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Feldspar AND lung cancer 1. Ultrastruct Pathol. 1995 May-Jun;19(3):167-73.

X-ray microanalysis of peripheral lung carcinomas.

Terzakis JA.

Department of Pathology, Lenox Hill Hospital, New York, New York, 10021-1883 USA.

A total of 15 cases of peripherally located lung carcinomas associated with scar (scar carcinoma) were studied by light microscopy and electron microscopy with energy-dispersive X-ray microanalysis (XMA). Results were compared to those of three autopsy lungs without significant pulmonary findings that served as controls. Fibrosis with scar formation characterized the 15 tumor cases. Particulate depositions including doubly refractile particles were also increased in the tumor group. XMA identified 25 elements with great complexity of particulate composition. Silicon was the most prominent element and was found in 16 of 18 cases studied. Kaolinite, feldspar, talc, muscovite, and silica were recognized. The fibrogenic properties of silicate compounds were emphasized, including their prominence in the lung tumor group. While the important concept of tumor desmoplasia was recognized, the study showed significant fibrosis in relation to fibrogenic materials, which undoubtedly preceded the appearance of the tumors. Also noted were the carcinogens uranium, cadmium, chromium, nickel, and arsenic, some of which were previously described as minor constituents of naturally occurring minerals.
PMID: 7631431 [PubMed - indexed for MEDLINE] Related citations

Feldspar dust AND lung cancer

J Toxicol Environ Health. 1988;25(1):35-56.

Fibrogenicity and carcinogenic potential of smelter slags used as abrasive blasting substitutes.
Stettler LE, Proctor JE, Platek SF, Carolan RJ, Smith RJ, Donaldson HM.

Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226.

This study was designed to examine the fibrogenic and carcinogenic potentials of three smelter slags (primary copper slag, secondary copper slag, and nickel slag) that have been used for a number of years as substitutes for sand in abrasive blasting operations. Seven groups of 85 male Fischer 344 rats (approximately 180 g) were used. Each group was given a single 20-mg dose of one of the following test materials via intratracheal instillation: primary copper slag, secondary copper slag, nickel slag, feldspar, Min-U-Sil, novaculite, or vehicle control. Chemical, particle size, and surface area analyses were performed for each test dust. Animals were weighed monthly, and ten animals per group were necropsied at the 6-, 12-, and 18-mo interim sacrifices. The terminal sacrifice was conducted at 22 mo. Hematoxylin and eosin stained histologic sections were prepared from designated formalin-fixed tissues collected at necropsy and examined microscopically. The pulmonary fibrogenic and carcinogenic potentials of the three smelter slags were compared histopathologically with feldspar, novaculite, Min-U-Sil, and vehicle controls. Only minimal to slight alveolar wall fibrosis was seen in the two copper slag groups, while the response seen with nickel slag was consistent with a foreign body reaction with minimal fibrosis seen in only an occasional animal. The major reaction seen in both the feldspar- and the novaculite-treated rats was a granulomatous inflammation with varying degrees of fibrosis associated with the granulomas. Significant numbers of primary lung tumors, principally adenocarcinomas and adenomas, were seen in the copper slag (p = 0.005 and p = 0.022 for the primary and secondary slags, respectively), in the feldspar (p = 0.007), in the novaculite (p less than 0.001), and in the Min-U-Sil (p less than 0.001) groups when compared to the vehicle control group. In addition, the Min-U-Sil and novaculite groups had significantly elevated pulmonary tumor proportions relative to the other treatments (p less than or equal to 0.002), with the Min-U-Sil being higher than the novaculite (p = 0.012). On the basis of the tumor incidence data, one must conclude that both copper slags tested in this study are carcinogenic to rats.



[PubMed - indexed for MEDLINE]

Mesothelioma AND granite dust

Singapore Med J. 1996 Apr;37(2):160-4.

Occupational respiratory diseases in Singapore.

Lee HS, Phoon WH, Wang SY, Tan KP.

Department of Industrial Health Ministry of Labour, Singapore.

Occupational respiratory disease statistics in Singapore from 1970 to 1993 were reviewed. Silicosis was the most common occupational respiratory disease in the 1970s and 1980s. About 78% of the cases were from granite quarries. With progressive reduction in dust levels and the closure of some quarries, there has been a decline in cases. From 1990 to 1993, occupational asthma was the most common occupational respiratory disease and more cases are expected with increasing awareness of the condition. The most common causative agent was isocyanates accounting for about 34% of cases. Of the asbestosis and malignant mesothelioma cases, about 70%-80% were from the one and only asbestos cement factory. With the closure of this factory and the increasing restrictions on the use of asbestos, cases of asbestosis are expected to decline in the long term. However, malignant mesothelioma cases may continue to surface because of the long latent period and the potential risk with low and brief exposures to asbestos. It is important to probe for possible occupational exposures (both present and past) in a patient with respiratory symptoms or disease. PMID: 8942254 [PubMed - indexed for MEDLINE] Related citations

MeSH Terms

MeSH Terms Data Collection Humans Incidence Occupational Diseases/diagnosis Occupational Diseases/epidemiology* Respiratory Tract Diseases/epidemiology* Respiratory Tract Diseases/etiology Risk Factors Singapore/epidemiology Am J Ind Med. 1995 May;27(5):625-40.

Mortality of a cohort of U.S. workers employed in the crushed stone industry, 1940-1980.
Costello J, Castellan RM, Swecker GS, Kullman GJ.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2845, USA.

The mortality of 3,246 males who had been employed 1 or more years during 1940-1980 at 20 crushed stone operations was evaluated for possible association between employment and death from lung cancer, pneumoconiosis, and other respiratory diseases. Four deaths were attributed to pneumoconiosis. Based on available work histories, at least two of these deaths were probably due to dust exposures in the crushed stone industry. Mortality attributed to pneumoconiosis and other nonmalignant respiratory diseases, including chronic obstructive lung disease, was significantly increased overall (SMR: 1.98; 95% CI: 1.21-3.05), and especially so for a subcohort of crushed stone workers that processed granite (SMR: 7.26; 95% CI: 1.97-18.59). With regard to lung cancer, overall SMRs were elevated (although not statistically significant). Analyzed by rock type, there was a significantly elevated lung cancer SMR among granite workers with at least 20 years latency (SMR: 3.35; 95% CI: 1.34-6.90). Although not definitive, results of this study are consistent with the hypothesis that exposure to respirable silica dust is a risk factor for lung cancer. PMID: 7611302

[PubMed - indexed for MEDLINE] Related citations

Mesotheliooma AND review 1-20

Nippon Eiseigaku Zasshi. 2011 May;66(3):562-7.

Mechanisms of asbestos-induced carcinogenesis.

Toyokuni S, Jiang L, Hu Q, Nagai H, Okazaki Y, Akatsuka S, Yamashita Y.

Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine.

Several types of fibrous stone called asbestos have been an unexpected cause of human cancer in the history. This form of mineral is considered precious in that they are heat-, friction-, and acidresistant, are obtained easily from mines, and can be modified to any form with many industrial merits. However, it became evident that the inspiration of asbestos causes a rare cancer called malignant mesothelioma. Because of the long incubation period, the peak year for malignant mesothelioma is expected to be 2025 in Japan. Thus, it is necessary to elucidate the mechanisms of asbestos-induced mesothelial carcinogenesis. In this review, we summarize the cutting edge results of our 5-year project funded by a MEXT grant, in which local iron deposition and the characteristics of mesothelial cells are the key issues. PMID: 21701088 [PubMed - in process] Free full text Related citations Pathol Oncol Res. 2011 Jun 7. [Epub ahead of print]

Primary Peritoneal Serous Papillary Carcinoma: A Clinical and Pathological Study.

Liu Q, Lin JX, Shi QL, Wu B, Ma HH, Sun GQ.

Departments of Obstetrics & Gynecology, and Pathology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, People's Republic of China.

Primary peritoneal serous papillary carcinoma (PPSPC) is a rare primary tumor of the peritoneum that found predominantly in elderly and post-menopausal women. The aim of our study is to review the clinical and pathologic information of 22 patients, and then try to summarize clinical behavior and pathological characteristics of PPSPC, in order to be better recognized of this entity in future. We retrospectively reviewed the data from 22 patients with PPSPC treated at our hospital from 1992 to 2008. All paraffin blocks were recut for periodic acid-Schiff diastase and immunohistochemical staining for CD15, cytokeratin7(CK7), cytokeratin20(CK20), S-100 protein, carcinoembryonic antigen (CEA), CA125, estrogen receptor(ER) and progesterone receptor(PR). The median age of the patients at the time of surgical staging was 56 years (range, 32-77 years). The most common presenting symptoms were abdominal distension (59.1%) and ascites (63.6%). Pretreatment CA125 levels were significant elevated in 90.5% patients. Optimal debulking was performed in 18 patients. All patients were consequently treated with platinum-based chemotherapy. Response to treatment is promising, and the median overall survival of all patients was 21.0 months (95% CI 16.9, 25.1 months). The positive rate of immunohistochemical staining was CD15 95.5%, CK7 90.9%, S100 protein 68.2%, CA125 59.1%, CK20 31.8%, ER 31.8%, CEA 27.3% and PR 9.1%, respectively. Gynecologist should be aware of PPSPC when abdominal distension, gross ascites and a raised level of CA125 in women without ovarian enlargement. Immunohistochemical staining might be helpful as accessory criteria for the differential diagnosis among the PPSPC, peritoneal malignant mesothelioma (PMM), primary epithelial ovarian carcinoma (PEOC) and peritoneal carcinomatosis from the gastrointestinal tumors (SPCGT). Cytoreductive surgery combined with pre/postoperative platinum-based chemotherapy may be effective for PPSPC patients. PMID: 21647781 [PubMed - as supplied by publisher] Related citations Rev Esp Med Nucl. 2011 Jun 2. [Epub ahead of print]

Usefulness of (18)F-FDG PET-CT in the presurgical assessment of malignant pleural

mesothelioma treated with neoadjuvant chemotherapy.

[Article in English, Spanish] Orcajo Rincn J, Alonso Farto JC, Rotger Regi A, Hernndez Prez R, Hualde AM, Prez Aradas V.

Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Maran, Madrid, Espaa.

Malignant pleural mesothelioma is a relatively rare, but highly aggressive, tumor, associated to exposure to asbestos, with a life expectancy between 9 and 17 months. Chest pain and dyspnea are the most frequent symptoms. The most commonly used therapy is surgery accompanied by chemotherapy. Preoperative assessment, after chemotherapy, has been done using magnetic resonance imaging and computed tomography (CT). However, these techniques cannot predict early response to therapy, because of the slow structural change of the tumor. The aim of this case report is to review and learn about the growing use of PET-CT imaging with (18)F-FDG in the preoperative staging of malignant pleural mesothelioma and its influence in selecting the most appropriate type of surgery. Copyright 2010 Elsevier Espaa, S.L. y SEMNIM. All rights reserved. PMID: 21641092 [PubMed - as supplied by publisher] Related citations Trends Pharmacol Sci. 2011 May 25. [Epub ahead of print]

Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.
Favoni RE, Florio T.


Department of Translational Oncology Research, Gene Transfer Laboratory, National Cancer Institute, Largo Rosanna Benzi, 10 16132 Genoa, Italy; Department of Oncology, Biology and Genetics, Section of Pharmacology, University of Genoa, Viale Benedetto XV, 2 16132 Genoa, Italy.

Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors. Copyright 2011 Elsevier Ltd. All rights reserved. PMID: 21620489 [PubMed - as supplied by publisher] Related citations Cancer Epidemiol Biomarkers Prev. 2011 Jun 21. [Epub ahead of print]

Does Exposure to Asbestos Cause Ovarian Cancer? A Systematic Literature Review and Meta-analysis.
Reid A, de Klerk N, Musk AW.

Authors' Affiliations: 1Centre for Medical Research, 2School of Population Health, 3Centre for Child Health Research, The University of Western Australia, Crawley, Perth; and 4Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.


INTRODUCTION: The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases, and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim of this study was to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer. METHODS: Fourteen cohort and two case-control studies were identified in Medline searches from 1950 to 2008. RESULTS: Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which reexamined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95% CI, 1.45-2.10) attenuating to 1.29 (95% CI, 0.97-1.73) in studies with confirmed ovarian cancers. CONCLUSION: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification. Cancer Epidemiol Biomarkers Prev; 20(7); 1-9. 2011 AACR. PMID: 21610219 [PubMed - as supplied by publisher] Related citations Diagn Cytopathol. 2011 May 14. doi: 10.1002/dc.21723. [Epub ahead of print]

Malignant biphasic peritoneal mesothelioma in a child: Fine-needle aspiration cytology, Histopathology, and immunohistochemical features along with review of literature.
Arora SK, Srinivasan R, Nijhawan R, Bansal D, Menon P.

Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Peritoneal mesotheliomas in children are of rare occurrance. We herein report the clinical, radiological, and pathological findings of a rare case of malignant peritoneal mesothelioma occurring in nine-year-old female child. The child presented with abdominal distension and awareness of a painless mass in the abdomen which on radiology appeared as a large heterogeneous pelvic mass with peritoneal deposits at multiple sites. To the best of our knowledge, this is the first case of a peritoneal malignant mesothelioma on which fine needle aspiration (FNA) was performed as first line investigation of the primary tumor. The cytological features, major differential diagnoses, and the pitfalls therein are discussed. Histopathology revealed biphasic pattern of mesothelioma which is again a rare pattern. Immunochemistry was carried out on the cell block made from the FNA as well as the biopsy specimen essentially showed the same features. There was positivity for vimentin, EMA, and cytokeratin 5/6 while WT1, calretinin, and CEA were negative; however, D2-40 showed diffuse membranous positivity in the epithelial areas and cytoplasmic positivity in the spindle areas confirming a mesothelioma. We emphasize the use of immunochemistry on cell block material for a confident diagnosis of mesothelioma in such cases. Diagn. Cytopathol. 2011; 2011 Wiley-Liss, Inc. Copyright 2011 Wiley-Liss, Inc. PMID: 21574263 [PubMed - as supplied by publisher] Related citations Curr Oncol Rep. 2011 May 15. [Epub ahead of print]

Malignant Pleural Mesothelioma.

Raja S, Murthy SC, Mason DP.

Department of Cardiothoracic Surgery, Cleveland Clinic Foundation, J4-1, 9500 Euclid Avenue, Cleveland, OH, 44195, USA,

Malignant pleural mesothelioma (MPM) is a relatively rare thoracic malignancy accounting for about 2000-3000 new cases per year. This cancer has been increasing in incidence and is

strongly associated with asbestos exposure. Also, it is characterized by insidious growth and clinical presentation at an advanced stage of disease. In the past, the treatment of this disease was limited to marginally effective chemotherapy and morbid surgery. This review explores the clinical presentation of MPM, its diagnostic approach and the relevant and recent studies that define the role of chemotherapy, radiation, and various surgical options. Currently, even with aggressive surgical interventions and multimodality strategies, cure remains elusive, although life prolongation has been achieved. Additionally, promising new therapies and interventions that are currently being studied are introduced in this review. PMID: 21573909 [PubMed - as supplied by publisher] Related citations Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1 Suppl):85S-88S.

Peritoneal mesothelioma: description of a case and review of literature.

Pedata P, Feola D, Laieta MT, Garzillo EM.

Department of Experimental Medicine, Occupational Medicine, Hygiene and Industrial Toxicology Section, Second University of Naples, Naples, Italy.

It is universally recognized by the scientific community that asbestos, widely used in the past in many industrial sectors, is responsible for the onset of certain diseases of pleural and peritoneal serous membranes; in particular, Peritoneal Mesothelioma (PM) is an exceptional case, extremely rare malignancy of the abdominal cavity. In this work we describe a 62 years-old man, formerly exposed to asbestos, complains of dyspepsia associated with pain, abdominal swelling and mild difficulty during inspiration. After intraoperative biopsy of three masses found in abdomen, malignant peritoneal mesothelioma was diagnosed. The patient subsequently was subjected to cycles of chemotherapy and multiple palliative paracentesis, the patient died after about 12 months from diagnosis. PMID: 21329571 [PubMed - indexed for MEDLINE] Related citations

Publication Types, MeSH Terms, Substances

Publication Types Case Reports Review MeSH Terms Asbestos/toxicity Hernia, Inguinal/complications Humans Male Mesothelioma/diagnosis Mesothelioma/etiology* Mesothelioma/pathology Middle Aged Peritoneal Neoplasms/diagnosis Peritoneal Neoplasms/etiology* Peritoneal Neoplasms/pathology Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1 Suppl):5S-10S.

Suppressive effect of asbestos on cytotoxicity of human NK cells.

Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, Nakano T, Miura Y, Hiratsuka J, Otsuki T.

Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan.

Asbestos, a naturally occurring fibrous mineral, causes malignant mesothelioma (MM). However, it takes a very long time to develop MM, which suggests that effects other than tumorigenicity of asbestos might contribute to the development of MM, and one of the possible targets is anti-tumor immunity. Therefore, we examined the effect of asbestos exposure on human natural killer (NK) cells using the cell line of YT-A1, Peripheral blood mononuclear cells (PBMCs) cultures and specimens from patients with MM. In particular, we focused on expression of NK cell-activating receptors, including NKG2D, 2B4 and NKp46. Analysis of the YT-CB5 subline of YT-A1, cultured with CB for over 5 months, showed a decrease in cytotoxicity with low expressions of NKG2D and 2B4, although there were no decreases after about one month. YT-CB5 showed decreases in phosphorylation of extracellular signal-regulated

kinase (ERK) and degranulation stimulated by antibodies to NKG2D. Peripheral blood (PB-) NK cells from MM patients also showed decreased cytotoxicity compared with healthy volunteers (HV), and was accompanied with low expression of NKp46 unlike YT-CB5. PBMCs cultured with CB resulted in decreased expression of NKp46 on NK cells, although this did not occur when using glass wool, an asbestos substitute. These results indicate that asbestos has the potential to suppress cytotoxicity of NK cells. In particular, it is noteworthy that both NK cells from MM patients and those from a culture of PBMCs derived from HVs with asbestos showed the same characteristic of decreased cytotoxicity with low expression of NKp46. PMID: 21329559 [PubMed - indexed for MEDLINE] Related citations

Publication Types, MeSH Terms, Substances

Publication Types Research Support, Non-U.S. Gov't Review MeSH Terms Animals Asbestos/toxicity* Cytotoxicity, Immunologic/drug effects* Extracellular Signal-Regulated MAP Kinases/metabolism Humans Killer Cells, Natural/drug effects* Killer Cells, Natural/immunology Multiple Myeloma/immunology Natural Cytotoxicity Triggering Receptor 1/analysis Phosphorylation Substances NCR1 protein, human Natural Cytotoxicity Triggering Receptor 1 Asbestos Extracellular Signal-Regulated MAP Kinases Cancer Chemother Pharmacol. 2011 Jul;68(1):1-15. Epub 2011 May 7.

Review on clinical trials of targeted treatments in malignant mesothelioma.

Jakobsen JN, Srensen JB.

Department of Oncology, Finsencentre, Copenhagen, Denmark,

PURPOSE: Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all clinical trials evaluating the effect of targeted treatments in MM. METHODS: An extensive literature search was performed in January 2011 using pubmed and medline. No constraints on publication date were applied. RESULTS: Thirty-two trials exploring 17 different targeted agents in MM were found. Treatment in firstand second-line targeted agents induced response rates ranging from 0-14% and 0-16%, respectively. The tyrosine kinase inhibitor sunitinib induced partial response in 10% and stable disease in 66% of MPM patients as second-line treatment. A preliminary analysis of a phase II/III trial suggests that addition of bevacizumab to pemetrexed and cisplatin first-line treatment significantly improves disease control (CR + PR + SD) in the bevacizumab arm (73.5%) compared with treatment with pemetrexed and cisplatin without bevacizumab (43.2%) (P = 0.010). Another phase II trial did not observe any significant clinical benefit of adding of bevacizumab to gemcitabine and cisplatin. CONCLUSIONS: Disease stabilization is reported in some patients with several targeted treatments and might be beneficial in subgroups of patients or in combination with classic chemotherapy. None of the hitherto explored targeted treatments can currently be recommended as standard treatment in MM. PMID:

21553148 [PubMed - in process] Asian Pac J Cancer Prev. 2011;12(2):543-7.

Primary pleuropulmonary neoplasms in childhood: fourteen cases from a single center.

Demir HA, Yalcin B, Ciftci AO, Orhan D, Varan A, Akyuz C, Kutluk T, Buyukpamukcu M.

Department of Pediatric Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey.

BACKGROUND: We aimed to review clinical characteristics, treatment results and outcome of pediatric patients with primary pleuropulmonary neoplasms. METHODS: Medical records of 14 cases diagnosed between 1972-2009 were reviewed retrospectively. RESULTS: The male/female ratio was 5/9 and the mean age at diagnosis was 9.1 years (2-16). All but one were symptomatic, presenting with fever, coughing, dyspnea, or weight loss. One patient presented with hemoptysis, and another with digital clubbing. One mesothelioma was diagnosed incidentally. Some 8/14 patients were initially diagnosed as having pneumonia (median delay in diagnosis of 2.5 months). Diagnoses included pleuropulmonary blastoma (PPB, n = 5), inflammatory pseudotumor (n = 3), mesothelioma (n = 2), mucoepidermoid carcinoma (MEC, n = 2), and carcinoid tumor (n = 2). Patients with PPB underwent surgery and received chemotherapy with or without radiotherapy. Two carcinoid tumor cases underwent surgery, one further received chemotherapy. Patients with mesothelioma were treated with chemotherapy. Inflammatory pseudotumors were all resected. Two cases with MEC received chemotherapy, one after surgery. 2/5 PPB patients survived without recurrence, 3 died; all carcinoid tumors and inflammatory pseudotumors were alive; 1/2 MEC patients was alive after 252 months, the other

one was lost without disease; 1/2 mesothelioma patients was alive without disease, the other was died. For all cases, median follow-up was 30.5 months (0.6-252). CONCLUSIONS: Primary pleuropulmonary tumors are rare but clinical presentation can be varied and delay in diagnosis is common. Children with persistent coughs, recurrent pneumonia or hemoptysis should be considered as indicators for early diagnosis, very important because the prognosis of these tumors varies with histology and stage. PMID: 21545227 [PubMed - in process] Related citations Curr Opin Pulm Med. 2011 Jul;17(4):247-54.

The diminishing role of surgery in pleural disease.

Davies HE, Rosenstengel A, Lee YG.

aConsultant in Respiratory Medicine, University Hospital Llandough, Cardiff and Vale University Health Board, Cardiff, UK bThe Prince Charles Hospital, Brisbane, Australia cDepartment of Medicine, University of Western Australia, Respiratory Department, Sir Charles Gairdner Hospital, Pleural Disease Unit, Lung Institute of Western Australia, Australia.

PURPOSE OF REVIEW: Pleural disease is common. Traditionally, many patients were subjected to surgery for diagnosis and treatment. Most pleural surgical procedures have not been subjected to high-quality clinical appraisal and their use is based on anecdotal series with selection bias. The evidence (or the lack) of benefits of surgery in common pleural conditions is reviewed. RECENT FINDINGS: Recent studies do not support the routine therapeutic use of surgery in patients with malignant pleural effusions, empyema or mesothelioma. Four randomized studies have failed to show significant benefits of thoracoscopic poudrage over bedside pleurodesis. Surgery as first-line

therapy for empyema was studied in four randomized studies with mixed results and no consistent benefits. Cumulative evidence suggests that radical surgery in mesothelioma, especially extrapleural pneumonectomy, is not justified. Advances in imaging modalities and histopathological tools have minimized the need for surgery in the workup of pleural effusions. Complications associated with surgery are increasingly recognized. SUMMARY: Surgery has associated perioperative risks and costs, and residual pain is not uncommon. Many conventional pleural surgeries have not been assessed in randomized studies. Pulmonologists should be aware of the evidence that supports surgical interventions, or the lack of it, in order to make informed clinical decisions and optimize patient care. PMID: 21537191 [PubMed - in process] Related citations J Toxicol Environ Health B Crit Rev. 2011;14(1-4):246-66.

Factors that impact susceptibility to fiberinduced health effects.

Below JE, Cox NJ, Fukagawa NK, Hirvonen A, Testa JR.

Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Illinois 60637, USA.

Asbestos and related fibers are associated with a number of adverse health effects, including malignant mesothelioma (MM), an aggressive cancer that generally develops in the surface serosal cells of the pleural, pericardial, and peritoneal cavities. Although approximately 80% of individuals with MM are exposed to asbestos, fewer than 5% of asbestos workers develop MM. In addition to asbestos, other mineralogical, environmental, genetic, and possibly viral factors might contribute to MM susceptibility. Given this complex etiology of MM, understanding susceptibility to MM needs to be a priority for investigators in order to reduce exposure of those most at risk to known environmental carcinogens. In this review, the current body of literature related to fiber-associated disease susceptibility including age, sex, nutrition, genetics, asbestos, and other mineral exposure is addressed with a focus on MM, and critical areas for further study are recommended.

PMID: 21534090 [PubMed - in process] Related citations

Publication Types
Publication Types Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. J Toxicol Environ Health B Crit Rev. 2011;14(1-4):76-121.

Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos.
Mossman BT, Lippmann M, Hesterberg TW, Kelsey KT, Barchowsky A, Bonner JC.

Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.

Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Speciesspecific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis.

PMID: 21534086 [PubMed - in process] Related citations J Toxicol Environ Health B Crit Rev. 2011;14(1-4):3-39.

Applying definitions of "asbestos" to environmental and "low-dose" exposure levels and health effects, particularly malignant mesothelioma.
Case BW, Abraham JL, Meeker G, Pooley FD, Pinkerton KE.

Department of Pathology and School of Environment, McGill University, Montreal, Quebec, Canada.

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review. PMID: 21534084 [PubMed - in process] Related citations

Publication Types
Publication Types

Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. J Thorac Oncol. 2011 Jun;6(6):1132-41.

Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma.
Chi A, Liao Z, Nguyen NP, Howe C, Gomez D, Jang SY, Komaki R.

*Department of Radiation Oncology, The University of Arizona, Tucson, Arizona; Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and Arizona Health Sciences Library, The University of Arizona, Tucson, Arizona.

INTRODUCTION: : Local therapy is becoming increasingly important as a part of the definitive treatment for malignant pleural mesothelioma after extrapleural pneumonectomy (EPP) because of the emergence of trimodality therapy consisted of chemotherapy, EPP, and adjuvant radiotherapy. Herein, we explore the current evidence and indications for adjuvant intensity-modulated radiotherapy (IMRT), as well as how to further improve this technique and adapt new technology in the delivering adjuvant radiotherapy in the setting of trimodality therapy. METHODS: : A systematic review of relevant studies identified through PubMed, ISI Web of Knowledge (Web of Science), the Cochrane Library, and the National Guideline Clearinghouse search engines was performed. RESULTS: : Local control remains poor despite the inclusion of conventional adjuvant radiation therapy in trimodality therapy. This can be improved by the delivery of adjuvant IMRT. However, IMRT can be associated with severe pulmonary toxicity if the radiation dose to the remaining lung is not kept to a very low level. This is especially true when patients are receiving chemotherapy.

New advances in technology can allow for lower doses to the contralateral lung, decreased treatment delivery time, and improved target dose coverage. CONCLUSION: : Excellent local control can be achieved through adjuvant IMRT after EPP for malignant pleural mesothelioma. Severe pulmonary toxicity may be avoided by setting stringent dose constraints for the contralateral lung. This can be aided by the advances in technology. Post-treatment surveillance may be reliably conducted by periodical [18F]-fluorodeoxyglucose-positron emission tomography imaging. PMID: 21532502 [PubMed - in process] Curr Treat Options Oncol. 2011 Jun;12(2):173-80.

Gene therapy for mesothelioma.

Vachani A, Moon E, Albelda SM.

Thoracic Oncology Research Laboratory, University of Pennsylvania, 1016E Abramson Research Center, 3615 Civic Center Blvd., Philadelphia, PA 19104-6160, USA.

Mesothelioma represents an especially good target for gene therapy since few effective therapies exist, the disease remained relatively localized until late in its course, the tumor can be accessed relatively easily through the chest wall, and the thin layer of mesothelial cells offers a large surface area for efficient, rapid, and diffuse gene transfer. Gene therapy trials in mesothelioma have shown safety, and some limited evidence of efficacy. We present a review of clinical trials that have been performed in mesothelioma and describe several new approaches currently being pursued. PMID: 21519819 [PubMed - in process] Related citations Curr Opin Pulm Med. 2011 Jul;17(4):242-6.

Outcome of patients with nonspecific pleuritis at thoracoscopy.

Wrightson JM, Davies HE.

aOxford NIHR Biomedical Research Centre, University of Oxford, UK bOxford Pleural Unit, Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK cDepartment of Respiratory Medicine, University Hospital Llandough, Cardiff and Vale University Health Board, Cardiff, UK.

PURPOSE OF REVIEW: The histological finding of pleural inflammation (pleuritis/fibrosis) is frequently found in pleural biopsies taken at thoracoscopy. This is a nonspecific finding, representing a common endpoint of many pleural conditions. Additional features, such as malignant cells, caseating granulomas and evidence of vasculitis, are required to make an aetiological histological diagnosis; in the absence of these features, the term 'nonspecific pleuritis/fibrosis' (NSP) is used. The cause of NSP is obscure and presents a particular dilemma: whether this apparently benign result represents a 'false-negative' sampling error in malignancy. RECENT FINDINGS: In a recent longitudinal follow-up study of 142 patients undergoing thoracoscopy, NSP was found in 31%. Of these, a likely cause for the NSP was found in 38% and malignancy occurred in 12%. These data were consistent with previous studies. SUMMARY: NSP is a histological diagnosis made in approximately 30-40% of patients with an undiagnosed exudative pleural effusion. The majority of cases adopt a benign course, although 8-12% may be subsequently found to have malignancy, particularly mesothelioma. In 25-91% no cause for the NSP is found; these patients are considered to have 'idiopathic pleuritis'. Prolonged follow-up, with occasionally further (usually more invasive) biopsies, is essential to rule out malignancy. PMID: 21519267 [PubMed - in process] Related citations Rev Med Inst Mex Seguro Soc. 2011 January-Februaryl;49(1):79-84.

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

[Article in Spanish] Ruiz-Tirado ML, Olvera-Rodrguez A, Daz-Barranco I, Ruiz-Romano A, Castillo-Ruiz N, Olvera-Quiroz SE.

Hospital General de Zona 1, Instituto Mexicano del Seguro Social, Tlaxcala, Tlaxcala, Mexico.

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. PMID: 21513666 [PubMed - as supplied by publisher] Related citations Ann Surg Oncol. 2011 Apr 22. [Epub ahead of print]

Summary of Prognostic Factors and Patient Selection for Extrapleural Pneumonectomy in the Treatment of Malignant Pleural Mesothelioma.
Cao C, Yan TD, Bannon PG, McCaughan BC.

The Systematic Review Group, The Baird Institute for Applied Heart and Lung Surgical Research, Sydney, Australia.

BACKGROUND: Extrapleural pneumonectomy (EPP) has been shown to improve long-term survival outcomes in selected patients with malignant pleural mesothelioma (MPM). The present study aimed to evaluate potential prognostic factors on overall survival for patients who underwent EPP for MPM and to examine the patient selection process in major referral centers that perform EPP. METHODS: A systematic review of the current literature was performed using 5 electronic databases. Relevant studies with prognostic data on overall survival for patients with MPM treated by EPP were included for review. Two reviewers independently assessed each included study. RESULTS: A total of 17 studies from 13 institutions containing the most updated and complete data on prognostic factors for patients with MPM who underwent EPP were included for review. A number of quantitative, clinical, and treatment-related factors were identified to have significant impact on overall survival. CONCLUSIONS: Patients with nonepithelial MPM and nodal involvement have consistently demonstrated to have a worse prognosis after EPP. Their eligibility as candidates for EPP should be questioned. The preoperative patient selection process currently differs greatly between institutions and should focus on identifying patients with nonepithelial histologic subtypes and nodal involvement to exclude them as EPP surgical candidates in the future. PMID: 21512863 [PubMed - as supplied by publisher] Related citations