Malignant Mesothelioma: Overcoming Diagnostic Hurdles.

Malignant pleural mesothelioma, an aggressive neoplasm frequently linked to asbestos exposure, is often detected at an advanced stage. This report details the case of a 58-year-old mason who presented with left-sided chest pain, and shortness of breath, accompanied by weight loss for a month. A positron emission tomography (PET) scan revealed increased uptake along the pleural surface, as well as in several mediastinal lymph nodes and the left supraclavicular lymph node. Thoracoscopy revealed the presence of multiple nodules on the costal pleura. Despite repeated negative results from pleural effusion cytology, cell block analysis, and pleural biopsies, the diagnosis of malignant mesothelioma (MM) was ultimately established through an ultrasound-guided (USG) biopsy of the left supraclavicular lymph node, with immunohistochemical confirmation using calretinin.

Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Colorectal Cancer and Asbestos Exposure: A Women's Health Perspective.

BACKGROUND: Colorectal cancer (CRC) is considered a "man's disease". However, emerging data show that females may have a higher prevalence of certain risk factors. A potential causal role of asbestos in CRC carcinogenesis has been suggested. This relationship is controversial, and only a few studies have focused on exposed female populations. The aim of this study was to review the scientific literature related to asbestos-related CRC incidence and mortality rates in female populations to address gender bias in the existing research. METHODS: A systematic review was performed following PRISMA statement. RESULTS: Fourteen studies reporting 92 cases in total were included. Most women were aged 50 years or older and were employed in occupational activities with high asbestos exposure (steel, textile, and asbestos-cement industry) for at least 10 years. In one single case, household asbestos exposure was reported. The colon was the primary location of the tumor in 47 out of 92 cases. Three women were also affected by synchronous or metachronous peritoneal mesotheliomas. CONCLUSIONS: This study revealed a general methodological "gender bias" in scientific research. A significantly higher representation of women in clinical studies is needed to clarify the link between asbestos exposure and the development of colorectal cancer.

Primary Peritoneal Mesothelioma Affecting the Greater Omentum That Mimicked an Omental Infarction: A Case Report.

Introduction: Malignant peritoneal mesothelioma (MPM) is a rare cancer that is associated with asbestos exposure. The diagnosis can be difficult given the nonspecific nature of presenting symptoms and the presence of concomitant confounding findings. Case Presentation: We report a 71-year-old male who presented with right lower quadrant pain and new-onset ascites. CT imaging of the abdomen/pelvis demonstrated omental stranding concerning for a possible omental infarction. Subsequent imaging showed persistent omental edema but no identifiable soft tissue mass. A biopsy of the omentum showed atypical mesothelial proliferation, but pathology was unable to determine if proliferation was a neoplastic versus reactive process. Surgical oncology performed a diagnostic laparoscopy that showed peritoneal studding of the omentum. Subsequent immunohistochemical staining of the omentum demonstrated preservation of BAP1 expression and loss of MTAP expression, consistent with peritoneal mesothelioma. Conclusion: MPM is a rare and aggressive cancer with an overall poor prognosis. The diagnosis of MPM can be difficult based on the nonspecific clinical presentation, insufficient imaging and laboratory testing, and the presence of concomitant confounding findings, such as with this patient and his admitting diagnosis of omental infarction. This case demonstrates the importance of developing a broad differential while maintaining an awareness of heuristics that can influence clinical decision-making.

Environmental asbestos exposure and lung cancer.

Apart from living near an asbestos industry site, mine, or in an asbestos-contaminated house, environmental asbestos exposure is observed in certain regions where the (natural) soil is 'contaminated' with asbestos (fibers). In this essay, we review the association between environmental asbestos exposure and lung cancer in Turkey. Other studies have also suggested that environmental asbestos exposure is able to increase the risk of lung cancer. Lung cancer associated with environmental asbestos exposure seems to be diagnosed at a younger age, and the risk for women is in the same range as that for men. Our data indicate that the relationship between exposure dose and risk is linear and that a safe threshold cannot be established. Therefore, people living in areas with increased chances of environmental asbestos exposure should be mentored to take part in smoking cessation programs and considered candidates for inclusion in lung cancer screening programs. There is an obvious need for additional studies on this topic.

Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.

Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.

Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.

Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.

Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.

Measurement and removal of asbestos in residential dwellings to be demolished-urban transformation experience in Izmir, Turkey.

Asbestos has been used extensively in the construction industry for its superior insulation properties before its health hazards were discovered and its use eventually banned. It is likely that many residential buildings built before the 2000s in Turkey contain asbestos. Therefore, it is important to raise awareness of the potential danger of asbestos exposure during demolition work and to identify asbestos-containing materials and ensure their safe removal and disposal. This study is executed to determine the residential dwellings containing asbestos in Izmir, Turkey. The research included field studies to determine asbestos presence in the buildings that were damaged during the 2020 earthquake. Air measurements and bulk samples were taken from 50 buildings that would go through the demolition process. Eleven buildings were found to contain asbestos which corresponds to 22%. The detected asbestos type was 60% chrysotile (white asbestos). Results could be helpful for future demolition work, which are conducted in the same region that includes buildings with similar properties. Also, it is expected that the database created for this study could be useful in other studies in Turkey, where accurate statistical data related with asbestos measurements is essentially non-existent.

A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax.

Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.

Colorectal Cancer: 35 Cases in Asbestos-Exposed Workers.

BACKGROUND: Asbestos is considered one of the major global work-related carcinogens. Some studies suggest a potential causal relationship between asbestos exposure and colorectal cancer (CRC). However, the role of asbestos in CRC carcinogenesis is still controversial. METHODS: 35 claims of occupational CRC among asbestos-exposed workers were reviewed. All claims were rejected by the Italian National Institute for Insurance against Accidents (INAIL) due to the "lack of scientific evidence in the causality" between asbestos exposure and CRC; causality was finally assessed in civil trials. All cases were categorized by age, gender, industry type, task, exposure and latency periods, anatomical location, and histopathological characteristics of CRC and concomitant respiratory diseases. RESULTS: Most workers were males aged 60 years or more and employed in occupational activities with extensive use of asbestos for over 20 years. In 31 out of 35 cases, CRC was diagnosed over 39 years after employment. Right-sided colic adenocarcinoma was diagnosed in nine cases; rectum was involved in eight cases. Respiratory comorbidities were observed in 22 workers. CONCLUSIONS: Our study provides some interesting points in the assessment of the causal relationship between asbestos exposure and CRC.

Mongolia: Failure of Total Banning of Asbestos.

The primary uses of asbestos in Mongolia are in thermal power plants, construction and at railway companies. There is, however, limited data on both asbestos consumption and asbestos related disease (ARD) in Mongolia. The purpose of this paper is to report on the failure to completely ban asbestos in Mongolia. To write this paper, available asbestos related literature, published nationally and internationally, and legal regulations, national standards and guidelines on asbestos control were reviewed. Mongolia consumed a total of 44,421.9 metric tons of asbestos containing materials (AMCs) between 1996 and 2014. As a key indicator of ARD, 54 cases of mesothelioma were diagnosed at the National Cancer Center by pathological testing of tissue samples between 1994 and 2013. In 2010, The government made the decision to stop all types of asbestos use under the Law on Toxic and Hazardous Substances. However, there was no nationwide action plan to gradually reduce asbestos use, promote substitutes and raise awareness of health hazards and economic burdens in the future from asbestos use. There was also no planning for safe removal of asbestos currently in place. After the banning of asbestos, thermal power plants told the government that they could not produce electricity without insulation of AMCs and substitution materials were economically not feasible. Due to pressure from the energy sector and inadequate awareness of asbestos hazards, the government changed the legal status on asbestos in 2011 as a restricted chemical. Asbestos is still allowed to be used, and workers and the general community are still unnecessarily exposed to this carcinogen.

ATG5 as biomarker for early detection of malignant mesothelioma.

OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups. RESULTS: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.

Lung cancer screening an asbestos exposed population: Existing lung cancer risk criteria are not sufficient.

BACKGROUND AND OBJECTIVE: Asbestos is a major risk factor for lung cancer, with or without tobacco smoke exposure. Low dose computed tomography (LDCT) screening for early lung cancer is effective but only when targeting high risk populations. This study aimed to analyse the effectiveness of LDCT screening in an asbestos exposed population and to compare lung cancer screening program (LCSP) eligibility criteria. METHODS: Participants in an asbestos health surveillance program, the Western Australia Asbestos Review Program, underwent at least one LDCT scan and lung function assessment as part of annual review between 2012 and 2017. Lung cancer cases were confirmed through linkage to the WA cancer registry. Theoretical eligibility for different screening programs was calculated. RESULTS: Five thousand seven hundred and two LDCT scans were performed on 1743 individuals. The median age was 69.8 years, 1481 (85.0%) were male and 1147 (65.8%) were ever-smokers (median pack-year exposure of 20.0). Overall, 26 lung cancers were detected (1.5% of the population; 3.5 cases per 1000 person-years of observation). Lung cancer was early stage in 86.4% and four (15.4%) cases were never smokers. Based on current lung screening program criteria, 1299 (74.5%) of this population, including the majority (17, 65.4%) of lung cancer cases, would not have been eligible for any LCSP. CONCLUSION: This population is at raised risk despite modest tobacco exposure. LDCT screening is effective at identifying early-stage lung cancer in this population and existing lung cancer risk criteria do not capture this population adequately.

Occupational asbestos exposure and survival among lung cancer patients.

OBJECTIVE: This study investigated the association between occupational asbestos exposure (OAE) and survival in patients with histologically confirmed lung cancer (LC). METHODS: This monocentric study was conducted in the Comprehensive Cancer Centre Léon Bérard, Lyon, France. A systematic screening has been in place since 2014 for occupational exposure to carcinogens using a self-assessment questionnaire sent to all patients newly diagnosed with histologically confirmed LC identified through the multidisciplinary LC board from 2014 to 2019. When the physician suspected a work-related exposure from the questionnaire including job history, an occupational cancer consultation was carried out to detail carcinogen exposures and assess if the LC was work-related. Demographics, clinical characteristics and survival data were extracted from medical records. The association between asbestos exposure and overall survival (hazard ratio and 95% confidence intervals) was estimated by Cox proportional hazards regression. RESULTS: Overall, 702 patients were eligible to the present study, including 180 patients with OAE. In the crude analysis, LCs assessed as moderately or highly attributable to OAE were associated with decreased overall survival (HR = 1.32, 95 %CI 1.04-1.67) compared to LC without OAE or with a low degree of imputability to OAE (median follow-up 28.8 months). After adjustment for confounding (age at diagnosis, smoking status, stage, brain metastasis at diagnosis, and histology), the association of OAE with overall survival was no longer statistically significant (HR = 1.21, 95 %CI 0.94-1.56). CONCLUSION: Overall survival in occupationally asbestos exposed LC patients may be decreased in comparison with non-exposed LC patients, warranting further investigations in larger studies.

Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.

Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.

Validation and Recalibration of the Asbestos Removal Exposure Assessment Tool (AREAT).

OBJECTIVES: The Asbestos Removal Exposure Assessment Tool (AREAT) was previously developed to estimate exposure to respirable asbestos fibres during abatement processes. The current study describes the validation and recalibration of the AREAT model with external data. During model validation, the AREAT model was expanded to be able to estimate asbestos exposure from an additional source category: 'unspecified asbestos remnants'. METHODS: The validation dataset (n = 281) was derived from exposure measurement studies where for each exposure measurement the AREAT model parameters were coded and estimates were calculated. Pearson correlation coefficients (r) and intra class correlation coefficients (icc) were calculated as an indication of the agreement between the AREAT estimates and measured concentrations. In addition, the bias and the proportion of measurements with higher concentrations than model estimates were calculated. To expand and investigate model performance on exposure from 'unspecified asbestos remnants', a separate dataset was created with measurements collected during working with unspecified asbestos remnants, and similar validation comparisons were performed. Lastly, linear regression techniques were used to investigate possible improvements in model parameters. The model was recalibrated on a combined dataset consisting of the validation dataset and the original calibration dataset to increase model robustness. RESULTS: The validation comparisons showed good relative agreement (r) between AREAT estimates and measurements (r = 0.73) and a moderate absolute agreement (icc = 0.53). The overall relative bias was 108%, indicating an overall overestimation of exposure, and 4% of the estimated concentrations were higher than the actual measured concentrations. For the data subset concerning unspecified asbestos remnants, a moderate correlation between model estimates and measurement outcomes was found (r = 0.63). However, based on the low number of data in this subset, and moderate r, it was decided that cleaning of unspecified asbestos remnants is out of scope until more data are available. The results of this validation study suggested that two input parameters (product type friable material, efficacy of control measure foam) underestimated exposure. The effects of these parameters were updated to improve model performance. Compared to the original model, the recalibrated model resulted in slightly higher explained variance (62% compared to 56%) and lower uncertainty (15 compared to 17.3). CONCLUSION: The original AREAT model provided reliable asbestos exposure estimates with a sufficient level of conservatism taking into account the 90-percentile estimates. The model was further improved via the addition of a new feature and recalibration to predict asbestos exposure during the clean-up of unspecified asbestos remnants.

Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada.

PURPOSE: Canada was a major global asbestos producer and consumer. Geographic patterns of Canadian asbestos use and mesothelioma, a highly fatal cancer linked to asbestos exposure, have not been previously reported. This study summarized key trends in mesothelioma incidence by geography and time in two Canadian provinces, Ontario and British Columbia (BC), and explored how past workforce characteristics and geographic trends in asbestos production and use may shape variations in regional rates of mesothelioma. METHODS: We report trends in mesothelioma incidence (1993-2016) for Ontario and British Columbia using population-based incidence data that were age-standardized to the 2011 Canadian population. Historical records of asbestos production and use were analyzed to geo-locate industrial point sources of asbestos in Ontario and BC. The prevalence of occupations in regions with the highest and lowest rates of mesothelioma in Ontario and BC were calculated using labor force statistics from the 1981 Canadian Census. RESULTS: Regional mesothelioma rates varied in both provinces over time; more census divisions in both Ontario and BC registered mesothelioma rates in the highest quintile of incidences during the period 2009 to 2016 than in any prior period examined. Certain occupations such as construction trades workers were more likely to be overrepresented in regions with high mesothelioma rates. CONCLUSION: This work explored how studying asbestos exposure and mesothelioma incidence at small-scale geographies could direct cancer surveillance and research to more targeted areas. Findings indicated that regional variations in mesothelioma could signal important differences in past occupational and potentially environmental exposures.