History Of Occupational Asbestos Exposure Research Articles

Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features.

Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using the FACETS algorithm. 210 patients were evaluable for LOH analysis using FACETS. In this cohort, GNH was detected in 10 cases (4.8%). Compared to non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, while SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, p=0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Out of three patients with GNH DPMs who received immune checkpoint blockade (ICB), two achieved a clinician assessed partial response. GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary ICB response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

Cytological Assessment of Desmoplastic Malignant Pleural Mesothelioma in an Autopsy Case.

Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy. A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization. Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.

Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases. Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Symptomatic Cerebral Metastases In Malignant Pleural Mesothelioma: A Rare Case Report

Abstract Casestudy: Malignant mesothelioma is an aggressive tumor with dismal prognosis. Incidence in the United States is approximately 3300 cases/year, and the most common site is the pleura. Although mesothelioma is usually a locally invasive tumor, distant metastases to liver, adrenal glands, kidney and contralateral lung have been described. Brain metastases are observed in less than 3% of metastatic cases and most have been detected incidentally at autopsy. Symptomatic brain metastases are unusual. We describe a case of a 77 year old gentleman with history of occupational asbestos exposure who presented with shortness of breath and dry cough. The radiological investigations revealed left pleural thickening with pleural effusion, which on biopsy proved to be biphasic malignant mesothelioma. Despite multi-modality therapy, the patient showed local disease progression. Following 37 months of initial diagnosis, he developed progressive left-sided weakness. Brain MRI revealed a 1.7 cm enhancing mass involving right posterior frontal lobe, with extensive edema in the surrounding tissue. On biopsy, mass was composed of nests and sheets of round-to-spindled cells with scant eosinophilic cytoplasm, separated by fibrous septa. Brisk mitotic activity and necrosis were present. There was a sharp border with adjacent brain parenchyma. The tumor was positive for WT-1, calretinin, and cytokeratins and negative for Ber-Ep4 and glial fibrillary acid protein by immunohistochemistry. The histological appearance of the tumor was similar to that of the pleural biopsy. Thus a diagnosis of metastatic malignant mesothelioma was made. This solitary metastasis was treated with resection and post-operative stereotactic radiation. The 3-month follow-up brain MRI revealed nodular enhancement within the cavity with multiple supra- and infra-tentorial enhancing lesions, and leptomeningeal enhancement, most consistent with progressing metastatic disease. With the advancements in treatment options that has improved survival in malignant mesothelioma patients, the pathologist and neurosurgeon should be aware of the diagnostic possibility intra-operatively which may alter the management.

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

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. Additionally, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The chief 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 non-neoplastic 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 3 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 the adjacent tissue of a case without occupational exposure. The presence of asbestos fibers in 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.

Abstract 5038: Chrysotile asbestos fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure

Abstract Asbestos describes a group of naturally occurring fibrous silicate mineral compounds. Its use dates back thousands of years but became widespread in the late 19th century through the late 20th century due to its favorable industrial properties, including its strength, flexibility and thermal properties, with peak use in the United States occurring in the 1970s. Asbestos has been associated with a number of chronic respiratory diseases, including malignancy, and was first linked to mesothelioma and lung cancer in the early to mid part of the 20th century. Despite the known health risks, asbestos is not universally banned and is still in use in many countries (including the United States), with an estimated 125 million occupationally-exposed individuals worldwide. In addition to mesothelioma and lung cancer, asbestos has also been implicated as a risk factor for squamous cancers involving the upper airway, in particular laryngeal and pharyngeal carcinoma, as indicated by recent meta-analyses; however, evidence for the latter associations is based solely on epidemiologic data from observational studies. The primary objective of this work was to attempt to strengthen the evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding the tumor, thus providing a more definitive biological link between exposure and disease. Six HPV-negative laryngeal and pharyngeal squamous cell carcinoma cases were selected from a large population-based case-control study of head and neck cancer, plus one case with no occupational exposure history as a control. Briefly, detailed occupational history was available for 1,056 head and neck cancer cases enrolled through major teaching hospitals located in Boston, Massachusetts. Occupational data was reviewed to identify those with an occupational history of asbestos exposure. Tissue cores were obtained from adjacent non-neoplastic tissue in tumor blocks from the initial primary tumor resection from a subset of 6 cases with a history of occupational-asbestos exposure and 1 case with no reported occupational exposure (control). A count of asbestos fibers >5um was performed on the cores from each case at Duke University using a scanning electron microscope equipped with an energy dispersive x-ray analyzer (EDXA). Despite the low volume of input tissue, chrysotile asbestos fibers were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure; all 3 cases had tumors originating in the larynx. This is the first study to demonstrate the presence of asbestos fibers in the larynx of cases with laryngeal squamous cell carcinoma, adding an additional line of physical evidence implicating asbestos as an etiologic factor for laryngeal squamous cell carcinoma. Citation Format: Stephanie K. Wronkiewicz, Victor Roggli, Damaris Kuhnell, Rondi A. Butler, Karl T. Kelsey, Scott M. Langevin. Chrysotile asbestos fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5038.

First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications

BackgroundThe PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported.Case presentationWe here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing.Discussion and conclusionsWe here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.

Peritoneal Mesothelioma: A Challenge to Medical Profession

Malignant peritoneal mesothelioma (MPM) is an extremely rare cancer of peritoneum. It is associated with very poor prognosis due to late presentation and non-specific symptoms. We present a case of primary peritoneal mesothelioma in a 54 year old Hispanic female. She presented with epigastric abdominal pain and bloating for 5 months in the background of chronic non-specific abdominal discomfort. She had no history of occupational asbestos exposure, family history of cancer, smoking or weight loss. Her hemoglobin and chemistry were normal. Initial abdominal CT showed non-specific changes including loculated intra-abdominal ascites and mild epiphrenic adenopathy. Patient was referred for diagnostic laparoscopy. However, surgeons did not proceed with a surgical intervention initially. Her upper endoscopy and cystoscopy were performed and were normal. Her prior colonoscopy was normal. Repeat abdominal CT scan 3 month later revealed moderate volume of abdominal and pelvic ascites, worsening epiphrenic adenopathy, and mildly thickened anterior urinary bladder wall. Diagnostic laparoscopy was performed. Numerous implants were found on serosal surface of internal organs, peritoneum and omentum. Pathology specimen was consistent with malignant mesothelioma-Epithelioid type. Patient underwent debulking surgery, including resection and reconstructions of right hemi-diaphragm, cholecystectomy, right colectomy, partial gastrectomy, distal pancreatectomy, splenectomy, transverse colectomy, with temporary loop ileostomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) and cisplatin therapy for 6 months. Patient is disease free at 3 years postoperatively, and she is doing well with close follow-up. Malignant peritoneal mesothelioma is very difficult to diagnose due to nonspecific clinical presentation and clinical course. Diagnosis requires high level of clinical suspicion. Diagnosis is based on good quality imaging, pathology and immunohistochemistry. MPM can be treated with debulking surgery and intra-peritoneal chemotherapy or radiotherapy.

Environmental asbestos exposure and risk of mesothelioma.

Mesothelioma is commonly considered an occupational disease occurring as a result of asbestos exposure in the workplace. Several avenues for environmental asbestos exposures have been described and may be associated with asbestos related disease, including mesothelioma. Worker take-home asbestos, or para-occupational exposure, has been well documented and is the most commonly reported pathway for asbestos exposure among mesothelioma cases that do not have history of occupational asbestos exposure. Observational studies have evaluated several communities with elevated mesothelioma incidence and environmental exposures attributed to local asbestos-related industries. Potential, but uncertain, mesothelioma risk also may be associated with general population asbestos exposure through contact with asbestos-containing commercial products, particularly housing materials that can be easily disturbed through normal activity. Finally, studies have described elevated mesothelioma incidence in several areas where populations are exposed to naturally occurring asbestos materials. These various environmental asbestos exposure pathways are poorly understood, and further studies should be pursued to evaluate their respective importance for population mesothelioma risk.

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

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

Elemental analysis of histological specimens: a method to unmask nano asbestos fibers.

There is an increasing amount of evidence that nanoparticles may enhance toxicological potential in comparison to the same material in the bulk form. The aim of this study was to develop a new method to unmask asbestos nanofibers from Formalin-Fixed Paraffin-Embedded (FFPE) tissue. For the first time, in this study we applied Energy Dispersive X-ray (EDX) microanalysis through transmission electron microscopy to demonstrate the presence of asbestos nanofibers in histological specimens of patients with possible occupational exposure to asbestos. The diagnostic protocol was applied to 10 randomly selected lung cancer patients with no history of previous asbestos exposure. We detected asbestos nanofibers in close contact with lung cancer cells in two lung cancer patients with previous possible occupational exposure to asbestos. We were also able to identify the specific asbestos iso-type, which in one of the cases was the same rare variety used in the workplace of the affected patient. By contrast, asbestos nanofibers were not detected in lung cancer patients with no history of occupational asbestos exposure.The proposed technique can represent a potential useful tool for linking the disease to previous workplace exposure in uncertain cases. Furthermore, Formalin-Fixed Paraffin-Embedded (FFPE) tissues stored in the pathology departments might be re-evaluated for possible etiological attribution to asbestos in the case of plausible exposure. Since diseases acquired through occupational exposure to asbestos are generally covered by workers’ insurance in most countries, the application of the protocol used in this study may have also relevant social and economic implications.

Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma

ObjectivesImmune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM). Materials and methodsA selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area. ResultsIncreased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone. ConclusionsOccupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.

Reduced lung function in smokers in a lung cancer screening cohort with asbestos exposure and pleural plaques.

While low dose computed tomography (LDCT) screening for lung cancer is recommended for high-risk smokers, ages 55-74 years, information about asbestos exposure may not be routinely elicited. Asbestos exposure is associated with declining respiratory function over time; however, the effect of a history of asbestos exposure in LDCT screening cohorts is limited. We report the relationship between asbestos exposure and pulmonary function in a cohort of heavy smokers with a history of occupational asbestos exposure, hypothesizing that these subjects will have additional decreased pulmonary function. We also examined relationships between spirometric measurements and the presence of isolated pleural plaques. A cross-sectional study was performed using data from the NYU Lung Cancer Biomarker Center cohort to compare study subjects with a history asbestos exposure primarily in the period since 1970 when tighter federal standards were in place (n = 359) to those without asbestos exposure (n = 1038) with respect to pulmonary function, LDCT lung imaging findings, and clinical symptoms. We further classified individuals with asbestos exposure by length of exposure time to examine the effect of duration of exposure on pulmonary function. Lastly, for asbestos-exposed participants, we examined the association of spirometric measurements with the presence of absence of isolated pleural plaques. Individuals with asbestos exposure had decreased FVC % predicted compared to those with no asbestos exposure (76% vs. 85% predicted, P < 0.01) and FEV1 % predicted (64% vs. 67% predicted, P < 0.01). Since there was no change in FEV1 /FVC ratio, the findings are consistent with restrictive impairment. Those with ≥20 years of exposure had a lower mean FVC % predicted compared to those with less than 20 years of exposure (74% vs. 78% predicted, P = 0.017). Individuals with asbestos exposure were more likely to have pleural plaques (P < 0.001) on CT. Those with isolated pleural plaques had lower mean % predicted FEV1 (P = 0.005) and FVC (P = 0.001) compared to those without pleural plaques. Occupational asbestos exposure in a cohort of heavy smokers was associated with a significant restrictive decline in pulmonary function, with longer duration of exposure associated with greater decline. The presence of isolated pleural plaques was also associated with reduced lung function.

Trends in Asbestos and Non-asbestos Fibre Concentrations in the Lung Tissues of Japanese Patients with Mesothelioma

We aimed to elucidate changes in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma over time. Lung tissues were obtained from 46 patients with mesothelioma who died or underwent surgery between 1971 and 2005. All of the patients had a history of occupational asbestos exposure. We classified patients into four groups according to the period during which their lung tissue was obtained. Asbestos and non-asbestos fibre concentrations were determined by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure. From the 1970s to the 2000s, we observed a decrease in the geometric mean of total asbestos concentration (67.4-1.05 million fibres per gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years, and the mean duration since the last exposure increased from 0.3 to 21.5 years. The percentage of longer fibres to total fibres tended to increase over time, whereas the mean fibre length did not differ significantly. The present study suggested that asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma who have occupational histories of asbestos exposure may have decreased from the 1970s to the 2000s.

Abstract 5475: National survey of malignant mesothelioma and asbestos exposure in Japan

Abstract A newspaper article published in June 2005 reported that 5 residents who lived near the now-closed asbestos cement pipe plant in Amagasaki developed pleural mesothelioma. The asbestos-related problems that the article described caused much social concern resulting in the so-called ‘Kubota shock.’ Patients who have a history of occupational asbestos exposure and have developed malignant mesothelioma are provided worker's compensation in Japan. However, among 878 cases of death due to mesothelioma in 2003, only 85 cases were actually compensated. Based on this, we initiated this retrospective survey and extracted 6,030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM including the association with asbestos exposure (AE). Among them, clinical diagnosis of MM was confirmed in 929 cases. The origin of MM included the pleura in 794 (85.5%) cases, the peritoneum in 123 (13.2%) cases, the pericardium in 7 (0.8%) cases, and the testicular tunica vaginalis in 5(0.5%) cases. The histological subtype of MM included 396 (55.9%) epithelioid, 154(21.7%) sarcomatoid, 126 (17.8%) biphasic, and 33 (4.7%) cases classified as other types. AE was indicated in 76.8% and pleural plaques were detected in 34.2% of all MM cases. Asbestos particles were determined in 103 MM cases. More than 1,000 asbestos particles per gram dried lung tissue were detected in 74.8%, and more than 5,000 particles were detected in 43.7% of the cases. We compared the patient characteristics and the diagnostic procedures of MM before and after the ‘Kubota shock’. Compared to the early phase of this study (2003-2005), the median age at diagnosis of MM was higher, the number of cases without definite diagnosis of MM was lower, the proportion of cases diagnosed by thoracoscopy was higher, and the percentage of the cases in which the occupational history was described in the medical record was significantly higher in the late phase (2006-2008). Our study confirmed that more than 70% of MM cases in Japan are associated with AE. The ‘Kubota shock’ might affect some features pertaining to MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5475. doi:1538-7445.AM2012-5475

Malignant pleural mesothelioma: A retrospective analysis of clinicopathological and survival data.

The aim of this study was to analyze the clinicopathological features of malignant pleural mesothelioma (MPM) and evaluate the therapeutic measures offered to patients with MPM and their impact on survival. Data was retrospectively collected from the medical records of 304 patients who presented to the Department of Clinical Oncology and Nuclear Medicine, Ain Shams University between January 2003 and December 2008. The mean age of patients was 52.1 years (range 24-87 years). One hundred and ninety patients (62.5%) came from endemic areas and/or gave history of occupational asbestos exposure. One hundred and sixty-nine patients received chemotherapy. There was a significant difference between the median survival for patients who received chemotherapy (9 months, 95% CI 7.69-10.30) and those who were offered best supportive care (2 months, 95% CI 0.09-3.91). Other factors that affected the survival negatively were: non-epithelial pathology (P= 0.001); age >50 years (P= 0.012); bad performance status (P= 0.001); non-platinum based chemotherapy (P= 0.0001); and progressive disease (P= 0.000). Cox regression analysis revealed that the factors that predicted shorter survival were patients being offered best supportive care rather than chemotherapy and progressive disease. MPM is a growing health problem in Egypt that needs more attention. The current analysis of data reflects the importance of maintaining a high index of suspicion to allow for early diagnosis, especially for cases that live in areas with high asbestos exposure and for people who work in occupations that expose them to asbestos as well as their family members. Prospective randomized trials comparing multimodality approaches to other forms of treatment and including quality of life assessment are warranted.

Malignant Mesothelioma: A Clinical Study of 238 Cases

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

Clinical investigation of malignant mesothelioma in Japan

The asbestos-related problems caused much social concern; however, no large-scale study was conducted about clinical features of MM in Japan. Patients with MM who have a history of occupational asbestos exposure (AE) are provided worker's compensation in Japan. However, only about 10% of MM cases were actually claimed and compensated. So there is still controversy over the association between MM and AE. The aim of this study is to investigate the clinical features of MM. We also aimed to clarify the association between MM and occupational AE in Japan. We examined the clinical features of MM cases. Clinical information was obtained including gender, age, site of origin, pathological subtype, radiological findings, and treatment outcome. To investigate the association between MM and AE, investigators interviewed all patients regarding work and residential history. Between January 2005 and December 2007, 105 cases (median age: 63years, range 35-80, male/female: 88/17) were diagnosed with MM in the Rosai Hospital group and related facilities. Among them, 94(89.5%) cases originated in the pleura, 7(6.7%) in the peritoneum, 2(1.9%) in the pericardium, and 1(0.9%) in the tunica vaginalis testis. There were 69(65.7%) epithelioid, 19(18.1%) biphasic, 16(15.2%) sarcomatoid, and 1 unclassified pathological subtypes of MM. A favorable survival rate was indicated in the patient group of MPM that underwent surgery compared to others, though it was not statistically significant (P=0.1743). The occupational AE was indicated in 89 cases (84.8%). Three patients had no history of occupational AE, but lived with someone who was in an occupation that handled asbestos. There were two patients in which AE was indicated in their life environment. Altogether, AE was indicated in 93(88.6%) patients. This study stresses the urgent need for physicians to acknowledge the association between MM and AE, and to inquire thoroughly regarding AE to the patients with MM.

Evaluation of the distribution of ferruginous bodies and the kind of asbestos fibers in the lungs in lung cancer cases with definite occupational history of asbestos exposure

The distribution of ferruginous bodies in the lungs of ten lung cancer patients with definite occupational history of asbestos exposure and the kind of core fibers in the center of the ferruginous bodies were evaluated. Six cases had a history of asbestos exposure in shipyards or Japanese naval dockyard, and the other four also had a definite history of occupational asbestos exposure. The largest number of ferruginous bodies was detected in the upper or middle lobes, but in only one case the lung cancer was present in the lobe in which the largest number of ferruginous bodies was detected. Therefore, the primary site of lung cancer is not dependent on the number of ferruginous bodies. The core of the ferruginous bodies was chrysotile in 7 cases, and amosite fibers were frequently detected in the three cases from the Japanese naval dockyard.

Epidemiologic survey of pleural plaques among inhabitants of Matsubase exposed to asbestos

A high prevalence of pleural plaques (41.5%, 148/357) was found during a mass screening for lung cancer in Matsubase town in 1988. The inhabitants of this town were carefully studied each year from 1988 to 1993. The vast majority (81.2%) of inhabitants over the age of 20 years underwent chest roentgenography at least once during this period. Pleural plaques were detected by CT in 938 subjects, which is 17.3% of those studied and 4.1% of the total population. A total of 89 had an occupational history of asbestos exposure, 64 (71.9%) of whom had pleural plaques. However, these subjects with occupational exposure accounted for only 6.8% of the 938 subjects, and therefore most of the pleural plaques seemed to have been caused by general environmental exposure. The incidence of plaques was greater in older subjects: among those in the seventh decade of life it was more than eight times higher than among those in the fourth decade of life. Anthophyllite was detected in the main asbestos mill. The concentrations of asbestos fibers in the air and water near the old asbestos mills and factories were not high. The death rates and the adjusted mortality rates due to lung cancer in Matsubase were lower than in surrounding towns and lower than in Kumamoto prefecture as a whole. These results indicate that there is now no environmental contamination by asbestos fibers in Matsubase town. No cases of malignant mesothelioma have been confirmed in this town during the past 17 years.