrations. Our studies validate the presence of CD30 antigen in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment. PMID:25589494

  16. Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma.

    PubMed

    Wu, Licun; Allo, Ghassan; John, Thomas; Li, Ming; Tagawa, Tetsuzo; Opitz, Isabelle; Anraku, Masaki; Yun, Zhihong; Pintilie, Melania; Pitcher, Bethany; Liu, Geoffrey; Feld, Ron; Johnston, Michael R; de Perrot, Marc; Tsao, Ming-Sound

    2017-02-15

    Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor-stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1-5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies. Clin Cancer Res; 23(4); 1060-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma.

    PubMed

    Friedberg, Joseph S; Culligan, Melissa J; Mick, Rosemarie; Stevenson, James; Hahn, Stephen M; Sterman, Daniel; Punekar, Salman; Glatstein, Eli; Cengel, Keith

    2012-05-01

    Radical pleurectomy (RP) for mesothelioma is often considered either technically unfeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. Thirty-eight patients (42-81 years) underwent RP-PDT. Thirty five of 38 (92%) patients also received systemic therapy. Standard statistical techniques were used for analysis. Thirty seven of 38 (97%) patients had stage III/IV cancer (according to the American Joint Committee on Cancer [AJCC manual 7th Edition, 2010]) and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was 1 postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) patients with epithelial subtypes, and 6.8 months for the 7/38 (18%) patients with nonepithelial subtypes. Median progression-free survival (PFS) was 9.6, 15.1, and 4.8 months, respectively. The median survival and PFS for the 20/31 (64%) patients with N2 epithelial disease were 31.7 and 15.1 months, respectively. It was possible to achieve a macroscopic complete resection using lung-sparing surgery in 97% of these patients with stage III/IV disease. The survival we observed with this approach was unusually long for the patients with the epithelial subtype but, interestingly, the PFS was not. The reason for this prolonged survival despite recurrence is not clear but is potentially related to preservation of the lung or some PDT-induced effect, or both. We conclude that the results of this lung-sparing approach are safe, encouraging, and warrant further investigation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma.

    PubMed

    Laury, Anna R; Hornick, Jason L; Perets, Ruth; Krane, Jeffrey F; Corson, Joseph; Drapkin, Ronny; Hirsch, Michelle S

    2010-05-01

    Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker

  19. Remote Recurrence of Benign Multicystic Peritoneal Mesothelioma.

    PubMed

    Lee, Caroline E; Agrawal, Anita

    2017-07-18

    Benign peritoneal cystic mesothelioma (BPCM) is a rare disease entity that arises from mesothelioma cells. We describe a rare case of BPCM recurrence 36 years after its initial presentation. A 62-year-old woman was referred to an outpatient gynaecologic oncology clinic with an incidental finding of multiple pelvic cysts. She had a preceding history of known BPCM treated with extensive debulking surgery. She presented after 36 years of clinical remission. A repeat laparotomy for a debulking surgical procedure confirmed a recurrence of BPCM. Our current case represents a woman with a remote recurrence of BPCM after initial optimal debulking surgery. Her clinical presentation of recurrence after 36 years illustrates the need for long-term follow-up and clinical suspicion in symptomatic patients with previously diagnosed BPCM. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  20. [Benign multicystic peritoneal mesothelioma. A case report].

    PubMed

    Lari, Federico; Castelli, Giuliano; Bragagni, Gianpaolo

    2012-02-01

    Benign multicystic peritoneal mesothelioma is a rare malignancy with unknown etiology, first described in 1980, which have been reported to date about 150 cases in the literature. Although the term "benign", used mainly to distinguish it from the classic malignant mesothelioma, a more aggressive cancer, is considered "borderline" in terms of aggression: it tends to local recurrence but cases of lymph node metastases or in other locations at a distance are not described. The symptoms are often vague and nonspecific (abdominal pain, enlarged abdomen and ascites). The common diagnostic imaging techniques (CT, MRI) may appear similar to ovarian or peritoneal cancer by more aggressive mesenchymal neoplasms. Histological examination, accurately with the aid of immunohistochemical techniques, is therefore essential for diagnosis. Treatment is surgical and consists of peritonectomy. After surgery, the prognosis is generally good. In 50% of cases may have local recurrences; so rigorous follow-up is indicated.

  1. Life Expectancy in Pleural and Peritoneal Mesothelioma

    PubMed Central

    Vavra-Musser, Kate; Lee, Jessica; Brooks, Jordan

    2017-01-01

    Background. Mesothelioma is a rare cancer with a historically dire prognosis. We sought to calculate life expectancies for patients with pleural or peritoneal mesothelioma, both at time of diagnosis and several years later, and to examine whether survival has improved in recent years. Methods. Data on 10,258 pleural and 1,229 peritoneal patients from the SEER US national cancer database, 1973–2011, were analyzed using the Cox proportional hazards regression model. Results. The major factors related to survival were age, sex, stage, grade, histology, and treatment. Survival improved only modestly over the study period: 0.5% per year for pleural and 2% for peritoneal. Conclusions. Life expectancies were markedly reduced from normal, even amongst 5-year survivors with the most favorable characteristics and treatment options. PMID:28239496

  2. Peritoneal mesothelioma: the site of origin matters.

    PubMed

    Kindler, Hedy Lee

    2013-01-01

    The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential-well-differentiated papillary mesothelioma and benign multicystic mesothelioma-are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)-approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.

  3. Erionite exposure and mesotheliomas in rats.

    PubMed Central

    Wagner, J. C.; Skidmore, J. W.; Hill, R. J.; Griffiths, D. M.

    1985-01-01

    Epidemiological and environmental surveys in the Cappadocian region of Turkey have linked the high incidence of pleural and peritoneal mesothelioma in the occupants of some villages with the zeolite fibres released from the locally occurring volcanic tuff. In view of the low ambient fibre concentrations and the extraordinary incidence of mesothelioma a study to test the hypothesis of high biological activity for the zeolite fibres was required. Experimental studies using both intrapleural inoculation and inhalation techniques have been undertaken with the erionite from this region and from Oregon in the United States. Additionally a non-fibrous zeolite from Japan and a synthetic non-fibrous zeolite of similar chemical composition to erionite have been included in the experiments. In these studies the samples from Oregon and Turkey produced a very high incidence of tumours. All the rats inoculated intrapleurally with Oregon erionite and almost all those inoculated with the Turkish fibre died with a mesothelioma. Inhalation of the Oregon erionite induced a similar effect. No other dusts we have investigated have produced this high incidence of tumours particularly following inhalation. These studies demonstrate that we now have a valuable new fibre for experimental study and a possible hazard to man in regions other then Turkey. PMID:2986668

  4. Diagnosis and treatment of malignant pleural mesothelioma.

    PubMed

    Rodríguez Panadero, Francisco

    2015-04-01

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

  5. Malignant Mesothelioma of the Epididymis: A Case Report.

    PubMed

    Robinson, Jed C; DeFranco, John N; Hollowell, Courtney M P

    2014-10-01

    Malignant mesothelioma of the epididymis is a very rare tumor. We report a case of a 33-year old male with a left hydrocele that presented for evaluation of infertility. Scrotal ultrasound revealed a left extratesticular mass. Final pathology revealed malignant mesothelioma involving the epididymis, with well differentiated epithelioid morphology. Metastatic workup was negative.

  6. Malignant Mesothelioma of the Epididymis: A Case Report

    PubMed Central

    Robinson, Jed C.; DeFranco, John N.; Hollowell, Courtney M. P.

    2014-01-01

    Malignant mesothelioma of the epididymis is a very rare tumor. We report a case of a 33-year old male with a left hydrocele that presented for evaluation of infertility. Scrotal ultrasound revealed a left extratesticular mass. Final pathology revealed malignant mesothelioma involving the epididymis, with well differentiated epithelioid morphology. Metastatic workup was negative. PMID:26195956

  7. Pleural Mesothelioma Presenting as Periumbilical Metastasis: The First Clinical Documentation

    PubMed Central

    Falkenstern-Ge, R. F.; Kimmich, M.; Bode-Erdmann, S.; Friedel, G.; Ott, G.; Kohlhäufl, M.

    2013-01-01

    Introduction. Pleural mesothelioma with metastasis to the subcutaneous tissue of the abdominal wall at first diagnosis and without penetration into the peritoneum is an extremely rare clinical presentation. Methods. Patients with pleural mesothelioma have low survival rate. Usually, the disease at presentation is confined to its site of origin (most often the pleural cavity). A 55-year-old man was referred to our center due to increasing dyspnea and a painful periumbilical mass in the anterior abdominal wall. CT scan revealed both advanced mesothelioma of the pleura and a tumor mass confined to the subcutaneous fatty tissue without penetration through the peritoneum. Results. Video-assisted thoracoscopy confirmed the diagnosis of epithelioid pleural mesothelioma, which was also confirmed by a biopsy of the periumbilical mass. Systemic chemotherapy with cisplatin and pemetrexed was initiated. Under the ongoing systemic chemotherapy, the evaluation revealed partial remission of pleura mesothelioma and its subcutaneous manifestation of the abdominal wall. Conclusion. Mesothelioma of the pleura with a simultaneous metastasis to the subcutaneous fatty tissue of the abdominal wall at presentation without penetration of peritoneum is a rare clinical presentation of mesothelioma disease. The knowledge of its natural history is very limited. This is the first ever clinical documentation of a patient with pleura mesothelioma and simultaneous subcutaneous manifestation of abdominal wall. PMID:23691382

  8. Intercellular communication in malignant pleural mesothelioma: properties of tunneling nanotubes

    PubMed Central

    Ady, Justin W.; Desir, Snider; Thayanithy, Venugopal; Vogel, Rachel I.; Moreira, André L.; Downey, Robert J.; Fong, Yuman; Manova-Todorova, Katia; Moore, Malcolm A. S.; Lou, Emil

    2014-01-01

    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 changes in TnT length over time in comparison to cell proliferation. 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. PMID:25400582

  9. Multicystic peritoneal mesothelioma: not always a benign disease.

    PubMed

    Singh, Ashish; Chatterjee, Parangama; Pai, Mahesh Chandra; Chacko, Raju Titus

    2013-04-01

    Mesothelioma is a slow-growing insidious lesion of neoplastic aetiology arising from the pleural, peritoneal or pericardial mesothelium. It shows a predilection for the surfaces of the pelvic viscera and has a high rate of recurrence after excision. Cystic mesotheliomas are not associated with asbestos exposure. We report a case of cystic mesothelioma of the peritoneum encasing the ovary, which presented as a cystic adnexal mass. As highlighted in this case and other recent reports, a cystic mesothelioma should not be referred to as a benign cystic mesothelioma, as it has potential for locoregional invasion, as well as distant nodal and serosal metastases. This tumour should be treated with aggressive cytoreductive surgery and appropriate chemotherapy. We review the differential diagnosis of this rare entity and suggest guidelines for its differentiation.

  10. Positive TTF-1 Expression in Malignant Mesothelioma: A Case Report

    PubMed Central

    Richter, Georg; Heidersdorf, Holger; Hirschfeld, Dieter; Krebbel, Friedhelm

    2016-01-01

    Patient: Female, 70 Final Diagnosis: Malignant mesothelioma Symptoms: — Medication: — Clinical Procedure: Radiation/Chemotherapy Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: The histopathological diagnosis of malignant mesothelioma is based mainly on the immunohistological profile of the neoplasia, using different immunohistochemical markers to distinguish between a malignant mesothelioma and a carcinoma. Case Report: A female patient presented with a right paravertebral rapidly growing tumor and severe pain. Based on the immunohistochemical findings, we present the first case of a malignant mesothelioma with immunohistochemical expression of thyroid transcription factor-1. Conclusions: The detection of a positive reaction for thyroid transcription factor-1 in the tumor cells may not exclude a malignant mesothelioma. PMID:26939861

  11. Diffuse malignant epithelioid mesothelioma in a background of benign multicystic peritoneal mesothelioma: a case report and review of the literature.

    PubMed

    Mino, Jeffrey S; Monteiro, Rosebel; Pigalarga, Rodolfo; Varghese, Sumi; Guisto, Laura; Rezac, Craig

    2014-02-05

    Peritoneal mesotheliomas are unusual entities with diverse origins and outcomes. Both benign and malignant variants exist. Benign multicystic peritoneal mesotheliomas (BMPMs), also known as multiple or multilocular peritoneal inclusion cysts, are extremely rare tumours arising from the peritoneal mesothelium covering the abdominal serous cavity. Even though these entities are considered benign tumours, BMPMs tend to recur after surgical resection, and in two cases have been reported to undergo malignant transformation. In contrast, diffuse malignant peritoneal mesotheliomas, while also quite rare, are the second most common form of malignant mesothelioma after the pleural variety with extremely high mortality and poor response to many treatments to date. We present a rare case of diffuse malignant peritoneal mesothelioma within a large component of a BMPM in a young man admitted to our service.

  12. Diffuse malignant epithelioid mesothelioma in a background of benign multicystic peritoneal mesothelioma: a case report and review of the literature

    PubMed Central

    Mino, Jeffrey S; Monteiro, Rosebel; Pigalarga, Rodolfo; Varghese, Sumi; Guisto, Laura; Rezac, Craig

    2014-01-01

    Peritoneal mesotheliomas are unusual entities with diverse origins and outcomes. Both benign and malignant variants exist. Benign multicystic peritoneal mesotheliomas (BMPMs), also known as multiple or multilocular peritoneal inclusion cysts, are extremely rare tumours arising from the peritoneal mesothelium covering the abdominal serous cavity. Even though these entities are considered benign tumours, BMPMs tend to recur after surgical resection, and in two cases have been reported to undergo malignant transformation. In contrast, diffuse malignant peritoneal mesotheliomas, while also quite rare, are the second most common form of malignant mesothelioma after the pleural variety with extremely high mortality and poor response to many treatments to date. We present a rare case of diffuse malignant peritoneal mesothelioma within a large component of a BMPM in a young man admitted to our service. PMID:24501333

  13. Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis

    PubMed Central

    Shin, Hyun Deok; Kim, Suk Bae

    2016-01-01

    Benign cystic mesothelioma (BCM) is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis. PMID:27403112

  14. Computed tomography of localized pleural mesothelioma

    SciTech Connect

    Dedrick, C.G.; McLoud, T.C.; Shepard, J.O.; Shipley, R.T.

    1985-02-01

    The computed tomographic (CT) features of six pathologically proven cases of fibrous mesothelioma were reviewed. There were no pathognomonic CT characteristics, but in all cases CT suggested or supported the preoperative diagnosis. CT findings included well delineated, often lobulated, noncalcified soft-tissue masses in close relation to a pleural surface, associated crural thickening, and absence of chest wall invasion. An obtuse angle of the mass with respect to the pleural surface was not particularly useful. Rather, a smoothly tapering margin was more characteristic of a pleural lesion.

  15. Radiation therapy for malignant pleural mesothelioma.

    PubMed

    Rosenzweig, K E; Giraud, P

    2017-02-01

    The treatment of malignant pleural mesothelioma with radiation has always been a technical challenge. For many years, conventional radiation therapy was delivered after extrapleural pneumonectomy with acceptable results. Novel radiation treatment techniques, such as intensity modulated radiation therapy (IMRT) were introduced, but the early experience with IMRT demonstrated troubling toxicity. Recent reports from institutions have demonstrated that with greater experience, IMRT, both in the setting of extrapleural pneumonectomy or pleurectomy, can be delivered safely. A recent study, SAKK 17/04, questions the role of using radiation after extrapleural pneumonectomy.

  16. Non-asbestos-related malignant pleural mesothelioma.

    PubMed

    Kanbay, Asiye; Ozer Simsek, Zuhal; Tutar, Nuri; Yılmaz, Insu; Buyukoglan, Hakan; Canoz, Ozlem; Demir, Ramazan

    2014-01-01

    Malignant pleural mesothelioma (MPM) is an uncommon tumor derived from mesothelial lining cells. MPM has been described as an insidious neoplasm because of its long latency period. The tumor is typically found in patients several decades after asbestos exposure. We herein describe a 26-year-old patient with MPM who presented with pleural effusion. The patient had not been exposed to asbestos or erionite. There are few case reports of non-asbestos-related MPM in young patients. We report this case to remind physicians to consider MPM in the differential diagnosis of pleural effusion in young patients without exposure to asbestos or erionitis.

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma. PMID:26136339

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

    PubMed

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

    2015-07-20

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma.

  20. Cystic peritoneal mesothelioma: report of a case.

    PubMed

    Cavallaro, Andrea; Berretta, Massimiliano; Lo Menzo, Emanuele; Cavallaro, Vincenzo; Zanghì, Antonio; Di Vita, Maria; Cappellani, Alessandro

    2011-01-01

    Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease with good short-term prognosis and rare malignant transformation. However, its biological significance remains unexplained. A neoplastic origin is considered by many authors to require a surgical excision, based on the high recurrence and progressive growth rate of the tumors. However, alternative or integrative treatment options have also been proposed. A 45-year-old woman presented to our unit with a history of occasional discomfort and pain in the left hip. On physical examination, we noticed a tough-elastic, fixed mass located in the iliac fossa. Computed tomography scan detected a mass with multiseptated cystic-like areas. Due to the similarity of these findings to a primitive sarcomatous tumor of the retroperitoneum, an arteriographic study was also performed. The patient underwent en bloc resection of the mass, including a segment of the sigmoid colon. The final pathologic diagnosis was cystic mesothelioma. Further studies are needed to better understand the etiology and pathogenesis of this rare disease, and to define a more tailored treatment plan.

  1. Advances in the management of peritoneal mesothelioma

    PubMed Central

    Raza, Ali; Huang, Wei-Ching; Takabe, Kazuaki

    2014-01-01

    Malignant peritoneal mesothelioma (PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Accordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1 (SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease. PMID:25206274

  2. Epidemiology of malignant mesothelioma--an outline.

    PubMed

    McDonald, J Corbett

    2010-11-01

    In the 1960s and 1970s, well designed case-referent studies put beyond doubt that exposure to airborne asbestos fibres was a cause of malignant mesothelioma. Some 35 cohort mortality studies in a large variety of industries during the 20-year period, 1974-1994, showed a wide range of outcomes, but in general that the risk was higher in exposures which included amphiboles rather than chrysotile alone. Real progress began, however, with discoveries along several lines: the link between pleural changes and mineralogy, the concept and importance of biopersistence, the developments in counting and typing mineral fibres in lung tissue, and data on amphibole mining in South Africa and Australia for comparison with that on chrysotile in Canada and Italy. This led to the recognition of the potential contamination in North America of chrysotile with tremolite. A survey in Canada in 1980-1988 and other surveys demonstrated that crocidolite, amosite, and tremolite could explain almost all cases of mesothelioma. Effective confirmation of this was finally achieved with data on vermiculite miners in Libby, Montana, in the years 1983-1999, where exposure was to tremolite-actinolite and/or other amphibole fibres alone.

  3. Recurrent chromosome 6 abnormalities in malignant mesothelioma.

    PubMed

    Ribotta, M; Roseo, F; Salvio, M; Castagneto, B; Carbone, M; Procopio, A; Giordano, A; Mutti, L

    1998-04-01

    The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.

  4. Pleural mesothelioma and neighborhood asbestos exposure

    SciTech Connect

    Fischbein, A.; Rohl, A.N.

    1984-07-06

    Widespread use and occupational exposure to asbestos in US shipyards, particularly during World War II, is one reason for the currently high incidence of asbestos-related diseases, including lung cancer and mesothelioma. There is typically a long latency period between asbestos exposure and resulting disease. A case report is presented which lends additional credence to the earlier suggestion that exposure to asbestos in the neighborhood of the shipyard may be related to the development of malignant mesothelioma in this particular patient. The identification of amosite asbestos fibers in the lung tissue of the patient provides plausible evidence for this etiologic connection. Amosite asbestos is not found in the lungs of persons from the general population, and its occurrence, therefore, indicates either an occupational exposure or an exposure to a specific environmental source. Although only a very small portion of the total amount of asbestos used consists of amosite, this asbestos type is commonly used in shipbuilding and repair and was used a great deal in the shipyard adjacent to which our patient worked.

  5. [Health expenditures for cases of pleural mesothelioma].

    PubMed

    Zocchetti, C

    2015-09-09

    Through the study of 65 cases of probable pleural mesothelioma currently under discussion in 4 criminal trials in the Lombardy Region, who died between 2002 and 2015, this study aimed to provide economical information regarding the health expenditures sustained by the Regional Health Service (RHS) for providing hospitalization, outpatient services and drugs to such patients. Health information regarding the services provided for the cases under study were electronically retrieved from the RHS information system. For each pleural mesothelioma case the costs (on average) were about 67,000 euros, 37,000 of which were spent after the date of diagnosis. Drugs formed the largest part of health expenditure (about 37,000 euros per person). Per capita expenditures showed a peak near (before and after) the date of diagnosis, rising when approaching the date of death and with increasing age of the patient, and did not vary with survival time. This information, reported for the first time in detail in this paper, will be useful for out-of-court agreements and for setting up reimbursement schemes, and describe per capita expenditures which are higher than estimations proposed in recent criminal trials in Italy and to those reported in the international literature.

  6. Benign Multicystic Peritoneal Mesothelioma: A Rare Tumour of the Abdomen

    PubMed Central

    Somasundaram, Soundappan; Khajanchi, Monty; Vaja, Tejas; Jajoo, Bhushan; Dey, Amit Kumar

    2015-01-01

    Benign multicystic peritoneal mesothelioma: a rare tumor of the abdomen, is a diagnostic dilemma. This report emphasizes the importance of diagnostic laparoscopy in the diagnosis of the tumour. PMID:25866695

  7. Primary pericardial mesothelioma detected by gallium-67 scintigraphy

    SciTech Connect

    Nishikimi, T.; Ochi, H.; Hirota, K.; Ikuno, Y.; Oku, H.; Takeuchi, K.; Takeda, T.

    1987-07-01

    We present a case report of a 73-yr-old woman with progressive systemic sclerosis who showed extensive pericardial uptake of /sup 67/Ga by scintigraphy. At autopsy, primary pericardial mesothelioma was found.

  8. Lung-Sparing Surgery May Boost Mesothelioma Survival

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162720.html Lung-Sparing Surgery May Boost Mesothelioma Survival Treatment nearly ... 23, 2016 (HealthDay News) -- Surgery that preserves the lung, when combined with other therapies, appears to extend ...

  9. Switching off malignant mesothelioma: exploiting the hypoxic microenvironment

    PubMed Central

    Nabavi, Noushin; Bennewith, Kevin L.; Churg, Andrew; Wang, Yuzhuo; Collins, Colin C.; Mutti, Luciano

    2016-01-01

    Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention. PMID:28191281

  10. Case report: peritoneal mesothelioma from asbestos in hairdryers.

    PubMed

    Dahlgren, James; Talbott, Patrick

    2015-01-01

    The relationship between mesothelioma and exposure to asbestos is well established. As a result, the use of asbestos in buildings, construction sites, and mines, as well as the implications of disease for the workers has received considerable attention. However, asbestos was also used in household equipment and consumer products, including hairdryers. To examine one case of peritoneal mesothelioma in a hairdresser and review the relevant literature on asbestos exposure from hairdryers. The subject's medical and occupational records were obtained and reviewed and a physical examination was performed. The results indicate that the subject developed peritoneal mesothelioma from her occupational exposure to asbestos containing hairdryers in accordance with the literature. Hairdryers are possible sources of asbestos exposure in patients with mesothelioma, and the asbestos exposure risk is higher for those who use hairdryers occupationally.

  11. Malignant mesothelioma mortality in the United States, 1999-2001.

    PubMed

    Bang, Ki Moon; Pinheiro, Germania A; Wood, John M; Syamlal, Girija

    2006-01-01

    Malignant mesothelioma is strongly associated with asbestos exposure. This paper describes demographic, geographic, and occupational distributions of mesothelioma mortality in the United States, 1999-2001. The data (n = 7,524) were obtained from the National Center for Health Statistics multiple-cause-of-death records. Mortality rates (per million per year) were age-adjusted to the 2000 U.S. standard population, and proportionate mortality ratios (PMRs) were calculated by occupation and industry, and adjusted for age, sex, and race. The overall age-adjusted mortality rate was 11.52, with males (22.34) showing a sixfold higher rate than females (3.94). Geographic distribution of mesothelioma mortality is predominantly coastal. Occupations with significantly elevated PMRs included plumbers/pipefitters and mechanical engineers. Industries with significantly elevated PMRs included ship and boat building and repairing, and industrial and miscellaneous chemicals. These surveillance findings can be useful in generating hypotheses and developing strategies to prevent mesothelioma.

  12. Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma.

    PubMed

    Hung, Yin P; Dong, Fei; Watkins, Jaclyn C; Nardi, Valentina; Bueno, Raphael; Dal Cin, Paola; Godleski, John J; Crum, Christopher P; Chirieac, Lucian R

    2017-09-14

    Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown. To investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors. We studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma. Identification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics. Anaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P = .02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or

  13. Benign peritoneal multicystic mesothelioma diagnosed and treated by laparoscopic surgery.

    PubMed

    Saad, Stefan; Brockmann, Michael; Maegele, Marc

    2007-10-01

    Benign cystic mesothelioma is a rare pathology predominantly encountered in females. The increased use of laparoscopy for abdominal pain, particularly in female patients, implies that surgeons are aware of the macro- and laparoscopic presentation of this tumor for adequate diagnosis and therapy. In this paper, we present the case of a young woman with benign multicystic mesothelioma in which only laparoscopy led to the appropriate diagnosis. Subsequently, the tumor was removed by laparoscopic surgery.

  14. Quantitative and analytical studies in the diagnosis of mesothelioma

    SciTech Connect

    Roggli, V.L. )

    1992-05-01

    The vast majority of patients with malignant mesothelioma of the pleura or peritoneum have an abnormal tissue asbestos content as assessed by digestion techniques. These procedures allow for the quantification of asbestos bodies, as well as numbers and types of mineral fibers. In general, analyses of mineral fiber content correlate well with occupational exposure history. Such analyses are useful for the identification of asbestos-related mesotheliomas and separation from those due to other causes.

  15. [Localized benign pleural mesothelioma observed at the Dakar University Hospital].

    PubMed

    Ndiaye, M; Hane, A A; Ba, M; Ndir, M; Ba, O; Diop-dia, D; Kandji, M; Ndiaye, S; Diatta, A; Toure, N O; Niang, A; Dia, Y; Thiam, A; Dangou, J M; Ndiaye, M

    2001-06-01

    We report two cases of localized benign pleural mesothelioma with different clinical features. Neuropsychiatric symptoms, including coma, hemiplegia, seizures and misbehavior predominated in the first case, associated with hypoglycemia. The symptoms in the second case were essentially respiratory (cough, dyspnea, and chest pain). Treatment consisted in thoracotomy and complete surgical resection. Histopathology revealed fusiform cells and collagen stroma. These two cases illustrate the diversity of clinical expression of benign localized pleural mesothelioma and confirm their complete resolution after surgical treatment.

  16. Pleural plaques and the risk of pleural mesothelioma.

    PubMed

    Pairon, Jean-Claude; Laurent, François; Rinaldo, Mickaël; Clin, Bénédicte; Andujar, Pascal; Ameille, Jacques; Brochard, Patrick; Chammings, Soizick; Ferretti, Gilbert; Galateau-Sallé, Françoise; Gislard, Antoine; Letourneux, Marc; Luc, Amandine; Schorlé, Evelyne; Paris, Christophe

    2013-02-20

    The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers. Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided. A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos). The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

  17. Relative risk of mesothelioma among railroad machinists exposed to chrysotile.

    PubMed

    Mancuso, T F

    1988-01-01

    This study challenges the assertion of low relative risk of chrysotile in the causation of mesothelioma. Data are provided on the time period use of various types of asbestos in the United States and in insulation materials. The focus of the study is on mesothelioma among railroad machinists employed in the steam locomotive era who were exposed to chrysotile. Within a cohort of machinists alive January 1, 1945, a sub-cohort method was applied to all successive machinists hired in each of the respective years (1920-1929) followed through 1986. The total cohort was 181 and the number of deaths 156, with 14 mesotheliomas identified among 41 cancer deaths. The findings demonstrated an extremely high relative risk for machinists exposed to chrysotile for the induction of mesothelioma in the individual year of hire cohorts. A similar observation was noted for other crafts hired in the same time period. One mesothelioma occurred for every 13 machinists hired in the succeeding years (1920-1929) and constituted 34% of all cancer deaths. It is concluded that chrysotile is far more hazardous in the induction of mesotheliomas and that the asbestos cancer risk in the steam locomotive eras was much higher than had been previously estimated.

  18. Software for Apportionment of Asbestos-Related Mesotheliomas.

    PubMed

    Ross, Robert M

    2016-01-01

    Patients with an asbestos-related mesothelioma may be legally entitled to financial compensation. In this context, a physician may be called upon to apportion the contribution of an asbestos containing product or facility where there was asbestos exposure in the development of that individual's mesothelioma. This task is mathematically not simple. It is a complex function of each and the entire individual's above-background asbestos exposures. Factors to be considered for each of these exposures are the amount of exposure to mesotheliogenic fibers, each of the asbestos containing products' potency to cause mesothelioma, and the time period when the exposures occurred relative to when the mesothelioma was diagnosed. In this paper, the known factors related to asbestos-related mesothelioma risk are briefly reviewed and the software that is downloadable and fully functional in a Windows® environment is also provided. This software allows for rapid assessment of relative contributions and deals with the somewhat tedious mathematical calculations. With this software and a reasonable occupational history, if it is decided that the mesothelioma was due to above-background asbestos exposure, the contribution of an asbestos containing product or a time period of asbestos exposure can be apportioned.

  19. Hyaluronan production increases the malignant properties of mesothelioma cells

    PubMed Central

    Li, Y; Heldin, P

    2001-01-01

    Malignant pleural mesotheliomas is in most cases associated with elevated amounts of hyaluronan. To investigate the importance of hyaluronan for the malignant properties of mesotheliomas, we have expressed murine hyaluronan synthase 2 (HAS2) in the non-hyaluronan producing mesothelioma cell line, Mero-25. We found that upon hyaluronan overproduction the mesothelioma cells changed their epitheloid character to a fibroblastic phenotype and were surrounded by pericellular matrices, the size of which correlated to the amount of synthesized hyaluronan. HAS2-transfected cells with the ability to synthesize about 520 ng hyaluronan/5 × 104cells/24 h exhibited about a 2-fold increase in the expression of the cell surface hyaluronan receptor CD44 and their locomotion increased compared to that of mock-transfected Mero-25 cells. Furthermore, the malignant properties of mesothelioma cell clones as determined by the ability to grow in a soft agar assay correlated to their hyaluronan production. These results provide evidence for an important role of hyaluronan in the aggressive spread of mesotheliomas in adjacent non-cancerous stromal tissues. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506502

  20. Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

    PubMed Central

    Hudson, Amanda L.; Weir, Chris; Moon, Elizabeth; Harvie, Rozelle; Klebe, Sonja; Clarke, Stephen J.; Pavlakis, Nick; Howell, Viive M.

    2014-01-01

    Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16INK4A/p14ARF and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies. PMID:25141917

  1. Modern management of malignant pleural mesothelioma

    PubMed Central

    Patel, Shivani C; Dowell, Jonathan E

    2016-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease that produces a significant worldwide health care burden. The majority of cases are associated with prior asbestos exposure, but recent studies have identified a possible genetic predisposition in a minority of patients. Historically, obtaining a pathologic diagnosis of MPM was challenging, but with current pathological techniques, a secure diagnosis is possible in the majority of patients. Curative therapy for MPM remains elusive, and the primary treatment option for fit patients is platinum-based chemotherapy. Encouraging recent reports suggest that there may be a benefit to the addition of bevacizumab to standard chemotherapy as well as with the use of immune checkpoint inhibitors in MPM. Selected patients may be considered for aggressive surgical approaches, but there is considerable controversy regarding the true benefit of surgery and multimodality therapy in this disease. PMID:28210162

  2. Hedgehog Signaling in Malignant Pleural Mesothelioma

    PubMed Central

    Felley-Bosco, Emanuela; Opitz, Isabelle; Meerang, Mayura

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition. PMID:26184317

  3. Hedgehog Signaling in Malignant Pleural Mesothelioma.

    PubMed

    Felley-Bosco, Emanuela; Opitz, Isabelle; Meerang, Mayura

    2015-07-08

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

  4. Photodynamic therapy for malignant pleural mesothelioma.

    PubMed

    Friedberg, Joseph S

    2012-10-01

    Surgery is the treatment option most likely to be associated with prolonged remission in patients with malignant pleural mesothelioma. However, it remains investigational and must always be combined with other modalities to treat the microscopic disease that remains after the most aggressive operations. Improvements in quality of life for appropriate patients with this rare yet incurable cancer may be obtained with less drastic lung-sparing surgical procedures along with intraoperative use of photodynamic therapy (PDT). Very encouraging survival results have been obtained with the combination of surgery and PDT, which requires the well-orchestrated collaborative effort of an extensive team of professionals, from thoracic surgeons and radiation oncologists to basic science researchers. Multi-institutional trials are necessary to duplicate these early findings and shed more light on the tumor-directed immune response of this surgically based multimodal treatment.

  5. Malignant mesothelioma: facts, myths, and hypotheses.

    PubMed

    Carbone, Michele; Ly, Bevan H; Dodson, Ronald F; Pagano, Ian; Morris, Paul T; Dogan, Umran A; Gazdar, Adi F; Pass, Harvey I; Yang, Haining

    2012-01-01

    Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. J. Cell. Physiol. 227: 44-58, 2012. © 2011 Wiley Periodicals, Inc. Copyright © 2011 Wiley Periodicals, Inc.

  6. Epidemiologic surveillance of mesothelioma in Umbria.

    PubMed

    Petrucci, Maria Saba; De Lio, Maria Cristina; D'Alò, Daniela; Stracci, Fabrizio; Masanotti, Giuseppe Michele

    2015-01-01

    Malignant mesothelioma (MM) is becoming a prominent health issue due to its low survival and for its increasing incidence in various countries. The objectives of this study were to evaluate epidemiological characteristics and trends of MM in the Umbrian Region for the period 2003-2013. All cases of MM reported to Umbrian Population Cancer Registry between 2003 and 2013. Incidence Annual Standardized Rates (ASRs) were analyzed for all histological types of MM. Estimated Annual Percent Change (APC) and joinpoint regression analysis were used to out light the time trend of MM. Geographical distribution of the relative risk for each municipality was calculated by Standardized Incidence Ratios SIRs. 191 (156 males) MM cases were recorded in Umbrian residents in the period 2003-2013. Pleural mesothelioma affected 92.1% of the total. Gender ratio M/F was 5.9:1. ASRs for MM was 3.2 among men and 0.6 among women. Joinpoint analysis showed a decrease in females APC -8.4 (95% IC -33.7-26.6) and an increase in males APC 5.8 (95% IC -0.9-13.0). An occupational exposure was identified in 43.7% of females and in 90.7% of males. The protracted cancer latency and the continued asbestos existence as environmental contaminant in existing buildings, as well as a carcinogenic risk for the workers involved in removing operations of material containing asbestos justifies the investment in a specific surveillance system. Also important would be to implement a national risk communication strategy addressed to the general population, environment surveillance of the high risk areas and guarantee that all workers involved that even may deal with asbestos are always fully equipped and trained, not only for their individual risk but also for the potential risk of non correct disposal.

  7. Malignant Mesothelioma: Facts, Myths and Hypotheses

    PubMed Central

    Carbone, Michele; Ly, Bevan H.; Dodson, Ronald F.; Pagano, Ian; Morris, Paul T.; Dogan, Umran A.; Gazdar, Adi F.; Pass, Harvey I.; Yang, Haining

    2011-01-01

    Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. PMID:21412769

  8. DATASET FOR REPORTING OF MALIGNANT MESOTHELIOMA OF THE PLEURA OR PERITONEUM: RECOMMENDATIONS FROM THE INTERNATIONAL COLLABORATION ON CANCER REPORTING (ICCR)

    PubMed Central

    Churg, Andrew; Attanoos, Richard; Borczuk, Alain C; Chirieac, Lucian R; Galateau-Sallé, Francoise; Gibbs, Allen; Henderson, Douglas; Roggli, Victor; Rusch, Valerie; Judge, Meagan J; Srigley, John R

    2016-01-01

    Context The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organisation formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologists (CAP-ACP) in association with the Canadian Partnership Against Cancer (CPAC), and the European Society of Pathology (ESP). Its goal is to produce common, internationally agreed, evidence-based datasets for use throughout the world. Objective and Design This paper describes a dataset developed by the ICCR expert panel for the reporting of malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of elements ‘required’ (mandatory) and ‘recommended’ (non-mandatory), which are based on a review of the most recent evidence and supported by explanatory commentary. Results Eight required elements and seven recommended elements were agreed by the expert panel to represent the essential information for the reporting of malignant mesothelioma of the pleura and peritoneum. Conclusions In time, the widespread utilisation of an internationally agreed, structured pathology dataset for mesothelioma will lead not only to improved patient management but provide valuable data for research and international benchmarking. PMID:27031777

  9. Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

    PubMed

    Churg, Andrew; Attanoos, Richard; Borczuk, Alain C; Chirieac, Lucian R; Galateau-Sallé, Françoise; Gibbs, Allen; Henderson, Douglas; Roggli, Victor; Rusch, Valerie; Judge, Meagan J; Srigley, John R

    2016-10-01

    -The International Collaboration on Cancer Reporting is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom; the College of American Pathologists; the Canadian Association of Pathologists-Association Canadienne des Pathologists, in association with the Canadian Partnership Against Cancer; and the European Society of Pathology. Its goal is to produce common, internationally agreed upon, evidence-based datasets for use throughout the world. -To describe a dataset developed by the Expert Panel of the International Collaboration on Cancer Reporting for reporting malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of "required" (mandatory) and "recommended" (nonmandatory) elements. -Based on a review of the most recent evidence and supported by explanatory commentary. -Eight required elements and 7 recommended elements were agreed upon by the Expert Panel to represent the essential information for reporting malignant mesothelioma of the pleura and peritoneum. -In time, the widespread use of an internationally agreed upon, structured, pathology dataset for mesothelioma will lead not only to improved patient management but also provide valuable data for research and international benchmarks.

  10. NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

    PubMed Central

    2012-01-01

    Background An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta (ß) activated within the inflammasome complex. NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1ß secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM. Methods 134 Italian patients with diagnosis of mesothelioma due (MMAE, n=69) or not (MMAF, n=65) to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos (HCAE) were genotyped for NLRP1 (rs2670660 and rs12150220) and NLRP3 (rs35829419 and rs10754558) polymorphisms. Results While NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE (0.55) than in HCAE (0.41) (p=0.011; OR=1.79) suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele (p=0.004; OR=0.52). Conclusion Although NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma. PMID:23031505

  11. Neurotensin expression and outcome of malignant pleural mesothelioma.

    PubMed

    Alifano, Marco; Loi, Mauro; Camilleri-Broet, Sophie; Dupouy, Sandra; Régnard, Jean François; Forgez, Patricia

    2010-02-01

    Malignant pleural mesothelioma is a frequently fatal disease and the impact of available treatments is globally poor. Identification of new prognostic factors would help in the understanding of disease progression and, possibly, patient management. Here, we evaluate the prognostic impact of the neurotensin (NTS) and its cognate receptor (NTSR1) known for mediating cellular proliferation, survival, invasiveness, and mobility. We studied a series of 52 consecutive patients with epithelioid malignant mesothelioma undergoing management with curative intent, by immunohistochemistry for the expression of NTS and NTSR1. Specimens were scored as 0, 1, or 2 for less than 10%, between 10 and 50%, or more than 50% of NTS positive staining in tumor cells, respectively. Immunohistochemistry revealed that NTS and NTSR1 expression was found in 71.1% and 90.4% of malignant mesotheliomas, respectively. Using univariate analysis, expression of NTS was significantly (p = 0.015) related with a poor prognosis, with median survivals of 11.0 months, 18.4 months, and 29.8 months in patients showing expression scored as 2, 1, and 0, respectively. Multivariate analysis showed that expression of NTS (p = 0.007) and non-surgical therapy (p = 0.004) were independent predictors of poor prognosis. In order to evaluate the role of NTS/NTSR1 complex in mesothelioma progression, in vitro cell invasion assays and wound healing were performed on the mesothelioma cell line, MSTO-211H, and showed that inhibition of the NTS system resulted in a significant reduction of both migration and collagen invasion of mesothelioma cells. The expression of NTS is identified as a prognostic marker in patients with malignant pleural mesothelioma (Patent EP 08305971.7).

  12. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2017-08-22

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  13. An autopsy case of malignant mesothelioma associated with asbestosis.

    PubMed

    Watanabe, M; Kimura, N; Kato, M; Iwami, D; Takahashi, M; Nagura, H

    1994-01-01

    An autopsy case of malignant mesothelioma with asbestosis caused by asbestos exposure for 17 years is reported. Autopsy revealed that mesothelioma spread extensively in all serosal tissues including pleura, pericardium, diaphragm, peritoneum and tunica vaginalis testis. Histopathologically, most of the tumor showed an epithelial form, but sarcomatous and microcystic patterns were also observed. The tumor cells had abundant glycogen and hyaluronic acid and, immunohistochemically, they were positive for cytokeratin, vimentin and epithelial membrane antigen (EMA). Long, slender microvilli were characteristically observed in these tumor cells. All of these data were compatible with malignant mesothelioma. Procollagen type I (procol.l) immunostaining was performed to reveal the mesenchymal character of mesothelioma. Both epithelial-type cells and sarcomatous-type cells showed positive staining for procol.l, although the latter showed stronger immunoreactivity. Immunostaining for procol.l was found to be one of the useful tools for distinguishing mesothelioma from adenocarcinoma. Using an extraction method for asbestos fibers, asbestos bodies were found in many tissues including lymph nodes, liver, small intestine, spleen, kidney, testis and pleura, in addition to lung parenchyma. Although multiple tumor metastases from an undetermined primary site is not ruled out, 'multifocal tumorigenesis' is suspected from the widespread deposit of asbestos fibers.

  14. Mapping the risk of mesothelioma due to neighborhood asbestos exposure.

    PubMed

    Kurumatani, Norio; Kumagai, Shinji

    2008-09-15

    Little is known about neighborhood exposure to asbestos and mesothelioma risk among residents around an industrial source of asbestos. To investigate the magnitude of the risk among residents by asbestos exposure levels and to determine the range of the area affected by asbestos. We calculated standardized mortality ratios of mesothelioma from 1995 to 2006 among the estimated population at risk that lived around a former large asbestos cement pipe plant in Amagasaki City, Japan, between 1957 and 1975, the time when the plant had used crocidolite and chrysotile. The distance between the plant and homes and relative asbestos concentrations obtained by diffusion equations involving meteorological conditions were used to determine asbestos exposure levels among residents. We identified 73 mesothelioma deaths of 35 men and 38 women who had no occupational exposure to asbestos. Among persons who had lived within a 300-m radius of the plant, the standardized mortality ratio of mesothelioma was 13.9 (95% confidence interval, 5.6-28.7) for men and 41.1 (95% confidence interval, 15.2-90.1) for women. When the study area was divided into five regions by relative asbestos concentration, standardized mortality ratios of mesothelioma declined, for both sexes, in a linear dose-dependent manner with concentration. The regions with a significantly elevated standardized mortality ratio reached 2,200 m from the plant in the same direction in which the wind predominantly blew. Neighborhood exposure to asbestos can pose a serious risk to residents across a wide area.

  15. Projection of mesothelioma mortality in Britain using Bayesian methods

    PubMed Central

    Tan, E; Warren, N; Darnton, A J; Hodgson, J T

    2010-01-01

    Background: Mesothelioma mortality has increased more than ten-fold over the past 40 years in Great Britain, with >1700 male deaths recorded in the British mesothelioma register in 2006. Annual mesothelioma deaths now account for >1% of all cancer deaths. A Poisson regression model based on a previous work by Hodgson et al has been fitted, which has allowed informed statistical inferences about model parameters and predictions of future mesothelioma mortality to be made. Methods: In the Poisson regression model, the mesothelioma risk of an individual depends on the average collective asbestos dose for the individual in a given year and an age-specific exposure potential. The model has been fitted to the data within a Bayesian framework using the Metropolis–Hastings algorithm, a Markov Chain Monte Carlo technique, providing credible intervals for model parameters as well as prediction intervals for the number of future cases of mortality. Results: Males were most likely to have been exposed to asbestos between the ages of 30 and 49 years, with the peak year of asbestos exposure estimated to be 1963. The estimated number of background cases was 1.08 cases per million population. Conclusion: Mortality among males is predicted to peak at approximately 2040 deaths in the year 2016, with a rapid decline thereafter. Approximately 91 000 deaths are predicted to occur from 1968 to 2050 with around 61 000 of these occurring from 2007 onwards. PMID:20628377

  16. Reactive oxygen species a double-edged sword for mesothelioma.

    PubMed

    Benedetti, Serena; Nuvoli, Barbara; Catalani, Simona; Galati, Rossella

    2015-07-10

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display 'asbestos-like' pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review.

  17. Reactive oxygen species a double-edged sword for mesothelioma

    PubMed Central

    Catalani, Simona; Galati, Rossella

    2015-01-01

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10–15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display ‘asbestos-like’ pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review. PMID:26078352

  18. Asbestos exposure and mesothelioma incidence and mortality in Bulgaria.

    PubMed

    Vangelova, Katya; Dimitrova, Irina

    2016-06-01

    Bulgaria totally banned the import, production and use of asbestos in 2005, but produced and used asbestos products during the last 3-4 decades of the 20th century. The aim of this study was to follow the incidence and mortality of mesothelioma in Bulgaria in relation to past occupational exposures. A literature search between 1960 and 2014 was conducted to obtain information on asbestos consumption, occupational exposure and asbestos-related diseases (ARDs). Data on registered mesotheliomas were provided by the National Cancer Register and data for recognized occupational ARDs were provided by the National Social Security Institute. An increase in the incidence of mesothelioma from 5 to 58 from 1993 to 2013, with 666 cases in the 21-year period, was registered. Incidence, mortality rates, deaths and male-to-female ratios and were lower in comparison to industrialized countries. The increase in mesothelioma incidence is considered as a consequence of more recent production and use of asbestos and asbestos products and the high occupational exposure between 1977 and 1989, while the lower rate of mesothelioma deaths and male-to-female ratio need to be investigated further.

  19. Emerging insights into the biology and therapy of malignant mesothelioma.

    PubMed

    Vogelzang, Nicholas J

    2002-12-01

    Malignant mesothelioma is an aggressive malignancy that may be caused by environmental carcinogens (asbestos and erionite), viruses (SV40), and genetic predisposition. Pleural malignant mesotheliomas are far more common than the peritoneal variants. Diagnosis relies on radiographic studies as well as histology and molecular biologic analyses. The prognostic scoring systems of the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer are the most useful of those currently available. These systems rate performance status, age, histology, and hematologic parameters as the best prognostic factors for mesothelioma. Most patients with mesothelioma are not candidates for surgical or radiotherapy treatment, and cytotoxic agents are the only options. Historically, no classes or combinations of agents consistently yielded response rates over 20%. Recently, pemetrexed has been evaluated in phase I, II, and III clinical trials with promising results. The phase II trial showed an overall response rate of 14.1% with a 1-year survival rate of 47.8%. A phase III trial of cisplatin versus cisplatin and pemetrexed closed in February 2002 and a final analysis was presented in May 2002. Novel targeted agents are also being tested in clinical trials among mesothelioma patients and include drugs inhibiting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, and platelet-derived growth factor receptor.

  20. Occurrence of malignant peritoneal mesothelioma after surgery and irradiation for cervical cancer

    SciTech Connect

    Beier, K.M.; Gallup, D.G.; Burgess, R.; Stock, R.J.

    1984-03-01

    Mesothelioma of the peritoneal cavity after irradiation is rare, and the diagnosis is sometimes difficult to establish. The following case is a report of a mesothelioma occurring 9 years after radiation therapy for carcinoma of the cervix. In this patient, who had a hysterectomy and bilateral oophorectomy 7 years prior to the mesothelioma diagnosis, the histologic, histochemical, and ultrastructural findings were all consistent with a diagnosis of malignant peritoneal mesothelioma. It is believed that this case is one of the first well-documented cases of peritoneal mesothelioma in a female who was treated by pelvic irradiation for another neoplasm.

  1. [Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

    PubMed

    Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

    2016-04-01

    Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

  2. High dose of ascorbic acid induces cell death in mesothelioma cells.

    PubMed

    Takemura, Yukitoshi; Satoh, Motohiko; Satoh, Kiyotoshi; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

    2010-04-02

    Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

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

    DOE PAGES

    Yang, Yi -Lin; Ni, Jian; Hsu, Ping -Chih; ...

    2015-07-27

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressedmore » and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.« less

  4. Susceptibility and resistance in the genesis of asbestos-related mesothelioma

    PubMed Central

    Bianchi, Claudio; Bianchi, Tommaso

    2008-01-01

    Asbestos is the principal agent in the etiology of malignant mesothelioma. However, a small proportion of people exposed to asbestos develop mesothelioma. This suggests the role of host factors in the genesis of the tumor. A genetic susceptibility is suggested by the occurrence of more mesothelioma cases among blood-related members of a single family. Such an occurrence reached about 4% in a large mesothelioma series. In some studies, mesothelioma patients showed higher prevalences of additional malignancies when compared with controls. This indicates a particular vulnerability to cancer in people with mesothelioma. Not rarely, very old persons heavily exposed to asbestos remain free from asbestos-related cancer, a fact indicating an absolute resistance to the oncogenic effects of asbestos. A relative resistance may be recognized in people severely exposed to asbestos who develop mesothelioma only after 60 years or more since the onset of the exposure. The long survivals, rarely observed among mesothelioma patients, have been attributed to a high efficiency of immune mechanisms. Mesotheliomas have been reported among people with severe immune impairment, such as acquired immunodeficiency syndrome patients or organ transplant recipients. The natural history of mesothelioma shows that a resistance to the oncogenic effects of asbestos does exist. Probably, such a resistance is due to the efficient immune mechanisms. To strengthen the defence mechanisms may represent a way for preventing mesothelioma among people exposed to asbestos. PMID:20040979

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

    SciTech Connect

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

    2015-07-27

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.

  6. Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States.

    PubMed

    Lemen, Richard A

    2016-01-01

    Mesothelioma, a rare tumor, is highly correlated with asbestos exposure. Mesothelioma, similar to all asbestos-related diseases, is dose/intensity dependent to some degree, and studies showed the risk of mesothelioma rises with cumulative exposures. Multiple processes occur in an individual before mesothelioma occurs. The impact of mesothelioma in the United States has been continuous over the last half century, claiming between 2,000 and 3,000 lives each year. Mesothelioma is a preventable tumor that is more frequently reported as associated with asbestos exposure among men than women. However, the rate of asbestos-associated mesothelioma is on the rise among women due to better investigation into their histories of asbestos exposure. It is of interest that investigators detected asbestos-associated cases of mesothelioma in women from nonoccupational sources-that is, bystander, incidental, or take-home exposures. It is postulated that asbestos-associated mesotheliomas, in both men and women, are likely underreported. However, with the implementation of the most recent ICD-10 coding system, the correlation of mesothelioma with asbestos exposure is expected to rise to approximately 80% in the United States. This study examined the demographic and etiological nature of asbestos-related mesothelioma.

  7. Accuracy of pathological diagnosis of mesothelioma cases in Japan: clinicopathological analysis of 382 cases.

    PubMed

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

    2009-11-01

    Incidences of mesothelioma are on the rise in Japan. However, the accurate frequency of mesothelioma occurrence is still unknown. The aim of this study is to clarify the accuracy of pathological diagnosis of mesothelioma. Among the 2742 mesothelioma death cases extracted from the document "Vital Statistics of Japan" for 2003-2005, pathological materials were obtained for 382 cases. After these materials were reviewed and immunohistochemical analyses were conducted, mesothelioma was diagnosed by discussions based on clinical and radiological information. Sixty-five cases (17.0%) were categorized as "definitely not/unlikely" mesotheliomas, and 273 cases (71.5%) were categorized as "probable/definite" mesotheliomas. The percentage of "probable/definite" pleural and peritoneal mesothelioma cases in males was 74.3% and 87.5%, respectively, and that of pleural cases in females was 59.2%; however, the percentage of "probable/definite" peritoneal cases in females was only 22.2%. These results suggest that the diagnostic accuracy of mesothelioma is relatively low in females and in cases of peritoneal and sarcomatoid subtype mesotheliomas; furthermore, approximately 15% of cases of deaths due to mesothelioma in Japan are diagnostically suspicious.

  8. [Recurrent benign multicystic peritoneal mesothelioma: Approach to this rare condition].

    PubMed

    García-Mayor Fernández, Ricardo Lucas; Fernández-González, María; López-Rodríguez, Alberto; Martínez-Almeida Fernández, Rafael

    Benign multicystic mesothelioma is a rare benign tumour derived from the peritoneal mesothelium. The aim of this paper is to present a case of this rare tumour and review the clinical features, diagnosis and treatment of this disease. The case is presented of a 22-year-old female diagnosed with multicystic mesothelioma after an urgent resection of intra-abdominal tumour in the context of acute abdominal pain. In the subsequent follow-up, the patient had a recurrence of the lesion, and at 2 years was treated by further resection. Benign multicystic mesothelioma is a benign tumour of unknown origin, and with a non-specific clinical manifestation. The most effective treatment is surgical, although there is a high tendency to local recurrence. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Ganglioneuroblastoma: Unusual presentation as a pleural mass mimicking mesothelioma.

    PubMed

    Jain, Bhawna Bhutoria; Ghosh, Sanchita; Das, Murari Mohan; Chattopadhyay, Sarbani

    2016-01-01

    Ganglioneuroblastoma (GNB) is a rare peripheral neuroblastic tumor that is derived from developing neuronal cells of the sympathetic nervous system, and usually occurs in young children. We present a case of GNB occurring as pleural mass in a 2-year-old boy, which led to diagnostic confusion. On fine-needle aspiration cytology (FNAC), it was misinterpreted as mesothelioma. He underwent thoracotomy with excision of the mass. Histopathological findings showed features of a biphasic tumor suggestive of mesothelioma. Immunohistochemistry (IHC) performed for mesothelioma markers were inconclusive. On review of the histology slides, GNB was considered, which was subsequently proven by IHC. The rarity of this tumor, along with its nearly restricted occurrence at a young age, necessitates a strong suspicion in patients presenting with a symptomatic intrathoracic mass.

  10. Multiple distant metastases in a case of malignant pleural mesothelioma

    PubMed Central

    Tertemiz, Kemal Can; Ozgen Alpaydin, Aylin; Gurel, Duygu; Savas, Recep; Gulcu, Aytac; Akkoclu, Atila

    2014-01-01

    Introduction Malignant pleural mesothelioma (MPM) is a malignant of mesodermal neoplasm and arises from multipotential mesothelial or subserosal cells of the pleura, pericardium and peritoneum. Case A seventy five year-old male patient was admitted with chest and lower limb pain. He was a heavy smoker and exposed to environmental asbestos in his childhood. PET-CT scans showed multiple pathological FDG uptakes in lungs and other organs. Biopsies performed from lung and anterior thigh muscles were reported as epitheloid type malignant pleural mesothelioma. Discussion We emphasize that unexpected distant metastases can be observed in MPM and occasionally primary diagnosis can be determined by the biopsy of the metastatic regions. This case also points out the role of PET-CT in the staging of malign mesothelioma by determining different metastatic sites. PMID:26029551

  11. Laparoscopic diagnosis of pleural mesothelioma presenting with pseudoachalasia

    PubMed Central

    Saino, Greta; Bona, Davide; Nencioni, Marco; Rubino, Barbara; Bonavina, Luigi

    2009-01-01

    Pseudoachalasia due to pleural mesothelioma is an extremely rare condition. A 70-year-old woman presented with progressive dysphagia for solid and liquids and a mild weight loss. A barium swallow study revealed an esophageal dilatation and a smoothly narrowed esophagogastric junction. An esophageal manometry showed absence of peristalsis. Endoscopy demonstrated an extrinsic stenosis of the distal esophagus with negative biopsies. A marked thickening of the distal esophagus and a right-sided pleural effusion were evident at computed tomography (CT) scan, but cytological examination of the thoracic fluid was negative. Endoscopic ultrasound showed the disappearance of the distal esophageal wall stratification and thickening of the esophageal wall. The patient underwent an explorative laparoscopy. Biopsies of the esophageal muscle were consistent with the diagnosis of epithelioid type pleural mesothelioma. An esophageal stent was placed for palliation of dysphagia. The patient died four months after the diagnosis. This is the first reported case of pleural mesothelioma diagnosed through laparoscopy. PMID:19630117

  12. Malignant mesothelioma in non-asbestos textile workers in Florence

    SciTech Connect

    Paci, E.; Dini, S.; Buiatti, E.; Seniori Costantini, A.; Lenzi, S.; Zappa, M.

    1987-01-01

    By means of a review of histological diagnosis in the Pathology Department of the University of Florence, suspected cases of malignant mesothelioma, diagnosed in the period 1979-1984, were identified. Study of histological specimens permitted the selection of 13 cases of malignant mesothelioma resident in the Province of Florence. To these cases, referents were matched for age, sex, and year of hospital admission, with residence weighted for the general population of the Province. Both cases and referents (or their next of kin) completed an occupational questionnaire detailing possible occupational exposures. Out of the 13 cases of mesothelioma, 6 were textile workers and 5 of these were rag-sorters. There were only 5 textile workers among the 52 controls. No asbestos cloth production plants have been in operation in the area from which the cases and referents are derived. Possible sources of exposure to asbestos in the textile industry of this area are discussed.

  13. Benign Cystic Peritoneal Mesothelioma Revealed by Small Bowel Obstruction

    PubMed Central

    Bray Madoué, Kaimba; Boniface, Moifo; Annick Laure, Edzimbi; Pierre, Herve

    2016-01-01

    Benign cystic peritoneal mesothelioma is a rare tumor which frequently occurs in women of reproductive age. Abdominal pain associated with pelvic or abdominal mass is the common clinical presentation. We report the case of a 22-year-old woman with a pathological proved benign cystic mesothelioma of the peritoneum revealed by a small bowel obstruction and a painful left-sided pelvic mass with signs of psoitis. Contrast enhanced abdominal CT-scan demonstrated a large pelvic cystic mass with mass effect on rectosigmoid and pelvic organs. The patient underwent surgical removal of the tumor. Pathological examination revealed the diagnosis of benign cystic mesothelioma of the peritoneum. The outcome was excellent with a 12-month recoil. PMID:27066288

  14. Advances in the systemic therapy of malignant pleural mesothelioma.

    PubMed

    Fennell, Dean A; Gaudino, Giovanni; O'Byrne, Kenneth J; Mutti, Luciano; van Meerbeeck, Jan

    2008-03-01

    Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

  15. Modeling Mesothelioma Risk Associated with Environmental Asbestos Exposure

    PubMed Central

    Maule, Milena Maria; Magnani, Corrado; Dalmasso, Paola; Mirabelli, Dario; Merletti, Franco; Biggeri, Annibale

    2007-01-01

    Background Environmental asbestos pollution can cause malignant mesothelioma, but few studies have involved dose–response analyses with detailed information on occupational, domestic, and environmental exposures. Objectives In the present study, we examined the spatial variation of mesothelioma risk in an area with high levels of asbestos pollution from an industrial plant, adjusting for occupational and domestic exposures. Methods This population-based case–control study included 103 incident cases of mesothelioma and 272 controls in 1987–1993 in the area around Casale Monferrato, Italy, where an important asbestos cement plant had been active for decades. Information collected included lifelong occupational and residential histories. Mesothelioma risk was estimated through logistic regression and a mixed additive–multiplicative model in which an additive scale was assumed for the risk associated with both residential distance from the plant and occupational exposures. The adjusted excess risk gradient by residential distance was modeled as an exponential decay with a threshold. Results Residents at the location of the asbestos cement factory had a relative risk for mesothelioma of 10.5 [95% confidence interval (CI), 3.8–50.1), adjusted for occupational and domestic exposures. Risk decreased rapidly with increasing distance from the factory, but at 10-km the risk was still 60% of its value at the source. The relative risk for occupational exposure was 6.0 (95% CI, 2.9–13.0), but this increased to 27.5 (95% CI, 7.8–153.4) when adjusted for residential distance. Conclusions This study provides strong evidence that asbestos pollution from an industrial source greatly increases mesothelioma risk. Furthermore, relative risks from occupational exposure were underestimated and were markedly increased when adjusted for residential distance. PMID:17637924

  16. Malignant Mesothelioma in a Motor Vehicle Mechanic.

    PubMed

    Meisenkothen, Christopher

    2017-02-01

    Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.

  17. Cellular and Molecular Parameters of Mesothelioma

    PubMed Central

    Ramos-Nino, Maria E.; Testa, Joseph R.; Altomare, Deborah A.; Pass, Harvey I.; Carbone, Michele; Bocchetta, Maurizio; Mossman, Brooke T.

    2009-01-01

    Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors. PMID:16795078

  18. Malignant peritoneal mesothelioma and Crohn disease.

    PubMed

    Butnor, Kelly J; Pavlisko, Elizabeth N; Sporn, Thomas A; Roggli, Victor L

    2017-03-01

    Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD. A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD. Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure. Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined. 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/.

  19. Photodynamic therapy of malignant mesothelioma of pleura

    NASA Astrophysics Data System (ADS)

    Warloe, Trond; Heyerdahl, Helen; Peng, Qian; Hoie, J.; Normann, E.; Solheim, O.; Moan, Johan; Giercksky, Karl-Erik

    1995-03-01

    Nine patients with malignant pleural mesothelioma underwent extensive surgery followed by intra-operative photodynamic therapy. Two mg/kg Photofrin was given 48 hours prior to surgery. The thoracic cavity and eventual remaining lung were exposed to 15 - 30 Joules/cm2 of 630 nm laser light. Tumor tissue was analyzed by microscopic photometrical techniques. Five patients with mixed or epithelioid tumors with fluorescence intensity > 100 gray level/pixel seemed to benefit from the given therapy. One patient was free of disease 18 months after treatment. Two patients were treated for metastasis after 12 months with no sign of intrathoracic recurrence. Both are still alive, one without further sign of disease 32 months after initial treatment. Two patients presented generalized disease after 9 and 13 months and intrathoracic recurrence several months later. Two patients with poorly differentiated tumors and 2 patients with moderate to highly differentiated tumors, but with fluorescence intensity < 100 gray level/pixel, presented recurrences after 4 months. PDT-efficiency seems to be predicted by the intensity and distribution of drug-induced fluorescence in tumor tissue. PDT may enhance the possibility to achieve complete local tumor control after excision. Multimodal therapeutic approach of local and systemic disease seems mandatory to further improve survival.

  20. Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings.

    PubMed

    Assaly, M; Bongiovanni, M; Kumar, N; Egger, J-F; Pelte, M-F; Genevay, M; Finci, V; Tschanz, E; Pache, J-C

    2008-08-01

    To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM). Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy. The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells. The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).

  1. [Benign multicystic peritoneal mesothelioma in a patient with Crohn disease].

    PubMed

    Fluxá, Daniela; Kronberg, Udo; Lubascher, Jaime; O'Brien, Andrés; Las Heras, Facundo; Ibáñez, Patricio; Quera, Rodrigo

    2016-12-01

    Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

  2. Use of automated image analysis in evaluation of Mesothelioma Tissue Microarray (TMA) from National Mesothelioma Virtual Bank.

    PubMed

    Amin, Waqas; Srinivasan, Malini; Song, Sang Yong; Parwani, Anil V; Becich, Michael J

    2014-02-01

    The National Mesothelioma Virtual Bank (NMVB) was established to provide annotated biospecimens to the mesothelioma research community. The resource provides tissue microarrays (TMA) to evaluate the biomarkers along with a variety of other resected mesothelioma specimens. In this manuscript, we describe the immunohistochemical evaluation of the mesothelioma TMA with three key antibodies that are used in making the diagnosis of mesothelioma, and compared the immunohistochemical assessment between manual scoring and image analysis. The TMA was assessed for the immunohistochemical expression of calretinin (N=39), cytokeratin (CK) 5/6 (N=33), and D2-40 (N=37). Immunohistochemistry was evaluated by semi-quantitative (manual) scoring using light microscope (MS) and by automated image analysis (AS). Calretinin staining was seen in both cytoplasmic and nuclear locations. CK5/6 stain was localized to the cytoplasm. D2-40 stain showed only membranous expression in our cases. • Based on the pathologist’s scores, calretinin was positive in 31 of the 39 cases (80%), CK 5/6 in 15 of the 33 cases (46%) and D2-40 in 18 of the 37 cases (49%). • The percent-positive agreement between manual scores and image analysis was 90% (35/39), 94% (31/33), and 95% (35/37) for calretinin, CK 5/6, and D2-40, respectively. There was a substantial agree-ment between manual and automated scores for calretinin (kappa = 0.614) and an almost perfect agreement for CK5/6 (kappa = 0.879) and D2-40 (kappa = 0.892). Our study confirms that the immunohistochemical staining pattern of mesotheliomas in the NMVB UPMC TMA is similar to other studies. Our findings also show that automated image analysis provides similar results to manual scoring by pathologists, and provides a reproducible, objective, and accurate platform for immunohistochemical assessment of biomarker expression. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Malignant mesothelioma incidence among talc miners and millers in New York State.

    PubMed

    Finkelstein, Murray M

    2012-10-01

    There is controversy about the potential for dust from the talc mines and mills of New York State to cause mesothelioma. Honda et al. published a study of mortality among New York talc workers and concluded that it was unlikely that the two deaths from mesothelioma were caused by talc ore dust. However, fibers of tremolite and anthophyllite have been found in the lungs of talc workers and Hull concluded that "New York talc exposure is associated with mesothelioma, and deserves further public health attention." Data concerning additional cases of mesothelioma in the cohort have been posted by NIOSH. I used information from the NIOSH website and the Honda report to analyze the incidence of mesothelioma during the years 1990-2007. There were at least five new cases of mesothelioma in the cohort and mesothelioma incidence rates were at least five (1.6-11.7) times the rate in the general population (P < 0.01). I conclude that: (1) mesothelioma has been diagnosed among members of the cohort at a rate in excess of that in the general population; (2) fibers of tremolite and anthophyllite have been detected in dust and the lungs of talc workers; and (3) these fibers are known causes of mesothelioma. It is prudent, on the balance of probabilities, to conclude that dusts from New York State talc ores are capable of causing mesothelioma in exposed individuals. Copyright © 2012 Wiley Periodicals, Inc.

  4. Mesothelioma of the tunica vaginalis: a series of eight cases with uncertain malignant potential.

    PubMed

    Brimo, Fadi; Illei, Peter B; Epstein, Jonathan I

    2010-08-01

    Well-differentiated papillary mesotheliomas have rarely been reported to involve the testis tunica vaginalis. While the classic histology of the originally described well-differentiated papillary mesotheliomas consisted of papillae lined by a single layer of bland cuboidal cells, more complex architectural patterns have been described. This report details our experience with eight paratesticular mesotheliomas that span the histological spectrum from classic well-differentiated papillary mesotheliomas to those with more complex patterns. We attempt to determine whether there are prognostic or immunohistochemical differences between these lesions and 28 diffuse malignant mesotheliomas. All cases had papillary/tubulopapillary in addition to more complex architectures (cribriform, condensed) and none showed evidence of invasion. Mitotic figures were present in seven cases and averaged 2.1 mitosis per 50 h.p.f. All cases showed mesotheliomas. Of five patients with follow-up information of more than 1 year, three patients were alive at 2, 3 and 9 years, and two died of unknown causes at 5 and 47 years, suggesting that these lesions behave more indolently than typical malignant mesotheliomas of the tunica vaginalis. If these cases were diffuse malignant mesotheliomas, one would have expected at least some of the patients to have died of disease within a couple of years after diagnosis. However, detailed and long-term follow-up were not sufficiently available to reach definitive conclusions on the true biological behavior of these tumors. The morphological continuum noted between our cases and classic well-differentiated papillary mesotheliomas, combined with their immunohistochemical profile and indolent behavior, contrasts with that of diffuse malignant mesotheliomas. We propose that these tunica vaginalis

  5. Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma.

    PubMed

    Xu, Jinfei; Kadariya, Yuwaraj; Cheung, Mitchell; Pei, Jianming; Talarchek, Jacqueline; Sementino, Eleonora; Tan, Yinfei; Menges, Craig W; Cai, Kathy Q; Litwin, Samuel; Peng, Hongzhuang; Karar, Jayashree; Rauscher, Frank J; Testa, Joseph R

    2014-08-15

    Malignant mesotheliomas are highly aggressive tumors usually caused by exposure to asbestos. Germline-inactivating mutations of BAP1 predispose to mesothelioma and certain other cancers. However, why mesothelioma is the predominate malignancy in some BAP1 families and not others, and whether exposure to asbestos is required for development of mesothelioma in BAP1 mutation carriers are not known. To address these questions experimentally, we generated a Bap1(+/-) knockout mouse model to assess its susceptibility to mesothelioma upon chronic exposure to asbestos. Bap1(+/-) mice exhibited a significantly higher incidence of asbestos-induced mesothelioma than wild-type (WT) littermates (73% vs. 32%, respectively). Furthermore, mesotheliomas arose at an accelerated rate in Bap1(+/-) mice than in WT animals (median survival, 43 weeks vs. 55 weeks after initial exposure, respectively) and showed increased invasiveness and proliferation. No spontaneous mesotheliomas were seen in unexposed Bap1(+/-) mice followed for up to 87 weeks of age. Mesothelioma cells from Bap1(+/-) mice showed biallelic inactivation of Bap1, consistent with its proposed role as a recessive cancer susceptibility gene. Unlike in WT mice, mesotheliomas from Bap1(+/-) mice did not require homozygous loss of Cdkn2a. However, normal mesothelial cells and mesothelioma cells from Bap1(+/-) mice showed downregulation of Rb through a p16(Ink4a)-independent mechanism, suggesting that predisposition of Bap1(+/-) mice to mesothelioma may be facilitated, in part, by cooperation between Bap1 and Rb. Drawing parallels to human disease, these unbiased genetic findings indicate that BAP1 mutation carriers are predisposed to the tumorigenic effects of asbestos and suggest that high penetrance of mesothelioma requires such environmental exposure.

  6. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

    ClinicalTrials.gov

    2017-08-17

    Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Malignant Solid Neoplasm; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

  7. Multicystic peritoneal mesothelioma: A short review.

    PubMed

    Zhang, Chi-Hao; Yu, Ji-Wei; Luo, Meng

    Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, predominantly affecting female patients during their reproductive years. The lesion is usually distributed diffusely in the abdomen and pelvis, but the peritoneum of the pelvic organs is the most common site. MCPM is composed of fluid-filled translucent cysts, connected by varying amounts of fibrous tissue, and lined by a layer of mesothelial cells. Because of the rarity of this disease, the pathogenesis and natural history of MCPM remain poorly understood and continuously debated. Some authors consider it to be a reactive process for its association with prior surgery or abdominal inflammation. But its high rate of local-regional recurrence, as well as its malignant potential, suggests a neoplastic etiology. Preoperative diagnosis is often very difficult. Imaging methods, such as ultrasound, computed tomography, and magnetic resonance imaging, are of little value for an accurate diagnosis of MCPM. The definitive diagnosis relies on histologic examination of target lesions combined with immunohistochemical stains. There is no consensus on the clinical management of MCPM, although surgical removal remains the first-line treatment of choice. But no standards have been reached concerning which surgical options-traditional debulking surgery or more aggressive one-should be chosen. Alternative therapeutic approaches include hand-off treatment, hormonal supplementation, laser vaporization, and sclerotherapy, and they all come with uncertain results. Moreover, the lesions show no response to adjuvant chemotherapy and radiotherapy. This article aimed to focus on those controversial problems in pathogenesis, natural history, diagnosis, and treatment strategies to help medical workers to better understand this rare disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Supplementary Prognostic Variables for Pleural Mesothelioma

    PubMed Central

    Giroux, Dorothy; Kennedy, Catherine; Ruffini, Enrico; Cangir, Ayten K.; Rice, David; Asamura, Hisao; Waller, David; Edwards, John; Weder, Walter; Hoffmann, Hans; van Meerbeeck, Jan P.; Rusch, Valerie W.

    2014-01-01

    Introduction: The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure). Methods: Supplementary prognostic variables were studied in three scenarios: (1) all data available, that is, patient pathologically staged and other CORE variables available (2) only clinical staging available along with CORE variables, and (3) only age, sex, histology, and laboratory parameters are known. Survival was analyzed by Kaplan–Meier, prognostic factors by log rank and stepwise Cox regression modeling after elimination of nonsignificant variables. p value less than 0.05 was significant. Results: A total of 2141 patients with best tumor, node, metastasis (TNM) stages (pathologic with/without clinical staging) had nonmissing age, sex, histology, and type of surgical procedure. Three prognostic models were defined. Scenario A (all parameters): best pathologic stage, histology, sex, age, type of surgery, adjuvant treatment, white blood cell count (WBC) (≥15.5 or not), and platelets (≥400 k or not) (n = 550). Scenario B (no surgical staging): clinical stage, histology, sex, age, type of surgery, adjuvant treatment, WBC, hemoglobin (<14.6 or not), and platelets (n = 627). Scenario C (limited data): histology, sex, age, WBC, hemoglobin, and platelets (n = 906). Conclusion: Refinement of these models could define not only the appropriate patient preoperatively for best outcomes after cytoreductive surgery but also stratify surgically treated patients after clinical and pathologic staging who do or do not receive adjuvant therapy. PMID:24807157

  9. Antiproliferative effect of Aurora kinase targeting in mesothelioma.

    PubMed

    Crispi, Stefania; Fagliarone, Claudia; Biroccio, Annamaria; D'Angelo, Carmen; Galati, Rossella; Sacchi, Ada; Vincenzi, Bruno; Baldi, Alfonso; Verdina, Alessandra

    2010-12-01

    The Aurora proteins are a small family of serine/threonine kinase that function in various stages of mitosis. Current interest in Aurora kinase relates to its role in tumours, and its potential as a therapeutic target. In this work we studied the expression of Aurora kinases A and B and related genes in human mesothelioma tissues and in five mesothelioma cell lines. Moreover, we analyzed the effects of ZM447439 (ZM), an Aurora kinase inhibitor, on cellular growth. Results evidenced an over-expression of Aurora kinase A and related genes in human mesothelioma tissues and an over-expression of Aurora kinases A and B in all cell lines. Moreover, we demonstrated that ZM447439 was able to inhibit cell growth in all cell lines and that this inhibition was due to a specific effect as demonstrated by the reduction in the level of Histone H3 phosphorylation. Our findings support a role of Aurora kinase in mesothelioma and the possibility of using Aurora kinase inhibitors in therapeutic modalities.

  10. Localized fibrous mesothelioma of pleura following external ionizing radiation therapy

    SciTech Connect

    Bilbey, J.H.; Mueller, N.L.M.; Miller, R.R.; Nelems, B.

    1988-12-01

    Carcinogenesis is a well-known complication of radiation exposure. Ionizing radiation also leads to an increased incidence of benign tumors. A 36-year-old woman had a localized fibrous mesothelioma of the pleura and an ipsilateral breast carcinoma 23 years after receiving external radiation therapy for treatment of a chest wall keloid.

  11. Immunotherapy and radiation therapy for malignant pleural mesothelioma

    PubMed Central

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

    2017-01-01

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

  12. [Case studies on the malignant mesothelioma in Pellezzano (SA)].

    PubMed

    Menegozzo, S; Izzo, F; Canfora, M L; Petronzio, M F; Santoro, M; Menegozzo, M

    2007-01-01

    41 malignant mesothelioma cases were reported between January 2000 and April 2007 in the province of Salerno. The small town of Pellezzano, near Salerno, has more cases than any other urban centre in the province; five mesothelioma cases (three male and two female) in Pellezzano (population 9,171 in 1991) means a standardized incidence rate of 32.7 males and 21.8 females per 100.000 inhabitants. That's very alarming, considering that in Italy mesothelioma standardized incidence rate per 100.000 inhabitants is 2,98 for males and 0,98 for females. Campania Mesothelioma Register aims to investigate which kind of exposure caused this abnormal incidence rate. All five patients answered the questionnaire and a team of doctors performed an on-the-spot investigation. The studies verified the existence of two kind of asbestos exposure, professional (Cotton Manufacture, Construction, Foundry) and environmental (cement-asbestos pre-fabricated since 1980 earthquake), that have to be analyzed further.

  13. Chemotherapy and Targeted Therapies for Unresectable Malignant Mesothelioma

    PubMed Central

    Kelly, Ronan Joseph; Sharon, Elad; Hassan, Raffit

    2011-01-01

    The global burden of mesothelioma is expected to increase in the coming decades. As a result the development of more effective therapies with an emphasis on personalized treatments based on validated prognostic and predictive biomarkers is an essential requirement. Progress has been made in the last decade with the development of newer generation anti-folates leading to the current standard of care of pemetrexed and cisplatin in patients with unresectable disease. However, the median overall survival of patients with this combination treatment is only 12 months. There is no consensus regarding second line therapy for patients who have progressed or not responded to pemetrexed based therapies although gemcitabine in combination with a platinum compound or single agent vinorelbine is a reasonable option. The development of effective targeted agents that are active in mesothelioma has to date been disappointing. Strategies involving the addition of bevacizumab to pemetrexed and cisplatin in the frontline setting, the histone deacetylase inhibitor vorinostat as second line therapy and studies evaluating the utility of maintenance therapy in mesothelioma.are all ongoing and appear promising. In addition clinical trials investigating immunotherapy and gene therapy in combination with chemotherapy could potentially improve the prognosis of patients with mesothelioma. PMID:21620512

  14. Mesotheliomas of the tunica vaginalis testis and hernial sacs.

    PubMed

    Grove, A; Jensen, M L; Donna, A

    1989-01-01

    Three histologically and immunohistochemically well-documented cases of mesothelioma of the tunica vaginalis testis and hernial sac are presented. Analysis and follow-up data on our three patients and a review of 30 previously reported cases have revealed a varied and often unpredictable clinical course. A classification into high- and lowgrade malignant tumours is suggested, based on clinical and pathological findings.

  15. Mesothelioma: you do not have to work for it.

    PubMed

    Ampleford, Elizabeth J; Ohar, Jill

    2007-12-01

    Asbestos pollution is a global problem. Asbestos exposure induced mesothelioma does not require an 'occupational' type of exposure. Bystander exposures may result in earlier age of disease onset and more aggressive disease progression as described in the following 3 case reports. Copyright 2007 Wiley-Liss, Inc.

  16. Consensus Report of the 2015 Weinman International Conference on Mesothelioma

    EPA Science Inventory

    On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the S...

  17. Consensus Report of the 2015 Weinman International Conference on Mesothelioma

    EPA Science Inventory

    On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the S...

  18. Vasculogenic mimicry in malignant mesothelioma: an experimental and immunohistochemical analysis.

    PubMed

    Pulford, Emily; Hocking, Ashleigh; Griggs, Kim; McEvoy, James; Bonder, Claudine; Henderson, Douglas W; Klebe, Sonja

    2016-12-01

    Vasculogenic mimicry, the process in which cancer cells form angiomatoid structures independent of or in addition to host angiogenesis has been recorded in several otherwise non-endothelial malignant neoplasms. This study describes evidence of routine vascular mimicry by human mesothelioma cell lines in vitro, when the cell lines are cultured alone or co-cultured with human umbilical vascular endothelial cells, with the formation of angiomatoid tubular networks. Vasculogenic mimicry is also supported by immunohistochemical demonstration of human-specific anti-mitochondria antibody labelling of tumour-associated vasculature of human mesothelioma cells xenotransplanted into nude mice, and by evidence of vascular mimicry in some biopsy samples of human malignant mesotheliomas. These studies show mosaic interlacing of cells that co-label or label individually for immunohistochemical markers of endothelial and mesothelial differentiation. If vascular mimicry in mesothelioma can be characterised more fully, this may facilitate identification of more specific and targeted therapeutic approaches such as anti-angiogenesis in combination with chemotherapy and immunotherapy or other therapeutic approaches.

  19. Vasculogenic mimicry in malignant mesothelioma: an experimental and immunohistochemical analysis.

    PubMed

    Pulford, Emily; Hocking, Ashleigh; Griggs, Kim; McEvoy, James; Bonder, Claudine; Henderson, Douglas W; Klebe, Sonja

    2016-10-28

    Vasculogenic mimicry, the process in which cancer cells form angiomatoid structures independent of or in addition to host angiogenesis has been recorded in several otherwise non-endothelial malignant neoplasms. This study describes evidence of routine vascular mimicry by human mesothelioma cell lines in vitro, when the cell lines are cultured alone or co-cultured with human umbilical vascular endothelial cells, with the formation of angiomatoid tubular networks. Vasculogenic mimicry is also supported by immunohistochemical demonstration of human-specific anti-mitochondria antibody labelling of tumour-associated vasculature of human mesothelioma cells xenotransplanted into nude mice, and by evidence of vascular mimicry in some biopsy samples of human malignant mesotheliomas. These studies show mosaic interlacing of cells that co-label or label individually for immunohistochemical markers of endothelial and mesothelial differentiation. If vascular mimicry in mesothelioma can be characterised more fully, this may facilitate identification of more specific and targeted therapeutic approaches such as anti-angiogenesis in combination with chemotherapy and immunotherapy or other therapeutic approaches.

  20. Malignant mesothelioma: a clinical study of 238 cases.

    PubMed

    Haber, Steven E; Haber, Jason M

    2011-01-01

    Malignant mesothelioma is a diffuse tumor arising in the pleura, peritoneum, or other serosal surface and is closely associated with asbestos exposure. An estimated 2,500 to 3,000 cases are diagnosed each year in the United States. Although there are individual case reports and small series detailing the clinical aspects of mesothelioma, few studies examine a large series of patients with malignant mesothelioma from the clinical perspective. This study reports on the findings of 238 cases of malignant mesothelioma from a private consultative medical practice. Most cases had a history of occupational asbestos exposure. The mean latency was 48.5 yr, with women having a longer latency than men. The mean age at diagnosis was 70. Survival overall was poor (mean 8.8 months), but treatment was beneficial (mean 11.3 versus 6.4 months). Epithelioid histology conferred a survival advantage over sarcomatoid and responded better to treatment. Our data support an inverse relationship between asbestos dose and latency.

  1. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    PubMed Central

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  2. Industrial-grade talc exposure and the risk of mesothelioma.

    PubMed

    Price, Bertram

    2010-07-01

    Industrial-grade talc deposits are complex mixtures of mineral particles and may vary substantially in composition across small geographical areas. Typical industrial-grade talc includes amphibole cleavage fragments, platy talc, serpentine minerals, talc in fibrous form, and a minor presence of transitional fibers. Industrial-grade talc was erroneously determined to be an asbestos-containing material due to an unintended consequence of Occupational Health and Safety Administration's (OSHA's) method for measuring airborne asbestos mandated in 1972. This error was repeated, most notably, by the National Institute for Occupational Safety and Health (NIOSH) in, 1980 for talc mined in northern New York State (NYS) by RT Vanderbilt Company (RTV). Subsequent exposure studies of northern NYS talc conducted through the, 1980s and one study published after, 2000 relied on the conclusion that talc was an asbestos-containing material to infer a causal relationship between talc and mesothelioma. The present review included (1) publications concerning talc's cancer-causing potential issued by organizations concerned with occupational and public health; (2) talc exposure studies and animal and cellular studies of RTV talc; (3) mesothelioma rates in northern NYS; and (4) mesothelioma mortality among RTV mining employees. The review indicated that failure to correctly identify the mineral characteristics of talc resulted in misleading reports concerning the carcinogenic potential of talc. However, the collective data from animal and cellular studies, mesothelioma rates in northern NYS, exposure studies, and a mortality analysis of RTV mining employees do not support a causal relationship between RTV talc and mesothelioma. This conclusion is applicable to all mineral components in RTV talc and to other industrial-grade talcs and mineral aggregates with the same components.

  3. Filing for workers’ compensation among Ontario cases of mesothelioma

    PubMed Central

    Payne, Jennifer Isabelle; Pichora, Erin

    2009-01-01

    BACKGROUND/OBJECTIVE: For many types of cancer, disease attribution to occupational exposures is difficult. Mesothelioma, however, is a ‘sentinel’ occupational cancer associated with asbestos exposure. The present study linked workers’ compensation claims data with cancer registry data to explore the completeness of reporting of mesothelioma to the Ontario Workplace Safety and Insurance Board (WSIB) according to characteristics of cases diagnosed among Ontario residents. METHODS: Two data sources were linked at the person level: the WSIB Occupational Disease Information and Surveillance System and the Ontario Cancer Registry. Filing rates were calculated as the proportion of Ontario Cancer Registry mesothelioma cases (International Classification of Diseases – Oncology code 905) that linked to a WSIB-filed cancer claim. Filing rates were calculated for the period 1980 to 2002, and trends were calculated by year, age and county of residence at diagnosis. RESULTS: The filing rate for compensation has increased little over the past 20 years, reaching a high of 43% in 2000. Overall, filing rates were highest among pleural mesothelioma cases among men (range 27% to 57%). Filing rates were highest among individuals 50 to 59 years of age and declined substantially throughout the retirement years. There was substantial variation in filing rates by area of residence, with the highest rate being in Lambton County, Ontario. CONCLUSION: The filing rate for compensation in Ontario was much lower than the estimated proportion of cases eligible for compensation. The increased filing rate in Lambton County was likely related to this community’s awareness of the association between asbestos and mesothelioma. Physicians can play an important role in educating patients of their potential entitlement to compensation benefits. PMID:19851532

  4. Filing for workers' compensation among Ontario cases of mesothelioma.

    PubMed

    Payne, Jennifer Isabelle; Pichora, Erin

    2009-01-01

    For many types of cancer, disease attribution to occupational exposures is difficult. Mesothelioma, however, is a 'sentinel' occupational cancer associated with asbestos exposure. The present study linked workers' compensation claims data with cancer registry data to explore the completeness of reporting of mesothelioma to the Ontario Workplace Safety and Insurance Board (WSIB) according to characteristics of cases diagnosed among Ontario residents. Two data sources were linked at the person level: the WSIB Occupational Disease Information and Surveillance System and the Ontario Cancer Registry. Filing rates were calculated as the proportion of Ontario Cancer Registry mesothelioma cases (International Classification of Diseases - Oncology code 905) that linked to a WSIB-filed cancer claim. Filing rates were calculated for the period 1980 to 2002, and trends were calculated by year, age and county of residence at diagnosis. The filing rate for compensation has increased little over the past 20 years, reaching a high of 43% in 2000. Overall, filing rates were highest among pleural mesothelioma cases among men (range 27% to 57%). Filing rates were highest among individuals 50 to 59 years of age and declined substantially throughout the retirement years. There was substantial variation in filing rates by area of residence, with the highest rate being in Lambton County, Ontario. The filing rate for compensation in Ontario was much lower than the estimated proportion of cases eligible for compensation. The increased filing rate in Lambton County was likely related to this community's awareness of the association between asbestos and mesothelioma. Physicians can play an important role in educating patients of their potential entitlement to compensation benefits.

  5. Intraperitoneal mesotheliomas induced in mice by a polycyclic aromatic hydrocarbon

    SciTech Connect

    Rice, J.M.; Anderson, L.M. ); Kovatch, R.M. )

    1989-01-01

    Female mice of 6 strains (C3H/HeN, BALB/c, C57BL/6N, DBA/2, NIH Swiss, and AKR/N) were given the polycyclic aromatic hydrocarbon carcinogen 3-methylcholanthrene (MC) intragastrically in olive oil at a dose of 20 mg/kg, weekly for 12 wk. Half were pretreated 24 h before each MC administration with intraperitoneal {beta}-naphthoflavone ({beta}-NF, 150 mg/kg in olive oil), a noncarinogenic inducer of certain cytochrome P-450 isozymes. Remaining mice were given olive oil prior to MC in the same fashion, or {beta}-NF in olive oil or olive oil alone without subsequent exposure to MC. All mice were killed when moribund or 13 mo after the start of treatment. Most of the mice, irrespective of treatment, exhibited signs of peritoneal injury, including inflammation, necrosis, granuloma formation, and mineralization. Mice of some of the strains also presented peritoneal mesotheliomas, in addition to a variety of other tumors. {beta}-NF pretreatment reduced the frequency of mesotheliomas: there was only one definite mesothelioma in any of the {beta}-NF-MC groups, in a C3H/He mouse. Most of the measotheliomas were mixed fibro-mesothelial type, sometimes with papillary epithelial excrescences. They typically grew in a botryoid pattern within the peritoneal cavity, coating the abdominal organs and sometimes actively invading these organs and the diaphragm. Some lesions exhibited pleomorphism, prominent giant cells, and frequent mitoses. In addition, several lesions consisting of severe mesothelial hyperplasia associated with tissue necrosis and inflammation were considered as possible early stages of mesothelioma development. It was postulated that peritoneal injury imposed by repeated intraperitoneal injection of oil acted as an enhancing factor for mesothelioma induction by MC.

  6. The role of 18F-FDG-PET/ceCT in peritoneal mesothelioma.

    PubMed

    Dubreuil, Julien; Giammarile, Francesco; Rousset, Pascal; Rubello, Domenico; Bakrin, Naoual; Passot, Guillaume; Isaac, Sylvie; Glehen, Olivier; Skanjeti, Andrea

    2017-04-01

    The aim of this study was to assess glucose metabolism of multicystic peritoneal mesothelioma and epithelioid peritoneal mesothelioma by fluorine-18 fluorodeoxyglucose (F-FDG)-PET/contrast-enhanced computed tomography (ceCT) and to assess its prognostic impact. Twenty-three (14 women) patients, without previous treatment, underwent F-FDG-PET/ceCT before peritoneal mesothelioma cytoreductive surgery and intraperitoneal chemotherapy. F-FDG-PET/ceCT was interpreted prospectively as positive or negative. Maximum standardized uptake value (SUVmax) of each lesion was measured retrospectively on the basis of postsurgery data. At laparotomy, disease extension was estimated with the Peritoneal Cancer Index. The median follow-up was 27 months (95% confidence interval: 12.9-37.8); progression-free survival (PFS) was recorded. Nine patients were affected by multicystic and 14 were affected by epithelioid peritoneal mesothelioma. PET showed mild focal uptake in one case of multicystic peritoneal mesothelioma, whereas in eight patients, no abnormal uptake was observed. PET was positive in 12/14 patients with epithelioid peritoneal mesothelioma. Sensitivity, specificity and accuracy were respectively 86, 89 and 87%; the qualitative assessment was statistically different (P=0.0020, χ). Multicystic peritoneal mesothelioma histology was significantly associated with lower SUVmaxlesion (P=0.0061), SUVmaxlesion/liver (P=0.0025), Peritoneal Cancer Index, younger age, and it was observed only in women.Recurrence was observed on nine patients affected by epithelioid peritoneal mesothelioma, whereas no recurrences were observed among multicystic peritoneal mesothelioma patients. SUVmaxlesion (P=0.0278) and age (P=0.0241) were significantly associated with PFS in patients with epithelioid peritoneal mesothelioma. F-FDG-PET/ceCT showed significant differences between multicystic and epithelioid peritoneal mesothelioma, whereas SUVmaxlesion was associated with PFS in the latter. Although

  7. Targeting Immunological Restrainers: Understanding the Immunology Behind Combination Chemoimmunotherapy to Improve the Treatment of Malignant Mesothelioma

    DTIC Science & Technology

    2014-12-01

    malignant mesothelioma. 1S. SUBJECT TERMS Mesothelioma, immunotherapy, chemotherapy. Combination therapy . 16. SECURITY CLASSIFICATION OF: 17...in the original proposal and highlights key research discoveries.  KEYWORDS:  Mesothelioma,  immunotherapy,  chemotherapy,  combination  therapy ...these therapies [1-3]. From these results we concluded that the P60 small molecule inhibitor of FoxP3 and the CCR4 antagonist were unlikely to be

  8. Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death.

    PubMed Central

    Ribak, J; Lilis, R; Suzuki, Y; Penner, L; Selikoff, I J

    1988-01-01

    Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a

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

    PubMed Central

    Admella Salvador, Carme; Feliu Canaleta, Josep; Llopis Manzanera, Juan; Barranco Sanz, Miguel Angel; Romero Martin, Juan Antoni; Bernal Salguero, Sergi

    2017-01-01

    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. PMID:28168071

  10. Calcification as a sign of sarcomatous degeneration of malignant pleural mesotheliomas: A new CT finding

    SciTech Connect

    Raizon, A.; Schwartz, A.; Hix, W.; Rockoff, S.D.

    1996-01-01

    We present two cases demonstrating, on CT examination, heavily calcified mass lesions associated with malignant pleural mesothelioma in workers occupationally exposed to asbestos. These masses proved to be osteogenic sarcomatous degeneration within mesotheliomas. The observation of dense calcification within a pleural mass should raise a suspicion of osteosarcomatous degeneration if it is seen in conjunction with other classic signs of malignant pleural mesothelioma. 8 refs., 5 figs.

  11. Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey.

    PubMed

    Roushdy-Hammady, I; Siegel, J; Emri, S; Testa, J R; Carbone, M

    2001-02-10

    Erionite present in stones used to build the villages of Karain and Tuzköy, Turkey, mined from nearby caves, is purported to cause mesothelioma in half of the villagers. We constructed genetic epidemiology maps to test whether some villagers were genetically predisposed to mesothelioma. Analysis of a six-generation extended pedigree of 526 individuals showed that mesothelioma was genetically transmitted, probably in an autosomal dominant way. This finding should lead to preventive strategies to lower the incidence of mesothelioma in future generations, and close monitoring of high-risk individuals might allow early detection and cure.

  12. Wilms' Tumor 1 Susceptibility (WT1) Gene Products are Selectively Expressed in Malignant Mesothelioma

    PubMed Central

    Amin, Kunjlata M.; Litzky, Leslie A.; Smythe, W. Roy; Mooney, Anne M.; Morris, Jennifer M.; Mews, Daphne J. Y.; Pass, Harvey I.; Kari, Csaba; Rodeck, Ulrich; Rauscher, Frank J.; Kaiser, Larry R.; Albelda, Steven M.

    1995-01-01

    The distinction between malignant mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike ot her tumor suppressor genes, is restricted mostly to mesenchymaly derived tissues, we hypothesized that the WTI gene products could serve as a potential marker for mesothelioma. The expression of WTI mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens. WTI mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WTI mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a52-to 54-kdprotein was present in 4 mesothelioma cell lines. Immunostanig with this antibody localizd the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WTI mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, inparticular, adenocarcinoma. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:7856747

  13. Pathology reporting of malignant pleural mesothelioma first diagnosis: A population-based approach.

    PubMed

    Ascoli, Valeria; Minelli, Giada; Cozzi, Ilaria; Romeo, Elisa; Carnovale Scalzo, Caterina; Ancona, Laura; Forastiere, Francesco

    2016-10-01

    Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize

  14. Multicystic mesothelioma--a rare case of ascites: case report.

    PubMed

    Manuc, M; Lamatic, C; Pop, C; Dobrea, C; Becheanu, G; Grasu, M; Iosif, D; Diculescu, M

    2007-01-01

    We present the case of a 37-year-old male, admitted to our clinic with abdominal tenderness, right supraclavicular tumour, and ascites. The presence of ascites was incidentally reported 6 years before, but no other evaluation was done at that moment or during this period. Abdominal ultrasound and CT scan revealed moderate ascites, perivascular adenopathies, and multiple abdominal cystic lesions, while thoracic CT scan revealed the same lesions in mediastinum. Laboratory data were within normal limits, including the tumoral markers, and the tests for hydatid cysts. A biopsy from the right supraclavicular nodule was performed, and based on usual and immunohistochemical stains (calretinin, mesotheline, CK 5/6, CK 7, CK18 diffusely positive in mesothelial cells, and CEA -M, bcl-2 and vimentin negative), suggested the diagnosis of mesothelioma. Based on these results, the diagnosis of "multicystic mesothelioma" was made. The patient was referred for surgery.

  15. Multicystic benign cystic mesothelioma presenting as a pelvic mass.

    PubMed

    Momeni, Mazdak; Pereira, Elena; Grigoryan, Gennadiy; Zakashansky, Konstantin

    2014-01-01

    Background. Benign cystic mesothelioma (BCM) is a rare tumor that arises from the abdominal peritoneum with a predilection to the pelvic peritoneum. For this reason, it can often mimic gynecologic malignancies. Case. A 47-year-old perimenopausal female presented reporting several weeks of abdominal distention associated with abdominal tenderness and constipation. Computed tomography revealed a 24 cm multiloculated pelvic mass, and tumor markers were notable for an elevated CA-125. The patient was taken to the operating room for an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingoophorectomy, and removal of pelvic mass. Final pathologic evaluation revealed a benign cystic mesothelioma. Conclusion. Classically these tumors present as large multicystic masses with thin-walled septations and on preoperative evaluation BCM can mimic many different disease entities including ovarian malignancies and cystic lymphangioma. Often diagnosis can only be made at time of surgery.

  16. Multicystic Benign Cystic Mesothelioma Presenting as a Pelvic Mass

    PubMed Central

    Pereira, Elena; Zakashansky, Konstantin

    2014-01-01

    Background. Benign cystic mesothelioma (BCM) is a rare tumor that arises from the abdominal peritoneum with a predilection to the pelvic peritoneum. For this reason, it can often mimic gynecologic malignancies. Case. A 47-year-old perimenopausal female presented reporting several weeks of abdominal distention associated with abdominal tenderness and constipation. Computed tomography revealed a 24 cm multiloculated pelvic mass, and tumor markers were notable for an elevated CA-125. The patient was taken to the operating room for an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingoophorectomy, and removal of pelvic mass. Final pathologic evaluation revealed a benign cystic mesothelioma. Conclusion. Classically these tumors present as large multicystic masses with thin-walled septations and on preoperative evaluation BCM can mimic many different disease entities including ovarian malignancies and cystic lymphangioma. Often diagnosis can only be made at time of surgery. PMID:24716035

  17. Environmental household exposures to asbestos and occurrence of pleural mesothelioma

    SciTech Connect

    Dodoli, D.; Del Nevo, M.; Fiumalbi, C.; Iaia, T.E.; Cristaudo, A.; Comba, P.; Viti, C.; Battista, G. )

    1992-01-01

    The authors reviewed the certificates of 39,650 deaths which occurred in the period 1975-1988 in Leghorn and of 45,900 in La Spezia (Italy) in the period 1958-1988. In total 262 cases have been recorded as pleural mesothelioma. The main occupational exposures occurred in the shipbuilding industry. Regarding non-occupational exposures to asbestos, 13 cases of mesothelioma were found in women who had washed the work clothes of their relatives at home; we also found other domestic uses of asbestos which were rarely or never discussed previously in the literature: six cases might be explained by the installation of fireproof or non-conductive materials in the domestic environment. These exposures probably are more frequent than realized until now.

  18. Peritoneal malignant mesothelioma metastatic to supraclavicular lymph nodes.

    PubMed

    Zannella, Stefano; Testi, Maria Adele; Cattoretti, Giorgio; Pelosi, Giuseppe; Zucchini, Nicola

    2014-09-01

    Distinguishing between malignant mesothelioma and reactive mesothelial hyperplasia is often inestimable, but may be a challenging gauntlet for pathologists. A 62-year-old man underwent appendectomy after the identification of a peritoneal mass and the histological examination showed mesothelial proliferation along the appendix surface with no clear images of infiltration. After a few months the patient developed mediastinal and supraclavicular lymphadenopathies, and a nodal biopsy showed mesothelial cell proliferation invading lymphatic sinuses, consistent with the cells seen in the abdominal cavity. Since overt morphologic criteria for malignancy were lacking and reactive mesothelial cell deposits have been documented in lymph nodes, a molecular investigation of the CDKN2A (henceforth simply p16) gene status via fluorescence in situ hybridization was performed, which showed homozygous deletion in 100% tumor cells. These data ruled out the hypothesis of reactive mesothelial cells inclusion in lymph nodes, thus confirming the diagnosis of epithelioid malignant mesothelioma. © The Author(s) 2014.

  19. [Malignant peritoneal mesothelioma. Case report and review of the literature].

    PubMed

    Ruiz-Tirado, María Luisa; Olvera-Rodríguez, Arturo; Díaz-Barranco, Irma; Ruiz-Romano, Agueda; Castillo-Ruiz, Natalia; Olvera-Quiroz, Silvia Eurydice

    2011-01-01

    A woman 88 years old with a clinical picture initiated eight days before characterized by asthenia, adynamia, hyporexia, increase of the abdominal perimeter, pain and constipation. Her husband worked at the automotive industry for more than 30 years (brakes specialist). She had a history of hypertension; abdominal ultrasound showed a metastatic liver of unknown origin and ascites. An ascites sample was gotten. Malignant cells matching with malignant peritoneal mesothelioma were observed. The patient died 30 days after the diagnosis. The peritoneal mesothelioma is a rare form of cancer that can be benign or malignant. Incidence rate increases with age. It is more frequent in men and over 60 years with a survival from five to twelve months after diagnosis. The most important risk factor is the chronic labor exposition to asbestos that includes the family. The diagnosis is difficult even for experts. Additionally, we present a brief review of the literature.

  20. Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma

    SciTech Connect

    Isobe, Hiroshi; Sridhar, K.S.; Doria, R.

    1995-01-01

    DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy. The median survival time of the patients with diploid tumors was 19, 16, and 14 months from the onset of symptoms, diagnosis, and treatment, respectively. The median survival in patients with aneuploid tumors was 8, 7, and 7 months from the onset of first symptoms, diagnosis, and treatment. Thus, patients with diploid tumors lived longer than patients with aneuploid tumors. These results suggest that DNA ploidy analysis may be of prognostic value in malignant mesothelioma. 31 refs., 2 figs., 3 tabs.

  1. Mesothelioma as a rapidly developing Giant Abdominal Cyst.

    PubMed

    Vyas, Dinesh; Pihl, Kerent; Kavuturu, Srinivas; Vyas, Arpita

    2012-12-20

    The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM). We describe a BCM arising in the retroperitoneal tis[sue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium), family history, social (alcohol, smoking) or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.

  2. Exposure to asbestos: psychological responses of mesothelioma patients

    SciTech Connect

    Lebovits, A.H.; Chahinian, A.P.; Holland, J.C.

    1983-01-01

    Thirty-eight patients with a diagnosis of malignant mesothelioma participated in a semi-structured interview to evaluate asbestos exposure, acquisition of increased risk information, and retrospective reporting of cognitive and behavioral reactions (particularly smoking behavior) to risk information. Twenty-eight patients (74%) had direct occupational contact with asbestos, and six patients (16%) reported indirect nonoccupational exposure to asbestos. Only two (10%) of the directly exposed patients acquired risk information from professional sources prior to diagnosis of mesothelioma. The most frequently reported reaction to learning of increased risk of cancer was a denial of the risk by minimizing personal exposure. Few patients reported being concerned about the information of increased risk. Smoking behavior did not change as a result of risk information, nor was there any increase in visits to physicians. Guidelines for psychosocial management of at-risk groups are recommended.

  3. Malignant pleural mesothelioma in a female lion (Panthera leo).

    PubMed

    Bollo, E; Scaglione, F E; Tursi, M; Schröder, C; Degiorgi, G; Belluso, E; Capella, S; Bellis, D

    2011-08-01

    An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4-20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope-Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Fertility preservation in a patient with benign multicystic peritoneal mesothelioma.

    PubMed

    Al-Safi, Zain A; Edil, Barish H; Post, Miriam D; Pearlman, Nathan W; Alvero, Ruben

    2014-09-01

    Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor. Surgery is the only effective treatment for BMPM, and affected tissues occasionally must be sacrificed to achieve adequate debulking. A 25-year-old female was diagnosed with BMPM. She was counseled on fertility preservation and had oocyte cryopreservation prior to her debulking. Fertility preservation through embryo or oocyte cryopreservation is a valuable option for patients at risk of losing reproductive tissues during extensive surgery and chemotherapy. © 2014 Wiley Periodicals, Inc.

  5. Pericardial mesothelioma in a Bengal tiger (Panthera tigris).

    PubMed

    Wiedner, Ellen B; Isaza, Ramiro; Lindsay, William A; Case, Allison L; Decker, Joshua; Roberts, John

    2008-03-01

    A 17-year-old Bengal tiger (Panthera tigris) presented with dyspnea and tachypnea. Radiographs revealed severe pleural and pericardial effusion, but no obvious mass. During attempts to remove the fluid under anesthesia, the cat developed cardiac tamponade and died. At necropsy, a nodular mass was found at the heart base and was identified as a pericardial mesothelioma. This is the first report of this tumor in any large cat.

  6. [Peritoneal mesothelioma with elevated amylase in the ascitic fluid].

    PubMed

    Carrión, A; Jover, R; Carnicer, F; García, M F; Aranda, F I; Martínez, J F; Griñó

    1995-03-01

    The case of a 42-year-old woman with no previous disease admitted for abdominal pain and ascites is presented. Analysis of the ascitic fluid demonstrated high concentrations of amylase with normal lipase. The diagnosis of peritoneal mesothelioma was obtained by laparotomy. This association has not been previously described. The authors suggest that this diagnostic possibility should be considered in patients without pancreatic disease and high amylase levels in ascitic fluid.

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

    DTIC Science & Technology

    2013-07-01

    of the military personnel of high-risk for this malignancy due to their potential long-term exposure to carcinogenic form of asbestos during their...model-Meso-rat sera. 3. We have the protocols approved for the first long-term animal study for the immune responses to the exposure to asbestos in...meanwhile, our new glycochip NYU-PGA-400 will no doubt provide far more asbestos exposure- and human Malignant Mesothelioma-relevant immuno-information as

  8. Overview of treatment related complications in malignant pleural mesothelioma

    PubMed Central

    Gill, Ritu R.

    2017-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm of the pleura related to asbestos exposure. Despite recent advances in therapy for MPM, the prognosis remains poor, with considerable treatment associated morbidity. Radiological assessment plays a central role in the timely identification and subsequent management of treatment related complications in MPM. This review highlights common and uncommon complications associated with and encountered in the post treatment phase. PMID:28706903

  9. Mesothelioma in vehicle mechanics: is the risk different for Australians?

    PubMed

    Kelsh, Michael A; Craven, Valerie A; Teta, Mary Jane; Mowat, Fionna S; Goodman, Michael

    2007-12-01

    The question of whether vehicle mechanics have an increased risk of mesothelioma has important public health implications. Calculations of relative risk using case reports from the Australian Mesothelioma Registry (AMR) indicate increased risks; however, this contrasts with the results of 19 epidemiologic studies that have found no association. To evaluate potential explanations for the discrepancy of findings from epidemiologic studies and AMR reports. We evaluated three hypotheses as possible explanations for the inconsistency between the AMR-based calculations and the findings from published epidemiologic studies: (i) differences in exposure characteristics of Australian vehicle mechanics versus vehicle mechanics in North America and Europe, (ii) limitations of the AMR data and (iii) errors in the risk calculations based on AMR data. We reviewed available exposure information specific to Australian vehicle mechanics and AMR data, obtained from the Australian National Occupational Health and Safety Commission, for this evaluation. We did not identify differences in workplace exposures, processes or fibre type among Australian vehicle mechanics compared to vehicle mechanics in other countries. Our analysis of primary AMR data identified several errors in exposure classification and in the assumptions used to calculate relative risk. Discrepancies between epidemiologic studies and AMR-based calculations cannot be explained by differences in exposure. These discrepancies are most likely attributable to inadequate occupational information and classification in the AMR from 1986 forward and to erroneous assumptions used to derive relative risk estimates for mesothelioma among Australian vehicle mechanics.

  10. Asymptomatic peritoneal carcinomatosis originating from benign cystic peritoneal mesothelioma.

    PubMed

    Iacoponi, S; Calleja, J; Hernandez, G; de la Cuesta, R Sainz

    2015-01-01

    Benign multicystic mesothelioma is a rare tumour that originates from the abdominal peritoneum with a predisposition to the pelvic peritoneum. It typically affects women of reproductive age. There have been less than 200 cases of this rare neoplasia reported to date. We present the case of a 35-year-old woman who was referred to our centre because of the detection of a peritoneal carcinomatosis during a gynaecological exam. A diagnostic laparoscopy was performed. The findings included multiple cysts appearing as 'a bunch of grapes' occupying the omentum. Biopsies were taken during the surgery and the results showed benign multicystic peritoneal mesothelioma. Benign multicystic mesothelioma can simulate other conditions, such as malignant ovarian tumours or cystic lymphangioma. It is often diagnosed accidentally during surgery performed for another reason. The diagnosis is interoperative, observing multicystic structures grouped as a 'bunch of grapes' containing clear fluid with thin walls made of connective tissue. Immunohistochemistry confirmed mesothelial origin. Surgery is considered the treatment of choice and is based on the removal of the cysts from the abdominal cavity. Hyperthermic intraperitoneal chemotherapy can be considered as a primary treatment in patients with recurrences or even as a part of primary treatment associated with surgery. Survival at 5 years is 100% and invasive or malignant progression is extraordinary. The treatment approach should be multidisciplinary, and the patient should be referred to a referral centre.

  11. Asymptomatic peritoneal carcinomatosis originating from benign cystic peritoneal mesothelioma

    PubMed Central

    Iacoponi, S; Calleja, J; Hernandez, G; de la Cuesta, R Sainz

    2015-01-01

    Benign multicystic mesothelioma is a rare tumour that originates from the abdominal peritoneum with a predisposition to the pelvic peritoneum. It typically affects women of reproductive age. There have been less than 200 cases of this rare neoplasia reported to date. We present the case of a 35-year-old woman who was referred to our centre because of the detection of a peritoneal carcinomatosis during a gynaecological exam. A diagnostic laparoscopy was performed. The findings included multiple cysts appearing as ‘a bunch of grapes’ occupying the omentum. Biopsies were taken during the surgery and the results showed benign multicystic peritoneal mesothelioma. Benign multicystic mesothelioma can simulate other conditions, such as malignant ovarian tumours or cystic lymphangioma. It is often diagnosed accidentally during surgery performed for another reason. The diagnosis is interoperative, observing multicystic structures grouped as a ‘bunch of grapes’ containing clear fluid with thin walls made of connective tissue. Immunohistochemistry confirmed mesothelial origin. Surgery is considered the treatment of choice and is based on the removal of the cysts from the abdominal cavity. Hyperthermic intraperitoneal chemotherapy can be considered as a primary treatment in patients with recurrences or even as a part of primary treatment associated with surgery. Survival at 5 years is 100% and invasive or malignant progression is extraordinary. The treatment approach should be multidisciplinary, and the patient should be referred to a referral centre. PMID:26715942

  12. Asbestos-related lung cancer and mesothelioma in Japan.

    PubMed

    Morinaga, K; Kishimoto, T; Sakatani, M; Akira, M; Yokoyama, K; Sera, Y

    2001-04-01

    In Japan, crocidolite had been used for asbestos cement pipe and spraying, and amosite had been used for building board and spraying. These two types of asbestos had stopped to use in Japan in the late 1970s. An extreme increase in imported asbestos (all 3 commercial types) was observed between 1960 and 1974. In 1960, 77,000 tons of asbestos were imported, and reached the peak as 352,316 tons in 1974. This extreme rise of asbestos imports corresponds with the recent rapid increase in mortality of malignant pleural mesothelioma. Between 1995 and 1999, an estimated mean annual death from pleural mesothelioma was about 500. The annual number of compensated occupational respiratory cancers due to asbestos exposure has also been increasing. Up to the end of March 2000, 162 cases with malignant mesothelioma and 197 cases with lung cancer were compensated. As for lung cancer, epidemiological studies are scanty in Japan. Limited environmental data of the working places in asbestos textile factories suggests that heavy asbestos exposure in the past made deaths from respiratory diseases. Less asbestos exposure will enable exposed workers to survive enough to reach cancer age. Even now smoking rate among males in Japan are over 50%. So lung cancer deaths caused by the interaction between smoking and asbestos exposure will be continuing.

  13. Diagnosis and management of patients with malignant peritoneal mesothelioma

    PubMed Central

    Burke, Allen P.

    2016-01-01

    Malignant peritoneal mesothelioma (MPM) is a rare neoplastic condition that arises, usually diffusely, from the serosal membranes of the abdominal cavity. MPM represents about 7% to 10% of all mesothelioma diagnoses and this translates into approximately 800 cases per year in the United States. The disease has variable tumor biology but progression, when it occurs, is almost always within the abdominal cavity. Although many patients can be successfully treated at initial presentation, the disease is almost always fatal in time. It afflicts men and women almost equally and the median age at presentation is 50 years. The diagnosis is made when a diffuse malignant process within the abdominal cavity is observed and a tissue sample reveals the characteristic histopathology and immunohistochemical profile of mesothelioma. Initial staging is usually via a cross sectional imaging study of the abdomen and pelvis making sure that the lower thorax is also assessed. If the disease burden and distribution is favorable then operative exploration, cytoreduction, and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered first line treatment in selected patients. Systemic pemetrexed and cisplatin (or gemcitabine) have modest response rates that are of limited duration. Research advances with novel systemic or intraperitoneal agents hold promise. PMID:26941986

  14. Basal lamina reduplication in malignant epithelioid pleural mesothelioma.

    PubMed

    Di Muzio, M; Spoletini, L; Strizzi, L; Procopio, A; Tassi, G; Casalini, A; Modesti, A

    1998-01-01

    Malignant mesothelioma of the pleura is divided in three morphological variants: epithelioid, sarcomatous, and biphasic. Histological similarities between epithelioid malignant mesothelioma (EMM) and lung adenocarcinoma are responsible for the difficult differential diagnosis. Monoclonal antibodies are useful for distinguishing the two neoplasms through immunohistochemical phenotyping, although many cases require ultrastructural characterization for definitive diagnosis. In this study, transmission electron microscopic observations of EMM were compared with those of peripheral adenocarcinoma of the lung (PAL). More specifically, the morphology of the basal lamina is described in 23 cases of EMM and 12 cases of PAL. Reduplication of the basal lamina (RBL) was found in 11 cases (48%) of EMM and in none of the PAL cases. The same cases were immunostained for type IV collagen and the localization of this basement membrane component corresponded to the areas where basal lamina was observed. Since RBL has been associated with neoplastic differentiation in other tumors, this novel feature in EMM needs to be evaluated in future prognostic studies in malignant mesothelioma of the pleura. Moreover, RBL expression in EMM may be an additional ultrastructural parameter used in the differential diagnosis between EMM and adenocarcinoma.

  15. Porcelain factory worker with asbestos-related mesothelioma.

    PubMed

    Tsou, Meng-Ting; Luo, Jiin-Chyuan J

    2009-10-01

    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.

  16. Well-differentiated papillary mesothelioma: a clinicopathological and immunohistochemical study of 18 cases with additional observation.

    PubMed

    Chen, Xiaochen; Sheng, Weiqi; Wang, Jian

    2013-04-01

    To present our experience with 18 cases of well-differentiated papillary mesothelioma (WDPM), with an emphasis on its relationship to adenomatoid tumour and multicystic mesothelioma. Eighteen cases of WDPM were retrieved. Twenty cases of multicystic mesothelioma were selected for comparative study. The WDPM patients comprised 14 females and four males, with age ranging from 18 to 60 years (median 37 years). The tumour involved the abdominal or pelvic peritoneum (14 cases), the pleura (two cases), and the testicular tunica vaginalis (two cases). The majority of WDPMs were incidental findings during surgery for a wide variety of conditions. Histologically, 13 cases were consistent with classical WDPM. Two cases had a combined component of adenomatoid tumour, and three cases contained coexisting areas of multicystic mesothelioma. Among the multicystic mesothelioma cases, four had adenomatoid tumour-like foci present in the stroma. Immunohistochemically, all cases of WDPM and multicystic mesothelioma, as well as the coexisting combined components, were positive for mesothelial markers, with a low Ki67 index. This study also showed that WDPM was negative for epithelial membrane antigen and desmin. The simultaneous occurrence of WDPM, adenomatoid tumour and multicystic mesothelioma in some cases suggested histogenetic relationships among these three less aggressive mesotheliomas. © 2012 Blackwell Publishing Ltd.

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

    SciTech Connect

    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.

  18. Immune Suppression Enhances Effectiveness of Mesothelioma Targeted Immunotoxin | Center for Cancer Research

    Cancer.gov

    Malignant mesothelioma is an aggressive cancer of the linings of the organs in the chest and the abdomen and is often caused by exposure to asbestos. Although patients with localized disease may be treated effectively with surgery, those with more-advanced mesothelioma have few approved treatment options.

  19. Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma.

    PubMed

    Kinnula, Vuokko L; Torkkeli, Tuula; Kristo, Paula; Sormunen, Raija; Soini, Ylermi; Pääkkö, Paavo; Ollikainen, Tiina; Kahlos, Katriina; Hirvonen, Ari; Knuutila, Sakari

    2004-08-01

    Mesothelioma represents an aggressive tumor type with high resistance to all treatment modalities. Its pathogenesis is strongly associated with exposure to asbestos fibers and probably with free radicals. One of the most important free radical scavenging enzymes, mitochondrial manganese superoxide dismutase (MnSOD), has been shown to be elevated in mesothelioma (K. Kahlos et al., 1998, Am. J. Respir. Cell Mol. Biol. 18:570-580). In the present study, we could detect intense ultrastructural accumulation of MnSOD in the mitochondrial compartment of malignant mesothelioma cells. There was no association between the immunohistochemical reactivity and the most common and functional polymorphic variant of MnSOD, the Ala to Val amino acid change at 9 position (16th amino acid from the beginning of the signal sequence), in the 31 mesothelioma cases investigated. Comparative genomic hybridization and fluorescence in situ hybridization did not reveal any changes in chromosome 6, where the MnSOD gene is located. Sequencing of the MnSOD promoter region in four mesothelioma cell lines showed similar nucleotide variables in the malignant and nonmalignant cells. Therefore, the intense expression of MnSOD in the mitochondria of mesothelioma cells does not appear be associated with any major chromosomal alterations or the polymorphism of MnSOD gene. Association with oxidative/nitrosative stress in mesothelioma using nitrotyrosine immunostaining pointed to a tendency for more intense reactivity in those mesotheliomas with higher MnSOD expression (P = 0.069).

  20. Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model.

    PubMed

    Minami, Daisuke; Takigawa, Nagio; Kato, Yuka; Kudo, Kenichiro; Isozaki, Hideko; Hashida, Shinsuke; Harada, Daijiro; Ochi, Nobuaki; Fujii, Masanori; Kubo, Toshio; Ohashi, Kadoaki; Sato, Akiko; Tanaka, Takehiro; Hotta, Katsuyuki; Tabata, Masahiro; Toyooka, Shinichi; Tanimoto, Mitsune; Kiura, Katsuyuki

    2015-10-01

    Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.

  1. p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer.

    PubMed

    Ito, Tomohiro; Hamasaki, Makoto; Matsumoto, Shinji; Hiroshima, Kenzo; Tsujimura, Tohru; Kawai, Toshiaki; Shimao, Yoshiya; Marutsuka, Kousuke; Moriguchi, Sayaka; Maruyama, Riruke; Miyamoto, Shingo; Nabeshima, Kazuki

    2015-06-01

    It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected. Copyright© by the American Society for Clinical Pathology.

  2. Fibulin-3 as a Blood and Effusion Biomarker for Pleural Mesothelioma

    PubMed Central

    Pass, Harvey I.; Levin, Stephen M.; Harbut, Michael R.; Melamed, Jonathan; Chiriboga, Luis; Donington, Jessica; Huflejt, Margaret; Carbone, Michele; Chia, David; Goodglick, Lee; Goodman, Gary E.; Thornquist, Mark D.; Liu, Geoffrey; de Perrot, Marc; Tsao, Ming-Sound; Goparaju, Chandra

    2012-01-01

    BACKGROUND New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker. METHODS We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay. RESULTS Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos

  3. National Mesothelioma Virtual Bank: A Platform for Collaborative Research and Mesothelioma Biobanking Resource to Support Translational Research.

    PubMed

    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).

  4. Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies

    PubMed Central

    Bononi, Angela; Napolitano, Andrea; Pass, Harvey I; Yang, Haining; Carbone, Michele

    2016-01-01

    Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: (i) molecular targeted approaches, i.e. the inhibiton of vascular endothelial growth factor with Bevacizumab; (ii) immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; (iii) inhibition of asbestos-induced inflammation, i.e. aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing. PMID:26308799

  5. Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE).

    PubMed

    Wali, Anil; Morin, Patrice J; Hough, Colleen D; Lonardo, Fulvio; Seya, Tsukasa; Carbone, Michele; Pass, Harvey I

    2005-04-01

    Malignant pleural mesothelioma (MPM) is a fatal neoplasm with no acceptable curative approaches. We used serial analysis of gene expression (SAGE) to compare the gene expression pattern of a surgically resected MPM to the autologous normal mesothelium. Intelectin gene overexpression (>139-fold) was found in the tumor. Online SAGE datasets revealed intelectin to be consistently present in mesothelioma(s), ovarian cancer, and colon cancer. Intelectin mRNA expression was found by RT-PCR in 4 of 5 resected MPM tumors, and Intelectin protein expression was confirmed by immunohistochemistry in 28 of 53 MPM tumors, and in 4 of 4 mesothelioma cell lines studied by Western blot. A marked induction in intelectin gene expression was observed among human primary mesothelial cells as a consequence of crocidolite asbestos exposure and simian virus 40 infection. Intelectin overexpression in mesothelioma could have potential screening, and therapeutic implications.

  6. Use of antibodies to carcinoembryonic antigen and human milk fat globule to distinguish carcinoma, mesothelioma, and reactive mesothelium.

    PubMed Central

    Marshall, R J; Herbert, A; Braye, S G; Jones, D B

    1984-01-01

    Antibodies raised against human milk fat globule (HMFG 1 and 2) and carcinoembryonic antigen were used in an immunoperoxidase technique to differentiate mesothelioma, carcinoma, and benign, reactive mesothelium. Sixteen mesotheliomas, 27 lung carcinomas, and 13 specimens of reactive mesothelium were examined. Staining for carcinoembryonic antigen was not seen in reactive mesothelium or mesothelioma but was present in 22 of 27 carcinomas. Mesothelioma and carcinoma usually stained with HMFG 1 and 2; reactive mesothelium did not. These three antibodies may help to distinguish carcinoma, mesothelioma, and reactive mesothelium. Images PMID:6094617

  7. Historical cohort study of US man-made vitreous fiber production workers: II. Mortality from mesothelioma.

    PubMed

    Marsh, G M; Gula, M J; Youk, A O; Buchanich, J M; Churg, A; Colby, T V

    2001-09-01

    As part of our ongoing mortality surveillance program for the US man-made vitreous fiber (MMVF) industry, we examined mortality from malignant mesothelioma using data from our 1989 follow-up of 3478 rock/slag wool workers and our 1992 follow-up of 32,110 fiberglass workers. A manual search of death certificates for 1011 rock/slag wool workers and 9060 fiberglass workers revealed only 10 death certificates with any mention of the word "mesothelioma." A subsequent review of medical records and pathology specimens for 3 of the 10 workers deemed two deaths as definitely not due to mesothelioma and one as having a 50% chance of being caused by mesothelioma. Two other deaths, for which only medical records were available, were given less than a 50% chance of being due to mesothelioma. Eight of the 10 decedents had potential occupational asbestos exposure inside or outside the MMVF industry. We also estimated the mortality risk from malignant mesothelioma in the cohort using two cause-of-death categorizations that included both malignant and benign coding rubrics. Using the more comprehensive scheme, we observed overall deficits in deaths among the total cohort and fiberglass workers and an overall excess among rock/slag wool workers. The excess in respiratory system cancer is largely a reflection of elevated lung cancer risks that we attributed mainly to confounding by smoking, to exposures outside the MMVF industry to agents such as asbestos, or to one or more of the several co-exposures present in many of the study plants (including asbestos). The second scheme, which focused on pleural mesothelioma in time periods when specific malignant mesothelioma coding rubrics were available, classified only one cohort death as being caused by malignant mesothelioma, compared with 2.19 expected deaths (local county comparison). We conclude that the overall mortality risk from malignant mesothelioma does not seem to be elevated in the US MMVF cohort.

  8. Environmental risk of mesothelioma in the United States: An emerging concern-epidemiological issues.

    PubMed

    Baumann, Francine; Carbone, Michele

    2016-01-01

    Despite predictions of decline in mesothelioma following the ban of asbestos in most industrial countries, the incidence is still increasing globally, particularly in women. Because occupational exposure to asbestos is the main cause of mesothelioma, it occurs four- to eightfold more frequently in men than women, at a median age of 74 years. When mesothelioma is due to an environmental exposure, the M:F sex ratio is 1:1 and the median age at diagnosis is ~60 years. Studying environmental risk of mesothelioma is challenging because of the long latency period and small numbers, and because this type of exposure is involuntary and unknown. Individual-based methods cannot be used, and new approaches need to be found. To better understand the most recent trends of mesothelioma in the United States, all mesothelioma deaths reported to the Centers for Disease Control and Prevention (CDC) during 1999-2010 were analyzed. Among all mesothelioma deaths in the United States, the 1920s birth cohort significantly predominated, and the proportion of younger cohorts constantly decreased with time, suggesting a decline in occupational exposure in these cohorts. The M:F mesothelioma sex ratio fell with time, suggesting an increased proportion of environmental cases. Environmental exposures occur in specific geographic areas. At the large scale of a state, mesotheliomas related to environmental exposure are diluted among occupational cases. The spatial analysis at a smaller scale, such as county, enables detection of areas with higher proportions of female and young mesothelioma cases, thus indicating possible environmental exposure, where geological and environmental investigations need to be carried out.

  9. Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma

    PubMed Central

    Creaney, Jenette; Yeoman, Deborah; Naumoff, Leanne K; Hof, Michelle; Segal, Amanda; Musk, Arthur William; De Klerk, Nicholas; Horick, Nora; Skates, Steven J; Horick, Bruce W S RobinsonNora

    2007-01-01

    Background The diagnosis of malignant mesothelioma is frequently difficult, the most common differential diagnosis being reactive pleural conditions and metastatic adenocarcinoma. Soluble mesothelin levels in serum have recently been shown to be highly specific and moderately sensitive for mesothelioma. As most patients with mesothelioma present with exudative effusions of either the pleura or the peritoneum, a study was undertaken to determine if levels of mesothelin were raised in these fluids and if the increased levels could help to distinguish mesothelioma from other causes of exudative effusion. Methods Pleural fluid was collected from 192 patients who presented to respiratory clinics (52 with malignant mesothelioma, 56 with non‐mesotheliomatous malignancies and 84 with effusions of non‐neoplastic origin). Peritoneal fluid was collected from 42 patients (7 with mesothelioma, 14 with non‐mesotheliomatous malignancies and 21 with benign effusions). Mesothelin levels were determined in effusion and serum samples by ELISA. Results Significantly higher levels of mesothelin were found in effusions of patients with mesothelioma; with a specificity of 98%, the assay had a sensitivity of 67% comparing patients with mesothelioma and those with effusions of non‐neoplastic origin. In 7 out of 10 cases mesothelin levels were raised in the effusion collected 3 weeks to 10 months before the diagnosis of mesothelioma was made; in 4 out of 8 of these, mesothelin levels were increased in the effusion but not in the serum. Conclusions Measurement of mesothelin concentrations in the pleural and/or peritoneal effusion of patients may aid in the differential diagnosis of mesothelioma in patients presenting with effusions. PMID:17356060

  10. Mesothelioma of tunica vaginalis of "uncertain malignant potential" - an evolving concept: case report and review of the literature

    PubMed Central

    2011-01-01

    Mesothelioma of tunica vaginalis is a rare neoplasm, typically demonstrating frankly malignant morphology and aggressive behavior. Rare cases of well-differentiated papillary mesotheliomas have also been reported, which, in contrast, demonstrate indolent behavior. There are, however, cases which do not fit into the well-differentiated or diffuse malignant mesothelioma categories and can be considered mesothelioma of tunica vaginalis of "uncertain malignant potential", which is an emerging diagnostic category. A 57-year-old man presented with a neoplasm in a hydrocele sac. The neoplasm was non-invasive, but showed focal complex and solid growth and it was difficult to categorize either as well-differentiated papillary mesotheliomas or malignant mesothelioma. After the initial limited resection, the patient underwent radical orchiectomy with hemiscrotectomy and is alive and without disease progression after 6 years. Documentation of these rare tumors will allow their distinction from true malignant mesotheliomas and will facilitate the development of specific treatment recommendations. PMID:21867523

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

    PubMed

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

    2015-10-01

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

  12. Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma.

    PubMed

    D'Amato-Brito, Cintia; Cipriano, Davide; Colin, Didier J; Germain, Stéphane; Seimbille, Yann; Robert, John H; Triponez, Frédéric; Serre-Beinier, Véronique

    2016-03-08

    Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in acute and chronic inflammatory diseases. MIF is overexpressed in various tumors. It displays a number of functions that provide a direct link between the process of inflammation and tumor growth. Our group recently identified the MIF-receptor CD74 as an independent prognostic factor for overall survival in patients with malignant pleural mesothelioma.In the present study, we compared the levels of expression of MIF and CD74 in different human mesothelioma cell lines and investigated their physiopathological functions in vitro and in vivo.Human mesothelioma cells expressed more CD74 and secreted less MIF than non tumoral MeT5A cells, suggesting a higher sensitivity to MIF. In mesothelioma cells, high MIF levels were associated with a high multiplication rate of cells. In vitro, reduction of MIF or CD74 levels in both mesothelioma cell lines showed that the MIF/CD74 signaling pathway promoted tumor cell proliferation and protected MPM cells from apoptosis. Finally, mesothelioma cell lines expressing high CD74 levels had a low tumorigenic potential after xenogeneic implantation in athymic nude mice.All these data highlight the complexity of the MIF/CD74 signaling pathway in the development of mesothelioma.

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

    PubMed Central

    Shen, Cheng; Lai, Yutian; Wang, Mingming; Che, Guowei

    2017-01-01

    Background Soluble mesothelin is beneficial to detect the progression and the treatment response of malignant pleural mesothelioma. However, the prognostic value of soluble mesothelin in malignant pleural mesothelioma remains unclear. Methods Hazard ratio with 95% CI was used to evaluate the prognostic value of soluble mesothelin and the effect of clinicopathological characteristics on the survival of malignant pleural mesothelioma. Results Eight eligible studies involving 579 patients were selected for this meta-analysis. The results showed that soluble mesothelin level was significantly correlated with the survival of malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000; heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant pleural mesothelioma was significantly correlated with some clinicopathological characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95% CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966). Conclusions The survival of malignant pleural mesothelioma is significantly correlated with tumor histology and tumor stage. Furthermore, high soluble mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma patients. PMID:28507279

  14. Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

    SciTech Connect

    Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W. )

    1991-01-01

    Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma.

  15. A case-control study of mesothelioma and employment in the Hawaii sugarcane industry.

    PubMed

    Sinks, T; Goodman, M T; Kolonel, L N; Anderson, B

    1994-07-01

    We conducted a case-control study of 93 mesothelioma cases and 281 cancer controls to determine whether sugarcane workers exposed to biogenic silica fibers were at increased risk of mesothelioma. We found no important excess risk of mesothelioma in sugarcane workers [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.4-3.8] when we excluded all control subjects with cancer of sites suspected of being associated with asbestos exposure. We could not identify any sugarcane workers who developed mesothelioma and worked in jobs where high exposure levels of biogenic silica fibers have been measured. We did confirm that mesothelioma risk in Hawaii is associated with probable occupational asbestos exposure. Work at the Pearl Harbor Naval Shipyard was associated with a 10-fold increase in mesothelioma when we excluded controls with cancer of sites related to asbestos exposure (OR = 10.1; 95% CI = 2.6-56.6). Work in the medical industry was also associated with an unexpected increased risk for mesothelioma (OR = 4.2; 95% CI = 1.2-15.5).

  16. [Malignant mesothelioma risk factors: experience in the General Hospital of Mexico].

    PubMed

    Hernández-Solís, Alejandro; Garcia-Hernández, Cyntia; Reding-Bernal, Arturo; Cruz-Ortiz, Humberto; Cicero-Sabido, Raúl

    2013-01-01

    Malignant mesothelioma is a neoplasm of bad prognosis, it is linked with asbestos contact, but there are cases without this antecedent. To investigate the relationship of asbestos exposition and other factors with malignant mesothelioma. Retrospective analysis of histologic confirmed cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking, exposure to wood smoke and to asbestos, were annotated in a paired case/control study 1: 1-3 with logistic regression model to identify risk factors for OR. 61 cases of malignant mesothelioma were confirmed by histopathologic study, 41 male and 20 female. Mean age was 56 years ± 13 years; 56 cases (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%) one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos. Model of logistic regression with four variables: history of familiar cancer, tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR= 3.083 and p > 0.05. No other variables found to be a risk factor for malignant mesothelioma. Exposure to asbestos is a risk factor for malignant mesothelioma, which is confirmed in this study, however it is important to extend the investigation of other possible causal factors of this disease.

  17. Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma

    PubMed Central

    D'Amato-Brito, Cintia; Cipriano, Davide; Colin, Didier J.; Germain, Stéphane; Seimbille, Yann; Robert, John H.; Triponez, Frédéric; Serre-Beinier, Véronique

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in acute and chronic inflammatory diseases. MIF is overexpressed in various tumors. It displays a number of functions that provide a direct link between the process of inflammation and tumor growth. Our group recently identified the MIF-receptor CD74 as an independent prognostic factor for overall survival in patients with malignant pleural mesothelioma. In the present study, we compared the levels of expression of MIF and CD74 in different human mesothelioma cell lines and investigated their physiopathological functions in vitro and in vivo. Human mesothelioma cells expressed more CD74 and secreted less MIF than non tumoral MeT5A cells, suggesting a higher sensitivity to MIF. In mesothelioma cells, high MIF levels were associated with a high multiplication rate of cells. In vitro, reduction of MIF or CD74 levels in both mesothelioma cell lines showed that the MIF/CD74 signaling pathway promoted tumor cell proliferation and protected MPM cells from apoptosis. Finally, mesothelioma cell lines expressing high CD74 levels had a low tumorigenic potential after xenogeneic implantation in athymic nude mice. All these data highlight the complexity of the MIF/CD74 signaling pathway in the development of mesothelioma. PMID:26883190

  18. A case of malignant pleural mesothelioma following exposure to atomic radiation in Nagasaki.

    PubMed

    Mizuki, M; Yukishige, K; Abe, Y; Tsuda, T

    1997-09-01

    We report the case of a 75-year-old Japanese man who developed malignant mesothelioma in the left hemithorax 50 years after the dropping of the atomic bomb on Nagasaki in 1945. This may be the first reported case of malignant mesothelioma following exposure to atomic radiation. Asbestos is the leading cause of malignant mesothelioma, but radiation therapy is the primary non-asbestos-related cause. In the case of radiation therapy, the interval between exposure and the occurrence of malignant mesothelioma tends to be many years. This patient was at a high risk of malignant mesothelioma as he had been exposed to radiation from the atomic bomb and may also have had a history of asbestos exposure at the munitions factory where he was employed as a shipbuilder for 2 years. It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. If thickening of the pleura or pleural effusion is found in atomic bomb survivors, malignant mesothelioma should be considered as one of the options in the differential diagnosis, even although the atomic bomb attacks occurred several decades ago.

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

    PubMed Central

    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

  20. Estimating the asbestos-related lung cancer burden from mesothelioma mortality

    PubMed Central

    McCormack, V; Peto, J; Byrnes, G; Straif, K; Boffetta, P

    2012-01-01

    Background: Quantifying the asbestos-related lung cancer burden is difficult in the presence of this disease's multiple causes. We explore two methods to estimate this burden using mesothelioma deaths as a proxy for asbestos exposure. Methods: From the follow-up of 55 asbestos cohorts, we estimated ratios of (i) absolute number of asbestos-related lung cancers to mesothelioma deaths; (ii) excess lung cancer relative risk (%) to mesothelioma mortality per 1000 non-asbestos-related deaths. Results: Ratios varied by asbestos type; there were a mean 0.7 (95% confidence interval 0.5, 1.0) asbestos-related lung cancers per mesothelioma death in crocidolite cohorts (n=6 estimates), 6.1 (3.6, 10.5) in chrysotile (n=16), 4.0 (2.8, 5.9) in amosite (n=4) and 1.9 (1.4, 2.6) in mixed asbestos fibre cohorts (n=31). In a population with 2 mesothelioma deaths per 1000 deaths at ages 40–84 years (e.g., US men), the estimated lung cancer population attributable fraction due to mixed asbestos was estimated to be 4.0%. Conclusion: All types of asbestos fibres kill at least twice as many people through lung cancer than through mesothelioma, except for crocidolite. For chrysotile, widely consumed today, asbestos-related lung cancers cannot be robustly estimated from few mesothelioma deaths and the latter cannot be used to infer no excess risk of lung or other cancers. PMID:22233924

  1. Asbestos-induced peritoneal mesothelioma in a construction worker.

    PubMed Central

    Fonte, Rodolfo; Gambettino, Salvatore; Melazzini, Mario; Scelsi, Mario; Zanon, Claudio; Candura, Stefano M

    2004-01-01

    Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent ascites after having been exposed to asbestos in the building industry for > 40 years. Liver function and histology were normal. Abdominal computed tomography initially excluded the presence of expansive processes, and no abnormal cells were found in the ascitic fluid. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum. Histopathology of bioptic samples revealed epithelioid neoplastic proliferation with a tubulopapillary pattern, falsely suggesting metastatic adenocarcinomatosis. In consideration of the occupational history, and after further diagnostic procedures had failed to identify the hypothetical primitive tumor, immunostaining of the neoplastic tissue was performed. Results were negative for carcinoembrionary antigen and the epithelial glycoprotein Ber-EP4, whereas results were positive for the mesothelial markers cytokeratins, calretinin, epithelial membrane antigen, and HBME-1, thus leading to the correct diagnosis of peritoneal epithelial mesothelioma. The Italian Workers' Compensation Authority recognized the occupational origin of the disease. Cytoreductive surgery associated with continuous hyperthermic peritoneal perfusion (cisplatin at 42 degrees C, for 1 hr) was performed. The disease relapsed after 4 months and was later complicated by a bowel obstruction requiring palliative ileostomy. The patient died 23 months after diagnosis. This case illustrates the insidious diagnostic problems posed by peritoneal mesothelioma, a tumor which often simulates other malignancies (e.g., metastatic carcinomas) at routine histopathological examination. Occupational history and immunohistochemistry are helpful for the correct

  2. [Malignant mesothelioma in garment sewing-machine workers].

    PubMed

    Barbieri, P G; Somigliana, Anna; Girelli, R; Lombardi, Sandra; Festa, R; Silvestri, S

    2008-01-01

    Due to poor information collected through patient interviews, a considerable number of malignant mesothelioma (MM) cases still remain classified as "unknown" asbestos exposure in the Italian Mesotelioma Registry (Re.Na.M). At the same time, some occupational asbestos exposures, which were previously unknown, have been demonstrated in certain types of work, i.e., in agriculture and in the textile industry. The aim of this research was to investigate the possible past occupational exposure to asbestos in clothing workers using sewing-machines. The MM cases were collected from the Mesothelioma Registry of Brescia. Work histories were obtained via a standardized questionnaire. Investigations were conducted in sewing-machine maintenance workshop in order to collect information regarding the possible use of asbestos parts. In addition, the use of asbestos friction materials and the use of insulated asbestos materials was checked in the clothing divisions by interviewing the management and maintenance workers of two companies where cases of MM were observed. The Mesothelioma Registry of Brescia identified and collected 10 MM cases with past work in the clothing industry: 6 used sewing-machines and 4 were self-employed tailors. The search for asbestos materials gave positive results as the use of friction materials had been widespread since the 1950's in all types of sewing-machines; in addition, asbestos materials were used to insulate some parts of the ironing equipment and the steam pipelines. The results of this investigation suggest assigning at least "possible occupational asbestos exposure" to those cases employed in clothing manufacture since the 1950's, who used sewing-machines or pressing machines, according to the Re.Na.M guidelines. Other possible occupational exposures to asbestos in this working sector cannot be excluded; when the simple interview of patients does not reveal such exposures further investigations are needed in order to demonstrate all the

  3. Malignant intraperitoneal mesothelioma-Başkent University experience

    PubMed Central

    Macuks, Ronalds; Özdemir, Halis; Dursun, Polat; Özen, Özlem Işıksaçan; Haberal, Nihan; Ayhan, Ali

    2011-01-01

    Objective To evaluate diagnostic and treatment results of malignant intraperitoneal mesothelioma in one setting. Materials and Method: 12 patients treated for malignant peritoneal mesothelioma from January 2007 to June 2009 in Başkent University Ankara Hospital, Department of Gynaecology and Obstetrics were evaluated. In a retrospective observational study design tumour stage, grade, differentiation, time from first symptoms, pleural involvement, peritoneal cancer index, surgical cytoreduction, chemotherapeutic regimen, number of cycles, disease free survival and overall survival were evaluated. Disease free survival, overall survival, time until first symptoms were researched. Results The main presenting symptom was abdominal distension. Primary cytoreductive surgery followed by chemotherapy was performed in 9 patients. In 6 patients completeness of cytoreductive score below 2 was achieved. As a first line chemotherapy the most often used was cisplatin in combination with pemetrexed. Themean time from first symptoms until the diagnosis was 1.9 months. Disease free survival of 4.4±1.0 months after completing particular treatment and overall 1-year survival of 85.7 % was observed. No correlations between first symptoms (0.27, p=0.52), time until the diagnosis (−0.29, p=0.44) and overall survival were observed. Similarly, correlations between peritoneal cancer index (0.25, p=0.67), prior surgical score (−.45, p=0.37), completeness of cytoreduction score (0.61, p=0.27) and overall survival were not observed. Conclusions Because of the low number of patients and different treatment approaches data from a particular patient setting are inconclusive, but from the literature there is evidence that patients with malignant intraperitoneal mesothelioma should undergo optimal cytoreduction and receive a combination of cisplatin and pemetrexed as a first line chemotherapy for intravenous or cisplatin in different chemotherapy regimens using the intraperitoneal

  4. Retroperitoneal approach for recurrent benign multicystic peritoneal mesothelioma.

    PubMed

    Bakhshi, Girish D; Wankhede, Kishor R; Tayade, Mukund B; Bhandarwar, Ajay H; Gore, Sandeep T; Choure, Dayanand D

    2013-01-25

    Benign multicystic peritoneal mesothelioma (BMPM) is an uncommon lesion. It presents as a lump in abdomen or a finding seen on imaging modalities. Surgery is the primary modality of treatment. However, it has a high recurrence rate; this results in adhesions and subsequent surgeries difficult. We present a case of recurrent BMPM in a female operated twice earlier in a rural centre. Imaging modalities showed majority of the lesion in paracolic and retroperitoneal region. Hence, retroperitoneal approach for surgery was taken. This avoided previous surgical adhesions. A brief case report on this novel approach and review of literature is presented.

  5. Retroperitoneal Approach for Recurrent Benign Multicystic Peritoneal Mesothelioma

    PubMed Central

    Bakhshi, Girish D.; Wankhede, Kishor R; Tayade, Mukund B.; Bhandarwar, Ajay H.; Gore, Sandeep T.; Choure, Dayanand D.

    2013-01-01

    Benign multicystic peritoneal mesothelioma (BMPM) is an uncommon lesion. It presents as a lump in abdomen or a finding seen on imaging modalities. Surgery is the primary modality of treatment. However, it has a high recurrence rate; this results in adhesions and subsequent surgeries difficult. We present a case of recurrent BMPM in a female operated twice earlier in a rural centre. Imaging modalities showed majority of the lesion in paracolic and retroperitoneal region. Hence, retroperitoneal approach for surgery was taken. This avoided previous surgical adhesions. A brief case report on this novel approach and review of literature is presented. PMID:24765496

  6. Benign multicystic mesothelioma masquerading as a urachal cyst.

    PubMed

    Marien, Tracy; Zhou, Min; Brucker, Benjamin

    2014-12-01

    Benign multicystic mesothelioma (BMM) is a benign intra-abdominal lesion that generally occurs in women in their reproductive years. A urachal cyst occurs when the epithelial-lined urachal canal fails to completely obliterate. We report a case of a 38-year-old female presenting with abdominal pain found to have a lesion highly suspicious for a urachal cyst. On pathologic evaluation the lesion was identified as a BMM. This is the first report of BMM presenting as a lesion suspected to be a urachal cyst.

  7. Chondrosarcoma of the Rib Mimicking Malignant Pleural Mesothelioma

    PubMed Central

    Furukawa, Masashi; Tao, Hiroyuki; Tanaka, Toshiki; Onoda, Hideko; Murakami, Tomoyuki; Okabe, Kazunori

    2016-01-01

    A 62-year-old man with a history of long-term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography. The computed tomography also revealed multiple plaques in the pleura. Malignant pleural mesothelioma was suspected, and thoracoscopic surgery was performed. Thoracoscopy revealed that the tumor location was extrapleural. Thus, excisional biopsy was performed. The tumor was histologically diagnosed as chondrosarcoma. Additional wide resection of the chest wall, including the fifth, sixth, and seventh ribs, was performed. Chest wall reconstruction was performed with a polypropylene mesh. PMID:26933413

  8. Epidemiology of pleural mesothelioma in North-western Italy (Piedmont)

    PubMed Central

    Rubino, G. F.; Scansetti, G.; Donna, A.; Palestro, G.

    1972-01-01

    Rubino, G. F., Scansetti, G., Donna, A., and Palestro, G. (1972).Brit. J. industr. Med.,29, 436-442. Epidemiology of pleural mesothelioma in North-western Italy (Piedmont). Fifty-four cases of mesothelioma of the pleura admitted to the Chest Surgery Centre or to the Department of Medicine of the University of Turin from 1960 to 1970 are reported. Thoracotomy was performed in 22. In the other 32 the diagnosis was based on the clinical, radiographic, and cytological findings and on the results of biopsy. In 50 cases (18 women and 32 men), the majority of whom had always or mostly lived in Piedmont, it was possible to ascertain the family history, previous residence, and occupation, mainly with the aid of information given by the patient's relatives. A similar investigation was made by the same interviewers into 50 other patients of the same sex and age admitted to the same institutions, using an identical technique. In the group with mesothelioma (only two of whom survived more than two years after the diagnosis had been made) occupational exposure to asbestos was demonstrated unequivocally in five men. Three other patients, including one woman, had lived with persons employed in the asbestos industry (16%). Exposure for occupational reasons seemed very likely in another patient, who had been a fireman in the Turin Arsenal for 40 years. One man in the control group had worked for two years in a cement-asbestos manufacturing company (2%). A re-appraisal of the histological sections and examination of new preparations made in the 22 cases operated on was done in the Department of Pathological Anatomy of the University of Turin, also with the purpose of confirming the diagnosis. This re-appraisal revealed the presence of asbestos bodies in the mesothelioma in one case, a woman who had never been exposed to asbestos for occupational or domestic reasons but who had always lived in one of the two regions of the Province of Turin with the highest number of asbestos

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

    PubMed Central

    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

  10. The role of asbestos fiber dimensions in the prevention of mesothelioma.

    PubMed

    Tomatis, Lorenzo; Cantoni, Susanna; Carnevale, Francesco; Merler, Enzo; Mollo, Franco; Ricci, Paolo; Silvestri, Stefano; Vineis, Paolo; Terracini, Benedetto

    2007-01-01

    A recent interpretation of the pathogenetic role of asbestos fiber size in the development of mesothelioma and in the possibility of mesothelioma prevention needs clarification. This point of view is based on a biased interpretation of the literature. Epidemiologic, experimental, and molecular evidence suggests that the arguments for the role of fiber size relative to dose, dose-response effect, and genetic susceptibility are scientifically unsound. Their proponent also states that means available in the past for the implementation of dust-control measures and/or personal protective equipment would not have contributed to reducing the frequency of mesothelioma among exposed subjects, an argument again based on invalid assumptions.

  11. Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review.

    PubMed

    Blomberg, Carl; Nilsson, Jonas; Holgersson, Georg; Edlund, Per; Bergqvist, Michael; Adwall, Linda; Ekman, Simon; Brattström, Daniel; Bergström, Stefan

    2015-05-01

    Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Mesothelioma: cases associated with non-occupational and low dose exposures

    PubMed Central

    Hillerdal, G.

    1999-01-01

    OBJECTIVES: To estimate the importance of low dose exposure to asbestos on the risk of mesothelioma. METHODS: A review of the literature. RESULTS AND CONCLUSIONS: There is no evidence of a threshold level below which there is no risk of mesothelioma. Low level exposure more often than not contains peak concentrations which can be very high for short periods. There might exist a background level of mesothelioma occurring in the absence of exposure ot asbestos, but there is no proof of this and this "natural level" is probably much lower than the 1- 2/million/year which has been often cited.   PMID:10492646

  13. Radiation therapy in the management of patients with mesothelioma

    SciTech Connect

    Gordon, W. Jr.; Antman, K.H.; Greenberger, J.S.; Weichselbaum, R.R.; Chaffey, J.T.

    1982-01-01

    The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free inteval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.

  14. P2×7 targeting inhibits growth of human mesothelioma

    PubMed Central

    Amoroso, Francesca; Salaro, Erica; Falzoni, Simonetta; Chiozzi, Paola; Giuliani, Anna Lisa; Cavallesco, Giorgio; Maniscalco, Pio; Puozzo, Andrea; Bononi, Ilaria; Martini, Fernanda; Tognon, Mauro; Virgilio, Francesco Di

    2016-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2×7 (P2RX7 or P2×7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2×7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2×7R antagonists, as well as by stimulation with the P2×7R agonist BzATP. Systemic administration of the selective P2×7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2×7R might be a novel target for the therapy of mesothelioma. PMID:27391069

  15. Benign multicystic mesothelioma of the peritoneum: a case report.

    PubMed

    Cavallaro, Antonio; Murazio, Marino; Modugno, Pietro; Vona, Alessio; Revelli, Luca; Potenza, Angelo Eugenio; Colli, Rosa

    2002-01-01

    The aim of this study is to report the experience of a case of benign multicystic mesothelioma of the peritoneum presented with acute appendicitis symptomatology. A 28 years old man with right lower and upper abdominal pain was admitted into hospital. Because of the clinical picture, the symptomatology and the leukocytosis a diagnosis of acute appendicitis was made and the patient underwent appendicectomy according to Mc Burney. At laparotomy some cc of purulent fluid were sucked and a cystic mass that contained clear fluid was revealed. In consequence of the incidental diagnosis a following middle laparotomy was made with a careful surgical excision of the mass and of the appendix. Macroscopically the lesion was identified like a neoplastic mass 25 centimeters in diameter, with a multicystic and fibrous-adipose aspect, with cysts 5 centimeters in diameter. The cystic spaces were lined by a layer of eptelial cells which presented positive reaction for cytokeratin and EMA, whereas endothelium markers were absent. The ultrastructural, morphological and immunohistochemical findings were diagnostic of a benign multicystic mesothelioma.

  16. Diagnosis and prognosis—review of biomarkers for mesothelioma

    PubMed Central

    Sun, Huan H.; Vaynblat, Allen

    2017-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA’s, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers. PMID:28706912

  17. Iron overload signature in chrysotile-induced malignant mesothelioma.

    PubMed

    Jiang, Li; Akatsuka, Shinya; Nagai, Hirotaka; Chew, Shan-Hwu; Ohara, Hiroki; Okazaki, Yasumasa; Yamashita, Yoriko; Yoshikawa, Yutaka; Yasui, Hiroyuki; Ikuta, Katsuya; Sasaki, Katsunori; Kohgo, Yutaka; Hirano, Seishiro; Shinohara, Yasushi; Kohyama, Norihiko; Takahashi, Takashi; Toyokuni, Shinya

    2012-11-01

    Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among the commercially used types of asbestos (chrysotile, crocidolite, and amosite), the carcinogenicity of chrysotile is not fully appreciated. Here, we show that all three asbestos types similarly induced MM in the rat peritoneal cavity and that chrysotile caused the earliest mesothelioma development with a high fraction of sarcomatoid histology. The pathogenesis of chrysotile-induced mesothelial carcinogenesis was closely associated with iron overload: repeated administration of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction, significantly reduced the period required for carcinogenesis; massive iron deposition was found in the peritoneal organs with high serum ferritin; and homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most frequent genomic alteration in human MM and in iron-induced rodent carcinogenesis, was observed in 92.6% of the cases studied with array-based comparative genomic hybridization. The induced rat MM cells revealed high expression of mesoderm-specific transcription factors, Dlx5 and Hand1, and showed an iron regulatory profile of active iron uptake and utilization. These data indicate that chrysotile is a strong carcinogen when exposed to mesothelia, acting through the induction of local iron overload. Therefore, an intervention to remove local excess iron might be a strategy to prevent MM after asbestos exposure.

  18. Clinical and Prognostic Features of Erionite-Induced Malignant Mesothelioma

    PubMed Central

    Demirer, Ersin; Ghattas, Christian F.; Radwan, Mohamed O.

    2015-01-01

    This review analytically examines the published data for erionite-related malignant pleural mesothelioma (E-MPM) and any data to support a genetically predisposed mechanism to erionite fiber carcinogenesis. Adult patients of age ≥18 years with erionite-related pleural diseases and genetically predisposed mechanisms to erionite carcinogenesis were included, while exclusion criteria included asbestos- or tremolite-related pleural diseases. The search was limited to human studies though not limited to a specific timeframe. A total of 33 studies (31042 patients) including 22 retrospective studies, 6 prospective studies, and 5 case reports were reviewed. E-MPM developed in some subjects with high exposures to erionite, though not all. Chest CT was more reliable in detecting various pleural changes in E-MPM than chest X-ray, and pleural effusion was the most common finding in E-MPM cases, by both tests. Bronchoalveolar lavage remains a reliable and relatively less invasive technique. Chemotherapy with cisplatin and mitomycin can be administered either alone or following surgery. Erionite has been the culprit of numerous malignant mesothelioma cases in Europe and even in North America. Erionite has a higher degree of carcinogenicity with possible genetic transmission of erionite susceptibility in an autosomal dominant fashion. Therapeutic management for E-MPM remains very limited, and cure of the disease is extremely rare. PMID:25683976

  19. Selective ascorbate toxicity in malignant mesothelioma: a redox Trojan mechanism.

    PubMed

    Ranzato, Elia; Biffo, Stefano; Burlando, Bruno

    2011-01-01

    We studied the mechanism of ascorbate toxicity in malignant mesothelioma (MMe) cells. Neutral red uptake showed that ascorbate, but not dehydroascorbate, was highly toxic in the MMe cell lines REN and MM98, and less toxic in immortalized (human mesothelial cells-htert) and primary mesothelial cells. Ascorbate transport inhibitors phloretin, sodium azide, and ouabain did not reduce ascorbate toxicity. Ascorbate promoted the formation of H(2)O(2) in the cell medium, and its toxicity was suppressed by extracellular catalase, but the concentration of endogenous catalase was higher in MMe cells than in normal cells. The confocal imaging of cells loaded with the dihydrhodamine 123 reactive oxygen species probe showed that ascorbate caused a strong increase of rhodamine fluorescence in MMe cells, but not in mesothelial cells. MMe cells showed a higher production of superoxide and NADPH oxidase (NOX)4 expression than did mesothelial cells. Two inhibitors of cellular superoxide sources (apocynin and rotenone) reduced ascorbate toxicity and the ascorbate-induced rise in rhodamine fluorescence. NOX4 small interfering RNA also reduced ascorbate toxicity in REN cells. Taken together, the data indicate that ascorbate-induced extracellular H(2)O(2) production induces a strong oxidative stress in MMe cells because of their high rate of superoxide production. This explains the selective toxicity of ascorbate in MMe cells, and suggests its possible use in the clinical treatment of malignant mesothelioma.

  20. Malignant mesothelioma due to asbestos exposure in dental tape.

    PubMed

    Markowitz, Steven B; Moline, Jacqueline M

    2017-05-01

    Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios. Am. J. Ind. Med. 60:437-442, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. [Asbestos exposure assessment in the first case of intrasplenic mesothelioma].

    PubMed

    Miscetti, Giorgio; Bodo, Patrizia; Lumare, A; Abbritti, E P; Garofani, Patrizia; Burani, V

    2016-01-20

    In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without  a history of asbestos exposure. To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history. Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was  carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM. Samples showed the presence of asbestos  fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile). The survey described the past occupational exposure to asbestos in a canning industry, where  the subject worked in the period 1982-1990,  unknown to the patient himself. The authors strongly confirm the  usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate  possible past occupational exposure to asbestos.

  2. Multicystic mesothelioma of the liver with secondary involvement of peritoneum and inguinal region.

    PubMed

    Di Blasi, Arturo; Boscaino, Amedeo; De Dominicis, Gianfranco; Marsilia, Giuseppina Marino; D'Antonio, Antonio; Nappi, Oscar

    2004-01-01

    A case of multicystic mesothelioma of the liver with secondary involvement of the pelvic peritoneum and the inguinal region is presented. The case is of interest because of its unusual location and peculiar biological behavior.

  3. Benign multicystic peritoneal mesothelioma in a cesarean-section scar presenting as a fungating mass.

    PubMed

    Cuartas, Juan E; Maheshwari, Aditya V; Qadir, Rabah; Cooper, Andrew J; Robinson, Philip G; Pitcher, J David

    2008-06-01

    We report a case of a benign multicystic mesothelioma, which presented as a fungating mass through the anterior abdominal wall and arose in a cesarean-section scar without direct peritoneal involvement. A wide local excision was done and the diagnosis was confirmed by histopathology and immunohistochemistry. The postoperative course was uneventful and the patient is asymptomatic at 3 years' follow-up. Although a history of previous abdominal surgery has been reported in a patient with benign multicystic mesothelioma, to the best of our knowledge, there is no report of a benign multicystic mesothelioma arising in a cesarean-section scar or presentation as a fungating skin mass. This unusual presentation may point to a traumatic or inflammatory etiology, although seeding of the wound during the previous surgeries is a more likely postulate. A pertinent review of the literature on benign multicystic mesothelioma is also presented.

  4. [High risk of pleural mesothelioma among the state railroad carriage repair workers].

    PubMed

    Gerosa, A; Ietri, E; Belli, S; Grignoli, M; Comba, P

    2000-01-01

    Exposure to asbestos in a facility for the repair of railroad carriages in Bologna was initially studied in 1980, when the Local Health Unit started a program of primary prevention on request of the Unions. At that time workers employed in jobs with high exposure to asbestos were identified. The mortality experience of these 173 subjects was investigated from 01.01.1979 through 31.12.1997, and compared to that of the population of Emilia Romagna. SMR for all causes was 69, with upper limit of the confidence interval lower than 100; this was largely due to a significant decrease of cardiovascular mortality. Among neoplasms, there was a significant excess of pleural mesothelioma (6 observed, 0.09 expected); one more subject died for peritoneal mesothelioma and one for malignant mesothelioma of unspecified site. About half of the subjects deceased for neoplastic disease (8/17) were affected by mesothelioma.

  5. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells

    PubMed Central

    Mezzapelle, Rosanna; Rrapaj, Eltjona; Gatti, Elena; Ceriotti, Chiara; Marchis, Francesco De; Preti, Alessandro; Spinelli, Antonello E.; Perani, Laura; Venturini, Massimo; Valtorta, Silvia; Moresco, Rosa Maria; Pecciarini, Lorenza; Doglioni, Claudio; Frenquelli, Michela; Crippa, Luca; Recordati, Camilla; Scanziani, Eugenio; de Vries, Hilda; Berns, Anton; Frapolli, Roberta; Boldorini, Renzo; D’Incalci, Maurizio; Bianchi, Marco E.; Crippa, Massimo P.

    2016-01-01

    Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment. PMID:26961782

  6. Cyclooxygenase-2, epidermal growth factor receptor, and aromatase signaling in inflammation and mesothelioma.

    PubMed

    Nuvoli, Barbara; Galati, Rossella

    2013-06-01

    Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy. ©2013 AACR

  7. Environmental exposure to asbestos and the exposure-response relationship with mesothelioma.

    PubMed

    Madkour, M T; El Bokhary, M S; Awad Allah, H I; Awad, A A; Mahmoud, H F

    2009-01-01

    An epidemiological and environmental study was carried out in Shubra El-Kheima city, greater Cairo, of the exposure-response relationship between asbestos and malignant pleural mesothelioma. Radiological screening was done for 487 people occupationally exposed to asbestos, 2913 environmentally exposed to asbestos and a control group of 979 with no history of exposure. Pleural biopsy was done for suspicious cases. The airborne asbestos fibre concentrations were determined in all areas. There were 88 cases of mesothelioma diagnosed, 87 in the exposed group. The risk of mesothelioma was higher in the environmentally exposed group than other groups, and higher in females than males. The prevalence of mesothelioma increased with increased cumulative exposure to asbestos.

  8. [The role of asbestos fibre dimensions in the pathogenesis and prevention of mesothelioma].

    PubMed

    Tomatis, Lorenzo; Cantoni, Susanna; Carnevale, Francesco; Merler, Enzo; Mollo, Franco; Ricci, Paolo; Silvestri, Stefano; Vineis, Paolo; Terracini, Benedetto

    2006-01-01

    The particular point of view, recently published by Gerolamo Chiappino, on the pathogenetic role of asbestos fibres size in the origin of mesothelioma and on the possibility of mesothelioma prevention until the middle of the '80s needs to be critically clarified. The suggestion of an exclusive role of ultrashort and ultrathin fibres in the origin of mesothelioma is based on a biased interpretation of the literature. A review of the epidemiological, experimental, and molecular literature suggests that Chiappino's statements on the role of dose, dose-response effect, and genetic susceptibility are scientifically unsound Chiappino states that, in the past, in the workplaces where use and exposure to asbestos were not stopped, any reduction in the intensity of exposure by means of dust control measures or personal protective equipment would not have contributed to reduce the frequency of mesothelioma. In the authors' opinion the underlying assumptions are invalid.

  9. Mineral fiber concentration in lung tissue of mesothelioma patients in Finland

    SciTech Connect

    Tuomi, T.; Segerberg-Konttinen, M.; Tammilehto, L.; Tossavainen, A.; Vanhala, E. )

    1989-01-01

    The mineral fibers in lung tissue samples of 19 mesothelioma patients and 15 randomly selected autopsy cases were analyzed using low-temperature ashing, scanning electron microscopy (SEM) and x-ray microanalysis. The fiber concentration ranged from 0.5 to 370 million fibers per gram of dry tissue in the mesothelioma group and from less than 0.01 to 3.2 million fibers per gram of dry tissue in the autopsy group. In 80% of the mesothelioma patients and in 20% of the autopsy cases, the fiber concentration exceeded 1 million fibers per gram of dry tissue. Amphibole asbestos fibers predominated in both groups, and only a few chrysotile fibers were found. In the lungs of six mesothelioma patients, anthophyllite was the main fiber type. The overall analytical precision of sample preparation and fiber counting with SEM was 22%.

  10. Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma.

    PubMed

    Wu, Di; Hiroshima, Kenzo; Yusa, Toshikazu; Ozaki, Daisuke; Koh, Eitetsu; Sekine, Yasuo; Matsumoto, Shinji; Nabeshima, Kazuki; Sato, Ayuko; Tsujimura, Tohru; Yamakawa, Hisami; Tada, Yuji; Shimada, Hideaki; Tagawa, Masatoshi

    2017-02-01

    Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.

  11. Benign multicystic peritoneal mesothelioma associated with hydronephrosis and colovesical fistula formation: report of a case.

    PubMed

    McCaffrey, James C; Foo, Fung J; Dalal, Neha; Siddiqui, Kamran H

    2009-01-01

    Mesotheliomas usually arise from the pleura and are malignant. We report an unusual case of benign peritoneal mesothelioma presenting in a 59-year-old woman. The disease resulted in bilateral hydronephrosis, colovesical fistula formation, recurrent small bowel obstruction and chronic abdominal pain. To date only a handful of cases have been reported and to the best of our knowledge, none has been so aggressive.

  12. Hsa-Mir-29c* is Linked to the Prognosis of Malignant Pleural Mesothelioma

    PubMed Central

    Pass, Harvey I.; Goparaju, Chandra; Ivanov, Sergey; Donington, Jessica; Carbone, Michele; Hoshen, Moshe; Cohen, Dalia; Chajut, Ayelet; Rosenwald, Shai; Dan, Harel; Benjamin, Sima; Aharonov, Ranit

    2010-01-01

    The inability to forecast outcomes for malignant mesothelioma prevents clinicians from providing aggressive multimodality therapy to the most appropriate individuals who may benefit from such an approach. We investigated whether specific microRNAs (miRs) could segregate a largely surgically-treated group of mesotheliomas into good or bad prognosis categories. A training set of 44 and a test set of 98 mesothelioma tumors were analyzed by a custom microRNA platform, along with 9 mesothelioma cell lines and 3 normal mesothelial lines. Functional implications as well as downstream targets of potential prognostic microRNAs were investigated. In both the training and test sets, hsa-miR-29c* was an independent prognostic factor for time to progression as well as survival after surgical cytoreduction. The miR was expressed at higher levels in epithelial mesothelioma, and the level of this miR could segregate patients with this histology into groups with differing prognosis. Increased expression of hsa-miR-29c* predicted a more favorable prognosis, and overexpression of the miR in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion, and colony formation. Moreover, major epigenetic regulation of mesothelioma is mediated by hsa-miR-29c* and was demonstrated through downregulation of DNA methyltransferases as well as upregulation of demethylating genes. A single microRNA has the potential to be a prognostic biomarker in mesothelioma, and validation of these findings as well as investigation of its downstream targets may give insight for potential therapies in the future. PMID:20160038

  13. Malignant pleural mesothelioma with osseous metastases and pathologic fracture of femoral neck.

    PubMed

    Lester, Todd; Xu, Haodong

    2008-10-01

    Malignant mesotheliomas occur in the pleura, peritoneum, pericardium, and tunica vaginalis. The majority of tumors are pleural in origin. The typical pattern of spread is usually contiguous or via implantation. Hematogenous or lymphatic metastasis is not uncommon; however, metastasis to bone has rarely been well documented. This is a case report of malignant pleural mesothelioma metastatic to the femur with a pathologic fracture of femoral neck.

  14. Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

    PubMed

    Robinson, Cleo; Alfonso, Helman; Woo, Samantha; Walsh, Amy; Olsen, Nola; Musk, Arthur W; Robinson, Bruce W S; Nowak, Anna K; Lake, Richard A

    2014-01-01

    Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.

  15. A case-control study of mesothelioma in Minnesota iron ore (taconite) miners.

    PubMed

    Lambert, Christine S; Alexander, Bruce H; Ramachandran, Gurumurthy; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Mandel, Jeffrey H

    2016-02-01

    An excess of mesothelioma has been observed in iron ore miners in Northeastern Minnesota. Mining and processing of taconite iron ore generate exposures that include elongate mineral particles (EMPs) of amphibole and non-amphibole origin. We conducted a nested case-control study of mesothelioma in a cohort of 68,737 iron ore miners (haematite and taconite ore miners) to evaluate the association between mesothelioma, employment and EMP exposures from taconite mining. Mesothelioma cases (N=80) were identified through the Minnesota Cancer Surveillance System (MCSS) and death certificates. Four controls of similar age were selected for each case with 315 controls ultimately eligible for inclusion. Mesothelioma risk was evaluated by estimating rate ratios and 95% CIs with conditional logistic regression in relation to duration of taconite industry employment and cumulative EMP exposure [(EMP/cc)×years], defined by the National Institute for Occupational Safety and Health (NIOSH) 7400 method. Models were adjusted for employment in haematite mining and potential exposure to commercial asbestos products used in the industry. All mesothelioma cases were male and 57 of the cases had work experience in the taconite industry. Mesothelioma was associated with the number of years employed in the taconite industry (RR=1.03, 95% CI 1.00 to 1.06) and cumulative EMP exposure (RR=1.10, 95% CI 0.97 to -1.24). No association was observed with employment in haematite mining. These results support an association between mesothelioma and employment duration and possibly EMP exposure in taconite mining and processing. The type of EMP was not determined. The potential role of commercial asbestos cannot be entirely ruled out. 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/

  16. Malignant Mesothelioma of Spermatic Cord in an Elderly Man With a History of Asbestos Exposure.

    PubMed

    D'Antonio, Antonio; Mastella, Federica; Colucci, Angelo; Silvestre, Gianmarco

    2016-01-01

    We report a case of malignant mesothelioma of the spermatic cord in 80-year-old man presented with retained testis, hydrocele, and right inguinal mass. The patient had a long history of asbestos exposure as a railway worker. The patient was submitted to inguinal radical orchiectomy. One year after surgery, the patient is alive without signs of disease. Malignant mesothelioma of spermatic cord is a very rare disease, but this diagnosis should be suspected in patient with a history of asbestos exposure.

  17. Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers.

    PubMed Central

    Lilis, R; Ribak, J; Suzuki, Y; Penner, L; Bernstein, N; Selikoff, I J

    1987-01-01

    To assess the prevalence of non-malignant chest x ray abnormalities in cases of mesothelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating interstitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of certainty were available. In some cases (20% for pleural mesothelioma, 11.6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchymal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25.4% of pleural mesotheliomas, 12.5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were interpreted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43.5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis. PMID:3606969

  18. FISH analysis of intrapulmonary malignant mesothelioma without a clinically detectable primary pleural lesion: an autopsy case.

    PubMed

    Hasegawa, Mizue; Sakai, Fumikazu; Sato, Akitoshi; Tsubomizu, Sayuri; Arimura, Ken; Katsura, Hideki; Koh, Eitetsu; Sekine, Yasuo; Wu, Di; Hiroshima, Kenzo

    2014-12-01

    Patients with malignant mesothelioma typically present with a pleural effusion or pleural thickening and masses. A rare autopsy case of mesothelioma presenting with multiple bilateral lung nodules without clinically detectable pleural lesions is presented. A definitive diagnosis of the video-assisted thoracic surgery specimen could not be made, though a pattern of fibrosis mimicking organizing pneumonia was identified. Despite corticosteroid therapy, follow-up chest computed tomography showed enlargement of multiple nodules accompanied by the appearance of pleural thickening and effusions. The patient died of respiratory failure 11 months after initial presentation. Autopsy and retrospective analysis of the video-assisted thoracic surgery specimen using a p16 fluorescence in situ hybridization assay showed p16 homozygous deletion. The final diagnosis was sarcomatoid mesothelioma, and the lung nodules were intrapulmonary metastases from a clinically undetectable pleural sarcomatoid mesothelioma. It is important both to consider the possibility of mesothelioma with unusual clinical, radiological and pathological presentations and to remember that p16 fluorescence in situ hybridization analysis can play an important role in the diagnosis of mesothelioma.

  19. Multicystic mesothelioma caused by endometriosis: 2 case reports and review of the literature.

    PubMed

    Kurisu, Yoshitaka; Tsuji, Motomu; Shibayama, Yuro; Yamada, Takashi; Ohmichi, Masahide

    2011-03-01

    Multicystic mesothelioma was described as a benign neoplasm in most reports. But, whether it is neoplastic or reactive is still controversial. Although multicystic mesothelioma is often accompanied by endometriosis, histologic findings of the lesion with endometriosis have not been well documented. In this report, 2 cases of multicystic mesothelioma with endometriosis were studied histologically. The first lesion consisted of multiple cysts having thin walls lined with single-layered cuboidal mesothelia, and in the cystic walls, small foci of endometriosis were found. The second lesion was next to the endometriotic cysts in the pelvic space. These histologic findings suggest that endometriosis greatly contributes to the origin of the lesions. In addition, from the review of the literature, cystic mesothelioma was divided into 2 categories, that is, neoplastic or non-neoplastic lesions. Differentiation of both disorders might be possible by the following: size of the lesion, macroscopic and microscopic solid proliferation, features of adenomatoid tumor, and common mesothelioma-like histology. In conclusion, multicystic mesothelioma accompanied by endometriosis is thought to be a secondary non-neoplastic lesion induced by adhesion or inflammation rather than a neoplasm.

  20. Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposure.

    PubMed

    Metintas, Muzaffer; Metintas, Selma; Ak, Guntulu; Erginel, Sinan; Alatas, Fusun; Kurt, Emel; Ucgun, Irfan; Yildirim, Huseyin

    2008-01-01

    This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure. Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed. A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma. Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely.

  1. Personalized Oncogenomics: Clinical Experience with Malignant Peritoneal Mesothelioma Using Whole Genome Sequencing

    PubMed Central

    Sheffield, Brandon S.; Tinker, Anna V.; Shen, Yaoqing; Hwang, Harry; Li-Chang, Hector H.; Pleasance, Erin; Ch’ng, Carolyn; Lum, Amy; Lorette, Julie; McConnell, Yarrow J.; Sun, Sophie; Jones, Steven J. M.; Gown, Allen M.; Huntsman, David G.; Schaeffer, David F.; Churg, Andrew; Yip, Stephen; Laskin, Janessa; Marra, Marco A.

    2015-01-01

    Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants) and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease. PMID:25798586

  2. [Surveillance of malignant mesothelioma cases and definition of asbestos exposure: 1997 ReNaM data].

    PubMed

    Nesti, Massimo; Marinaccio, Alessandro; Chellini, Elisabetta

    2003-01-01

    The main objectives of the National Mesothelioma Register (ReNaM), set up by the National Institute for Prevention and Occupational Safety (ISPESL), are: (a) the estimate of malignant mesothelioma incidence in Italy, (b) the definition of exposure to asbestos, (c) the identification of unknown contamination sources, still present on the territory. Cased diagnosed in 1997 in Piedmont, Liguria, Emilia-Romagna, Tuscany and Apulia are reported, regions with more than 17 million inhabitants (30% of national population). ReNaM has facilitated the identification of mesothelioma cases and the description of the previous asbestos exposure in a large geographical area of the country, even though in some regions the definition of exposure to asbestos is not complete. 429 cases are recorded, of which 326 (76%) have been defined as definite malignant mesothelioma. The standardized annual incidence rate just for pleural definite mesothelioma is 1.51 x 100,000 inhabitants (2.26 for males and 0.79 for females). The exposure to asbestos has been defined for 198 mesothelioma cases with histological diagnosis: 125 cases (63%) refer to professional exposure, 10 (5%) to environmental exposure, 5 (2.5%) to domestic exposure. The adoption of a well-constructed national database, the up-date of guidelines and the recent starting up of ReNaM in other italian regions (Lombardy, Veneto, Marche, Campania, Basilicata and Sicily) will shortly lead to obtaining a major representativeness of the Italian situation.

  3. Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969–2009)

    PubMed Central

    Van den Borre, Laura; Deboosere, Patrick

    2014-01-01

    Background: Although Belgium was once a major international manufacturer of asbestos products, asbestos-related diseases in the country have remained scarcely researched. Objectives: The aim of this study is to provide a descriptive analysis of Belgian mesothelioma mortality rates in order to improve the understanding of asbestos health hazards from an international perspective. Methods: Temporal and geographical analyses were performed on cause-specific mortality data (1969–2009) using quantitative demographic measures. Results were compared to recent findings on global mesothelioma deaths. Results: Belgium has one of the highest mesothelioma mortality rates in the world, following the UK, Australia, and Italy. With a progressive increase of male mesothelioma deaths in the mid-1980s, large differences in mortality rates between sexes are apparent. Mesothelioma deaths are primarily concentrated in geographic areas with proximity to former asbestos industries. Conclusions: Asbestos mortality in Belgium has been underestimated for decades. Our findings suggest that the location of asbestos industries is correlated with rates of mesothelioma, underlining the need to avert future asbestos exposure by thorough screening of potential contaminated sites and by pursuing a global ban on asbestos. PMID:24999848

  4. Pleural mesothelioma in Sweden: an analysis of the incidence according to the use of asbestos

    PubMed Central

    Jarvholm, B.; Englund, A.; Albin, M.

    1999-01-01

    OBJECTIVE: To investigate if the preventive measures taken to reduce the occupational exposure to asbestos have resulted in a decreased incidence of pleural mesothelioma in Sweden. METHODS: The incidence of pleural mesothelioma between 1958 and 1995 for birth cohorts born between 1885 and 1964 was investigated. The cases of pleural mesothelioma were identified through the Swedish Cancer Register. RESULTS: In 1995, around 80 cases of pleural mesothelioma could be attributed to occupational exposure to asbestos. There is an increasing incidence in more recent birth cohorts in men. The incidence was considerably higher in the male cohort born between 1935 and 1944 than in men born earlier. CONCLUSIONS: The annual incidence of pleural mesothelioma attributable to occupational exposure to asbestos is today larger than all fatal occupational accidents in Sweden. The first asbestos regulation was adopted in 1964 and in the mid 1970s imports of raw asbestos decreased drastically. Yet there is no obvious indication that the preventive measures have decreased the risk of pleural mesothelioma. The long latency indicates that the effects of preventive measures in the 1970s could first be evaluated around 2005.   PMID:10448315

  5. Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969-2009).

    PubMed

    Van den Borre, Laura; Deboosere, Patrick

    2014-01-01

    Although Belgium was once a major international manufacturer of asbestos products, asbestos-related diseases in the country have remained scarcely researched. The aim of this study is to provide a descriptive analysis of Belgian mesothelioma mortality rates in order to improve the understanding of asbestos health hazards from an international perspective. Temporal and geographical analyses were performed on cause-specific mortality data (1969-2009) using quantitative demographic measures. Results were compared to recent findings on global mesothelioma deaths. Belgium has one of the highest mesothelioma mortality rates in the world, following the UK, Australia, and Italy. With a progressive increase of male mesothelioma deaths in the mid-1980s, large differences in mortality rates between sexes are apparent. Mesothelioma deaths are primarily concentrated in geographic areas with proximity to former asbestos industries. Asbestos mortality in Belgium has been underestimated for decades. Our findings suggest that the location of asbestos industries is correlated with rates of mesothelioma, underlining the need to avert future asbestos exposure by thorough screening of potential contaminated sites and by pursuing a global ban on asbestos.

  6. Germline BAP1 mutational landscape of asbestos-exposed malignant mesothelioma patients with family history of cancer

    PubMed Central

    Ohar, Jill A.; Cheung, Mitchell; Talarchek, Jacqueline; Howard, Suzanne E.; Howard, Timothy D.; Hesdorffer, Mary; Peng, Hongzhuang; Rauscher, Frank J.; Testa, Joseph R.

    2015-01-01

    Heritable mutations in the BAP1 tumor suppressor gene predispose individuals to mesothelioma and other cancers. However, a large-scale assessment of germline BAP1 mutation incidence and associated clinical features in mesothelioma patients with a family history of cancer has not been reported. Therefore, we examined the germline BAP1 mutation status of 150 mesothelioma patients with a family history of cancer, 50 asbestos-exposed control individuals with a family history of cancers other than mesothelioma, and 153 asbestos-exposed individuals without familial cancer. No BAP1 alterations were found in control cohorts, but were identified in 9 of 150 mesothelioma cases (6%) with a family history of cancer. Alterations among these cases were characterized by both missense and frameshift mutations, and enzymatic activity of BAP1 missense mutants was decreased compared to wild-type BAP1. Furthermore, BAP1 mutation carriers developed mesothelioma at an earlier age that was more often peritoneal than pleural (5 of 9), and exhibited improved long-term survival compared to mesothelioma patients without BAP1 mutations. Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, including mesothelioma and ocular/cutaneous melanomas, as well as renal, breast, lung, gastric, and basal cell carcinomas. Collectively, these findings suggest that mesothelioma patients presenting with a family history of cancer should be considered for BAP1 genetic testing to identify those individuals who might benefit from further screening and routine monitoring for the purpose of early detection and intervention. PMID:26719535

  7. Sarcomatoid Type Primary Pericardial Mesothelioma with a Long-term Survival after the Onset of Cardiac Tamponade.

    PubMed

    Saisho, Chika; Ishii, Hidenobu; Edakuni, Nobutaka; Imamura, Yohei; Tokito, Takaaki; Kinoshita, Takashi; Azuma, Koichi; Yamada, Kazuhiko; Hoshino, Tomoaki

    Primary pericardial malignant mesothelioma is a very rare clinical entity and its prognosis is very poor. We herein report a 67-year-old man who presented with pericardial mesothelioma that was diagnosed 21 months after the onset of cardiac tamponade as the initial manifestation. Despite undergoing pericardiocentesis and surgical pericardial fenestration at the onset of cardiac tamponade, we were unable to make a conclusive diagnosis of mesothelioma based on the cytological and histological findings. This unusual case had a relatively long progression-free period without treatment before the appearance of pleural tumors that showed the histological features of malignant sarcomatoid mesothelioma.

  8. Rarity of malignant mesothelioma prior to the widespread commercial introduction of asbestos: the Mount Sinai autopsy experience 1883-1910.

    PubMed

    Strauchen, James A

    2011-06-01

    Most malignant mesotheliomas are related to asbestos exposure. Whether malignant mesothelioma occurs in the absence of asbestos exposure remains unsettled. To address this question we reviewed a series of 2,025 autopsies performed at the Mount Sinai Hospital between 1883 and 1910, prior to the widespread commercial introduction of asbestos. Retrospective autopsy review. No cases of malignant mesothelioma were identified in 2,025 autopsies performed between 1883 and 1910. Malignant mesothelioma was rare prior to the widespread commercial introduction of asbestos. Copyright © 2011 Wiley-Liss, Inc.

  9. Mucin-positive epithelial mesotheliomas: a histochemical, immunohistochemical, and ultrastructural comparison with mucin-producing pulmonary adenocarcinomas.

    PubMed

    Hammar, S P; Bockus, D E; Remington, F L; Rohrbach, K A

    1996-01-01

    Pathologists routinely use histochemistry, immunohistochemistry, and electron microscopy to differentiate epithelial mesotheliomas from pulmonary adenocarcinomas. Epithelial mesotheliomas are usually mucicarmine-, PAS-diastase, and carcinoembryonic antigen-negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine- and PAS-diastase-positive, and about 90% express polyclonal carcinoembryonic antigen. During a pathologic evaluation of pleural neoplasms between 1975 and 1990, 10 epithelial mesotheliomas were identified that were mucicarmine- and in some instances PAS-diastase-positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four mesotheliomas focally expressing carcinoembryonic antigen. The mucicarmine, PAS-diastase, and carcinoembryonic antigen staining were usually eradicated or reduced in intensity by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive mucin reactions. In three cases the epithelial mesotheliomas showed focal regions of mucicarmine, PAS-d-, and Alcian blue-hyaluronidase-resistant staining. In contrast, 10 mucicarmine-, PAS-diastase-, Alcian blue-, and carcinoembryonic antigen-positive pulmonary adenocarcinomas were not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of well- to moderately well-differentiated epithelial mesotheliomas, the mucin-positive epithelial mesotheliomas often showed medium-electron-dense secretory material covering the microvilli, aggregates of medium electron-dense material in association with the microvilli, producing an ultrastructural morphology that has been observed only in epithelial mesotheliomas.

  10. Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.

    PubMed

    Ohar, Jill A; Cheung, Mitchell; Talarchek, Jacqueline; Howard, Suzanne E; Howard, Timothy D; Hesdorffer, Mary; Peng, Hongzhuang; Rauscher, Frank J; Testa, Joseph R

    2016-01-15

    Heritable mutations in the BAP1 tumor suppressor gene predispose individuals to mesothelioma and other cancers. However, a large-scale assessment of germline BAP1 mutation incidence and associated clinical features in mesothelioma patients with a family history of cancer has not been reported. Therefore, we examined the germline BAP1 mutation status of 150 mesothelioma patients with a family history of cancer, 50 asbestos-exposed control individuals with a family history of cancers other than mesothelioma, and 153 asbestos-exposed individuals without familial cancer. No BAP1 alterations were found in control cohorts, but were identified in nine of 150 mesothelioma cases (6%) with a family history of cancer. Alterations among these cases were characterized by both missense and frameshift mutations, and enzymatic activity of BAP1 missense mutants was decreased compared with wild-type BAP1. Furthermore, BAP1 mutation carriers developed mesothelioma at an earlier age that was more often peritoneal than pleural (five of nine) and exhibited improved long-term survival compared to mesothelioma patients without BAP1 mutations. Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, including mesothelioma and ocular/cutaneous melanomas, as well as renal, breast, lung, gastric, and basal cell carcinomas. Collectively, these findings suggest that mesothelioma patients presenting with a family history of cancer should be considered for BAP1 genetic testing to identify those individuals who might benefit from further screening and routine monitoring for the purpose of early detection and intervention.

  11. Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology.

    PubMed

    McDonald, A D; Case, B W; Churg, A; Dufresne, A; Gibbs, G W; Sébastien, P; McDonald, J C

    1997-12-01

    In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of

  12. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    SciTech Connect

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

    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

  13. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities

    PubMed Central

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-01-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents’ lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2+/−) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2+/− mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2+/− mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15Ink4b, p16Ink4a and p19Arf or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2+/− mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation. PMID:17272307

  14. Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities.

    PubMed

    Andujar, Pascal; Lecomte, Céline; Renier, Annie; Fleury-Feith, Jocelyne; Kheuang, Laurence; Daubriac, Julien; Janin, Anne; Jaurand, Marie-Claude

    2007-07-01

    Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.

  15. [Pleural mesothelioma: impact of the staging for the therapeutic strategy].

    PubMed

    Greillier, L; Scherpereel, A; Astoul, P

    2007-10-01

    Realistic improvement has been recently done for the treatment of malignant pleural mesothelioma. Besides new findings for the epidemiology of the disease, medico-social impact for patients, the knowledge of biological parameters for diagnosis, prognosis and future therapeutic targets as well, the early diagnosis of the disease mainly based on more extended practice of thoracoscopy allows in association with new imaging techniques a careful staging of the disease and consequently new therapeutic implications. Indeed if new balistic assessment of the disease improves the efficacy of radiotherapy and new combined chemotherapy have shown antitumoral responses, surgical strategy takes part in the armamenterium for this disease and combined with others therapeutic modalities seems to be a raisonnable approach despite the lack of prospective, comparative, randomized study and the drawback of current staging. However, the most important point is the multidisciplinary concertation induced by the management of this disease which represents a "model" in thoracic oncology.

  16. Benign mesothelioma of peritoneum presenting as a pelvic mass.

    PubMed

    Asghar, Samina; Qureshi, Navid; Awan, Ali

    2008-11-01

    A large solitary multiloculated pelvic cyst in a 40-year-old woman with chronic pelvic pain was diagnosed to be a Multicystic Benign Mesothelioma (MBM) of peritoneum at laparotomy. Operative findings showed dense adhesions between uterus and bladder anteriorly, small intestines and pouch of Douglas posteriorly, a right ovarian cyst cm containing clear serous fluid and two nodular deposits were seen in the pouch of Douglas, small multiple deposits was found over the mesentery of small intestine and parietal peritoneum. Total abdominal hysterectomy with bilateral oophorectomy and infracolic omentectomy was done. During surgery, there was injury to the small intestine hence, resection of 10 inches of small intestine with re-anastomosis was carried out. Postoperative recovery was satisfactory. At 3 years follow-up, patient is symptom-free.

  17. Photodynamic therapy for malignant pleural mesothelioma: the future of treatment?

    PubMed

    Friedberg, Joseph S

    2011-02-01

    Malignant pleural mesothelioma is a deadly incurable cancer, with a median survival of approximately 9 months. The best available chemotherapy, arguably the standard of care, only yields a 40% response rate and an 11-week extension in median survival. Surgery, the modality most likely to be associated with prolonged remission, remains investigational and must always be combined with other modalities in an effort to treat the microscopic disease that will remain even after the most aggressive operations. One such modality, photodynamic therapy, is a light-based cancer treatment that has features making it particularly well suited as a component of a surgery-based multimodal treatment plan. Utilizing intraoperative photodynamic therapy has enabled development of a less drastic surgical procedure that is also yielding some encouraging survival results. A unique aspect of photodynamic therapy is its stimulation of a tumor-directed immune response, a feature that offers promise for designing future treatments.

  18. Photodynamic therapy as an innovative treatment for malignant pleural mesothelioma.

    PubMed

    Friedberg, Joseph S

    2009-01-01

    Photodynamic therapy (PDT) of the pleura is an experimental treatment aimed at eradicating residual microscopic disease after macroscopic complete resection of malignant pleural mesothelioma (MPM) by means of intracavitary administration. A light-based treatment, PDT consists of 3 components: a nontoxic photosensitizing compound, oxygen, and visible light. The treatment is FDA-approved for several oncological targets, but remains experimental for MPM. PDT can be combined with lung-sparing pleurectomy and decortication and does not preclude other treatments such as adjuvant chemotherapy and/or radiation therapy. Additionally, PDT appears to bolster an immunologic effect by rendering the cancer cells that have been destroyed by the light-activated photosensitizer more presentable to the immune system. Local control and survival rates have been sufficiently rewarding to merit ongoing development of this combination of surgical technique and PDT.

  19. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    PubMed Central

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM. PMID:27512676

  20. NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

    PubMed

    Ettinger, David S; Wood, Douglas E; Akerley, Wallace; Bazhenova, Lyudmila A; Borghaei, Hossein; Camidge, David Ross; Cheney, Richard T; Chirieac, Lucian R; D'Amico, Thomas A; Dilling, Thomas; Dobelbower, Michael; Govindan, Ramaswamy; Hennon, Mark; Horn, Leora; Jahan, Thierry M; Komaki, Ritsuko; Lackner, Rudy P; Lanuti, Michael; Lilenbaum, Rogerio; Lin, Jules; Loo, Billy W; Martins, Renato; Otterson, Gregory A; Patel, Jyoti D; Pisters, Katherine M; Reckamp, Karen; Riely, Gregory J; Schild, Steven E; Shapiro, Theresa A; Sharma, Neelesh; Swanson, Scott J; Stevenson, James; Tauer, Kurt; Yang, Stephen C; Gregory, Kristina; Hughes, Miranda

    2016-07-01

    These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

  1. Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma

    PubMed Central

    Blackham, Aaron U.; Levine, Edward A.

    2013-01-01

    Malignant peritoneal mesothelioma (MPM) is a rare and aggressive neoplasm that is largely resistant to traditional anti-cancer therapies. For years it has been considered a terminal condition and once diagnosed, patients generally survived less than a year despite aggressive treatment. Although rare, the worldwide incidence of MPM continues to rise, in part due to its association with asbestos exposure. Patients usually present with non-specific symptoms of abdominal distension and pain making the diagnosis challenging. In recent years, aggressive cytoreductive surgery with the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival in patients with MPM treated at multiple centers worldwide. This review article briefly highlights the presentation, diagnosis, and natural history of MPM. We then explore the available treatment options with primary focus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMID:24039630

  2. Immunotherapy prospects in the treatment of lung cancer and mesothelioma

    PubMed Central

    Lievense, Lysanne A.; Hoogsteden, Henk C.; Hegmans, Joost P.

    2014-01-01

    A very recent finding is the role of immune activation in cancer. The assumption that stimulating the patient’s immune system to attack tumors is a valuable treatment option in malignant diseases has gained more acceptance. However the high immunosuppressive effects caused by the tumor limits this beneficial effect. There is a delicate balance between immunoactivation and immunosuppression in a patient. Especially in non small cell lung cancer (NSCLC), the role of immunosuppressive cells hampering immune activation is high. But also in small cell lung cancer (SCLC) and mesothelioma immunosuppressive activity is high. This is suggested to be related to the type of tumor, advanced stage of the disease, and the tumor load. In this review, we provide an overview of the progress and challenges in the immunotherapeutic approaches in lung cancer. We conclude with the concept that immunotherapy in thoracic malignancies must be tailored made to the balance of the immune system. PMID:25806279

  3. Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

    SciTech Connect

    Ivanov, Sergey V.; Ivanova, Alla V.; Goparaju, Chandra M.V.; Chen, Yuanbin; Beck, Amanda; Pass, Harvey I.

    2009-05-08

    Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.

  4. Advanced, recurrent mesothelioma growth mimicking an aortic dissection.

    PubMed

    Pankhania, Miran; Hardiment, Kate; Marathe, Mandar

    2011-02-02

    In the emergency setting, a cold, clammy, dyspnoeic patient presenting with interscapular chest pain and unequal blood pressures suggests an acute aortic dissection until proven otherwise. By means of a case report, the authors detail one such patient who presented identically to one having an acute aortic dissection. Initial assessment showed unequal blood pressures in left and right arms, a resting tachycardia and indistinct heart sounds. Fluid resuscitation failed to improve the patient's physiological parameters and they rapidly deteriorated. The medical history included mesothelioma and atrial fibrillation. Existing investigations were reviewed and after thorough consideration of the patient's premorbid state and likely prognosis, the decision was made to palliate. The patient died shortly after being transferred to the oncology ward. Imaging is therefore integral to the assessment and management of a patient in whom an aortic dissection is feared.

  5. Oncolytic virotherapy for human malignant mesothelioma: recent advances.

    PubMed

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM.

  6. Malignant pleural mesothelioma in bakers and pastry cooks.

    PubMed

    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.

  7. Overview of the biochemical and genetic processes in malignant mesothelioma*

    PubMed Central

    de Assis, Leonardo Vinícius Monteiro; Isoldi, Mauro César

    2014-01-01

    Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM. PMID:25210967

  8. Multipoint targeting of the PI3K/mTOR pathway in mesothelioma

    PubMed Central

    Zhou, S; Liu, L; Li, H; Eilers, G; Kuang, Y; Shi, S; Yan, Z; Li, X; Corson, J M; Meng, F; Zhou, H; Sheng, Q; Fletcher, J A; Ou, W-B

    2014-01-01

    Background: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis. Methods: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations. Results: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation. Conclusions: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for

  9. Restricted Field IMRT Dramatically Enhances IMRT Planning for Mesothelioma

    SciTech Connect

    Allen, Aaron M. Schofield, Deborah; Hacker, Fred; Court, Laurence E.; Czerminska, Maria M.S.

    2007-12-01

    Purpose: To improve the target coverage and normal tissue sparing of intensity-modulated radiotherapy (IMRT) for mesothelioma after extrapleural pneumonectomy. Methods and Materials: Thirteen plans from patients previously treated with IMRT for mesothelioma were replanned using a restricted field technique. This technique was novel in two ways. It limited the entrance beams to 200{sup o} around the target and three to four beams per case had their field apertures restricted down to the level of the heart or liver to further limit the contralateral lung dose. New constraints were added that included a mean lung dose of <9.5 Gy and volume receiving {>=}5 Gy of <55%. Results: In all cases, the planning target volume coverage was excellent, with an average of 97% coverage of the planning target volume by the target dose. No change was seen in the target coverage with the new technique. The heart, kidneys, and esophagus were all kept under tolerance in all cases. The average mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy with the new technique was 6.6 Gy, 3.0%, and 50.8%, respectively, compared with 13.8 Gy, 15%, and 90% with the previous technique (p < 0.0001 for all three comparisons). The maximal value for any case in the cohort was 8.0 Gy, 7.3%, and 57.5% for the mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy, respectively. Conclusion: Restricted field IMRT provides an improved method to deliver IMRT to a complex target after extrapleural pneumonectomy. An upcoming Phase I trial will provide validation of these results.

  10. Radical Pleurectomy and Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma

    PubMed Central

    Friedberg, Joseph S.; Culligan, Melissa J.; Mick, Rosemarie; Stevenson, James; Hahn, Stephen M.; Sterman, Daniel; Punekar, Salman; Glatstein, Eli; Cengel, Keith

    2015-01-01

    Background Radical pleurectomy (RP) for mesothelioma is often considered either technically infeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. Methods 38 patients (42–81 years) underwent RP-PDT. 35/38 (92%) patients also received systemic therapy. Standard statistical techniques were employed for analysis. Results 37/38 (97%) patients had Stage III/IV (AJCC) cancer and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was one postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) epithelial patients and 6.8 months for the 7/38 (18%) nonepithelial patients. The median progression free survivals were 9.6, 15.1 and 4.8 months, respectively. The median and progression free survivals for the 20/31 (64%) epithelial patients with N2 disease were 31.7 and 15.1 months, respectively. Conclusions It was possible to achieve a macroscopic complete resection utilizing lung-sparing surgery in 97% of these stage III/IV patients. The survival we observed with this approach was unusually long for the epithelial subtype patients but, interestingly, the progression free survival was not. The reason for this prolonged survival in spite of recurrence is not clear, but is potentially related to preservation of the lung and/or some PDT-induced effect. We conclude that the results of this lung-sparing approach are safe, encouraging and warrant further investigation. PMID:22541196

  11. [Malignant Mesothelioma Registry from Piedmont. Incidence in 1990-1995].

    PubMed

    Ivaldi, C; Dalmasso, P; Nesti, M; Magnani, C

    1999-01-01

    This paper describes methods and results of the Piedmont Malignant Mesothelioma Registry. The Registry is active since 1990 and collects all histologically confirmed incident cases of malignant mesothelioma (m.m.) occurring in the residents of Piedmont. In the period 1990-95, 346 cases of pleural m.m. (211 males and 135 females) and 41 (28 males and 13 females) of peritoneal m.m. have been observed. Amongst the inhabitants of the Local Health Authority of Casale Monferrato, where manufacturing of cement asbestos has determined serious asbestos exposures both in the work place and general environment, there have been 105 pleural m.m. and 17 peritoneal m.m. (incidence rate were 15.6 for men and 13.0 for women and 3.6 for men and 0.6 for women respectively). Leaving out the Local Health Authority (LHA) of Casale Monferrato, the annual incidence rate in Piedmont (for 10(5) person-years, age standardised on the 1981 Italian population), has been 1.0 in men and 0.6 in women for the pleural m.m. (respectively 154 and 87 cases) and 0.09 and 0.06 for peritoneal m.m. (14 and 10 cases). Possible cases of m.m. (cytological and/or x-ray diagnosis) have been searched in the file of hospital admission and discharges (SDO) in 1994-95: 46 additional cases were found, with a 25% increase in incidence rates. The analysis of incidence according to geographical aggregations (defined according to the LHA borders) has identified, besides some already known important sources of exposures, as Casale Monferrato and the LHA of Lanzo (Balangero mine), other areas with excess of incidence as the LHA's of Galliate and Caluso which show an increased incidence of pleural m.m. in men or Vercelli and Chieri with increased incidence of pleural m.m. in women. These observation deserves further analysis.

  12. Pleural mesothelioma in New Caledonia: associations with environmental risk factors.

    PubMed

    Baumann, Francine; Maurizot, Pierre; Mangeas, Morgan; Ambrosi, Jean-Paul; Douwes, Jeroen; Robineau, Bernard

    2011-05-01

    High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. We studied the spatial and temporal variation of MM and its association with environmental factors. We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia.

  13. Mesothelioma mortality surveillance and asbestos exposure tracking in Italy.

    PubMed

    Fazzo, Lucia; Minelli, Giada; De Santis, Marco; Bruno, Caterina; Zona, Amerigo; Marinaccio, Alessandro; Conti, Susanna; Pirastu, Roberta; Comba, Pietro

    2012-01-01

    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. 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. 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. The results may contribute to detect asbestos exposure and to set priorites for environmental remediation.

  14. Pleural Mesothelioma in New Caledonia: Associations with Environmental Risk Factors

    PubMed Central

    Baumann, Francine; Maurizot, Pierre; Mangeas, Morgan; Ambrosi, Jean-Paul; Douwes, Jeroen; Robineau, Bernard

    2011-01-01

    Background High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. Objectives We studied the spatial and temporal variation of MM and its association with environmental factors. Methods We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space–time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. Results The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41–137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2–4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2–16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Conclusions Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia. PMID:21193386

  15. Proteome Screening of Pleural Effusions Identifies Galectin 1 as a Diagnostic Biomarker and Highlights Several Prognostic Biomarkers for Malignant Mesothelioma*

    PubMed Central

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

    2014-01-01

    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. Paratesticular mesothelioma. Report of a case with comprehensive review of literature.

    PubMed

    Bisceglia, Michele; Dor, David Ben; Carosi, Illuminato; Vairo, Matteo; Pasquinelli, Gianandrea

    2010-01-01

    Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The sole plausible causative factor so far ascertained in the pathogenesis of these tumors is asbestos, which however is found in only around 30% to 40% of such cases. The age range of affected individuals is wide, mostly adults and the elderly, but also includes young people and children. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. When hydrocele is the presenting symptom, these tumors are often clinically overlooked and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the tunica vaginalis, but primary tumors of the spermatic cord and epididymis are also on record. Tumors arising from the peritoneal mesothelium of a hernia sac are excluded from this group. The correct diagnosis is almost always made after histologic examination of the operative specimen. Immunohistochemistry and electron microscopy are always helpful and sometimes necessary tools for diagnosis. So far very few cases have been identified or suspected preoperatively on cytologic examination. Three clinicopathologic types of malignant mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary mesothelioma, well-differentiated papillary mesothelioma, and multicystic mesothelioma. The histologic subtypes are almost always pure epithelial or biphasic. The differential diagnosis is mainly with serous papillary tumors arising from Mullerian vestiges, but several diverse primary or secondary tumors also need to be considered. A clinicopathologic evaluation of a case of tunical diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting point for this general review.

  17. Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials

    PubMed Central

    Mansfield, Aaron S.; Symanowski, James T.; Peikert, Tobias

    2014-01-01

    Rationale Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes. Objectives Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials. Methods We searched PubMed for “mesothelioma” with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors. Measurements and Main Results We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review. Conclusion Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete

  18. Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models

    PubMed Central

    Barbone, Dario; Follo, Carlo; Echeverry, Nohemy; Gerbaudo, Victor H.; Klabatsa, Astero; Bueno, Raphael; Felley-Bosco, Emanuela; Broaddus, V. Courtney

    2015-01-01

    Malignant pleural mesothelioma is a highly chemoresistant solid tumor. We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/mTOR inhibitors. Here, we investigate the activity of GDC-0980, a novel dual PI3K/mTOR inhibitor, which has been proposed to be effective in mesothelioma. In this work, we aimed to identify mechanisms and markers of efficacy for GDC-0980 by utilizing 3D models of mesothelioma, both in vitro multicellular spheroids and ex vivo tumor fragment spheroids grown from patient tumor samples. We found that a subset of mesothelioma spheroids is sensitive to GDC-0980 alone and to its combination with chemotherapy. Unexpectedly, this sensitivity did not correlate with the activation of the Akt/mTOR pathway. Instead, sensitivity to GDC-0980 correlated with the presence of constitutive ATG13 puncta, a feature of autophagy, a cellular program that supports cells under stress. In tumor fragment spheroids grown from 21 tumors, we also found a subset (n = 11) that was sensitive to GDC-0980, a sensitivity that also correlated with the presence of ATG13 puncta. Interference with autophagy by siRNA of ATG7, an essential autophagic protein, increased the response to chemotherapy, but only in the sensitive multicellular spheroids. In the spheroids resistant to GDC-0980, autophagy appeared to play no role. In summary, we show that GDC-0980 is effective in mesothelioma 3D models that display ATG13 puncta, and that blockade of autophagy increases their response to chemotherapy. For the first time, we show a role for autophagy in the response to chemotherapy of 3D models of mesothelioma and propose ATG13 as a potential biomarker of the therapeutic responsiveness of mesothelioma. PMID:26284517

  19. In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

    PubMed Central

    Feng, Mingqian; Zhang, Jingli; Anver, Miriam; Hassan, Raffit; Ho, Mitchell

    2011-01-01

    Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo. PMID:21479131

  20. Syntenic Relationships between Genomic Profiles of Fiber-Induced Murine and Human Malignant Mesothelioma

    PubMed Central

    Jean, Didier; Thomas, Emilie; Manié, Elodie; Renier, Annie; de Reynies, Aurélien; Lecomte, Céline; Andujar, Pascal; Fleury-Feith, Jocelyne; Galateau-Sallé, Françoise; Giovannini, Marco; Zucman-Rossi, Jessica; Stern, Marc-Henri; Jaurand, Marie-Claude

    2011-01-01

    Malignant mesothelioma (MM) is an aggressive tumor with a poor prognosis mainly linked to past asbestos exposure. Murine models of MM based on fiber exposure have been developed to elucidate the mechanism of mesothelioma formation. Genomic alterations in murine MM have now been partially characterized. To gain insight into the pathophysiology of mesothelioma, 16 murine and 35 human mesotheliomas were characterized by array-comparative genomic hybridization and were screened for common genomic alterations. Alteration of the 9p21 human region, often by biallelic deletion, was the most frequent alteration in both species, in agreement with the CDKN2A/CDKN2B locus deletion in human disease and murine models. Other shared aberrations were losses of 1p36.3–p35 and 13q14–q33 and gains of 5p15.3–p13 regions. However, some differences were noted, such as absence of recurrent alterations in mouse regions corresponding to human chromosome 22. Comparison between altered recurrent regions in asbestos-exposed and non–asbestos-exposed patients showed a significant difference in the 14q11.2–q21 region, which was also lost in fiber-induced murine mesothelioma. A correlation was also demonstrated between genomic instability and tumorigenicity of human mesothelioma xenografts in nude mice. Overall, these data show similarities between murine and human disease, and contribute to the understanding of the influence of fibers in the pathogenesis of mesothelioma and validation of the murine model for preclinical testing. PMID:21281820

  1. Pleural mesothelioma in household members of asbestos-exposed workers in Friuli Venezia Giulia, Italy.

    PubMed

    D' Agostin, Flavia; de Michieli, Paola; Negro, Corrado

    2017-05-08

    Malignant mesothelioma is closely associated to asbestos exposure. One such exposure may occur through contact with occupationally exposed household members and their belongings. This study examines the features of pleural mesothelioma attributable only to asbestos brought home by another family member. The data sources were 1063 mesothelioma cases diagnosed between 1995 and 2014, from the Friuli Venezia Giulia Mesothelioma Register. In all cases the diagnosis of mesothelioma was based on the pathology report. Exposure information and demographic data were acquired by an occupational medical standardized questionnaire/interview. Household-exposure mesothelioma cases included 33 women and 2 men. Relationships were: wives (N = 22), daughters (N = 9), sons (N = 2), and mothers (N = 2). Asbestos exposure in the workers predominantly occurred in shipyards. Out of the 35 pleural cases, 19 were epithelial, 9 biphasic, 3 sarcomatoid, and 4 not specified. The mean age at diagnosis was 77 years old. The mean latency was 59 years, with wives having a significant shorter latency than offspring. Latency was not significantly related to morphology and asbestosis. The overall mean survival was 16 months (median 11 months) but treatment was beneficial (mean 16 months vs. 7 months). Biphasic/sarcomatoid histology and presence of asbestosis were associated with a decreased survival, although not with statistical significance. Our data confirms that household exposure increases the risk for pleural mesothelioma amongst women with no history of occupational asbestos exposure. This is an ongoing problem in many countries, as well as in Italy, where the evaluation of a framework for the compensation of these cases is under debate. Int J Occup Med Environ Health 2017;30(3):419-431.

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

    PubMed

    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

  3. MALIGNANT PLEURAL MESOTHELIOMA WITHOUT ASBESTOS EXPOSURE WITH DISTANT METASTASIS IN A PERIPHERAL LYMPH NODE: A CASE REPORT

    PubMed Central

    Kant, Surya; Verma, Sanjay Kumar; Sanjay

    2008-01-01

    SUMMARY Malignant mesothelioma is an uncommon pleural neoplasm and usually associated with inhalation exposure to asbestos. About 20% of the patients have no demonstrable exposure to asbestos. It rarely metastasizes in peripheral lymph nodes. Here is a case report of malignant pleural mesothelioma without asbestos exposure with cervical lymph node metastasis PMID:20396658

  4. Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway.

    PubMed

    Trombino, Sonya; Cesario, Alfredo; Margaritora, Stefano; Granone, PierLuigi; Motta, Giovanni; Falugi, Carla; Russo, Patrizia

    2004-01-01

    This study presents data suggesting that both human mesothelioma (cell lines and human mesothelioma biopsies) and human normal mesothelial cells express receptors for acetylcholine and that stimulation of these receptors by nicotine prompted cell growth via activation of nicotinic cholinergic receptors. Thus, these data demonstrate that: (a) human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells express functionally alpha-7 nicotinic acethlycholine receptors, evaluated by alpha-bungarotoxin-FITC binding, receptor binding assay, Western blot, and reverse transcription-PCR; (b) choline acetyltransferase immunostaining is present in mesothelioma cells; (c) mesothelioma cell growth is modulated by the cholinergic system in which agonists (i.e., nicotine) has a proliferative effect, and antagonists (i.e., curare) has an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle; (d) nicotine induces Ca(+2) influx, evaluated by [(45)Ca(2+)] uptake, and consequently activation of mitogen-activated protein kinase pathway (extracellular signal-regulated kinase and p90(RSK) phosphorylation), evaluated by Western blot; and (e) apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of nuclear factor-kappaB complexes and phosphorylation of Bad at Ser(112); curare proapoptotic via G(0)-G(1) arrest p21(waf-1) dependent but p53 independent). The involvement of the nonneuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies.

  5. An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation.

    PubMed

    Cheung, Mitchell; Kadariya, Yuwaraj; Pei, Jianming; Talarchek, Jacqueline; Facciolo, Francesco; Visca, Paolo; Righi, Luisella; Cozzi, Ilaria; Testa, Joseph R; Ascoli, Valeria

    2015-10-01

    We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family. 

  6. Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug.

    PubMed

    Tamminen, J A; Parviainen, V; Rönty, M; Wohl, A P; Murray, L; Joenväärä, S; Varjosalo, M; Leppäranta, O; Ritvos, O; Sengle, G; Renkonen, R; Myllärniemi, M; Koli, K

    2013-08-26

    Malignant mesothelioma is a form of cancer that is highly resistant to conventional cancer therapy for which no major therapeutic advances have been introduced. Here, we identify gremlin-1, a known bone morphogenetic protein inhibitor crucial for embryonic development, as a potential therapeutic target for mesothelioma. We found high expression levels of gremlin-1 in the mesothelioma tumor tissue, as well as in primary mesothelioma cells cultured from pleural effusion samples. Downregulation of gremlin-1 expression by siRNA-mediated silencing in a mesothelioma cell line inhibited cell proliferation. This was associated with downregulation of the transcription factor slug as well as mesenchymal proteins linked to cancer epithelial-to-mesenchymal transition. Further, resistance to paclitaxel-induced cell death was associated with high gremlin-1 and slug expression. Treatment of gremlin-1-silenced mesothelioma cells with paclitaxel or pemetrexed resulted in efficient loss of cell survival. Finally, our data suggest that concomitant upregulation of fibrillin-2 in mesothelioma provides a mechanism for extracellular localization of gremlin-1 to the tumor microenvironment. This was supported by the demonstration of interactions between gremlin-1, and fibrillin-1 and -2 peptides as well as by colocalization of gremlin-1 to fibrillin microfibrils in cells and tumor tissue samples. Our data suggest that gremlin-1 is also a potential target for overcoming drug resistance in mesothelioma.

  7. Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug

    PubMed Central

    Tamminen, J A; Parviainen, V; Rönty, M; Wohl, A P; Murray, L; Joenväärä, S; Varjosalo, M; Leppäranta, O; Ritvos, O; Sengle, G; Renkonen, R; Myllärniemi, M; Koli, K

    2013-01-01

    Malignant mesothelioma is a form of cancer that is highly resistant to conventional cancer therapy for which no major therapeutic advances have been introduced. Here, we identify gremlin-1, a known bone morphogenetic protein inhibitor crucial for embryonic development, as a potential therapeutic target for mesothelioma. We found high expression levels of gremlin-1 in the mesothelioma tumor tissue, as well as in primary mesothelioma cells cultured from pleural effusion samples. Downregulation of gremlin-1 expression by siRNA-mediated silencing in a mesothelioma cell line inhibited cell proliferation. This was associated with downregulation of the transcription factor slug as well as mesenchymal proteins linked to cancer epithelial-to-mesenchymal transition. Further, resistance to paclitaxel-induced cell death was associated with high gremlin-1 and slug expression. Treatment of gremlin-1-silenced mesothelioma cells with paclitaxel or pemetrexed resulted in efficient loss of cell survival. Finally, our data suggest that concomitant upregulation of fibrillin-2 in mesothelioma provides a mechanism for extracellular localization of gremlin-1 to the tumor microenvironment. This was supported by the demonstration of interactions between gremlin-1, and fibrillin-1 and -2 peptides as well as by colocalization of gremlin-1 to fibrillin microfibrils in cells and tumor tissue samples. Our data suggest that gremlin-1 is also a potential target for overcoming drug resistance in mesothelioma. PMID:23978876

  8. Mesothelioma trends in the ACT and comparisons with the rest of Australia.

    PubMed

    Korda, Rosemary J; Clements, Mark S; Armstrong, Bruce K; Trevenar, Susan M; Chalker, Elizabeth B; Newman, Leah A; Kirk, Martyn D

    2016-09-30

    Inhalation of asbestos fibres is the predominant cause of malignant mesothelioma. Domestic exposure to asbestos is a major community concern in the Australian Capital Territory (ACT) because of loose-fill asbestos home insulation. Little is known about how trends in mesothelioma rates in the ACT compare with those elsewhere. The objective of this study was to describe trends in mesothelioma rates in the ACT and compare them with those for the rest of Australia. We used de-identified data from the ACT Cancer Registry (1982- 2014), and the Western Australia (WA) Cancer Registry and the Australian Cancer Database (1982-2011). We calculated crude mesothelioma rates, by 3-year periods, for the ACT and for the rest of Australia (excluding WA). We used Poisson regression to analyse mesothelioma trends from 1994 to 2011 (complete reporting period) using an indirect standardisation approach to adjust for age and sex. There were 140 mesothelioma cases reported to the ACT Cancer Registry between 1982 and 2014 - 81% male and 19% female. Between 1994 and 2011, age- and sex-adjusted mesothelioma rates in the ACT increased over time, on average by 12% per 3-year period (relative risk [RR] 1.12; 95% confidence interval [CI] 0.99, 1.26). Compared with the rest of Australia (excluding WA), ACT rates were, on average, lower (RR 0.84; 95% CI 0.69, 1.02), but they increased at a higher rate (RR 1.12 per 3-year period; 95% CI 0.99, 1.27). These results are strongly influenced by the higher rate of mesothelioma observed in the ACT in 2009-2011, when ACT rates became similar to those for the rest of Australia (excluding WA). Although mesothelioma rates may have increased more in the ACT than the rest of Australia (excluding WA) during the past two decades, there is considerable uncertainty in the trends. More information is needed regarding the health risks associated with living in a house with loose-fill asbestos insulation. This is the subject of further studies within the ACT Asbestos

  9. [Compensation of malignant mesothelioma as an occupational disease in Lower Normandy, from 1995 to 2002].

    PubMed

    Le Neindre, B; Bouvier, V; Galateau-Sallé, F; de Quillacq, A; Launoy, G; Letourneux, M

    2007-04-01

    Despite the close relation between occupational exposure to asbestos and malignant mesothelioma, the compensation of this disease is still far from being the rule. The objective of this study is to assess the compensation process of all the cases of occupational mesothelioma recorded by the regional mesothelioma registry between September 1995 and August 2002, and to make suggestions for improvement of the compensation of future cases. Lifetime exposure to asbestos was assessed for each of the 141 mesothelioma cases observed in Lower Normandy during this time period, and 105 cases could be related to a possible, probable, or very probable occupational exposure to this mineral. Data about notification and compensation of these occupational diseases were gathered with the help of all health insurance organisms concerned. Except for five cases in which insurance conditions did not allow any compensation, compensation of occupational mesothelioma occurred in 85% of the cases. This high rate was probably the result of the existence of an early asbestos industry in this region, and of the particular awareness of the Norman population about asbestos-related diseases, as well as of the epidemiological follow-up of mesothelioma in Lower Normandy. When notified for compensation, all cases but one were actually compensated, and the lag-time between notification and compensation proved to decrease since 1995, with an average delay reaching 91,1 days in 2002. Patients who did not report their disease were older than those who did, and the lack of knowledge of medical practitioners about compensation procedures seems to be an important matter in this issue. In order to improve the rate of compensation of occupational malignant mesothelioma cases, information about the usual occupational origin of the disease should be delivered systematically to the general practitioner of each patient. This could be done by pathologists, when they diagnose malignant mesothelioma, and/or by

  10. Well-differentiated papillary mesothelioma of the uterine serosa identified at cesarean section: a case report.

    PubMed

    Lanneau, Grainger S; McLaughlin, Donna; O'Boyle, John; Magann, Everett F; Morrison, John C

    2005-11-01

    Peritoneal mesotheliomas encompass a variety of benign and malignant neoplasms. Well-differentiated papillary mesothelioma (WDPM) is uncommon, is thought to be of low malignant potential and is often discovered incidentally during abdominal or pelvic surgery. We describe a highly unusual case in which WDPM arising from the uterine serosa was identified at the time of cesarean delivery. A 21-year-old primigravida underwent cesarean delivery at term for arrest of the active phase of labor. A 2-cm, polypoid lesion was excised from the posterior uterine fundus; final pathology showed well-differentiated papillary mesothelioma. Subsequent examination and computed tomography were negative. A follow-up laparoscopic examination with abdominal washing for cytology and peritoneal biopsies revealed no residual disease. Survey of the pelvic cavity during cesarean section is important. Knowledge of the variable disease spectrum of mesothelioma is important in patient counseling and management. Differentiating between WDPM and malignant mesothelioma, other peritoneal tumors and implants from primary sites is necessary to avoid overtreatment.

  11. Multi-institutional experience of diffuse intra-abdominal multicystic peritoneal mesothelioma.

    PubMed

    Chua, T C; Yan, T D; Deraco, M; Glehen, O; Moran, B J; Sugarbaker, P H

    2011-01-01

    This study was undertaken to measure survival of patients with multicystic peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy through a multi-institutional collaboration. A multi-institutional data registry, established by the Peritoneal Surface Oncology Group, was used to identify patients with peritoneal mesothelioma and the subgroup with multicystic tumours, treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Outcomes for this subgroup are reported. The primary endpoint was overall survival. A secondary endpoint was the incidence of treatment-related complications. Of 405 patients with peritoneal mesothelioma, 26 (6·4 per cent) had multicystic tumours. There were 20 women and six men with a mean(s.d.) age of 42(12) years. The median peritoneal carcinomatosis index (PCI) was 14 (range 6-39). There was no perioperative mortality. Six patients developed grade III or IV complications. After a median follow-up of 54 (range 5-129) months, all 26 patients were still alive. Multicystic peritoneal mesothelioma appears to be a distinct subtype of peritoneal mesothelioma, where long-term survival may be achieved through cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  12. Increased mesothelioma incidence in New Zealand: the asbestos-cancer epidemic has started.

    PubMed

    Kjellstrom, T; Smartt, P

    2000-11-24

    To examine the incidence and mortality patterns for malignant mesothelioma and pleural cancer in New Zealand between 1962-1996, and relate these to past use of asbestos. Data concerning cases of mesothelioma 1962-1996, deaths from pleural and lung cancers 1974-1996, and data on imports of raw asbestos and asbestos products were obtained from government registers and publications. Time trends were analysed using different models. Mesothelioma incidence rates have increased progressively in New Zealand since the 1960s, and reached 25 per million for men in 1995. The increase follows an exponential model departing from a crude 'background rate' of 1-2 per million in 1984, and is particularly steep in males 50 to 60 years of age. The incidence is expected to double by 2010. New Zealand has entered an unrivalled period of occupational cancer deaths resulting from past workplace exposure to airborne asbestos fibres. The steep rise in mesothelioma incidence is likely to be accompanied by increases in other asbestos related diseases such as lung cancer. The unique causal association between mesothelioma and asbestos may be used to monitor changes in the public health impact of these exposures. The notification by medical practitioners of all potential asbestos related conditions/exposures to the Occupational Safety and Health (OSH) service is of great importance.

  13. Oxidative Status and Acute Phase Reactants in Patients with Environmental Asbestos Exposure and Mesothelioma

    PubMed Central

    Sezgi, Cengizhan; Taylan, Mahsuk; Selimoglu Sen, Hadice; Evliyaoğlu, Osman; Kaya, Halide; Abakay, Ozlem; Abakay, Abdurrahman; Tanrıkulu, Abdullah Cetin; Senyiğit, Abdurrahman

    2014-01-01

    Background and Objectives. The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects. Methods. Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured. Results. Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P < 0.001, P = 0.007, P < 0.0001, P < 0.001, and P < 0.001, resp.). Transferrin was lower in the mesothelioma group than in the other two groups (P < 0.001). The asbestos group had higher TOL, TAC, α1-antitrypsin, and transferrin levels (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.), as well as lower OSI and ferritin levels as compared to the control group (P < 0.001 and P < 0.001). Conclusions. We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy. PMID:24592197

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

    PubMed

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

    2017-06-01

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

  15. Small-molecule inhibition of oncogenic eukaryotic protein translation in mesothelioma cells.

    PubMed

    Chen, Esther Z; Jacobson, Blake A; Patel, Manish R; Okon, Aniekan M; Li, Shui; Xiong, Kerry; Vaidya, Abhishek J; Bitterman, Peter B; Wagner, Carston R; Kratzke, Robert A

    2014-08-01

    Deranged cap-mediated translation is implicated in the genesis, maintenance and progression of many human cancers including mesothelioma. In this study, disrupting the eIF4F complex by antagonizing the eIF4E-mRNA-cap interaction is assessed as a therapy for mesothelioma. Mesothelioma cells were treated with 4Ei-1, a membrane permeable prodrug that when converted to the active drug, 7-benzyl guanosine monophosphate (7Bn-GMP) displaces capped mRNAs from the eIF4F complex. Colony formation was measured in mesothelioma treated with 4Ei-1 alone or combined with pemetrexed. Proliferation was examined in cells treated with 4Ei-1. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation in lysates exposed to 4Ei-1. 4Ei-1 treatment resulted in a dose dependent decrease in colony formation and cell viability. Combination therapy of 4Ei-1 with pemetrexed further reduced colony number. Formation of eIF4F cap-complex decreased in response to 4Ei-1 exposure. 4Ei-1 is a novel prodrug that reduces proliferation, represses colony formation, diminishes association of eIF4F with the mRNA cap, and sensitizes mesothelioma cells to pemetrexed.

  16. Malignant mesotheliomas in Kure City, Japan: The relationship of asbestos exposure

    SciTech Connect

    Kishimoto, T.; Sato, T.; Ono, T.; Okada, K.; Masuda, Y.; Ito, H. )

    1989-01-01

    Eighteen patients with malignant mesothelioma were seen at Kure Mutual Aid Hospital over a 10-year period. According to occupational history, chest x-ray manifestations, and evidence of asbestos bodies in the tissue, 13 of these cases were definitely thought to be due to exposure to asbestos as a result of two or three of these items testing positive. Kure City is one of the major ship-building cities in Japan since the 1920s. Most of the 18 patients worked in ship building before and during World War II. Malignant mesothelioma appeared about 40 years after their first exposure to asbestos. In western countries, most malignant mesotheliomas are thought to be induced by exposure to asbestos fibers. Consequently, there has been a serious effort to deal with this problem recently, including lowering rate of exposure. In Japan, however, there have been few reports that asbestos fibers caused malignant mesothelioma. This report suggests that an increased incidence of malignant mesotheliomas in a specific area of Japan may also be due to exposure to asbestos fibers.

  17. Differential diagnosis between mesothelioma and adenocarcinoma: a multimodal approach based on ultrastructure and immunocytochemistry

    SciTech Connect

    Bedrossian, C.W.; Bonsib, S.; Moran, C. )

    1992-05-01

    Most compensations for asbestos-related deaths secondary to cancer center around mesothelioma and bronchogenic carcinoma. The differential diagnosis between mesothelioma and adenocarcinoma is a common and troublesome one, necessitating the correlation between clinical history, radiographic findings, and pathologic examination of tissues and cells. We describe a multimodal approach based on the use of routine and special stains, immunocytochemistry, and electron microscopy for distinguishing between mesothelioma and adenocarcinoma. Once a malignant diagnosis is arrived at by careful pathological examination, the tumor is classified as mesothelioma if mesothelial cells are identified as the constituent cells of the neoplasm. Mesothelial cells are recognized by (1) their main ultrastructural features: slender and elongated microvilli, abundant intermediate filaments, and lacking secretory granules; and (2) their characteristic immunocytochemical reactivity: positivity for cytokeratin, EMA, and vimentin, and negativity for carcinoembryonic antigen (CEA), B72-3, Leu-M1, and other gland-cell markers. A variety of methods have been attempted in an effort to distinguish between reactive and malignant mesothelial cells. In practice, however, such distinction depends more on experience and expertise than in any fool-proof ancillary tests. A number of these tests are discussed along with the illustration of classical and unusual examples of mesothelioma and other pleural tumors.

  18. Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir.

    PubMed

    Catalani, Simona; Palma, Francesco; Battistelli, Serafina; Nuvoli, Barbara; Galati, Rossella; Benedetti, Serena

    2017-02-20

    Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment. Reduced expression of procaspase-3 and increased expression of PARP p85 fragment were observed in both infected and uninfected mesothelioma cells, indicating apoptosis induction by CDV in a virus-independent manner. Similarly, the increase of the pro-apoptotic proteins p53, cytochrome c and caspase-3, the decrease of the survival protein Bcl-x, and the increment of Bax/Bcl-2 ratio revealed the occurrence of apoptosis in CDV-treated FTC-133. The presence of nuclear DNA fragmentation confirmed apoptotic cell death by CDV. Overall, our findings warrant further investigations to explore the therapeutic potential of CDV for human mesothelioma and follicular thyroid carcinoma.

  19. [Mesothelioma in construction workers: risk estimate, lung content of asbestos fibres, claims for compensation for occupational disease in the Veneto Region mesothelioma register].

    PubMed

    Merler, E; Bressan, Vittoria; Somigliana, Anna

    2009-01-01

    Work in the construction industry is causing the highest number of mesotheliomas among the residents of the Veneto Region (north-east Italy, 4,5 million inhabitants). To sum up the results on occurrence, asbestos exposure, lung fibre content analyses, and compensation for occupational disease. Case identification and asbestos exposure classification: active search of mesotheliomas that were diagnosed via histological or cytological examinations occurring between 1987 and 2006; a probability of asbestos exposure was attributed to each case, following interviews with the subjects or their relatives and collection of data on the jobs held over their lifetime. Risk estimate among construction workers: the ratio between cases and person-years, the latter derived from the number of construction workers reported by censuses. Lung content of asbestos fibres: examination of lung specimens by Scanning Electron Microscope to determine number and type of fibres. Claims for compensation and compensation awarded: data obtained from the National Institute for Insurance against Occupational Diseases available for the period 1999-2006. of 952 mesothelioma cases classified as due to asbestos exposure, 251 were assigned to work in the construction industry (21 of which due to domestic of environmental exposures), which gives a rate of 4.1 (95% CI 3.6-4.8) x 10(5) x year among construction workers. The asbestos fibre content detected in the lungs of 11 construction workers showed a mean of 1.7 x 10(6) fibres/g dry tissue (range 350,000-3 million) for fibres > 1 micro, almost exclusively due to amphibole fibres. 62% of the claims for compensation were granted but the percentage fell to less than 40% when claims were submitted by a relative, after the death of the subject. The prevalence of mesothelioma occurring among construction workers is high and is associated with asbestos exposure; the risk is underestimated by the subjects and their relatives. All mesotheliomas occurring among

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

    PubMed

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

    2014-01-01

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

  1. Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban

    PubMed Central

    Hillerdal, Gunnar

    2016-01-01

    OBJECTIVES We updated the Swedish component of the Nordic Occupational Cancer (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma. METHODS The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs) for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously. RESULTS A total of 3,716 incident mesotheliomas were recorded (21.1% in women). We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma. CONCLUSIONS Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure. PMID:27866405

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

    PubMed

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

    2016-05-01

    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 reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

  3. Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease.

    PubMed

    Nuvoli, Barbara; Germoni, Sabrina; Morosetti, Carlotta; Santoro, Raffaela; Cortese, Giancarlo; Masi, Serena; Cordone, Iole; Galati, Rossella

    2014-03-21

    Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.

  4. Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease

    PubMed Central

    2014-01-01

    Background Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. Results We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. Conclusion The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment. PMID:24655565

  5. Estimating the incidence of malignant mesothelioma in Vietnam: a pilot descriptive cancer registration study

    PubMed Central

    Soeberg, Matthew J.; Luong, Mai Anh; Tran, Van Thuan; Tran, Anh Thanh; Nguyen, Thị Thu Huyen; Bui, Dieu; Nguyen, Thi Hoai Nga; Takahashi, Ken; van Zandwijk, Nico

    2016-01-01

    Introduction Global asbestos consumption has shifted toward lower income countries, particularly in the Asian region including Vietnam where asbestos and asbestos-containing products have been imported since the late 1960s. Methods This pilot descriptive epidemiological study aimed to provide contemporary estimates of malignant mesothelioma incidence (histological subtype M9050/3; ICD-O-3) by gender and age group as recorded across nine cancer registries in Vietnam. Results We identified 148 incident cases of malignant mesothelioma during 1987–2013. The majority of cases were recorded in the Hanoi region (n = 93) and were aged 55 years or older (n = 96). Discussion By carefully reviewing existing cancer registry records in Vietnam, we identified a larger number of malignant mesothelioma cases than previously estimated. We recommend the use of cancer registry data in tracking future asbestos-related disease in Vietnam. PMID:27388204

  6. NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.

    PubMed

    Chow, Melvyn T; Tschopp, Jürg; Möller, Andreas; Smyth, Mark J

    2012-11-01

    Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.

  7. Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

    SciTech Connect

    Fox, Simon A.; Richards, Alex K.; Kusumah, Ivonne; Perumal, Vanathi; Bolitho, Erin M.; Mutsaers, Steven E.; Dharmarajan, Arun M.

    2013-10-11

    Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.

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

    PubMed

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

    2017-03-27

    Malignant pleural mesothelioma is a rare tumor with a poor prognosis. The only universally recognized pathological prognostic factor is histopathological subtype with a shorter survival in non-epithelioid subtypes. Recently, a grading of epithelioid mesothelioma on surgical resection has been proposed. The aim of our work is to assess the prognostic role of several histopathological factors on a retrospective cohort of 116 patients diagnosed as a pleural mesothelioma for more than 95% of patients on pleural biopsy. Our work shows that mitotic count <3/10 HPF (p < 0.0001), the lack of necrosis (p = 0.0379), mild nuclear atypia (p = 0.0054), the lack of atypical mitoses (p = 0.0265), a nucleoli size <3 μm (p = 0.0139), and a nucleoli absent or visible at 200× or higher magnification (p = 0.0170) are significantly associated with a better median overall survival in epithelioid mesothelioma. The presence of atypical mitoses was found to be related to a worse median survival in non-epithelioid mesothelioma. Mitotic count, necrosis, nuclear atypia, and nucleoli size are not associated with overall survival in non-epithelioid mesothelioma. Our work highlights that histopathological prognostic factors can be assessed on pleural biopsies and can predict reliably median overall survival. This is of interest in order to define subgroups of patients who could benefit of different therapies and select patients who could benefit of surgical excision.

  9. Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues.

    PubMed

    Markowitz, Steven

    2015-06-01

    Asbestos-related diseases persist, because millions of workers have had prior exposure and many industrializing countries continue to use asbestos. Globally, an estimated 107,000 people die annually from lung cancer, malignant mesothelioma, and asbestosis due to occupational asbestos exposure. Malignant mesothelioma and lung cancer are caused by all major types of asbestos. Asbestos causes more lung cancer deaths than malignant mesothelioma of the pleura; most cases of the latter are due to asbestos exposure. The cancer risk increases with cumulative asbestos exposure, with increased risk even at low levels of exposure to asbestos. Based on empirical studies, an estimated cumulative occupational exposure to asbestos of 1 fiber/mL-year substantially raises malignant mesothelioma risk. No safe threshold for asbestos exposure has been established for lung cancer and mesothelioma. The validity of fiber-type risk assessments depends critically on the quality of exposure assessments, which vary considerably, leading to a high degree of uncertainty. Asbestos exposure without asbestosis and smoking increases the risk of lung cancer. The joint effect of asbestos and smoking is supra-additive, which may depend in part on the presence of asbestosis. Asbestos workers who cease smoking experience a dramatic drop in lung cancer risk, which approaches that of nonsmokers after 30 years. Studies to date show that longer, thinner fibers have a stronger association with lung cancer than shorter, less thin fibers, but the latter nonetheless also show an association with lung cancer and mesothelioma. Low-dose chest computed tomographic scanning offers an unprecedented opportunity to detect early-stage lung cancers in asbestos-exposed workers.

  10. Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma.

    PubMed

    La Vecchia, Carlo; Boffetta, Paolo

    2012-05-01

    The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3-15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case-control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.

  11. Diagnosis and treatment of benign multicystic peritoneal mesothelioma

    PubMed Central

    Wang, Tian-Bao; Dai, Wei-Gang; Liu, Da-Wei; Shi, Han-Ping; Dong, Wen-Guang

    2013-01-01

    Benign multicystic peritoneal mesothelioma (BMPM) is a rare cystic mesothelial lesion that occurs predominantly in reproductive aged women. A 56-year-old Caucasian male was admitted to our surgical department with a chief complaint of a painful mass in his right lower abdomen for almost 2 years. The physical examination revealed a palpable painful mass. Computed tomography demonstrated an irregular, cystic tumor in his right lower abdomen. There was no obvious capsule or internal septations. No enhancement after intravenous administration of contrast was noted. An exploratory laparotomy was performed, and a multicystic tumor and adherent to the caecum was noted. The walls of the cysts were thin and smooth, filled with clear fluid, and very friable. An en bloc resection of the tumor, including appendix and caecum, was performed. Histological examination revealed multiple cysts lined with flattened simple epithelial cells, and the capsule walls of the cysts were composed of fibrous tissue. Immunohistochemical analysis documented positive expression of mesothelial cells and calretinin. The final diagnosis was BMPM. The patient was well at 6-mo follow-up. BMPM is exceedingly rare lesion. A complete resection of the tumor is required. The diagnosis of BMPM is based on pathological analysis. PMID:24151400

  12. Diagnosis and treatment of benign multicystic peritoneal mesothelioma.

    PubMed

    Wang, Tian-Bao; Dai, Wei-Gang; Liu, Da-Wei; Shi, Han-Ping; Dong, Wen-Guang

    2013-10-21

    Benign multicystic peritoneal mesothelioma (BMPM) is a rare cystic mesothelial lesion that occurs predominantly in reproductive aged women. A 56-year-old Caucasian male was admitted to our surgical department with a chief complaint of a painful mass in his right lower abdomen for almost 2 years. The physical examination revealed a palpable painful mass. Computed tomography demonstrated an irregular, cystic tumor in his right lower abdomen. There was no obvious capsule or internal septations. No enhancement after intravenous administration of contrast was noted. An exploratory laparotomy was performed, and a multicystic tumor and adherent to the caecum was noted. The walls of the cysts were thin and smooth, filled with clear fluid, and very friable. An en bloc resection of the tumor, including appendix and caecum, was performed. Histological examination revealed multiple cysts lined with flattened simple epithelial cells, and the capsule walls of the cysts were composed of fibrous tissue. Immunohistochemical analysis documented positive expression of mesothelial cells and calretinin. The final diagnosis was BMPM. The patient was well at 6-mo follow-up. BMPM is exceedingly rare lesion. A complete resection of the tumor is required. The diagnosis of BMPM is based on pathological analysis.

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

    SciTech Connect

    Maasilta, P. )

    1991-03-01

    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.

  14. Photodynamic Therapy for Lung Cancer and Malignant Pleural Mesothelioma

    PubMed Central

    Simone, Charles B.; Cengel, Keith A.

    2014-01-01

    Photodynamic therapy (PDT) is a form of non-ionizing radiation therapy that uses a drug, called a photosensitizer, combined with light to produce singlet oxygen (1O2) that can exert anti-cancer activity through apoptotic, necrotic, or autophagic tumor cell death. PDT is increasingly being used to treat thoracic malignancies. For early-stage non-small cell lung cancer (NSCLC), PDT is primarily employed as an endobronchial therapy to definitively treat endobronchial or roentgenographically occult tumors. Similarly, patients with multiple primary lung cancers may be definitively treated with PDT. For advanced or metastatic NSCLC and small cell lung cancer (SCLC), PDT is primarily employed to palliate symptoms from obstructing endobronchial lesions causing airway compromise or hemoptysis. PDT can be used in advanced NSCLC to attempt to increase operability or to reduce the extent of operation required, and selectively to treat pleural dissemination intraoperatively following macroscopically complete surgical resection. Intraoperative PDT can be safely combined with macroscopically complete surgical resection and other treatment modalities for malignant pleural mesothelioma (MPM) to improve local control and prolong survival. This report reviews the mechanism of and rationale for using PDT to treat thoracic malignancies, details prospective and major retrospectives studies of PDT to treat NSCLC, SCLC, and MPM, and describes improvements in and future roles and directions of PDT. PMID:25499640

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

    PubMed

    Simone, Charles B; Cengel, Keith A

    2014-12-01

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

  16. A genome-wide association study for malignant mesothelioma risk.

    PubMed

    Cadby, Gemma; Mukherjee, Sutapa; Musk, A W Bill; Reid, Alison; Garlepp, Mike; Dick, Ian; Robinson, Cleo; Hui, Jennie; Fiorito, Giovanni; Guarrera, Simonetta; Beilby, John; Melton, Phillip E; Moses, Eric K; Ugolini, Donatella; Mirabelli, Dario; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma; Matullo, Giuseppe; Robinson, Bruce; Creaney, Jenette; Palmer, Lyle J

    2013-10-01

    Malignant mesothelioma (MM) is a uniformly fatal tumour of mesothelial cells. MM is caused by exposure to asbestos however most individuals with documented asbestos exposure do not develop MM. Although MM appears to aggregate within families, the genetics of MM susceptibility is a relatively unexplored area. The aim of the current study was to identify genetic factors that contribute to MM risk. A genome-wide association analysis of 2,508,203 single nucleotide polymorphisms (SNPs) from 428 MM cases and 1269 controls from Western Australia was performed. Additional genotyping was performed on a sample of 778 asbestos-exposed Western Australian controls. Replication of the most strongly associated SNPs was undertaken in an independent case-control study of 392 asbestos-exposed cases and 367 asbestos-exposed controls from Italy. No SNPs achieved formal genome-wide statistical significance in the Western Australian study. However, suggestive results for MM risk were identified in the SDK1, CRTAM and RASGRF2 genes, and in the 2p12 chromosomal region. These findings were not replicated in the Italian study, although there was some evidence of replication in the region of SDK1. These suggestive associations will be further investigated in sequencing and functional studies. Copyright © 2013. Published by Elsevier Ireland Ltd.

  17. Malignant mesothelioma of the pleura in Trieste, Italy.

    PubMed

    Giarelli, L; Bianchi, C; Grandi, G

    1992-01-01

    One hundred and seventy malignant pleural mesotheliomas seen at necropsy at the Institute of Pathological Anatomy of the Trieste University during the period 1968-1987 were reviewed. The series included 153 men and 17 women, aged between 33 and 92 years (median 70 years). Lifetime work histories were obtained from the patients' relatives by personal or telephone interviews in 162 cases. A majority of the male subjects had been employed in "naval" work, 99 people having worked in the ship-building industry, 19 in the navy and merchant marine, and 7 in docks. A variety of trades appeared in the remaining histories. Work histories were indicative of occupational exposure to asbestos in 150 cases. A further 5 patients with negative or insufficient data showed asbestos bodies in routine lung sections and 5 women had a history of domestic exposure. A majority of the patients had had their first exposure before 1950. The intervals between first exposure and death ranged from 14 to 71 years (median 48 years).

  18. Fowlpox-based survivin vaccination for malignant mesothelioma therapy

    PubMed Central

    Bertino, Pietro; Panigada, Maddalena; Soprana, Elisa; Bianchi, Valentina; Bertilaccio, Sabrina; Sanvito, Francesca; Rose, Aaron H.; Yang, Haining; Gaudino, Giovanni; Hoffmann, Peter R.; Siccardi, Antonio; Carbone, Michele

    2013-01-01

    Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available. In this study, we evaluated the therapeutic efficacy of a novel survivin-based vaccine by subcutaneous or intraperitoneum injection of BALB/c mice with murine fiber-induced MM tumor cells followed by vaccination with recombinant Fowlpox virus replicons encoding survivin. Vaccination generated significant immune responses in both models, leading to delayed tumor growth and improved animal survival. Flow cytometry and immunofluorescence analyses of tumors from vaccinated mice showed CD8+ T cell infiltration, and real-time PCR demonstrated increased mRNA and protein levels of immunostimulatory cytokines. Analyses of survivin peptide-pulsed spleen and lymph node cells from vaccinated mice using ELISPOT and intracellular cytokine staining confirmed antigen-specific, interferon-γ-producing CD8+ T cell responses. In addition pentamer-based flow cytometry showed that vaccination generated survivin-specific CD8+ T cells. Importantly, vaccination did not affect fertility or induce autoimmune abnormalities in mice. Our results demonstrate that vaccination with recombinant Fowlpox expressing survivin improves T cell responses against aggressive MM tumors and may form the basis for promising clinical applications. PMID:23335100

  19. Current Issues in Malignant Pleural Mesothelioma Evaluation and Management

    PubMed Central

    Ai, Jing

    2014-01-01

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

  20. Multicellular contractility contributes to the emergence of mesothelioma nodules

    NASA Astrophysics Data System (ADS)

    Czirok, Andras

    Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

  1. Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma

    PubMed Central

    Huang, Liyan; Cai, Muyan; Zhang, Xu; Wang, Fang; Chen, Likun; Xu, Meng; Yang, Ke; Chen, Zhen; Wang, Xiaokun; Fu, Liwu

    2017-01-01

    Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR. PMID:28337371

  2. Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.

    PubMed

    Tunesi, Sara; Ferrante, Daniela; Mirabelli, Dario; Andorno, Silvano; Betti, Marta; Fiorito, Giovanni; Guarrera, Simonetta; Casalone, Elisabetta; Neri, Monica; Ugolini, Donatella; Bonassi, Stefano; Matullo, Giuseppe; Dianzani, Irma; Magnani, Corrado

    2015-10-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    PubMed

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

    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.

  4. Induction of tunica vaginalis mesotheliomas in rats by xenobiotics.

    PubMed

    Maronpot, R R; Zeiger, E; McConnell, E E; Kolenda-Roberts, H; Wall, H; Friedman, M A

    2009-01-01

    To better understand the relevance of tunica vaginalis mesotheliomas (TVM) to human cancer risk, we examined the nature of TVM responses in 21 published rat cancer bioassays against the backdrop of the biology and molecular biology of mesothelium, and of spontaneous and treatment-induced TVM. Although relatively rare in all species including humans, TVM are seen most frequently in F344 male rats, as opposed to other rat strains, and are causally associated with the high background incidence of Leydig-cell tumors of the testes of these rats. Hormone imbalance brought about by perturbations of the endocrine system is proposed as a key factor leading to both spontaneous and treatment-associated TVM. Of 21 F344 rat studies with a treatment-associated TVM response, 7 were judged to have a nonsignificant to marginal response, 11 had a robust TVM response, and 3 were noninformative due to early mortality from other induced tumors. Of the 11 chemicals with robust responses, 8 were directly mutagenic in Salmonella and 3 are known to be mutagenic after metabolism. Only 2 of the 7 with nonsignificant to marginal responses were Ames test positive. TVM induction is a male F344 rat-specific event, and chemicals/agents that induce only TVM in the male F344 rat from a typical two-sex rat and mouse chronic bioassay are likely irrelevant in human risk assessment.

  5. Benign mesothelioma of the appendix: an incidental finding in a case of sigmoid diverticular disease

    PubMed Central

    Bansal, A; Zakhour, H D

    2006-01-01

    Benign multicystic mesothelioma is a well recognised but rare entity. The aim of this report is to describe a case of a small mesothelial proliferation of the peritoneum. A 58 year old postmenopausal woman presented with left sided abdominal pain and altered bowel habit. Radiological investigations (barium enema and computed tomography scan of the abdomen and pelvis) were undertaken. An operation was performed for symptomatic sigmoid diverticular disease. Unusually, the appendix was adherent to the sigmoid colon. Microscopy revealed a benign mesothelioma. The patient remains symptom free to date. PMID:16394291

  6. Peritoneal cystic mesothelioma: an electron microscopic and immunohistochemical study of two male patients.

    PubMed Central

    Sienkowski, I K; Russell, A J; Dilly, S A; Djazaeri, B

    1986-01-01

    The clinical, pathological, and ultrastructural features of two cases of peritoneal cystic mesothelioma occurring in men were studied. The results of immunohistochemical staining for CAM 5.2, epithelial membrane antigen, carcinoembryonic antigen, and Factor VIII related antigen are reported for the first time and compared with the staining results of two peritoneal cystic lymphangiomas. Although resembling cystic lymphangioma by light microscopy, cystic mesothelioma may have a greater tendency for local recurrence. Staining for CAM 5.2 or epithelial membrane antigen may facilitate the differentiation of these two entities. Images PMID:2422221

  7. Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma.

    PubMed

    Vivero, Marina; Bueno, Raphael; Chirieac, Lucian R

    2017-09-08

    Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural

  8. Asymptomatic localized pleural amyloidosis mimicking malignant pleural mesothelioma: report of a case.

    PubMed

    Nakano, Tomoyuki; Endo, Shunsuke; Tetsuka, Kenji; Fukushima, Noriyoshi

    2016-01-01

    We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma.

  9. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis).

    PubMed

    Kim, Su-Min; Oh, Yeonsu; Oh, Suk-Hun; Han, Jeong-Hee

    2016-03-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.

  10. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis)

    PubMed Central

    KIM, Su-Min; OH, Yeonsu; OH, Suk-Hun; HAN, Jeong-Hee

    2015-01-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk. PMID:26568187

  11. Mesothelioma with signet-ring cell features: report of 23 cases.

    PubMed

    Ordóñez, Nelson G

    2013-03-01

    Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signet-ring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that

  12. Statins Do Not Alter the Incidence of Mesothelioma in Asbestos Exposed Mice or Humans

    PubMed Central

    Robinson, Cleo; Alfonso, Helman; Woo, Samantha; Walsh, Amy; Olsen, Nola; Musk, Arthur W.; Robinson, Bruce W. S.; Nowak, Anna K.; Lake, Richard A.

    2014-01-01

    Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44–2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61–1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos. PMID:25093718

  13. Phrenic Nerve Paralysis as the Initial Presentation in Pleural Sarcomatoid Mesothelioma

    PubMed Central

    Makimoto, Go; Fujiwara, Keiichi; Fujimoto, Nobukazu; Yamadori, Ichiro; Sato, Toshio; Kishimoto, Takumi

    2014-01-01

    A 74-year-old man was referred to our hospital because of persistent cough. A chest radiograph revealed an elevation of the right diaphragm. Computed tomography (CT) images revealed a small nodule localized on the right mediastinum. Five months later, the nodule had grown and was diagnosed as malignant pleural mesothelioma (MPM) by a CT-guided needle biopsy. The patient underwent combined chemotherapy, but the disease progressed rapidly and he passed away. On autopsy, microscopic findings and immunohistological examinations supported the diagnosis of sarcomatoid mesothelioma. Therefore, we diagnosed this rare case as localized sarcomatoid MPM showing phrenic nerve paralysis as an initial presentation. PMID:25076889

  14. Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients

    PubMed Central

    Nishimura, Yasumitsu; Kumagai-Takei, Naoko; Matsuzaki, Hidenori; Lee, Suni; Maeda, Megumi; Kishimoto, Takumi; Fukuoka, Kazuya; Nakano, Takashi; Otsuki, Takemi

    2015-01-01

    Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme+ cells in CD8+ lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8+ lymphocytes may be stimulated by some kind of “nonself” cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma. PMID:26161391

  15. Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients.

    PubMed

    Nishimura, Yasumitsu; Kumagai-Takei, Naoko; Matsuzaki, Hidenori; Lee, Suni; Maeda, Megumi; Kishimoto, Takumi; Fukuoka, Kazuya; Nakano, Takashi; Otsuki, Takemi

    2015-01-01

    Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.

  16. MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma.

    PubMed

    Robinson, Cleo; Walsh, Amy; Larma, Irma; O'Halloran, Sean; Nowak, Anna K; Lake, Richard A

    2011-01-01

    Animal models provide an important tool for investigating the biology of cancer and for testing the efficacy of novel treatments. Here we describe several aspects of the transgenic MexTAg mouse that develops asbestos-induced mesothelioma. Targeted expression of the TAg transgene causes mesothelioma to develop more rapidly after asbestos exposure in wild-type mice with 100% incidence compared to 30% incidence in wild-type mice. MexTAg mice do not develop spontaneous mesothelioma and exhibit a very low incidence of other tumours. Here we show that TAg does not affect the aggressiveness or rate of progression of the mesotheliomas, suggesting that the oncogene alters only the rate at which disease is initiated. The instillation of an alternative inflammatory agent, thioglycollate, did not induce mesotheliomas, demonstrating acute inflammation is not sufficient for tumour development in MexTAg mice. We found that neither the age of a mouse at the time of exposure nor its gender were prognostic factors. MexTAg mice with mesotheliomas respond to treatment with a cytotoxic drug in a similar way to that of patients with mesothelioma, demonstrating the validity of the model. We also show that long-term treatment with a COX-2 inhibitor prior to the development of disease does not have a survival benefit, suggesting that this is not a useful cancer prevention therapy for asbestos-exposed individuals. The model is robust and suitable for testing a wide variety of protocols and a range of translational studies.

  17. Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno-histochemical approach using a panel of monoclonal antibodies.

    PubMed

    Tuttle, S E; Lucas, J G; Bucci, D M; Schlom, J; Primus, J

    1990-10-01

    A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas.

  18. The development and deployment of Common Data Elements for tissue banks for translational research in cancer – An emerging standard based approach for the Mesothelioma Virtual Tissue Bank

    PubMed Central

    Mohanty, Sambit K; Mistry, Amita T; Amin, Waqas; Parwani, Anil V; Pople, Andrew K; Schmandt, Linda; Winters, Sharon B; Milliken, Erin; Kim, Paula; Whelan, Nancy B; Farhat, Ghada; Melamed, Jonathan; Taioli, Emanuela; Dhir, Rajiv; Pass, Harvey I; Becich, Michael J

    2008-01-01

    Background Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) – compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). Methods The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). Results Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data

  19. Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma.

    PubMed

    Andrici, Juliana; Jung, Jason; Sheen, Amy; D'Urso, Lisa; Sioson, Loretta; Pickett, Justine; Parkhill, Thomas R; Verdonk, Brandon; Wardell, Kathryn L; Singh, Arjun; Clarkson, Adele; Watson, Nicole; Toon, Christopher W; Gill, Anthony J

    2016-05-01

    Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma.

  20. Combination chemotherapy for advanced sarcomas of bone and mesothelioma utilizing rubidazone and DTIC: a Southwest Oncology Group Study.

    PubMed

    Zidar, B L; Benjamin, R S; Frank, J; Lane, M; Baker, L H

    1983-02-01

    Twenty-three patients with disseminated bony sarcoma and 23 patients with malignant mesothelioma were evaluable in a Southwest Oncology Group (SWOG) clinical trial utilizing rubidazone and DTIC. One partial remission (PR) was observed in a previously untreated patient with metastatic Ewing's sarcoma. One patient with giant cell tumor of bone had an improvement, short of PR. Thirteen patients with osteogenic sarcoma and 23 with malignant mesothelioma had no response to this combination of drugs. The major toxic effects of therapy included nausea, vomiting, and myelosuppression, especially leukopenia; no cardiac toxicity was noted. We conclude that the combination of rubidazone and DTIC is inactive in bony sarcoma and mesothelioma.

  1. An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urgüp in Anatolia.

    PubMed Central

    Baris, Y I; Sahin, A A; Ozesmi, M; Kerse, I; Ozen, E; Kolacan, B; Altinörs, M; Göktepeli, A

    1978-01-01

    The 575 inhabitants of the remote Anatolian village of Karain suffered 11 deaths from pleural mesothelioma in 1975/76 and there were five cases of fibrosing pleurisy. In the previous five years there had been 25 cases of mesothelioma. Calcified pleural plaques were common on survey radiography. Asbestos does not occur in the local soil or rock, nor is it handled in the village, but a few fibres were found in the water. Fibres were also found in the pleural tissue of two of five cases examined. Inhabitants of the neighbouring villages are free of mesothelioma. Images PMID:663877

  2. Dramatic tumour response to pemetrexed single-agent in an elderly patient with malignant peritoneal mesothelioma: a case report

    PubMed Central

    Fasola, Gianpiero; Puglisi, Fabio; Follador, Alessandro; Aita, Marianna; Di Terlizzi, Silvia; Belvedere, Ornella

    2006-01-01

    Background To date, there is no standard treatment for unresectable malignant peritoneal mesothelioma; either best supportive care or systemic chemotherapy with palliative intent are accepted options. Case presentation Here, we report the case of a 79-year old patient with malignant peritoneal mesothelioma who was treated with pemetrexed single-agent and obtained an impressive long-lasting response. Conclusion Single-agent pemetrexed is a treatment option for malignant peritoneal mesothelioma in selected elderly patients or in patients with unpaired performance status. PMID:17176466

  3. Consensus Report of the 2015 Weinman International Conference on Mesothelioma

    PubMed Central

    Carbone, Michele; Kanodia, Shreya; Chao, Ann; Miller, Aubrey; Wali, Anil; Weissman, David; Adjei, Alex; Baumann, Francine; Boffetta, Paolo; Buck, Brenda; de Perrot, Marc; Dogan, A. Umran; Gavett, Steve; Gualtieri, Alessandro; Hassan, Raffit; Hesdorffer, Mary; Hirsch, Fred R.; Larson, David; Mao, Weimin; Masten, Scott; Pass, Harvey I.; Peto, Julian; Pira, Enrico; Steele, Ian; Tsao, Anne; Woodard, Gavitt Alida; Yang, Haining; Malik, Shakun

    2017-01-01

    On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group’s efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are

  4. Consensus Report of the 2015 Weinman International Conference on Mesothelioma.

    PubMed

    Carbone, Michele; Kanodia, Shreya; Chao, Ann; Miller, Aubrey; Wali, Anil; Weissman, David; Adjei, Alex; Baumann, Francine; Boffetta, Paolo; Buck, Brenda; de Perrot, Marc; Dogan, A Umran; Gavett, Steve; Gualtieri, Alessandro; Hassan, Raffit; Hesdorffer, Mary; Hirsch, Fred R; Larson, David; Mao, Weimin; Masten, Scott; Pass, Harvey I; Peto, Julian; Pira, Enrico; Steele, Ian; Tsao, Anne; Woodard, Gavitt Alida; Yang, Haining; Malik, Shakun

    2016-08-01

    On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group's efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are

  5. Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

    PubMed Central

    Magge, Deepa; Zenati, Mazen S.; Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Ramalingam, Lekshmi; Jones, Heather; Zureikat, Amer H.; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

    2014-01-01

    Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC. PMID:24322529

  6. Experience with peritoneal mesothelioma at the Milan National Cancer Institute

    PubMed Central

    Deraco, Marcello; Baratti, Dario; Cabras, Antonello Domenico; Zaffaroni, Nadia; Perrone, Federica; Villa, Raffaella; Jocollè, Jenny; Balestra, Maria Rosaria; Kusamura, Shigeki; Laterza, Barbara; Pilotti, Silvana

    2010-01-01

    Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor. Therapeutic options have traditionally been limited and ineffective. The biologic and molecular events correlated with poor responsiveness to therapy are still poorly understood. In recent years, an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome, as compared to historical controls. Since 1995, at the National Cancer Institute (NCI) of Milan (Italy), patients with DMPM have been treated with CRS and hyperthermic intra-peritoneal chemotherapy (HIPEC). In the present paper, clinical experiences and basic science investigations on DMPM at Milan NCI are reviewed. Peri-operative and long-term outcome results with CRS and HIPEC are presented. Clinico-pathological prognostic factors were investigated by multivariate analysis. The pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our institution. The prevalence and prognostic role of telomere maintenance mechanisms, which account for the limitless cell replicative potential of many malignancies, were studied. The dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic strategies. On this basis, the expression of survivin and other IAP family members (IAP-1, IAP-2, and X-IAP), the pro-apoptotic protein Smac/DIABLO, and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were analyzed. Finally, analyses of EGFR, PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets. PMID:21160925

  7. Onconase Mediated NFKβ Down-Regulation in Malignant Pleural Mesothelioma

    PubMed Central

    Goparaju, Chandra M.; Blasberg, Justin D.; Volinia, Stefano; Palatini, Jeff; Ivanov, Sergey; Donington, Jessica S.; Croce, Carlo; Carbone, Michele; Yang, Haining; Pass, Harvey I.

    2011-01-01

    Purpose Treatment of malignant pleural mesothelioma (MPM) with Ranpirnase (Onconase) results in disruption of protein translation and cell apoptosis. We hypothesize that Onconase acts via down regulation of nuclear factor kappa B (NFKβ) by specific microRNAs (miRNA) and that interference of this pathway could have implications for MPM resistance to chemotherapy. Experimental Design Three immortalized MPM cell lines (H2959, H2373, and H2591) were exposed to Onconase at 0–20 µg/mL. Cell counts were measured at 48 and 72 hours. Gene expression in miRNA-enriched RNA was validated by RT-PCR. The functional implications of miRNA expression were evaluated by transfecting miRNA mimics or inhibitors into MPM cell lines, and performing Matrigel™ invasion, cell proliferation, soft agar colony formation, and scratch closure assays. Effects on NFKβ expression and downstream targets including ABC transporters, BCL-xl, and IAP were assessed by RT-PCR and Western Blotting. Results Treatment with 20µg/mL of Onconase significantly decreased cell count and invasion. Hsa-miR-17* was significantly upregulated and hsa-miR-30c significantly down-regulated by Onconase treatment in all cell lines. Forced expression of hsa-miR-17* mimic and hsa-miR-30c inhibitor each significantly decreased functional activity of Onconase in all assays. NFKB1(p50) expression and downstream targets were also decreased with Onconase treatment as well as with forced expression miRNA mimic and inhibitors. Conclusions Onconase treatment caused a significant decrease in cell proliferation, invasion, and in expression of certain miRNAs. Recapitulation of the resultant miRNA expression pattern with hsa-miR-17* mimic and hsa-miR-30c inhibitor resulted in downregulation of NFKB1 and reduced malignant behavior in functional assays. Thus, Onconase likely exerts its anti-tumor effect through these miRNAs. PMID:21317924

  8. Genomic events associated with progression of pleural malignant mesothelioma

    PubMed Central

    Ivanov, Sergey V.; Miller, Jeremy; Lucito, Robert; Tang, Chunlao; Ivanova, Alla V.; Pei, Jianming; Carbone, Michele; Cruz, Christina; Beck, Amanda; Webb, Craig; Nonaka, Daisuke; Testa, Joseph R.; Pass, Harvey I.

    2008-01-01

    Pleural malignant mesothelioma (MM) is an aggressive cancer with a very long latency and a very short median survival. Little is known about the genetic events that trigger MM and their relation to poor outcome. The goal of our study was to characterize major genomic gains and losses associated with MM origin and progression and assess their clinical significance. We performed Representative Oligonucleotide Microarray Analysis (ROMA) on DNA isolated from tumors of 22 patients who recurred at variable interval with the disease after surgery. The total number of copy number alterations (CNA) and frequent imbalances for patients with short time (<12 months from surgery) and long time to recurrence were recorded and mapped using the Analysis of Copy Errors (ACE) algorithm. We report a profound increase in CNA in the short-time recurrence group with most chromosomes affected, which can be explained by chromosomal instability associated with MM. Deletions in chromosomes 22q12.2, 19q13.32, and 17p13.1 appeared to be the most frequent events (55-74%) shared between MM patients followed by deletions in 1p, 9p, 9q, 4p, 3p and gains in 5p, 18q, 8q, and 17q (23-55%). Deletions in 9p21.3 encompassing CDKN2A/ARF and CDKN2B were characterized as specific for the short-term recurrence group. Analysis of the minimal common areas of frequent gains and losses identified candidate genes that may be involved in different stages of MM: OSM (22q12.2), FUS1 and PL6 (3p21.3), DNAJA1 (9p21.1), and CDH2 (18q11.2-q12.3). Imbalances seen by ROMA were confirmed by Affymetrix genome analysis in a subset of samples. PMID:18973227

  9. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    PubMed Central

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  10. National survey of malignant mesothelioma and asbestos exposure in Japan.

    PubMed

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

    2012-03-01

    In the present study, malignant mesothelioma (MM) cases in Japan were investigated retrospectively. We extracted records for 6030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM, including its association with asbestos exposure (AE). Of all these cases, a clinical diagnosis of MM was confirmed for 929. The origin of MM included the pleura in 794 cases (85.5%), the peritoneum in 123 cases (13.2%), the pericardium in seven cases (0.8%), and the testicular tunica vaginalis in five cases (0.5%). The histological subtypes of MM included 396 epithelioid (55.9%), 154 sarcomatoid (21.7%), 126 biphasic (17.8%), and 33 cases (4.7%) classified as "other types". Of all the MM cases, AE was indicated in 76.8% and pleural plaques were detected in 34.2%. The number of asbestos particles was determined in 103 cases of MM. More than 1000 asbestos particles per gram dried lung tissue were detected in 74.8% of cases and more than 5000 particles were detected in 43.7% of cases. We compared patient characteristics and the diagnostic procedures for MM before and after the "Kubota shock". Compared with the early phase of this study (2003-2005), the median age at diagnosis of MM was higher, the number of cases without definite diagnosis of MM was lower, the proportion of cases diagnosed by thoracoscopy was higher, and the percentage of cases in which the occupational history was described in the medical records was significantly higher in the later phase (2006-2008). Our study confirmed that more than 70% of MM cases in Japan are associated with AE. The "Kubota shock" may affect some features pertaining to MM.

  11. The established and future biomarkers of malignant pleural mesothelioma.

    PubMed

    Panou, V; Vyberg, M; Weinreich, U M; Meristoudis, C; Falkmer, U G; Røe, O D

    2015-06-01

    Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.

  12. CREB-Induced Inflammation Is Important for Malignant Mesothelioma Growth

    PubMed Central

    Westbom, Catherine M.; Shukla, Anurag; MacPherson, Maximilian B.; Yasewicz, Elizabeth C.; Miller, Jill M.; Beuschel, Stacie L.; Steele, Chad; Pass, Harvey I.; Vacek, Pamela M.; Shukla, Arti

    2015-01-01

    Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB-silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor-bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos-induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation. PMID:25111229

  13. Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression

    PubMed Central

    Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G.; Longley, Daniel B.; Bueno, Raphael; Sugarbaker, David J.; Fennell, Dean A.; Broaddus, V. Courtney

    2012-01-01

    When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies. PMID:23300762

  14. Benign Cystic Mesothelioma of the Peritoneum: A Rare Case and Review of the Literature

    PubMed Central

    Khuri, Safi; Gilshtein, Hayim; Abboud, Wisam; Assalia, Ahmad; Kluger, Yoram

    2012-01-01

    A 19-year-old male presented with right lower quadrant pain. Imaging studies revealed a cystic peritoneal mass. At surgery, a large peritoneal mass was excised. The pathology report revealed a benign cystic mesothelioma, and a right hemicolectomy with cytoreductive surgery was completed. PMID:23341809

  15. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report.

    PubMed

    Takemoto, Shuji; Kawano, Ryosuke; Honda, Kazumi; Nakazono, Aki; Shimamatsu, Kazuhide

    2012-05-14

    Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

  16. [Peritoneal mesothelioma: treatment with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy].

    PubMed

    Passot, G; Cotte, E; Brigand, C; Beaujard, A-C; Isaac, S; Gilly, F-N; Glehen, O

    2008-01-01

    Diffuse malignant peritoneal mesothelioma is a rare and lethal disease. Locoregional treatments combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) seem to improve prognosis. Cytoreductive surgery and HIPEC was performed in 22 patients at the Centre Hospitalier-Lyon Sud between 1989 and 2006. A retrospective analysis of survival was carried out to assess clinical and histological prognostic factors. Nineteen patients with diffuse malignant peritoneal mesothelioma were included (16 epithelial, 3 biphasic and 3 multicystic forms). Sixteen patients presented stage 3 or 4 peritoneal mesothelioma according to the Gilly classification. Optimal cytoreductive surgery was performed for 11 patients (complete macroscopic resection or residual tumor nodules less than 2.5mm). No post-operative deaths occurred but 9 patients (47%) presented grade III or IV post-operative complications. The overall median survival was 36.9 months; completeness of cytoreduction was the only significant prognostic factor. Cytoreductive surgery combined with HIPEC may improve the length of survival for patients with diffuse malignant peritoneal mesothelioma; such patients should be treated in specialized centers.

  17. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report

    PubMed Central

    2012-01-01

    Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery. PMID:22583977

  18. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women

    PubMed Central

    Gordon, Ronald E; Fitzgerald, Sean; Millette, James

    2014-01-01

    Background: Cosmetic talcum powder products have been used for decades. The inhalation of talc may cause lung fibrosis in the form of granulomatose nodules called talcosis. Exposure to talc has also been suggested as a causative factor in the development of ovarian carcinomas, gynecological tumors, and mesothelioma. Purpose: To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women. Methods: Transmission electron microscope (TEM) formvar-coated grids were prepared with concentrations of one brand of talcum powder directly, on filters, from air collections on filters in glovebox and simulated bathroom exposures and human fiber burden analyses. The grids were analyzed on an analytic TEM using energy-dispersive spectrometer (EDS) and selected-area electron diffraction (SAED) to determine asbestos fiber number and type. Results: This brand of talcum powder contained asbestos and the application of talcum powder released inhalable asbestos fibers. Lung and lymph node tissues removed at autopsy revealed pleural mesothelioma. Digestions of the tissues were found to contain anthophyllite and tremolite asbestos. Discussion: Through many applications of this particular brand of talcum powder, the deceased inhaled asbestos fibers, which then accumulated in her lungs and likely caused or contributed to her mesothelioma as well as other women with the same scenario. PMID:25185462

  19. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.

    PubMed

    Gordon, Ronald E; Fitzgerald, Sean; Millette, James

    2014-10-01

    Cosmetic talcum powder products have been used for decades. The inhalation of talc may cause lung fibrosis in the form of granulomatose nodules called talcosis. Exposure to talc has also been suggested as a causative factor in the development of ovarian carcinomas, gynecological tumors, and mesothelioma. To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women. Transmission electron microscope (TEM) formvar-coated grids were prepared with concentrations of one brand of talcum powder directly, on filters, from air collections on filters in glovebox and simulated bathroom exposures and human fiber burden analyses. The grids were analyzed on an analytic TEM using energy-dispersive spectrometer (EDS) and selected-area electron diffraction (SAED) to determine asbestos fiber number and type. This brand of talcum powder contained asbestos and the application of talcum powder released inhalable asbestos fibers. Lung and lymph node tissues removed at autopsy revealed pleural mesothelioma. Digestions of the tissues were found to contain anthophyllite and tremolite asbestos. Through many applications of this particular brand of talcum powder, the deceased inhaled asbestos fibers, which then accumulated in her lungs and likely caused or contributed to her mesothelioma as well as other women with the same scenario.

  20. Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

    PubMed Central

    Kresoja-Rakic, Jelena; Kapaklikaya, Esra; Ziltener, Gabriela; Dalcher, Damian; Santoro, Raffaella; Christensen, Brock C.; Johnson, Kevin C.; Schwaller, Beat; Weder, Walter; Stahel, Rolf A.; Felley-Bosco, Emanuela

    2016-01-01

    Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the −161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this −161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells. PMID:26848772

  1. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema

    PubMed Central

    Fujita, Kohei; Kim, Young Hak; Nakatani, Koichi; Mio, Tadashi

    2015-01-01

    Key Clinical Message Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases. PMID:26509028

  2. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema.

    PubMed

    Fujita, Kohei; Kim, Young Hak; Nakatani, Koichi; Mio, Tadashi

    2015-10-01

    Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases.

  3. Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas.

    PubMed

    Dacic, Sanja; Kothmaier, Hannelore; Land, Stephanie; Shuai, Yongli; Halbwedl, Iris; Morbini, Patrizia; Murer, Bruno; Comin, Camilla; Galateau-Salle, Françoise; Demirag, Funda; Zeren, Handan; Attanoos, Richard; Gibbs, Alan; Cagle, Philip; Popper, Helmut

    2008-12-01

    Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.

  4. Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells.

    PubMed

    Saho, Satomi; Satoh, Hiroki; Kondo, Eisaku; Inoue, Yusuke; Yamauchi, Akira; Murata, Hitoshi; Kinoshita, Rie; Yamamoto, Ken-Ichi; Futami, Junichiro; Putranto, Endy Widya; Ruma, I Made Winarsa; Sumardika, I Wayan; Youyi, Chen; Suzawa, Ken; Yamamoto, Hiromasa; Soh, Junichi; Tomida, Shuta; Sakaguchi, Yoshihiko; Saito, Ken; Iioka, Hidekazu; Huh, Nam-Ho; Toyooka, Shinichi; Sakaguchi, Masakiyo

    2016-12-01

    S100A11, a small Ca(2+) binding protein, acts extracellularly as a mediator of cancer progression. That raises the question of how a protein that lacks the classical secretory signal is able to be secreted outside cells without being damaged. Some insights into this question have been obtained, and there has been accumulating evidence indicating a pivotal role of a non-classical vesicle-mediated pathway using lysosomes or peroxisomes for the protein secretion. To obtain a more precise insight into the secretory mechanism of S100A11, we first screened representative cancer cells exhibiting significantly active secretion of S100A11. From the results of profiling, we turned our attention to aggressive cancer mesothelioma cells. In mesothelioma cells, we found that abundant dimeric S100A11 was produced selectively in the peroxisome after transportation of monomeric S100A11 through an interaction with PEX14, a peroxisome membrane protein, resulting in peroxisomal secretion of dimerized S100A11. In an extracellular environment in vitro, dimerized S100A11 promoted mesothelial cell invasion indirectly with the help of fibroblast cells. Overall, the results indicate that the peroxisome functions as an essential vesicle for the production of dimerized S100A11 and the subsequent secretion of the protein from mesothelioma cells and that peroxisome-mediated secretion of dimerized S100A11 might play a critical role in mesothelioma progression in a tumor microenvironment.

  5. Comparative Elongated Mineral Particle Toxicology & Erionite’s Apparent  High Potency for Inducing Mesothelioma

    EPA Science Inventory

    Recent NHEERL research under EPA's Libby Action Plan has determined that elongated particle relative potency for rat pleural mesothelioma is best predicted on the basis of total external surface area (TSA) of slightly acid leached test samples which simulate particle bio-durabili...

  6. Mesothelioma and anti-Ma paraneoplastic syndrome; heterogeneity in immunogenic tumours increases.

    PubMed

    Archer, Hilary Anne; Panopoulou, Aikaterini; Bhatt, Nidhi; Edey, Anthony James; Giffin, Nicola Jane

    2014-02-01

    We present a patient with opsoclonus and diffuse cerebellar signs who had an anti-Ma2 antibody-associated paraneoplastic syndrome secondary to a sarcomatoid mesothelioma. This case highlights the importance of early tumour detection, instigation of therapeutic measures, and the heterogeneity of underlying malignancies in neurological paraneoplastic syndromes.

  7. Malignant pleural mesothelioma in a 17-year old boy: A case report and literature review

    PubMed Central

    Pérez-Guzmán, C.; Barrera-Rodríguez, R.; Portilla-Segura, J.

    2016-01-01

    Background Malignant pleural mesothelioma is a rare, invasive and often fatal neoplasm that develops in the thin layer of tissue surrounding the lungs known as the pleura. Although rare, mesotheliomas do occur in the young; their characteristics are distinct from those of older patients. Case presentation This is a case report of a 17-year-old boy who had moderate dyspnea, cough, right-sided pleuritic chest pain, fever, headache and no weight loss. Physical examination showed a right pleural effusion and chest roentgenograms revealed a homogenous opacity on lower right hemithorax. Biochemical analysis of pleural fluid showed hemorrhagic/turbid effusion compatible with exudate. It was initially treated as an empyema. The pleural fluid culture was negative. Adenosine deaminase level was 34.3 U/L (admission) and 19.02 U/L (two weeks after). Pleural fluid smear and culture for Mtb were negative. During the open pleural biopsy, thickened pleura and multiple pale yellow nodules in the lung were observed. The histopathological report was compatible with malignant pleural mesothelioma. With this diagnosis, a chemotherapy regimen with cisplatin was initiated. After two cycles, the patient had no clinical and radiological improvement. The patient is currently under regular follow up. Conclusion MPM is rare in young adults and its clinical presentation makes it different from mesothelioma in elderly patients, so it will be necessary to identify the new risk factors that can identify these patients. PMID:27222787

  8. Malignant pleural mesothelioma in a 17-year old boy: A case report and literature review.

    PubMed

    Pérez-Guzmán, C; Barrera-Rodríguez, R; Portilla-Segura, J

    2016-01-01

    Malignant pleural mesothelioma is a rare, invasive and often fatal neoplasm that develops in the thin layer of tissue surrounding the lungs known as the pleura. Although rare, mesotheliomas do occur in the young; their characteristics are distinct from those of older patients. This is a case report of a 17-year-old boy who had moderate dyspnea, cough, right-sided pleuritic chest pain, fever, headache and no weight loss. Physical examination showed a right pleural effusion and chest roentgenograms revealed a homogenous opacity on lower right hemithorax. Biochemical analysis of pleural fluid showed hemorrhagic/turbid effusion compatible with exudate. It was initially treated as an empyema. The pleural fluid culture was negative. Adenosine deaminase level was 34.3 U/L (admission) and 19.02 U/L (two weeks after). Pleural fluid smear and culture for Mtb were negative. During the open pleural biopsy, thickened pleura and multiple pale yellow nodules in the lung were observed. The histopathological report was compatible with malignant pleural mesothelioma. With this diagnosis, a chemotherapy regimen with cisplatin was initiated. After two cycles, the patient had no clinical and radiological improvement. The patient is currently under regular follow up. MPM is rare in young adults and its clinical presentation makes it different from mesothelioma in elderly patients, so it will be necessary to identify the new risk factors that can identify these patients.

  9. Malignant peritoneal mesothelioma in an inguinal hernial sac: an unusual presentation.

    PubMed

    Aggarwal, M; Lakhar, B; Shetty, D; Ullal, S

    2000-01-01

    Malignant peritoneal mesothelioma, which is a rare neoplasm, usually presents with abdominal complaints. Though such tumours have been reported from tunica vaginalis testis presenting as para-testicular mass, there is only one documented case of the tumour arising from the inguinal hernial sac. In this paper, we are reporting a rare presentation of this tumour.

  10. Comparative Elongated Mineral Particle Toxicology & Erionite’s Apparent  High Potency for Inducing Mesothelioma

    EPA Science Inventory

    Recent NHEERL research under EPA's Libby Action Plan has determined that elongated particle relative potency for rat pleural mesothelioma is best predicted on the basis of total external surface area (TSA) of slightly acid leached test samples which simulate particle bio-durabili...

  11. Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma.

    PubMed

    Sage, Elizabeth K; Kolluri, Krishna K; McNulty, Katrina; Lourenco, Sofia Da Silva; Kalber, Tammy L; Ordidge, Katherine L; Davies, Derek; Gary Lee, Y C; Giangreco, Adam; Janes, Sam M

    2014-07-01

    Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.

  12. Oncogenic mutation profiling in new lung cancer and mesothelioma cell lines

    PubMed Central

    Lam, David CL; Luo, Susan Y; Deng, Wen; Kwan, Johnny SH; Rodriguez-Canales, Jaime; Cheung, Annie LM; Cheng, Grace HW; Lin, Chi-Ho; Wistuba, Ignacio I; Sham, Pak C; Wan, Thomas SK; Tsao, Sai-Wah

    2015-01-01

    Background Thoracic tumor, especially lung cancer, ranks as the top cancer mortality in most parts of the world. Lung adenocarcinoma is the predominant subtype and there is increasing knowledge on therapeutic molecular targets, namely EGFR, ALK, KRAS, and ROS1, among lung cancers. Lung cancer cell lines established with known clinical characteristics and molecular profiling of oncogenic targets like ALK or KRAS could be useful tools for understanding the biology of known molecular targets as well as for drug testing and screening. Materials and methods Five new cancer cell lines were established from pleural fluid or biopsy tissues obtained from Chinese patients with primary lung adenocarcinomas or malignant pleural mesothelioma. They were characterized by immunohistochemistry, growth kinetics, tests for tumorigenicity, EGFR and KRAS gene mutations, ALK gene rearrangement and OncoSeq mutation profiling. Results These newly established lung adenocarcinoma and mesothelioma cell lines were maintained for over 100 passages and demonstrated morphological and immunohistochemical features as well as growth kinetics of tumor cell lines. One of these new cell lines bears EML4-ALK rearrangement variant 2, two lung cancer cell lines bear different KRAS mutations at codon 12, and known single nucleotide polymorphism variants were identified in these cell lines. Discussion Four new lung adenocarcinoma and one mesothelioma cell lines were established from patients with different clinical characteristics and oncogenic mutation profiles. These characterized cell lines and their mutation profiles will provide resources for exploration of lung cancer and mesothelioma biology with regard to the presence of known oncogenic mutations. PMID:25653542

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

    PubMed

    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.

  14. Analyses of Radiation and Mesothelioma in the US Transuranium and Uranium Registries

    PubMed Central

    Fulcher, Keri; Nagarajan, Sumitha; McCord, Stacey; Fallahian, Naz Afarin; Hoffman, Heather J.; Haver, Cary; Tolmachev, Sergei

    2013-01-01

    Objectives. We examined the relationship between radiation and excess deaths from mesothelioma among deceased nuclear workers who were part of the US Transuranium and Uranium Registries. Methods. We performed univariate analysis with SAS Version 9.1 software. We conducted proportionate mortality ratio (PMR) and proportionate cancer mortality ratio (PCMR) analyses using the National Institute for Occupational Safety and Health Life Table Analysis System with the referent group being all deaths in the United States. Results. We found a PMR of 62.40 (P < .05) and a PCMR of 46.92 (P < .05) for mesothelioma. PMRs for the 4 cumulative external radiation dose quartiles were 61.83, 57.43, 74.46, and 83.31. PCMRs were 36.16, 47.07, 51.35, and 67.73. The PMR and PCMR for trachea, bronchus, and lung cancer were not significantly elevated. Conclusions. The relationship between cumulative external radiation dose and the PMR and PCMR for mesothelioma suggests that external radiation at nuclear facilities is associated with an increased risk of mesothelioma. The lack of a significantly elevated PMR and PCMR for trachea, bronchus, and lung cancer suggests that asbestos did not confound this relationship. PMID:23409888

  15. Environmental malignant mesothelioma in southern Anatolia: a study of fifty cases.

    PubMed Central

    Zeren, E H; Gümürdülü, D; Roggli, V L; Zorludemir, S; Erkişi, M; Tuncer, I

    2000-01-01

    Malignant mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. Although occupational malignant mesothelioma is still the most common form of this lesion, naturally contaminated soil can play an important role in the development of environmental malignant mesothelioma in some parts of the world. Fifty cases of malignant mesothelioma (MM) from southern Turkey with no occupational history of asbestos exposure were reviewed regarding pathologic and clinical features. A case of hyaline fibrous plaque of the pleura was also included in this series. Histologically the cases were classified as epithelial (36 cases); sarcomatous (7 cases); and biphasic (7 cases). One of the sarcomatous cases was desmoplastic. Ultrastructural examination of the tumor tissue in three cases revealed long-surface microvilli in epithelial cells. Interstitial cells of the lung in one case showed electron-dense asbestos fibers in the cytoplasm. Mineralogical analyses of the lung tissue in three cases of MM and the case of pleural plaque showed high amounts of asbestos fibers most consistent with tremolite and actinolite. The clinical and pathologic features of our cases support that the environmental inhalation of asbestos is still a major health problem in some parts of Turkey. PMID:11102295

  16. Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

    PubMed Central

    2012-01-01

    Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

  17. Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy.

    PubMed

    Lee, Michael; Alexander, H Richard; Burke, Allen

    2013-08-01

    Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread. Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed. There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n=24), asbestos exposure (n=5) and radiation (n=2). Extra-pleural mesothelioma was present in all groups except type B (total n=7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p=0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p<0.001). Degree of invasion was strongly correlated with CCR (p=0.007), necrosis (p<0.0001), nuclear grade (p<0.0001), and mitotic rate (p=0.001), but not PCI (p=0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2

  18. Malignant mesothelioma and asbestos exposure among auto mechanics: appraisal of scientific evidence.

    PubMed

    Wong, O

    2001-10-01

    In 1986 the U.S. Environmental Protection Agency (EPA) issued an official guideline on the prevention of asbestos disease among auto mechanics. In the EPA guideline, malignant mesothelioma was listed as a consequence of exposure to asbestos fibers from brake linings and clutch facings among auto mechanics. EPA formulated its 1986 opinion by relying solely on a few outdated case reports and not on epidemiologic studies. A review of the literature indicates that there are six epidemiologic studies providing relevant information on malignant mesothelioma among auto mechanics. Three of the six studies had already been published by 1986, the year in which EPA issued its guideline. The results of the six studies were remarkably consistent in that all six studies reported no increased risk of malignant mesothelioma among auto mechanics. The relative risks reported in the six studies ranged from 0.62 to 1.00. Based on a meta-analysis of the combined data of all six studies consisting of approximately 1500 malignant mesothelioma cases, the mesothelioma relative risk for auto mechanics is 0.90 (95% confidence interval 0.66-1.23). An application of Hill's causation criteria to epidemiologic data of malignant mesothelioma among auto mechanics clearly demonstrates that auto mechanics do not have an increased risk of malignant mesothelioma as a result of exposure to asbestos fibers from brake linings and clutch facings. However, in spite of the scientific evidence, EPA has not modified or revised its 1986 guideline. Occupational regulatory policies and guidelines, when based on proper scientific evidence, are invaluable and can prevent avoidable diseases in workers or other exposed individuals in the general public. On the other hand, it is the regulators' responsibility to develop, modify, and revise policies and guidelines in accordance with the most relevant and the latest scientific data. In this instance EPA as a regulator has not fulfilled its responsibility of providing

  19. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: preliminary results and survival analysis.

    PubMed

    Hubert, Julien; Thiboutot, Eva; Dubé, Pierre; Cloutier, Alexis-Simon; Drolet, Pierre; Sideris, Lucas

    2015-03-01

    Peritoneal mesothelioma is a rare disease with poor prognosis. The present study reports single center experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy with oxaliplatin (HIPEC-OX) over an eight-year period. Prospectively collected data of all consecutive patients with epithelial or multicystic peritoneal mesothelioma from August 2004 to October 2012 was analyzed. Patients with sarcomatoid or biphasic peritoneal mesothelioma were not included due to general poor prognosis. Treatment consisted in CRS and HIPEC-OX (460 mg/m(2)) at 43 °C during 30 min. For statistical analysis, Kaplan-Meier survival curves were plotted and compared using log-rank tests. Cox proportional-hazards regression model was used to analyze the influence of different variables on survival. Nineteen patients with peritoneal mesothelioma underwent laparotomy with CRS and HIPEC-OX with curative intent (15 epithelial, and 4 multicystic). Mean follow-up was 36.7 months. The estimated one-year and three-year overall survival rates were respectively 100% and 91%. The estimated one-year and three-year disease-free survival rates were respectively 77% and 50%. Complications were graded according to the Clavien-Dindo classification [1] and major complications occurred in 57% of cases. There was no postoperative mortality. Histological grade was not a prognostic factor of disease-free survival (p = 0.37). When comparing survival results as well as morbidity-mortality rates, the present study shows that CRS and HIPEC-OX is a valid treatment for peritoneal mesothelioma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Diffuse mesothelioma of the peritoneum: correlation between histological and clinical parameters and survival in 73 patients.

    PubMed

    Liu, Sandy; Staats, Paul; Lee, Michael; Alexander, H Richard; Burke, Allen P

    2014-12-01

    There are few studies addressing survival of diffuse peritoneal mesotheliomas (DPM).In this study, survival data were obtained retrospectively from 73 patients treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42 months. Mesotheliomas were classified as well differentiated papillary (WDPM, n = 2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3). Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were assessed surgically.There were no deaths in the WDPM, MCM, and epithelioid DPM with ≤ grade 1 invasion. There was a stepwise decrease in overall survival from invasive TPM, S/DM, and BPM (p < 0.0001). By univariate analysis, advanced age (p = 0.01), incomplete CCR (p < 0.001), PCI (p = 0.004), mitotic count (p < 0.001), nuclear grade (p < 0.0001), stromal inflammation (p = 0.013), depth of invasion (p < 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p < 0.0001) were associated with decreased overall survival. By multivariate analysis, only sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR 2-3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant variables associated with decreased overall survival.DPM form a spectrum of indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a prognosis intermediate between biphasic mesotheliomas and invasive TPM. The presence and degree of invasion, sarcomatoid features, and inflammatory stroma are poor prognostic indicators.

  1. Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma

    PubMed Central

    Gawrych, Katarzyna; Casjens, Swaantje; Brik, Alexander; Lehnert, Martin; Taeger, Dirk; Pesch, Beate; Kollmeier, Jens; Bauer, Torsten T.; Johnen, Georg; Brüning, Thomas

    2017-01-01

    The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance. PMID:28321148

  2. The next mesothelioma wave: mortality trends and forecast to 2030 in Brazil.

    PubMed

    Algranti, Eduardo; Saito, Cézar Akiyoshi; Carneiro, Ana Paula Scalia; Moreira, Bruno; Mendonça, Elizabete Medina Coeli; Bussacos, Marco Antonio

    2015-10-01

    There are limited data on mesothelioma mortality in industrializing countries, where, at present, most of the asbestos consumption occurs. To analyze temporal trends and to calculate mortality rates from mesothelioma and cancer of the pleura in Brazil from 2000 to 2012 and to estimate future mortality rates. We retrieved records of deaths from mesothelioma (ICD-10C45) and cancer of the pleura (ICD-10C38.4) from 2000 to 2012 in adults aged 30 years and over. Crude and age-standardized mortality rates (ASMR) were calculated. Rate ratios of mean crude mortality for selected municipalities were compared to the Brazilian rate. A regression was carried out of the annual number of deaths against asbestos consumption using a Generalized Additive Model (GAM). The best model was chosen to estimate the future burden and peak period of deaths. There were 929C45 and 1379 C38.4 deaths. The ratio of men to women for C45 was 1.4. A positive trend in C45 numbers was observed in Brazil (p=0.0012), particularly in São Paulo (p=0.0004) where ASMRs presented an increasing linear trend (p=0.0344). Selected municipalities harboring asbestos manipulation presented 3.7-11 fold rate ratios of C45 compared to Brazil. GAM presented best fits for latencies of 34 years or more. It is estimated that the peak incidence of C45 mortality will occur between 2021 and 2026. The observed ASMRs and the gender ratio close to 1 suggest underreporting. Even so, deaths are increasing and mesothelioma clusters were identified. Compared to industrialized countries Brazil displays a 15-20 year lag in estimated peak mesothelioma mortality which is consistent with the lag of asbestos peak consumption in the country. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Malignant mesothelioma in Australia 2015: Current incidence and asbestos exposure trends.

    PubMed

    Soeberg, Matthew J; Leigh, James; van Zandwijk, Nico

    2016-01-01

    Australia is known to have had the highest per-capita asbestos consumption level of any nation, reaching a peak in the 1970s. Although crocidolite was effectively banned in the late 1960s, and amosite use ceased in the mid 1980s, a complete asbestos ban was not implemented until 2003. This resulted in an epidemic of asbestos-related disease, which has only now reached its peak. Between 1982 and 2011, 13,036 individuals were newly diagnosed with malignant mesothelioma, with 690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981 from retrospective searches and the first 2 years of the Australian Mesothelioma Program. The age-standardized malignant mesothelioma incidence rate has leveled off in the last 10 years (2.8 per 100,000 in 2011). There has been a marked increase over time in the age-specific incidence rates for individuals aged 75 years or older. Data from the current Australian Mesothelioma Registry on asbestos exposure history in Australia is available for 449 subjects diagnosed between July 1, 2010, and April 1, 2015. This asbestos exposure history data show that 60% (n = 268) of cases had probable or possible occupational asbestos exposure, with trade-based jobs being the most frequent sources of occupational asbestos exposure. In addition, out of the 449 cases, 377 were recorded as having probable or possible nonoccupational asbestos exposure. Continuous vigilance toward changes over time in the settings in which people are exposed to asbestos and in the descriptive epidemiology of malignant mesothelioma is recommended to enable a comprehensive understanding of the current and future impact of asbestos-related diseases in Australia.

  4. MESOTHELIOMA OF PLEURA AND PERITONEUM FOLLOWING EXPOSURE TO ASBESTOS IN THE LONDON AREA

    PubMed Central

    Newhouse, Muriel L.; Thompson, Hilda

    1965-01-01

    A series of 83 patients from the London Hospital with a diagnosis of mesothelioma confirmed by necropsy or biopsy has been studied for possible exposure to asbestos. The series consisted of 41 men and 42 women; 27 of the patients had peritoneal and 56 pleural tumours. The earliest death recorded was in 1917, but only 10 of the series died before 1950 and 40 (48%) between 1960 and 1964. In 76 of the series full occupational and residential histories were obtained. Forty (52·6%) gave a history of occupational or domestic (living in the same house as an asbestos worker) exposure to asbestos compared with nine (11·8%) out of 76 patients from the same hospital suffering from other diseases (p < 0·001). None of the 17 suspected cases of mesothelioma, rejected on pathological grounds, was found to have had any exposure to asbestos. There was also evidence that neighbourhood exposures may be important. Among those with no evidence of occupational or domestic exposures, 30·6% of the mesothelioma patients and 7·6% of the in-patients with other diseases lived within half a mile of an asbestos factory (p < 0·01). Out of the 31 patients with occupational exposures only 10 were in jobs scheduled under the Asbestos Regulations of 1931. The interval between first exposure and the development of the terminal illness of mesothelioma ranged between 16 and 55 years. In 47 patients in the mesothelioma series, lung tissue or sputum was available for examination. In 30 (62·5%), either asbestosis or asbestos bodies were present. PMID:5836565

  5. [Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].

    PubMed

    Lipp, Michael Josef; Jusufi, Maximilian Stanley; Backer, Christoph; Feyerabend, Bernd; Weilert, Hauke; Oldhafer, Karl Jürgen

    2017-03-01

    The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

    Cancer.gov

    Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

  7. An exception that proves the rule: recurrence free survival five years after extrapleural pneumonectomy for malignant pleural mesothelioma.

    PubMed

    Treasure, Tom; Macbeth, Fergus

    2014-11-18

    Are case reports at all relevant and useful? A case report of an unusual case of mesothelioma prompts a discussion and concludes that they do have a role but that their observations and conclusions need to be treated with care.

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

    PubMed

    Bruno, Caterina; Tumino, Rosario; Fazzo, Lucia; Cascone, Giuseppe; Cernigliaro, Achille; De Santis, Marco; Giurdanella, Maria Concetta; Nicita, Carmela; Rollo, Patrizia Concetta; Scondotto, Salvatore; Spata, Eugenia; Zona, Amerigo; Comba, Pietro

    2014-01-01

    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. Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. 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. 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.

  9. Genomic Profiling of Malignant Peritoneal Mesothelioma Reveals Recurrent Alterations in Epigenetic Regulatory Genes BAP1, SETD2, and DDX3X

    PubMed Central

    Joseph, Nancy M.; Chen, Yunn-Yi; Nasr, Anthony; Yeh, Iwei; Talevich, Eric; Onodera, Courtney; Bastian, Boris C.; Rabban, Joseph T.; Garg, Karuna; Zaloudek, Charles; Solomon, David A.

    2016-01-01

    Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations which drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional 2 cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas the 2 tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies

  10. MicroRNA and mRNA Features of Malignant Pleural Mesothelioma and Benign Asbestos-Related Pleural Effusion

    PubMed Central

    Ak, Guntulu; Tomaszek, Sandra C.; Kosari, Farhad; Metintas, Muzaffer; Jett, James R.; Metintas, Selma; Yildirim, Huseyin; Dundar, Emine; Dong, Jie; Aubry, Marie Christine; Wigle, Dennis A.; Thomas, Charles F.

    2015-01-01

    Introduction. We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion. Methods. Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols. Results. We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway. Conclusions. Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma. PMID:25756049

  11. Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis.

    PubMed

    Wu, Di; Hiroshima, Kenzo; Matsumoto, Shinji; Nabeshima, Kazuki; Yusa, Toshikazu; Ozaki, Daisuke; Fujino, Michio; Yamakawa, Hisami; Nakatani, Yukio; Tada, Yuji; Shimada, Hideaki; Tagawa, Masatoshi

    2013-01-01

    The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.

  12. Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles.

    PubMed

    Andujar, Pascal; Lacourt, Aude; Brochard, Patrick; Pairon, Jean-Claude; Jaurand, Marie-Claude; Jean, Didier

    2016-01-01

    Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.

  13. Intracavitary 'T4 immunotherapy' of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells.

    PubMed

    Klampatsa, Astero; Achkova, Daniela Y; Davies, David M; Parente-Pereira, Ana C; Woodman, Natalie; Rosekilly, James; Osborne, Georgina; Thayaparan, Thivyan; Bille, Andrea; Sheaf, Michael; Spicer, James F; King, Juliet; Maher, John

    2017-05-01

    Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy. T-cells from mesothelioma patients were uniformly amenable to T4 genetic modification and expansion/enrichment thereafter using IL-4. Patient-derived T4(+) T-cells were activated upon contact with a panel of four mesothelioma cell lines, leading to cytotoxicity and cytokine release in all cases. Adoptive transfer of T4 immunotherapy to SCID Beige mice with an established bioluminescent LO68 mesothelioma xenograft was followed by regression or eradication of disease in all animals. Despite the established ability of T4 immunotherapy to elicit cytokine release syndrome in SCID Beige mice, therapy was very well tolerated. These findings provide a strong rationale for the clinical evaluation of intracavitary T4 immunotherapy to treat mesothelioma. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

    SciTech Connect

    Tamminen, Jenni A.; Yin, Miao; Rönty, Mikko; Sutinen, Eva; Pasternack, Arja; Ritvos, Olli; Myllärniemi, Marjukka; Koli, Katri

    2015-03-01

    Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. - Highlights: • Activin-A and activin-B are highly expressed in mesothelioma. • Mesothelioma cell migration and invasive growth can be blocked with sActR2B. • Activin induced Smad3 activity is attenuated in invasive mesothelioma cells. • Activins induce ERK activity in mesothelioma cells.

  15. Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma.

    PubMed

    Kuraoka, Masatsugu; Amatya, Vishwa J; Kushitani, Kei; Mawas, Amany S; Miyata, Yoshihiro; Okada, Morihito; Kishimoto, Takumi; Inai, Kouki; Nishisaka, Takashi; Sueda, Taijiro; Takeshima, Yukio

    2017-08-01

    As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.

  16. Multicystic malignant mesothelioma of the tunica vaginalis with an unusually indolent clinical course.

    PubMed

    Sawada, Kohji; Inoue, Keiji; Ishihara, Tsuyoshi; Kurabayashi, Atsushi; Moriki, Toshiaki; Shuin, Taro

    2004-07-01

    We report an extremely rare case of a multicystic malignant mesothelioma in the tunica vaginalis with an unusually indolent clinical course. A 48-year-old man presented with a one-month history of painless swelling of right scrotal contents. Ultrasonography and computed tomography (CT) revealed a multicystic mass in the right scrotal sac with evidence of neither distant nor lymph node metastases. The testicular tumor markers were within the normal limits. Inguinal orchiectomy was performed under the suspicion of a malignant tumor. The cystic tumor consisted of fibrocellular, microcystic and adenomatoid elements microscopically was diagnosed biphasic malignant mesothelioma of tunica vaginalis but no invasion into the testis, epididymis and also scrotum. The patient has been disease-free for 72 months and is being followed on an outpatient basis with no further adjuvant therapy.

  17. Differentiating a large abdominal cystic lymphangioma from multicystic mesothelioma: report of a case.

    PubMed

    Nagata, Hiroshi; Yonemura, Yutaka; Canbay, Emel; Ishibashi, Haruaki; Narita, Makoto; Mike, Makio; Kano, Nobuyasu

    2014-07-01

    We report a case of retroperitoneal cystic lymphangioma in a 30-year-old woman who presented with abdominal distention and pain. Imaging studies revealed a large, thin-walled multicystic mass occupying the whole abdomen. Based on a preoperative diagnosis of multicystic mesothelioma, we performed laparotomy, which revealed a tumor arising from the gastropancreatic ligament in the posterior wall of the omental bursa. We resected the tumor completely, without the adjacent viscera. The final pathological diagnosis was cystic lymphangioma, based on the immunohistochemical findings of positive CD31 and CD34 expression, the presence of smooth muscle confirmed by smooth muscle antigen and desmin, and negative calretinin, WT-1 and cytokeratins 5/6 expression. Multicystic mesotheliomas and cystic lymphangiomas are so similar in morphology that immunohistochemical staining should be fully utilized to differentiate them.

  18. Benign multicystic mesothelioma with concurrent colonic adenocarcinoma: a report of two cases.

    PubMed

    Husain, Anwar; Ozdemirli, Metin

    2012-10-01

    Benign multicystic mesothelioma (BMM) is a rare tumoral lesion of the peritoneum often discovered incidentally upon surgery, laparoscopy, or radiographical imaging in females of childbearing age. The etiology and question as to whether these lesions occur via a neoplastic or reactive process still remain unknown. In this report, we present two cases of BMM detected in females with concurrent colonic adenocarcinoma arising in the ileocecal region. The tumors were present in the serosa surrounding the colonic adenocarcinoma in one case, and in the omentum in the other case, which grossly mimicked peritoneal seeding of carcinoma. An immunohistochemical analysis revealed that the cells lining the cystic spaces in both lesions were positive for keratin and calretinin, confirming their mesothelial origin. To the best of our knowledge, these cases represent the first documented examples of multicystic mesothelioma concurrent with colonic adenocarcinoma.

  19. Appendiceal mucinous cystadenoma associated with pseudomyxoma peritonei and multicystic peritoneal mesothelioma: report of a case.

    PubMed

    Kusuyama, T; Fujita, M

    1995-01-01

    An extremely rare case of mucinous cystadenoma developing to pseudomyxoma peritonei together with multicystic peritoneal mesothelioma is herein reported. The patient was 25-year-old Japanese woman who underwent an appendectomy under the diagnosis of acute appendicitis because of right lower abdominal pain. The patient histopathologically demonstrated appendiceal mucocele with pseudomyxoma peritonei. She underwent a laparotomy in our unit following detailed examinations. Several cystic tumors measuring from 3 to 5 cm in diameter were found in the omentum, and thus omentectomy, partial cecectomy and left oophorectomy were all performed to resect the tumors. Immunostaining and electron microscopy showed the appendiceal lesion to be mucinous cystadenoma, while the peritoneal lesion was multicystic mesothelioma. To our knowledge, this is the first report in the world literature of this rare combination of diseases.

  20. Mesothelioma associated with use of drywall joint compound: a case series and review of literature.

    PubMed

    Dahlgren, James; Peckham, Trevor

    2012-01-01

    Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers. We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types. Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.

  1. [Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy].

    PubMed

    Magnani, Corrado; Ancona, Laura; Baldassarre, Antonio; Bressan, Vittoria; Cena, Tiziana; Chellini, Elisabetta; Cuccaro, Francesco; Ferrante, Daniela; Legittimo, Patrizia; Luberto, Ferdinando; Marinaccio, Alessandro; Mattioli, Stefano; Menegozzo, Simona; Merler, Enzo; Miligi, Lucia; Mirabelli, Dario; Musti, Marina; Oddone, Enrico; Pavone, Venere; Perticaroli, Patrizia; Pettinari, Aldo; Pirastu, Roberta; Ranucci, Alessandra; Romeo, Elisa; Sala, Orietta; Scarnato, Corrado; Silvestri, Stefano

    2016-01-01

    This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

  2. [Peritoneal mesothelioma: an inusual clinical presentation in a patient without exposure to asbestos].

    PubMed

    Ponce Lorenzo, J; Giménez Ortiz, A; Aparisi Aparisi, F; Fleitas Kanonnikoff, T; Montalar Salcedo, J

    2007-02-01

    Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium. The predominant cause is inhalation exposure to asbestos. We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy.

  3. p53 Expression in a Malignant Mesothelioma Patient during Seven-Year Follow-up

    PubMed Central

    Koo, So-My; Kim, Dong Won; Kim, Ki-Up; Kim, Yang-Ki

    2014-01-01

    Malignant mesothelioma (MM) is the aggressive tumor of serosal surfaces. There are crude pathogenetic results regarding the biology of MM. Coordinated upregulations of p53 gene expression are shown in malignancies. We believed that there are changes in the p53 expression with transformation from reactive hyperplasia to MM. A 65-year-old male was admitted the hospital because of left pleuritic chest pains in 2004. Chest computed tomography (CT) results showed left pleural effusions with loculation and pleural thickening. Pathologic findings revealed reactive mesothelial hyperplasia. In 2008, the patient again felt left pleuritic chest pains. Chest CT showed progressive thickening of the left pleura. Pathologic diagnosis was atypical mesothelial hyperplasia. In 2011, chest CT showed progressive thickening of his left pleura. He was diagnosed with well-differentiated papillary mesothelioma. Serial change was analyzed by immunohistochemical staining for p53 of pleural tissues. There were no remarkable changes in p53 expressions during the transformation to MM. PMID:25024722

  4. Mesothelioma: has patient had contact with even small amount of asbestos

    SciTech Connect

    Not Available

    1987-03-27

    Mesothelioma, primarily an asbestos-related cancer, has traditionally been tracked through the incidence rate in workers handling asbestos directly. Now, epidemiologists are recording cases of the tumor in persons who have worked with materials containing even small quantities of asbestos. The lower concentrations of asbestos were thought by many to have minimized the susceptibility of workers to mesothelioma. But as cases of the malignant tumor appeared in tradesmen, epidemiologists began to suspect that the concentration level of the fibers was not the prime concern. Further studies showed that one fiber of a certain length can lodge in the pleura of the lung, and 40 years later, the patient will exhibit signs of dyspnea, chest pain, or both.

  5. Malignant mesothelioma in a patient with anthophyllite asbestos fibres in the lungs.

    PubMed

    Phillips, James Ian; Murray, Jill

    2010-06-01

    The amphibole asbestos, anthophyllite, is associated with asbestos-related disease in humans, along with mesothelioma in animal models. In humans, however, there are only three cases of histologically proven malignant mesothelioma of the pleura associated with anthophyllite that have been documented in the English-language literature. A fourth case is presented in a man who lived in South Africa and had anthophyllite in his lung. Anthophyllite was never commercially mined in South Africa. Using scanning electron microscopy, his lung fibre burden was calculated to be 358,000 fibres and 31,000 asbestos bodies per gram of dry weight of lung tissue. The mean aspect ratio of the anthophyllite fibres in the lung was 41.2 (SD = 28.8). No other types of asbestos were detected in the lung. His exposure was almost certainly occupational. He worked in the plastic manufacturing industry and was exposed to talc and asbestos blankets that were used to insulate machinery.

  6. Primary malignant pericardial mesothelioma with increased serum mesothelin diagnosed by surgical pericardial resection: A case report.

    PubMed

    Kurosawa, Takeyuki; Sugino, Keishi; Isobe, Kazutoshi; Hata, Yoshinobu; Fukasawa, Yuri; Homma, Sakae

    2016-11-01

    A 37-year-old female smoker without a history of exposure to asbestos was referred to our hospital with persistent pericardial effusion. Chest computed tomography imaging examination revealed an irregular thickened pericardium with large amounts of pericardial effusion and a small pleural effusion. Fluorodeoxyglucose (FDG) positron emission tomography imaging demonstrated intrapericardial FDG accumulation. Blood tests revealed an increase in serum mesothelin levels. Examination of a surgically resected specimen revealed a grayish-white thickening of the pericardium, with a straw-colored mucinous pericardial effusion. Histopathological examination confirmed the diagnosis of epithelioid malignant mesothelioma. Although the patient's condition temporarily improved, with decreased levels of serum mesothelin during chemotherapy with carboplatin and pemetrexed, she succumbed to cardiac tamponade 18 months after the initial onset of the symptoms. Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and refractory disorder. Thus, an early definitive diagnosis and timely treatment are crucial for the management of PMPM.

  7. A systematic literature review comparing the psychological care needs of patients with mesothelioma and advanced lung cancer.

    PubMed

    Ball, Hannah; Moore, Sally; Leary, Alison

    2016-12-01

    Psychological distress which adversely affects a person's experience of cancer has been shown to be highly prevalent in patients with mesothelioma. Historically, the assumption has been made that the evidence guiding the supportive care needs for lung cancer is relevant to those with mesothelioma. The objective of the study was to evaluate if the psychological care needs differ between patients with pleural mesothelioma and those with advanced lung cancer. A search of MEDLINE, CINAHL, PsycARTICLES, Psychology and Behavioural Sciences Collection, PsycINFO databases, grey literature and the Cochrane Library of Systematic Reviews identified 17 studies meeting a predefined inclusion criteria. These were critically appraised for quality. Data relating to psychological experiences was extracted which was then synthesised narratively and through a process of meta ethnography. Common themes identified across the studies created 10 key concepts. These were uncertainty, normality, hope/hopelessness, stigma/blame/guilt, family/carer concern, physical symptoms, experience of diagnosis, iatrogenic distress, financial/legal and death and dying. Key similarities and differences were identified between the mesothelioma and lung cancer evidence. There is limited research exploring the lived experiences of those with mesothelioma and lung cancer, with the majority of them having methodological and/or reporting concerns compromising the conclusions made. However, reoccurring themes in the evidence were found suggesting a number of areas where the psychological experience of mesothelioma differs from that of advanced lung cancer. These findings warrant further research to explore further and if proven, the need for the provision of specialist mesothelioma care services is affirmed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Are Current or Future Mesothelioma Epidemics in Hong Kong the Tragic Legacy of Uncontrolled Use of Asbestos in the Past?

    PubMed Central

    Tse, Lap Ah; Yu, Ignatius Tak-sun; Goggins, William; Clements, Mark; Wang, Xiao Rong; Au, Joseph Siu-kie; Yu, Kai Shing

    2010-01-01

    Background Because of the long latent period of asbestos-related mesothelioma, investigators suggest that the high incidence of this disease will continue in the coming decades. Objectives We describe the time trends of mesothelioma incidence and its relationship to historical consumption of asbestos in Hong Kong and project future trends of mesothelioma incidence. Methods We obtained local annual consumption of total asbestos for 1960–2006 (converted to kilograms per person per year). Age-standardized incidence rates (ASIRs) of mesothelioma were computed and depicted on graphs using the centered moving average method. Indirectly standardized rates were regressed on a transformation of consumption data that assumed that the latency between asbestos exposure and mesothelioma diagnosis followed a normal distribution with a mean ± SD of 42 ± 10.5 years. Results ASIRs for males started to increase substantially in 1994 and were highest in 2004; for females, ASIRs climbed in the 1980s and in the early 1990s but have fluctuated without obvious trends in recent years. The highest asbestos consumption level in Hong Kong was in 1960–1963 and then decreased sharply afterward. Using past asbestos consumption patterns, we predict that the mesothelioma incidence rate for males will peak in 2009, with the number of cases peaking in 2014, and then slowly decline in the coming decades. Conclusions Hong Kong experienced an epidemic of mesothelioma from 2000 to 2006 that corresponded with the peak of local asbestos consumption in the early 1960s assuming an average latent period of 42 years. The incidence is anticipated to decline in the coming decades but may not decrease back to the background risk level (the risk unrelated to asbestos exposure). PMID:20064790

  9. Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.

    PubMed Central

    Mayall, F G; Jacobson, G; Wilkins, R

    1999-01-01

    AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level. CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further. Images PMID:10474522

  10. Benign multicystic peritoneal mesothelioma (BMPM) - case report and review of the literature.

    PubMed

    Dzieniecka, Monika; Kałużyński, Andrzej

    2011-01-01

    Benign multicystic peritoneal mesothelioma (BMPM), also known as multilocular peritoneal inclusion cyst, is a rare tumour that occurs mainly in women at their reproductive age. The aetiology and pathogenesis are controversial. It originates from any abdominal peritoneal or pleural surface. The biological behaviour of BMPM is usually clinically benign. Here we present a case report of BMPM from our department with a review of the literature.

  11. Imaging appearance of benign multicystic peritoneal mesothelioma: a case report and review of the literature.

    PubMed

    Mehta, Varun; Chowdhary, Varun; Sharma, Richa; Golia Pernicka, Jennifer S

    Benign multicystic peritoneal mesothelioma (BMPM) is a rare entity with fewer than 150 reported cases in the literature. Here we discuss a case of BMPM in a 22-year old female as presented to our urban community hospital, review epidemiology and clinical presentations of this entity, and perform a comprehensive literature review of various CT, US, and MR imaging features of BMPM. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells

    SciTech Connect

    Thayanithy, Venugopal; Babatunde, Victor; Dickson, Elizabeth L.; Wong, Phillip; Oh, Sanghoon; Ke, Xu; Barlas, Afsar; Fujisawa, Sho; Romin, Yevgeniy; Moreira, André L.; Downey, Robert J.; Steer, Clifford J.; Subramanian, Subbaya; Manova-Todorova, Katia; Moore, Malcolm A.S.; Lou, Emil

    2014-04-15

    Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24–48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3–1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells. - Highlights: • Exosomes derived from malignant cells can stimulate an increased rate in the formation of tunneling nanotubes. • Tunneling nanotubes can serve as conduits for intercellular transfer of these exosomes. • Most notably, exosomes derived from benign mesothelial cells had no effect on nanotube formation. • Cells forming nanotubes were enriched in lipid rafts at a greater number compared with cells not forming nanotubes. • Our findings suggest causal and potentially synergistic association of exosomes and

  13. Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma.

    PubMed

    Chaouche-Mazouni, Siham; Scherpereel, Arnaud; Zaamoum, Rima; Mihalache, Adriana; Amir, Zine-Charaf; Lebaïli, Nemcha; Delaire, Baptiste; Gosset, Pierre

    2015-08-01

    Epithelioid malignant pleural mesothelioma (MPM) can easily be confused with lung adenocarcinomas (ACAs). In serous effusion, claudin (cldn) 3 is shown to be useful in the diagnosis of mesothelioma vs ACAs. Cldn15 is reported to be overexpressed in epithelioid mesothelioma and absent in human airway epithelium. The aim was to assess the value of cldn3 and cldn4 compared to that of BerEp4 and thyroid transcription factor-1 (TTF1) in differentiating lung ACA from epithelioid MPM and to examine the expression of cldn15 in these tumors. The expression of cldn3, cldn4, cldn15, BerEp4, and TTF1 was examined by immunohistochemistry in a total of 62 human specimen including 28 epithelioid MPMs and 34 ACAs of the lung. In lung ACA, cldn4 was strongly expressed in all 34 (100%) specimens followed by cldn3 in 33 (97%) of 34. BerEp4 was expressed in 32 (94.1%) of 34. TTF1 reacted for only 20 (58.82%) of 34 cases of lung ACA. In MPM specimens, the expression of cldn3 and4 as well as that of TTF1 was completely absent. In contrast, BerEp4 was focally expressed in 5 (17.85%) of 28 cases of epithelioid MPM. Cldn15 was strongly expressed in 53% pf epithelioid MPMs but also in 50% of lung ACAs. Its expression was moderate in normal pleura and limited in normal lung. Cldn3 and cldn4 appear to be the best performing carcinoma markers in discriminating lung ACA from mesothelioma compared with BerEp4 and TTF1. There is no differential expression of cldn15 between the 2 pathologies. However, the limited cldn15 expression in normal tissues and high expression in tumors make it an attractive candidate for cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma in an insulation worker.

    PubMed Central

    Fischbein, A; Luo, J C; Pinkston, G R

    1991-01-01

    Asbestos associated diseases consist of both benign and malignant conditions. A rare constellation of asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma occurring in a patient with long term occupational exposure to airborne asbestos fibres is presented. The observation illustrates the powerful disease-causing potential of occupational exposure to asbestos. A brief discussion of multiple primary neoplasms associated with exposure to asbestos is also presented. Images PMID:2039746

  15. Malignant mesothelioma induced by asbestos and zeolite in the mouse peritonenal cavity

    SciTech Connect

    Suzuki, Y.; Kohyama, N.

    1984-10-01

    The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. Tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinoma of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis.

  16. Combined laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a patient with peritoneal mesothelioma.

    PubMed

    Esquivel, Jesus; Averbach, Andrew

    2009-08-01

    The role of minimally invasive, laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported by several centers around the world, mainly to palliate intractable ascites in patients with extensive peritoneal surface malignancies who are not candidates for a complete cytoreduction. In this paper, we report on the first case of combined laparoscopic cytoreductive surgery and HIPEC with curative intent in a patient with limited peritoneal mesothelioma.

  17. Effective induction of death in mesothelioma cells with magnetite nanoparticles under an alternating magnetic field.

    PubMed

    Matsuda, Shofu; Nakajima, Eri; Nakanishi, Takuya; Hitsuji, Airi; Zhang, Hong; Tanaka, Akane; Matsuda, Hiroshi; Momma, Toshiyuki; Osaka, Tetsuya

    2017-12-01

    With the objective of finding an avenue for development of magnetic hyperthermia as an effective mesothelioma treatment, the influence of heating by magnetite nanoparticles (MNPs) with a diameter of ~40nm, which were incorporated into cells and then subjected to AC magnetic field, on induction of cell death was investigated in all three histological subtypes of human mesothelioma cells (i.e., epithelioid NCI-H28, sarcomatoid NCI-H2052, and biphasic MSTO-211H cells). Cellular uptake of MNPs was observed in all cell types, but the amount of MNPs incorporated per cell into MSTO-211H cells was smaller than in NCI-H28 and NCI-H2052 cells. On the other hand, cell death induced by cellular uptake of MNPs was observed specifically in MSTO-211H cells. Hence, when cells are heated by intracellular MNPs under AC magnetic field, a high degree of cell mortality in NCI-H28 and NCI-H2052 cells is induced by the temperature increase derived from the high amount of intracellular MNPs, but the combination of intracellular heating and cell-type-specific toxicity of MNPs induced high rates of cell death in MSTO-211H cells even at a lower temperature. Almost all of the heated cells were dead after 24-h incubation at 37°C in all histological subtypes. Additionally, higher mortalities were observed in all three types of mesothelioma cells after MNPs-heating, as compared to the heating with a thermostatic bath. Herein, the significance of cellular uptake of MNPs for effectively inducing cell death in mesothelioma has been demonstrated in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Radiotherapy applications of patients with malignant mesothelioma: A single center experience

    PubMed Central

    Akmansu, Muge; Erpolat, Ozge Petek; Goksel, Fatih; Tunc, Evrim; Ozturk, Can

    2012-01-01

    Background In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms. Aim The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma. Materials and methods Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy. Results Prophylactic radiation was applied to 27 patients with 4–15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6–18 MV photon and/or 4–12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases. Conclusion Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes. PMID:24416534

  19. Mesothelioma: Identification of the Key Molecular Events Triggered by BAP1

    DTIC Science & Technology

    2014-09-01

    amounts of asbestos that would normally not cause MM in the population at large. In order to study the mechanism(s), we assembled a unique cohort and...BAP1 status regulate NF-kB activity and HMGB1 release, and we also found that monoallelic BAP1 loss increases susceptibility to low doses of asbestos ...by using a mouse model. 15. SUBJECT TERMS mesothelioma, BAP1, asbestos , mechanisms 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18

  20. Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment.

    PubMed

    Betrouni, Nacim; Munck, Camille; Bensoltana, Wael; Baert, Grégory; Dewalle-Vignion, Anne-Sophie; Scherpereel, Arnaud; Mordon, Serge

    2017-02-22

    Complete and homogeneous illumination of the target is necessary for the success of a photodynamic therapy (PDT) procedure. In most applications, light dosimetry is done using detectors placed at strategic locations of the target. In this study we propose a novel approach based on the combination of light distribution modeling with spatial localization of the light applicator for real time estimation and display of the applied dose on medical images. The feasibility approach is demonstrated for intrapleural PDT of malignant pleural mesothelioma.

  1. Detection of malignant mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens.

    PubMed

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

    2015-04-01

    Mesothelioma is a form of cancer generally caused from previous exposure to asbestos. Although it was considered a rare neoplasm in the past, its incidence is increasing worldwide due to extensive use of asbestos. In the current practice of medicine, the gold standard for diagnosing mesothelioma is through a pleural biopsy with subsequent histologic examination of the tissue. The diagnostic tissue should demonstrate the invasion by the tumor and is obtained through thoracoscopy or open thoracotomy, both being highly invasive surgical operations. On the other hand, thoracocentesis, which is removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. In this study, we aim at detecting and classifying malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Accordingly, a computerized method is developed to determine whether a set of nuclei belonging to a patient is benign or malignant. The quantification of chromatin distribution is performed by using the optimal transport-based linear embedding for segmented nuclei in combination with the modified Fisher discriminant analysis. Classification is then performed through a k-nearest neighborhood approach and a basic voting strategy. Our experiments on 34 different human cases result in 100% accurate predictions computed with blind cross validation. Experimental comparisons also show that the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. According to our results, we conclude that nuclear structure of mesothelial cells alone may contain enough information to separate malignant mesothelioma from benign mesothelial proliferations. © 2015 International Society for Advancement of Cytometry.

  2. Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma

    SciTech Connect

    Manning, L.S.; Bowman, R.V.; Davis, M.R.; Musk, A.W.; Robinson, B.W. )

    1989-10-01

    Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM (n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls (n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 +/- 3% lysis by controls vs 34 +/- 3% lysis by patients with MM, P less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 +/- 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.

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

    PubMed

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

    2010-09-01

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

  4. An autopsy case of primary pericardial mesothelioma in arc cutter exposed to asbestos through talc pencils.

    PubMed

    Fujiwara, Hiroshi; Kamimori, Takao; Morinaga, Kenji; Takeda, Yoshiki; Kohyama, Norihiko; Miki, Yoshihiro; Inai, Kouki; Yamamoto, Satoru

    2005-04-01

    An autopsy case of a primary pericardial mesothelioma in a 53-year-old arc cutter is reported. He had often had the chance to inhale dust generated by sharpening the slate pencils composed of talc. He was admitted for heart failure due to pericardial tumor, but later died. The tumor was mainly located on the pericardium with a thickness of about 2.5 cm. Small nodular disseminations were observed in the left parietal pleura. Microscopically, tumor cells were epithelial-like and rich in histochemical demonstrable hyaluronic acid. Findings of immunohistochemical markers revealed keratin (+), EMA (+), calretinin (+), and CEA (-), which were characteristics of mesothelioma of epithelial type. The number of asbestos bodies (AB) in the lung parenchyma was increased (2026 AB/gram dry lung tissue). Subsequent transmission electron microscopic examination equipped with an energy dispersive X-ray analyzer revealed that the fibers identified in the lungs were fibrous talc and actinolite. These findings suggested that this patient had been occupationally exposed to asbestos contaminated in the talc pencils, which induced the development of primary pericardial mesothelioma.

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

    PubMed Central

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

    2014-01-01

    Background Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model. Conclusion Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials. PMID:23760546

  6. A 26-Year-Old Male with Mesothelioma Due to Asbestos Exposure

    PubMed Central

    Zarogoulidis, P.; Orfanidis, M.; Constadinidis, T. C.; Eleutheriadou, E.; Kontakiotis, T.; Kerenidi, T.; Sakkas, L.; Courcoutsakis, N.; Zarogoulidis, K.

    2011-01-01

    Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009. PMID:21776278

  7. microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma

    PubMed Central

    Walter, Robert Fred Henry; Vollbrecht, Claudia; Werner, Robert; Wohlschlaeger, Jeremias; Christoph, Daniel Christian; Schmid, Kurt Werner; Mairinger, Fabian Dominik

    2016-01-01

    Background Malignant pleural mesothelioma (MPM) is a highly aggressive tumour first-line treated with a combination of cisplatin and pemetrexed. MDM2 and P14/ARF (CDKN2A) are upstream regulators of TP53 and may contribute to its inactivation. In the present study, we now aimed to define the impact of miRNA expression on this mechanism. Material and Methods 24 formalin-fixed paraffin-embedded (FFPE) tumour specimens were used for miRNA expression analysis of the 800 most important miRNAs using the nCounter technique (NanoString). Significantly deregulated miRNAs were identified before a KEGG-pathway analysis was performed. Results 17 miRNAs regulating TP53, 18 miRNAs regulating MDM2, and 11 miRNAs directly regulating CDKN2A are significantly downregulated in MDM2-expressing mesotheliomas. TP53 is downregulated in MDM2-negative tumours through miRNAs with a miSVR prediction score of 11.67, RB1 with a prediction score of 8.02, MDM2 with a prediction score of 4.50 and CDKN2A with a prediction score of 1.27. Conclusion MDM2 expression seems to impact miRNA expression levels in MPM. Especially, miRNAs involved in TP53-signaling are strongly decreased in MDM2-positive mesotheliomas. A better understanding of its tumour biology may open the chance for new therapeutic approaches and thereby augment patients' outcome. PMID:26918730

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

    PubMed

    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.

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

    PubMed

    Washimi, Kota; Yokose, Tomoyuki; Yamashita, Makiko; Kageyama, Taihei; Suzuki, Katsuo; Yoshihara, Mitsuyo; Miyagi, Yohei; Hayashi, Hiroyuki; Tsuji, Shoutaro

    2012-01-01

    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.

  10. Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

    PubMed Central

    Washimi, Kota; Yokose, Tomoyuki; Yamashita, Makiko; Kageyama, Taihei; Suzuki, Katsuo; Yoshihara, Mitsuyo; Miyagi, Yohei; Hayashi, Hiroyuki; Tsuji, Shoutaro

    2012-01-01

    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. PMID:22768319

  11. BAP1 protein is a progression factor in malignant pleural mesothelioma.

    PubMed

    Arzt, Lisa; Quehenberger, Franz; Halbwedl, Iris; Mairinger, Thomas; Popper, Helmut H

    2014-01-01

    Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time--the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.

  12. Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects.

    PubMed

    Komurcuoglu, Berna; Cirak, A Kadri; Kirakli, S Cenk; Polat, Gulru; Yucel, Nur; Usluer, Ozan; Erer, Onur; Balci, Gunseli; Gayaf, Mine; Guldaval, Filiz; Aktogu, Serir; Guclu, Salih; Ozsoz, Ayse; Halilcolar, Huseyin

    2014-01-01

    Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma. One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined. Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors. We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.

  13. Adenomatoid mesothelioma with intranuclear inclusion bodies: a case report with cytological and histological findings.

    PubMed

    Kawai, Toshiaki; Kawashima, Katsuhiko; Serizawa, Hiromi; Miura, Hiroyuki; Kyeongil, Kim

    2014-05-01

    We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball-like clusters, with a tubular pattern, composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S(8) . Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

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

    PubMed

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

    2014-02-01

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

  15. Lung cancer and mesothelioma risk assessment for a population environmentally exposed to asbestos.

    PubMed

    Bourgault, Marie-Hélène; Gagné, Michelle; Valcke, Mathieu

    2014-03-01

    Asbestos-related cancer risk is usually a concern restricted to occupational settings. However, recent published data on asbestos environmental concentrations in Thetford Mines, a mining city in Quebec, Canada, provided an opportunity to undertake a prospective cancer risk assessment in the general population exposed to these concentrations. Using an updated Berman and Crump dose-response model for asbestos exposure, we selected population-specific potency factors for lung cancer and mesothelioma. These factors were evaluated on the basis of population-specific cancer data attributed to the studied area's past environmental levels of asbestos. We also used more recent population-specific mortality data along with the validated potency factors to generate corresponding inhalation unit risks. These unit risks were then combined with recent environmental measurements made in the mining town to calculate estimated lifetime risk of asbestos-induced lung cancer and mesothelioma. Depending on the chosen potency factors, the lifetime mortality risks varied between 0.7 and 2.6 per 100,000 for lung cancer and between 0.7 and 2.3 per 100,000 for mesothelioma. In conclusion, the estimated lifetime cancer risk for both cancers combined is close to Health Canada's threshold for "negligible" lifetime cancer risks. However, the risks estimated are subject to several uncertainties and should be confirmed by future mortality rates attributed to present day asbestos exposure.

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

    PubMed

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

    2017-10-01

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

  17. Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.

    PubMed

    Goodman, Julie E; Peterson, Michael K; Bailey, Lisa A; Kerper, Laura E; Dodge, David G

    2014-02-01

    Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians' exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.

  18. Glycodelin is a potential novel follow-up biomarker for malignant pleural mesothelioma

    PubMed Central

    Schneider, Marc A.; Muley, Thomas; Kahn, Nicolas C.; Warth, Arne; Thomas, Michael; Herth, Felix J.F.; Dienemann, Hendrik; Meister, Michael

    2016-01-01

    Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. Soluble mesothelin-related peptide (SMRP), osteopontin or EFEMP1 (Fibulin-3) are well described biomarkers for malignant mesothelioma with moderate sensitivity and specificity. In this study, we characterized the expression of glycodelin, a marker for risk pregnancy, in MPM by RNA and protein analyses and investigated its potential as a MPM biomarker. We were able to detect glycodelin in the serum of MPM patients. Compared to benign lung diseases, the serum levels were significant increased. Patients with high glycodelin serum levels revealed a worse overall survival. The glycodelin serum levels correlated with the tumor response to treatment. A comparison of SMRP and glycodelin serum measurement in a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin was highly expressed in MPM tumors. Analyses of a tissue micro array indicated that the immunomodulatory form glycodelin A was expressed in MPM and correlated with the survival of the patients. Altogether, glycodelin seems to be a new potential biomarker for the aggressive malignant pleural mesothelioma. PMID:27713145

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

    PubMed Central

    Pesce, Elisa; Mutti, Luciano; Murer, Bruno; Grosso, Stefano; Ricciardi, Sara; Brina, Daniela; Biffo, Stefano

    2015-01-01

    eIF6 is an antiassociation factor that regulates the availability of active 80S. Its activation is driven by the RACK1/PKCβ axis, in a mTORc1 independent manner. We previously described that eIF6 haploinsufficiency causes a striking survival in the Eμ-Myc mouse lymphoma model, with lifespans extended up to 18 months. Here we screen for eIF6 expression in human cancers. We show that Malignant Pleural Mesothelioma tumors (MPM) and a MPM cell line (REN cells) contain high levels of hyperphosphorylated eIF6. Enzastaurin is a PKC beta inhibitor used in clinical trials. We prove that Enzastaurin treatment decreases eIF6 phosphorylation rate, but not eIF6 protein stability. The growth of REN, in vivo, and metastasis are reduced by either Enzastaurin treatment or eIF6 shRNA. Molecular analysis reveals that eIF6 manipulation affects the metabolic status of malignant mesothelioma cells. Less glycolysis and less ATP content are evident in REN cells depleted for eIF6 or treated with Enzastaurin (Anti-Warburg effect). We propose that eIF6 is necessary for malignant mesothelioma growth, in vivo, and can be targeted by kinase inhibitors. PMID:26462016

  20. Management of malignant pleural mesothelioma - part 1: epidemiology, diagnosis, and staging : Consensus of the Austrian Mesothelioma Interest Group (AMIG).

    PubMed

    Geltner, Christian; Errhalt, Peter; Baumgartner, Bernhard; Ambrosch, Gerhard; Machan, Barbara; Eckmayr, Josef; Klikovits, Thomas; Hoda, Mir Alireza; Popper, Helmut; Klepetko, Walter

    2016-09-01

    Malignant pleural mesothelioma is a rare malignant disease that in the majority of cases is associated with asbestos exposure. The incidence in Europe is about 20 per million inhabitants and it is increasing worldwide. Initial symptoms are shortness of breath, pleural effusion, cough, and chest pain. The typical growth pattern is along the pleural surface; however, infiltration of the lung and/or mediastinal and chest wall structures can occur in a more advanced stage. Ultimately, distant metastases outside the chest can result. Several histological subtypes of pleural mesothelioma exist, which must be differentiated from either benign diseases or metastases in the pleural space by other tumor entities. This differential diagnosis can be very difficult and a large panel of immunohistochemical markers is required to establish the exact diagnosis. The standard procedure for confirming the disease and obtaining sufficient tissue for the diagnosis is videothoracoscopy. Full thickness biopsies are required, while transthoracic needle puncture of pleural fluid or tissue is considered to be insufficient for a cytological diagnosis. Complete and detailed staging is mandatory for categorization of the disease as well as for therapeutic decision making.