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Bibliography on: Mesothelioma and Asbestos

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ESP: PubMed Auto Bibliography 17 Sep 2019 at 01:48 Created: 

Mesothelioma and Asbestos

Mesothelioma is a rare, but deadly form of cancer that is often (nearly always) associated with prior exposure to asbestos. The latency between exposure and disease onset is long, usually 20-50 years, making this a difficult cause-effect system to study.

Created with PubMed® Query: asbestos AND mesothelioma NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-09-16

Kim RY, Sterman DH, AR Haas (2019)

Malignant Mesothelioma: Has Anything Changed?.

Seminars in respiratory and critical care medicine, 40(3):347-360.

Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.

RevDate: 2019-09-12

Huang Q, YJ Lan (2019)

Colorectal cancer and asbestos exposure-an overview.

Industrial health [Epub ahead of print].

The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer Standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer Standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.

RevDate: 2019-09-03

Abdelgied M, El-Gazzar AM, Alexander WT, et al (2019)

Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.

Particle and fibre toxicology, 16(1):34 pii:10.1186/s12989-019-0316-2.

BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years.

RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant.

CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.

RevDate: 2019-09-05

Cavallari I, Urso L, Sharova E, et al (2019)

Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives.

Frontiers in oncology, 9:740.

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to asbestos exposure. Although the risk factors for MPM are well-known, the majority of MPM patients are diagnosed at an advanced stage and have a very poor prognosis. Circulating biomarkers for early diagnosis remain to be identified, and the current standard for MPM diagnosis relies on pleural biopsies. Robust non-invasive tests for the screening of asbestos-exposed subjects are therefore an important unmet clinical need. This review provides a critical summary of recent liquid biopsy-based studies aimed at discovering novel blood-based circulating biomarkers for the early diagnosis and prognostic stratification of MPM patients.

RevDate: 2019-08-31

Vimercati L, Cavone D, Delfino MC, et al (2019)

Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register.

Environmental health : a global access science source, 18(1):78 pii:10.1186/s12940-019-0512-4.

BACKGROUND: Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.

METHODS: A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.

RESULTS: Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.

CONCLUSIONS: The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.

RevDate: 2019-09-01

Hassan D, S Ligato (2019)

Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature.

Case reports in pathology, 2019:2732674.

Introduction: Localized malignant mesotheliomas, defined as sharply circumscribed tumors of the serosal membrane with the microscopic appearance of diffuse malignant mesothelioma, are rare tumors; their behavior and prognosis are uncertain. Intrahepatic mesotheliomas are postulated to arise from mesothelial cells of Glisson's capsule.

Case Presentation: A 69-year-old female with no history of asbestos exposure presented with a one-month history of increasing abdominal pain associated with constitutional symptoms. Computerized Tomography (CT) scan of the abdomen and pelvis revealed a sizable soft tissue mass within the right paracolic gutter, abutting the inferior hepatic margin, the lateral abdominal wall, and descending colon. Ultrasound-guided biopsy of the mass suggested a poorly differentiated hepatocellular carcinoma. There was no disease elsewhere on PET scan. Surgical resection of the mass was performed. Pathological assessment suggested the tumor to be arising from the liver with invasion of the liver, abdominal wall musculature, and the adventitial surface of the ascending colon. A final diagnosis of localized biphasic malignant peritoneal mesothelioma with rhabdoid features was rendered based on morphology and the result of immunohistochemical studies. The abdominal wall margin was positive. The patient progressed over the course of 6 months despite receiving adjuvant chemotherapy and immunotherapy with metastases and a decline in performance status and was transitioned to hospice.

Conclusion: Localized malignant peritoneal mesotheliomas are rare tumors that may present clinically as a liver mass and simulate primary hepatic or secondary tumors. Definitive diagnosis is obtained by surgical resection in most cases. The clinical outcome is variable with most cases having a poor outcome.

RevDate: 2019-09-04

Li Z, Jiang L, Chew SH, et al (2019)

Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.

Redox biology, 26:101297 pii:S2213-2317(19)30731-1 [Epub ahead of print].

Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H+. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2- and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.

RevDate: 2019-08-20

Keshava HB, Tang A, Siddiqui HU, et al (2019)

Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.

World journal of surgery pii:10.1007/s00268-019-05132-6 [Epub ahead of print].

BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival.

METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression.

RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy.

CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.

RevDate: 2019-08-28

Hoffmann PR, Hoffmann FW, Premeaux TA, et al (2019)

Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models.

Frontiers in oncology, 9:720.

Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment.

RevDate: 2019-08-17

Bousema JE, van de Luijtgaarden KM, Wilhelmus S, et al (2019)

Acute severe abdominal pain in a young woman caused by a well-differentiated papillary mesothelioma of the peritoneum.

BMJ case reports, 12(8): pii:12/8/e229769.

Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.

RevDate: 2019-08-31

Consonni D, Migliore E, Barone-Adesi F, et al (2019)

Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.

Environmental research, 177:108636.

BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.

METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).

RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).

CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.

RevDate: 2019-08-16

Betti M, Aspesi A, Sculco M, et al (2019)

Genetic predisposition for malignant mesothelioma: A concise review.

Mutation research, 781:1-10.

Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.

RevDate: 2019-08-15

Barone-Adesi F, Ferrante D, Chellini E, et al (2019)

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

Occupational and environmental medicine, 76(9):611-616.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.

METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.

RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.

CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

RevDate: 2019-08-14

Gudmundsson G, K Tomasson (2019)

[Asbestos and its effects on health of Icelanders - review].

Laeknabladid, 105(7):327-334.

Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.

RevDate: 2019-08-14

Jiang Y, Mei Z, Cao H, et al (2019)

Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review.

Cancer biology & therapy [Epub ahead of print].

Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.

RevDate: 2019-08-13

Boffetta P, Righi L, Ciocan C, et al (2019)

Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.

Annals of oncology : official journal of the European Society for Medical Oncology pii:5548996 [Epub ahead of print].

RevDate: 2019-08-17

Munson PB, Hall EM, Farina NH, et al (2019)

Exosomal miR-16-5p as a target for malignant mesothelioma.

Scientific reports, 9(1):11688 pii:10.1038/s41598-019-48133-0.

Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.

RevDate: 2019-08-13

Luberto F, Ferrante D, Silvestri S, et al (2019)

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

Environmental health : a global access science source, 18(1):71 pii:10.1186/s12940-019-0510-6.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.

METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.

RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.

CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.

RevDate: 2019-08-07

Corti A, Bonetti J, Dominici S, et al (2019)

Induction of gamma-glutamyltransferase activity and consequent prooxidant reactions in human macrophages exposed to crocidolite asbestos.

Toxicological sciences : an official journal of the Society of Toxicology pii:5544276 [Epub ahead of print].

Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiols, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at sub-toxic concentrations (50-250 ng/1,000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent prooxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.

RevDate: 2019-08-06

Wronkiewicz SK, Roggli VL, Hinrichs BH, et al (2019)

Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:10.1038/s41379-019-0332-7 [Epub ahead of print].

Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.

RevDate: 2019-08-05

Jacobs NFB, Towle KM, Finley BL, et al (2019)

An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.

Critical reviews in toxicology [Epub ahead of print].

Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published "no-observed adverse effect level, best estimate" for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.

RevDate: 2019-08-05

Marsh GM, Ierardi AM, Benson SM, et al (2019)

Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.

Inhalation toxicology [Epub ahead of print].

Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.

RevDate: 2019-08-03

Butnor KJ, Pavlisko EN, Sporn TA, et al (2019)

Mesothelioma of the tunica vaginalis testis.

Human pathology pii:S0046-8177(19)30133-9 [Epub ahead of print].

Malignant mesothelioma arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathologic findings of mesothelioma of the TVT in one of the largest series to date. Design Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases and their clinicopathologic features were recorded. Eighteen men with malignant mesothelioma (MM) and two with well-differentiated papillary mesothelioma (WDPM) of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72years (range, 32-85years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, seven of whom presented with hydrocele and five with inguinal hernia. The other five had a clinically recognized mass. Seven of the men underwent herniorrhapy, seven radical orchiectomy, three hydrocelectomy, and three paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and six were biphasic. Among the six men with MM who had ≥6months follow-up, one was alive with no evidence of disease at six months and five were known to have died of disease 8-74months (median=31.5months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the two men initially diagnosed with WDPM, one was alive without evidence of disease five years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement two years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33years (range, 2-46years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases and pleural plaques had been found in four. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases.

RevDate: 2019-08-29

Sorahan TM (2019)

Cancer incidence in UK electricity generation and transmission workers, 1973-2015.

Occupational medicine (Oxford, England), 69(5):342-351.

BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied.

AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers.

METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates.

RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer.

CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.

RevDate: 2019-08-03

Churg A, Galateau-Salle F, Roden AC, et al (2019)

Malignant mesothelioma in situ: morphologic features and clinical outcome.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:10.1038/s41379-019-0347-0 [Epub ahead of print].

The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called "benign asbestos effusion." We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.

RevDate: 2019-08-02

Itano H, Takeda T, Yamada T, et al (2019)

Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature.

General thoracic and cardiovascular surgery pii:10.1007/s11748-019-01182-8 [Epub ahead of print].

Heterologous mesothelioma is a very rare subtype of sarcomatoid mesothelioma characterized by the presence of malignant heterologous elements. A 69-year-old man with a strong history of asbestos exposure presented with a 5-cm mass in his chest wall, destroying the right 5th rib and spreading along the parietal pleura, on a CT. Biopsy revealed heterologous mesothelioma with osteosarcomatous elements, following which left extrapleural pneumonectomy was performed with combined resection of pericardium, hemidiaphragm, and 4th, 5th, and 6th costal segments. A small cytokeratin-positive epithelioid component in the resected tumor definitively confirmed the diagnosis. Post-operative chemotherapy and intensity-modulated radiotherapy were undertaken. After 12-month disease-free period post treatment, rapid intraperitoneal recurrence resulted in death. Autopsy revealed no tumors in the left thorax. We present here a case of heterologous osteosarcomatous pleural mesothelioma that followed a unique clinical course after trimodality therapy. In addition, literature of 54 cases of the similar heterologous mesothelioma was reviewed.

RevDate: 2019-08-01

Gogou E, Hatzoglou C, Zarogiannis SG, et al (2019)

Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.

Medicina (Kaunas, Lithuania), 55(8): pii:medicina55080419.

Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.

RevDate: 2019-08-02

Borrelli E, Babcock Z, S Kogut (2019)

Costs of medical care for mesothelioma.

Rare tumors, 11:2036361319863498 pii:10.1177_2036361319863498.

Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95% confidence interval: US$20,819-US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements.

RevDate: 2019-07-29

Lee MJ, Kuehne N, Hueniken K, et al (2019)

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.

Molecular carcinogenesis [Epub ahead of print].

Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.

RevDate: 2019-08-02

Di Somma S, Iannuzzi CA, Passaro C, et al (2019)

The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.

Frontiers in oncology, 9:564.

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus.

RevDate: 2019-08-20

Krówczyńska M, E Wilk (2019)

Environmental and Occupational Exposure to Asbestos as a Result of Consumption and Use in Poland.

International journal of environmental research and public health, 16(14): pii:ijerph16142611.

Asbestos is harmful to human health; exposure to asbestos causes a wide range of asbestos-related diseases.

AIM: Malignant mesothelioma (MM) is unique to occupational and environmental asbestos exposure.

METHODS: Environmental asbestos exposure was examined in relation to asbestos use and manufacturing, the quantity of the asbestos-containing products still in use, the concentrations of asbestos fibres in the air and the number of MM cases diagnosed each year per county.

RESULTS: The correlation coefficient of the measurements of the asbestos fibre concentrations in the air and the quantity of asbestos-cement products in use is high and amounts to 0.68. Meanwhile, the correlation coefficient of the measurements of asbestos fibre concentrations in air and MM morbidity rate resulting from environmental exposure calculated for particular counties in provinces is low and amounts to 0.37. The highest MM morbidity rate was observed for Małopolskie and Śląskie, a typical industrial area of Poland.

CONCLUSIONS: There are MM cases which are still attributable to occupational asbestos exposure, although MM cases resulting from environmental exposure to asbestos have an increased MM risk. Poland is among those countries with a low MM incidence rate, which seems to be an underestimation of environmental asbestos exposure. As long as asbestos-cement products are used in the environment, actions should be undertaken to protect public health.

RevDate: 2019-08-05

Korchevskiy A, Rasmuson JO, EJ Rasmuson (2019)

Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.

Inhalation toxicology, 31(5):180-191.

Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (RM) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO2, total Fe oxides or total equivalent Fe3+ as Fe2O3, and MgO. Modeled potency factors increase as the aspect ratio, SiO2, and total Fe oxide (or Fe2O3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.

RevDate: 2019-07-17

Henley SJ, Peipins LA, Rim SH, et al (2019)

Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.

Journal of women's health (2002) [Epub ahead of print].

Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.

RevDate: 2019-07-19

Zona A, Iavarone I, Buzzoni C, et al (2019)

[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report].

Epidemiologia e prevenzione, 43(2-3 Suppl 1):1-208.

INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings.

METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs.

RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system.

CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.

RevDate: 2019-07-22

Mumma MT, Sirko JL, Boice JD, et al (2019)

Mesothelioma mortality within two radiation monitored occupational cohorts.

International journal of radiation biology [Epub ahead of print].

Purpose: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation. Methods and materials: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung. Results: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos. Conclusions: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.

RevDate: 2019-07-12

Williams M, Cheng YY, Kirschner MB, et al (2019)

Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma.

Oncotarget, 10(41):4125-4138 pii:27010.

MicroRNA downregulation is frequent in malignant pleural mesothelioma (MPM), but the mechanisms responsible for loss of miR-15/16 and miR-193a are yet to be elucidated and were investigated in this study. Copy Number Variation (CNV) of microRNA-coding genes was analyzed in MPM cells by digital droplet PCR (ddPCR) and revealed heterozygous loss of miR-193a and miR-15a/16-1, but no change in miR-15b/16-2. Epigenetic control of microRNA expression was inferred following decitabine and Trichostatin A (TSA) treatment which did not substantially affect microRNA expression. Knockdown of c-Myc expression led to upregulation of SMC4, miR-15b and 16, and to a lesser extent DLEU2 and miR-15a, whereas c-Myc overexpression repressed microRNA expression. Chromatin immunoprecipitation (ChIP) assays confirmed the interaction of c-Myc with the DLEU2 and SMC4 promoters. Tumor microRNA expression was determined in samples from MPM patients, with samples of pleura from cardiac surgery patients used as controls. In tumor samples, a strong correlation was observed between the expression of miR-15b and 16 (R2=0.793), but not miR-15a and 16. Our data suggest that in MPM, the downregulation of miR-15/16 is due to transcriptional repression by c-Myc, primarily via control of the miR-15b/16-2 locus, while miR-193a-3p loss is due to genomic deletion.

RevDate: 2019-07-10

Taylor L, Cooper D, A Aujayeb (2019)

Malignant deciduoid mesothelioma: a rare variant of epithelioid mesothelioma.

BMJ case reports, 12(7): pii:12/7/e229945.

We describe a case of a deciduoid mesothelioma, a rare variant of epithelioid mesothelioma, which is associated with a very poor prognosis. A review of the relevant literature is also included. The patient was a man with probable asbestos exposure and presented with classic features of pleural malignancy. Diagnosis was reached with close correlation between clinical, radiological and pathological findings.

RevDate: 2019-09-03

Consonni D, Calvi C, De Matteis S, et al (2019)

Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.

Occupational and environmental medicine, 76(8):545-553.

OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy.

METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education.

RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency.

CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.

RevDate: 2019-07-08

Carbone M, Adusumilli PS, Alexander HR, et al (2019)

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

CA: a cancer journal for clinicians [Epub ahead of print].

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

RevDate: 2019-07-21

Tsao A, Nakano T, Nowak AK, et al (2019)

Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.

Seminars in oncology, 46(2):145-154.

Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.

RevDate: 2019-08-28
CmpDate: 2019-08-28

Terakawa H, Gabata R, Haba Y, et al (2019)

[A Case of Peritoneal Mesothelioma Diagnosed by Ileus].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(6):1081-1083.

The present case involved a man aged about 70 years. He visited our hospital with the main complaint of abdominal pain. We diagnosed him with intestinal obstruction, and we decided to perform surgery. White knot sections were spread inside the abdominal cavity, and the small intestine appeared as a single block. This block was resected and examined for peritoneal mesothelioma. Peritoneal mesothelioma is thought to have incubation period of 20-25 years after exposure to asbestos, and the number of affected patients will increase in the future. In some cases, peritoneal mesothelioma occurs only in the peritoneum; therefore, diagnosis often becomes difficult. Once intestinal obstruction occurs, administering chemotherapy is difficult. Therefore, early diagnosis is thought to be very important.

RevDate: 2019-07-11
CmpDate: 2019-07-11

Liu XH, Wu H, Huang YF, et al (2019)

[Clinical characteristics of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis: a report of 6 cases].

Zhonghua yi xue za zhi, 99(24):1893-1897.

Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.

RevDate: 2019-07-03

Jiménez-Ramírez C, Casjens S, Juárez-Pérez CA, et al (2019)

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

Lung pii:10.1007/s00408-019-00244-1 [Epub ahead of print].

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.

METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.

RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.

CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

RevDate: 2019-08-13
CmpDate: 2019-08-13

Numano T, Higuchi H, Alexander DB, et al (2019)

MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.

Cancer science, 110(8):2485-2492.

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.

RevDate: 2019-08-13

Guazzelli A, Meysami P, Bakker E, et al (2019)

What can independent research for mesothelioma achieve to treat this orphan disease?.

Expert opinion on investigational drugs, 28(8):719-732.

Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.

RevDate: 2019-08-26

Pyana Kitenge J, Kapinga Kayembe D, Tshibangu Muamba M, et al (2019)

Malignant mesothelioma in Sub-Saharan Africa: A case report from Lubumbashi, DR Congo.

Environmental research, 176:108556.

Although asbestos has been used throughout Africa in the past decades, no reports of asbestos-related malignant mesothelioma are available from sub-Saharan Africa, except from South Africa and Zimbabwe. We present a case of a 39-year-old man who died from a histologically proven malignant mesothelioma of the peritoneum in Lubumbashi, DR Congo. No occupational exposure to asbestos could be found in his history. In view of his young age, we speculated that he had been exposed to asbestos as a child, which was highly plausible because he had grown up in one of the numerous mining estates of the region. The houses of these estates were often built with asbestos-containing materials, notably roofs made of corrugated asbestos-cement. The possibility of past domestic or environmental exposure to asbestos was substantiated by the identification of chrysotile and crocidolite fibres in samples of asbestos-cement collected from the home where the patient had lived as a child. To our knowledge, this is the first report of malignant mesothelioma from a country in the Central African region. We expect that heightened awareness and improved diagnosis will lead to the detection of more asbestos-related diseases in Africa.

RevDate: 2019-08-04

Tsao MS, Carbone M, Galateau-Salle F, et al (2019)

Pathologic Considerations and Standardization in Mesothelioma Clinical Trials.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer pii:S1556-0864(19)30502-7 [Epub ahead of print].

The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)-International Association for the Study of Lung Cancer-Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.

RevDate: 2019-06-28

Ospina D, Villegas VE, Rodríguez-Leguizamón G, et al (2019)

Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos.

Cancer management and research, 11:4997-5012 pii:205723.

Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.

RevDate: 2019-07-29

Ledda C, Caltabiano R, Vella F, et al (2019)

Fibulin-3 as biomarker of malignant mesothelioma.

Biomarkers in medicine, 13(10):875-886.

Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.

RevDate: 2019-08-26

Ramos-Bonilla JP, Cely-García MF, Giraldo M, et al (2019)

An asbestos contaminated town in the vicinity of an asbestos-cement facility: The case study of Sibaté, Colombia.

Environmental research, 176:108464.

INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town.

METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas.

RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 105 persons-year for males and 1.6 × 105 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos.

CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.

RevDate: 2019-06-21

Marsili D, Canepa A, Mossone N, et al (2019)

Environmental Health Education for Asbestos-Contaminated Communities in Italy: The Casale Monferrato Case Study.

Annals of global health, 85(1):.

BACKGROUND: Environmental health education contributes towards increasing awareness of communities to prevent exposure to hazardous substances. Casale Monferrato, the operating site for the Eternit asbestos-cement factory from 1907 to 1986, is a prioritized asbestos-contaminated site for remediation in Italy. The area is prone to severe asbestos-related diseases. About 50 cases of mesothelioma are diagnosed in Casale Monferrato annually; mesothelioma has been shown to be caused by occupational, environmental and domestic asbestos exposure.

OBJECTIVES: The goal of this paper is to analyze the Casale Monferrato case study in terms of youth engagement in environmental health education initiatives on asbestos risk and health impact. The paper aims at underlining the lessons learned in order to share the success of this initiative with other communities living in asbestos-contaminated sites in different countries.

METHODS: Peer education methodology has been used through the Asbestos Classroom to involve teachers, students and other local stakeholders in training activities, in selection of the contents for educational materials and interactive tools, as well as in choosing the presentation process for the aforementioned knowledge sharing instruments.

FINDINGS: From November 2014 to June 2018, 185 high school students and teachers were trained through the Asbestos Classroom. Through December 2018, they trained 3,241 classroom visitors. The Classroom relies on an inclusive participative process in which young people play a key role in the network of relationships within their community.

CONCLUSIONS: The paper corroborates the importance of engaging the educational system in communication efforts aimed at fostering collective awareness on environmental risk and health-related impacts for communities living in industrially contaminated sites. Considering the global dimension of the asbestos contamination and disease burden, this experience might be of relevance both in countries that banned asbestos and in those where asbestos is not yet prohibited.

RevDate: 2019-06-24

Metintas M, Ak G, Metintas S, et al (2019)

Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.

Journal of bronchology & interventional pulmonology, 26(3):210-218.

BACKGROUND: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.

METHODS: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.

RESULTS: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.

CONCLUSION: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.

RevDate: 2019-07-24

Catino A, de Gennaro G, Di Gilio A, et al (2019)

Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma.

Cancers, 11(6): pii:cancers11060831.

Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.

RevDate: 2019-06-17

Alchami FS, Attanoos RL, Gibbs A, et al (2019)

Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.

Applied immunohistochemistry & molecular morphology : AIMM [Epub ahead of print].

BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.

MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.

RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.

CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.

RevDate: 2019-06-15

Tsim S, Paterson S, Cartwright D, et al (2019)

Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.

Lung cancer (Amsterdam, Netherlands), 133:123-129.

OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.

MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.

RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.

CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.

RevDate: 2019-07-08
CmpDate: 2019-07-08

Zan X, Wang Y, Shi J, et al (2019)

Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.

Medicine, 98(24):e16028.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.

METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.

RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.

CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.

ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.

PROSPERO REGISTRATION NUMBER: CRD42019125880.

RevDate: 2019-06-12

Taylor BH, Warnock C, A Tod (2019)

Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.

BMJ open respiratory research, 6(1):e000413 pii:bmjresp-2019-000413.

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer linked to asbestos exposure and inhalation. As with other cancers, receiving a diagnosis of MPM is challenging and distressing. Particular challenges are associated with communicating a diagnosis of MPM, including explaining the disease and its prognosis, treatment options and legal and financial implications. Receiving A Diagnosis Of Mesothelioma (RADIO Meso) aimed to understand the experience of communicating a diagnosis of MPM from the perspective of patients, family carers and health professionals.

Methods: This qualitative study comprised 31 individual interviews with patients, family carers and health professionals. This was followed by two group interviews (n=42) and an electronic consultation exercise (n=39).

Results: This study provides unique insight into the mesothelioma diagnostic experience of patients, family carers and health professionals. Key findings include the importance of regarding diagnosis as a process, and provision of continuity and consistency. The clinical nurse specialist and effective multidisciplinary team working provided vital contributions to successful mesothelioma diagnostic communication. Facilitators to diagnostic communication included honesty and timeliness in communication, partnership working and maintaining a patient-centred approach. Challenges to enhancing mesothelioma diagnosis communication included accessing ongoing training, ensuring a suitable clinical environment and being able to allocate appropriate time.

Conclusion: The RADIO Meso study highlights factors that influence the communication of a diagnosis of MPM from the perspectives of individual patients and family carers. These findings provide the basis for a set of recommendations that can be used by health professionals to improve the MPM diagnostic experience.

RevDate: 2019-08-27
CmpDate: 2019-08-27

Takada K, Fujimoto N, Ozeki T, et al (2019)

Small intestinal intussusception in an adult.

Journal of clinical pathology, 72(7):510.

RevDate: 2019-06-06

Louw A, Badiei A, Creaney J, et al (2019)

Advances in pathological diagnosis of mesothelioma: what pulmonologists should know.

Current opinion in pulmonary medicine, 25(4):354-361.

PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.

RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.

SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.

RevDate: 2019-06-11

Santos Seoane SM, Yano Escudero R, V Arenas García (2019)

An unexpected cause of dysphagia: pleural mesothelioma.

Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva, 111(6):494-495.

Malignant mesothelioma usually originates from the pleura or peritoneum, and has a poor prognosis. The incidence of this type of tumor is increasing worldwide, which is probably a result of occupational or environmental exposure to asbestos. In 90% dyspnea, chest pain or a combination of both are usually the initial symptoms. Dysphagia only occurs in 1.4% and is very rare as the initial symptom. We present the case of a middle-aged patient, in whom the initial symptom was dysphagia, so an endoscopy was performed. This showed extrinsic compression of the esophagus that was demonstrated when performing the chest X-ray, in which it was revealed a posterior mediastinal mass surrounding the esophagus concentrically without mucosal invasion.

RevDate: 2019-06-16

Konen T, Johnson JE, Lindgren P, et al (2019)

Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota.

Environmental research, 175:449-456.

BACKGROUND: A vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant.

OBJECTIVE: We conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant.

METHODS: Cohort members alive in 1988 (n = 5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988-2011). Mortality rates of the cohort (2001-2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories.

RESULTS: We identified seven cases of mesothelioma, with elevated incidence only in females (PIR = 11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR = 1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females = 18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation.

CONCLUSIONS: Community exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.

RevDate: 2019-06-10

Kettunen E, Savukoski S, Salmenkivi K, et al (2019)

CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.

BMC cancer, 19(1):507 pii:10.1186/s12885-019-5652-y.

BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.

METHODS: We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.

RESULTS: We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.

CONCLUSIONS: We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.

RevDate: 2019-07-10
CmpDate: 2019-07-10

Colombino E, Capella S, Casalinuovo F, et al (2019)

Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.

The Science of the total environment, 683:267-274.

Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.

RevDate: 2019-08-07

Kamiya H, Peters S, Sodhi-Berry N, et al (2019)

Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.

Annals of work exposures and health, 63(7):719-728.

OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.

METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.

RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.

CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.

RevDate: 2019-07-16

Galani V, Varouktsi A, Papadatos SS, et al (2019)

The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.

Cancer chemotherapy and pharmacology, 84(2):241-253.

Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.

RevDate: 2019-06-14

Waqar AB, Menzies D, Casey M, et al (2019)

Paraneoplastic phenomenon in mesothelioma.

Thorax, 74(7):719-720.

A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.

RevDate: 2019-09-05

Milosevic V, Kopecka J, Salaroglio IC, et al (2019)

Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.

International journal of cancer [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.

RevDate: 2019-06-29

Scagliotti GV, Gaafar R, Nowak AK, et al (2019)

Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.

The Lancet. Respiratory medicine, 7(7):569-580.

BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.

METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged ≥18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.

FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5·3 months (IQR 2·8-7·3) in the nintedanib group and 5·1 months (2·7-7·8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6·8 months [95% CI 6·1-7·0]) and the placebo group (7·0 months [6·7-7·2]; HR 1·01 [95% CI 0·79-1·30], p=0·91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).

INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.

FUNDING: Boehringer Ingelheim.

RevDate: 2019-05-17

MacRae RM, Ashton M, Lauk O, et al (2019)

The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.

Lung cancer (Amsterdam, Netherlands), 132:24-27.

Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14th International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.

RevDate: 2019-07-09

Rosner D, Markowitz G, M Chowkwanyun (2019)

"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.

American journal of public health, 109(7):969-974.

The recent lawsuits against Johnson & Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson & Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art.

RevDate: 2019-06-19

de Boer NL, van Kooten JP, Burger JWA, et al (2019)

Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.

BMJ open, 9(5):e026779 pii:bmjopen-2018-026779.

INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.

INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.

RevDate: 2019-07-11

Loomis D, Richardson DB, L Elliott (2019)

Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.

American journal of industrial medicine, 62(6):471-477.

BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse.

METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.

RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.

CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.

RevDate: 2019-07-26

Salaroglio IC, Kopecka J, Napoli F, et al (2019)

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 14(8):1458-1471.

INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.

METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.

RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8%) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival.

CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.

RevDate: 2019-05-12

Labrèche F, Kim J, Song C, et al (2019)

The current burden of cancer attributable to occupational exposures in Canada.

Preventive medicine, 122:128-139.

Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.

RevDate: 2019-06-12

Fitzgerald RC, JM Rhodes (2019)

Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.

British journal of cancer, 120(12):1099-1104.

Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer "slops", we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.

RevDate: 2019-05-22

Barsky AR, Cengel KA, Katz SI, et al (2019)

First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.

Cureus, 11(2):e4102.

Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.

RevDate: 2019-08-19
CmpDate: 2019-08-19

Cui Y, Zha Y, Li T, et al (2019)

Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile.

Environmental science and pollution research international, 26(18):18708-18718.

Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.

RevDate: 2019-07-17

Nowak AK, McDonnell A, A Cook (2019)

Immune checkpoint inhibition for the treatment of mesothelioma.

Expert opinion on biological therapy, 19(7):697-706.

INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.

AREAS COVERED: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.

EXPERT OPINION: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.

RevDate: 2019-05-23

Macedo RF, Cerqueira EMFP, Algranti E, et al (2019)

High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.

American journal of industrial medicine, 62(6):503-510.

OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.

METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).

RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively.

CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.

RevDate: 2019-07-06

Oey H, Daniels M, Relan V, et al (2019)

Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.

Carcinogenesis, 40(6):724-734.

Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.

RevDate: 2019-04-29

Shih AR, RL Kradin (2019)

Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.

American journal of industrial medicine, 62(5):448-452.

Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.

RevDate: 2019-05-01

Rakhra A, Munir A, Chilukuri RS, et al (2019)

A Rare Case of Malignant Mesothelioma Presenting with Systemic Lupus Erythematosus Seropositivity: A Case Report and Review of Literature.

Cureus, 11(2):e4092.

While malignant mesothelioma may initially present in a variety of ways, it is uncommon to present with systemic lupus erythematosus (SLE) seropositivity and thus obscuring its diagnosis. Our case involves a 75-year-old Caucasian male with a past medical history of essential hypertension, remote prostate cancer status post prostatectomy, and lifetime nontobacco use presenting with progressive shortness of breath over one month. After a negative cardiac assessment, a postcardiac catheterization chest X-ray (CXR) revealed a right-sided moderate-to-large pleural effusion that, on further workup, was found to be exudative. Effusion studies were negative for malignancy and bacterial growth. Recurrent accumulation of fluid after a thoracentesis one week prior prompted an autoimmune work up. Positive markers included antinuclear antibodies, anti-double stranded DNA antibodies, and anti-histone antibodies, while anti-Smith antibodies were negative. Although SLE was initially suspected based on serologies, no clinical signs or symptoms were present to fulfill the diagnosis criteria. A trial of oral prednisone resulted in decreased pleural effusion size with no further recurrence. Additional studies included a CT scan of the chest that showed pleural masses confirmed with biopsy to be epithelioid mesothelioma. Given the patient's age and new diagnosis of malignant mesothelioma, we hypothesized that the presence of autoantibodies was likely false positives due to acquired autoantibodies with age, hyperactivity of the immune system from malignancy, and possible prior asbestos exposure.

RevDate: 2019-05-20

Zona A, Fazzo L, Minelli G, et al (2019)

Peritoneal mesothelioma mortality in Italy: Spatial analysis and search for asbestos exposure sources.

Cancer epidemiology, 60:162-167.

BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities.

METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.

RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.

CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.

RevDate: 2019-08-15
CmpDate: 2019-08-15

Nagamatsu Y, Oze I, Aoe K, et al (2019)

Physician requests by patients with malignant pleural mesothelioma in Japan.

BMC cancer, 19(1):383 pii:10.1186/s12885-019-5591-7.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.

METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.

RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.

CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.

RevDate: 2019-06-22

Christofidou-Solomidou M, Pietrofesa RA, Park K, et al (2019)

Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.

Toxicology and applied pharmacology, 375:81-93.

BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.

METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.

RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.

CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.

SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.

RevDate: 2019-04-17

Boffetta P, Donato F, Pira E, et al (2019)

Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.

International archives of occupational and environmental health pii:10.1007/s00420-019-01433-4 [Epub ahead of print].

PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.

METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.

RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).

CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.

RevDate: 2019-08-26
CmpDate: 2019-08-26

Fedrigotti A, Riccadonna A, D Riccadonna (2019)

"Candido's List": the workers of Collotta Cis & Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.

Annali dell'Istituto superiore di sanita, 55(1):90-93.

The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.

RevDate: 2019-08-26
CmpDate: 2019-08-26

Parolari G (2019)

An outbreak of cancer and asbestosis among former amosite-exposed subjects in Ledro Valley, Italy. From discovery to environmental cleanup.

Annali dell'Istituto superiore di sanita, 55(1):80-89.

Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.

RevDate: 2019-08-26
CmpDate: 2019-08-26

Marsili D, Magnani C, Canepa A, et al (2019)

Communication and health education in communities experiencing asbestos risk and health impacts in Italy.

Annali dell'Istituto superiore di sanita, 55(1):70-79.

INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.

METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.

DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.

CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.

RevDate: 2019-04-22

Finkelstein MM (2019)

A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.

Toxicology and applied pharmacology, 371:1-2.

Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.

RevDate: 2019-04-04

Warby A, Dhillon HM, Kao S, et al (2019)

A survey of patient and caregiver experience with malignant pleural mesothelioma.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer pii:10.1007/s00520-019-04760-x [Epub ahead of print].

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.

METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.

RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.

PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).

CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.

RevDate: 2019-05-20

Lococo F, Di Stefano T, Rapicetta C, et al (2019)

Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.

Lung, 197(3):387-390.

We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.

RevDate: 2019-04-04

Haygarth M, Zaw KK, Yachmenikova V, et al (2019)

Bilateral diffuse pulmonary infiltrates secondary to malignant peritoneal mesothelioma - A rare clinical presentation.

Respiratory medicine case reports, 26:326-327 pii:S2213-0071(19)30018-8.

Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.

RevDate: 2019-07-29
CmpDate: 2019-07-29

Muralidhar V, Raghav P, Das P, et al (2019)

A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.

BMJ case reports, 12(3): pii:12/3/e227882.

India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.

RevDate: 2019-04-12

Reid A, Franklin P, Berry G, et al (2019)

Response to letter by Farioli et al.

Occupational and environmental medicine, 76(5):356.

RevDate: 2019-08-06

Koutros S, Lubin JH, Graubard BI, et al (2019)

Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.

American journal of epidemiology pii:5423749 [Epub ahead of print].

We extended the mortality follow-up of a cohort of 25,460 workers employed at eight acrylonitrile (AN)-producing facilities in the United States by 21 years. Based on 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and mortality. Standardized mortality ratios (SMR) based on deaths through December 31, 2011 were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios (HR) were estimated by Cox proportional hazards regression. All-cause mortality and mortality from total cancer were less than expected compared with the U.S. population. We observed an excess of death due to mesothelioma (SMR=2.24,95%CI:1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (N=808 deaths), with an HR>12.1 ppm-year vs Unexposed=1.43 (95%CI:1.13-1.81, p-trend=0.05), lagged 10-yrs, that was robust in sensitivity analyses adjusting for smoking and co-exposures including asbestos. Mortality from bladder cancer (HR, lagged 10 years>2.56 ppm vs Unexposed=2.96 (95%CI:1.38-6.34,p-trend=0.02) and pneumonitis (HR>3.12 ppm-year vs Unexposed=4.73 (95%CI:1.42-15.76,p-trend=0.007) was also associated with AN exposure. This study provides additional evidence of an association between AN exposure and lung cancer, as well as possible increased mortality from bladder cancer and pneumonitis.

RevDate: 2019-08-12

Kennedy JM (2019)

The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.

Forensic science, medicine, and pathology, 15(3):458-462.

Pseudomesotheliomatous carcinomas (PMC) are rare tumors that clinically, macroscopically, and sometimes histologically resemble malignant pleural mesotheliomas. We report a case of a 91 year woman who was found to have diffuse nodular pleural thickening and a lung mass during a workup for persistent cough. She declined rapidly and died before a histologic diagnosis could be made. Postmortem examination revealed a tumor that diffusely involved the pleural surface with local extension into the chest wall, pericardium, and diaphragm along with a concurrent lung mass. Histologic examination showed poorly-differentiated cells predominantly arranged in sheets, cords, and nests with focal glandular differentiation. An immunohistochemical panel of calretinin, WT1, BEREP4, MOC31, and TTF1 confirmed the diagnosis of primary lung adenocarcinoma. The macroscopic, histologic, and immunohistochemical features used to distinguish metastatic and primary lung adenocarcinoma from epithelioid malignant mesothelioma are discussed. The distinction of malignant mesothelioma from pseudomesotheliomatous carcinoma is important for medicolegal reasons regarding asbestos related compensation claims.

RevDate: 2019-03-29

Algranti E, Ramos-Bonilla JP, Terracini B, et al (2019)

Prevention of Asbestos Exposure in Latin America within a Global Public Health Perspective.

Annals of global health, 85(1):.

BACKGROUND: Asbestos consumption in Latin America (LA) amounts to 10% of yearly global production. Little is known about the impact of asbestos exposure in the region.

OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.

DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.

RevDate: 2019-06-23

Linton A, Blinman P, Kao S, et al (2019)

Patterns of care and survival of older patients with malignant pleural mesothelioma.

Journal of geriatric oncology, 10(4):573-576.

OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.

MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70 years, 70-80 years or > 80 years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).

RESULTS: We identified 910 patients; 41% were aged <70 years, 40% were aged 70-80 years, and 19% were aged >80 years old. Median OS decreased with increasing age: 13.5 months in <70 years, 9.5 months in 70-80 years and 7.1 months in >80 years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p < .001) for patients <70 and 70-80 years receiving chemotherapy (16.8 vs 7.0 months; 13.9 vs 5.8 months respectively), but not for patients >80 years.

CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.

RevDate: 2019-03-27

Grosso F, Croce A, Libener R, et al (2019)

Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.

Tumori [Epub ahead of print].

PURPOSE:: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.

METHODS:: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.

RESULTS:: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.

CONCLUSIONS:: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).

Timelines

ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.

Biographies

Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )