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Bibliography on: Mesothelioma and Asbestos

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ESP: PubMed Auto Bibliography 14 Nov 2024 at 02:04 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®)

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RevDate: 2024-11-13
CmpDate: 2024-11-13

Wu Y, Zhao Y, Yu L, et al (2024)

Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib.

The Journal of international medical research, 52(11):3000605241287320.

Malignant mesothelioma is a rare highly invasive tumour originating from the mesothelial cells of the pleura, peritoneum and pericardium. Malignant pleural mesothelioma (MPM) is the most common type in all malignant mesothelioma. The onset of MPM is associated with exposure to asbestos and it can have an incubation period of up to 40 years. The incidence of MPM has been increasing worldwide in recent years, so more attention has been focused on its diagnosis, treatment and prognosis. Activating mutations, amplifications and fusions/rearrangements of the anaplastic lymphoma kinase receptor tyrosine kinase (ALK) gene are commonly seen in patients with non-small cell lung cancer. However, it is rare in MPM. This current case report describes a female patient with advanced MPM with an ALK gene fusion mutation. In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.

RevDate: 2024-11-08

Guglielmo P, Crivellaro C, Castello A, et al (2024)

Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [[18]F]FDG Alternatives.

Molecular diagnosis & therapy [Epub ahead of print].

Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([[18]F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[[18]F]FDG alternatives". Articles focused solely on [[18]F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [[18]F]/gallium-68 ([[68]Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [[18]F]Fluorothymidine ([[18]F]FLT), methionine labeled with carbon-11 ([[11]C]MET), and fluoromisonidazole labeled with fluorine-18 ([[18]F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [[18]F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [[18]F]FDG was similar to the other radiopharmaceuticals ([[68]Ga]/[18F]-labeled FAPI compounds, [[18]F]FLT, [[18]F]FMISO, [[11]C]MET, and [[68]Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [[18]F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.

RevDate: 2024-11-08

Gold LT, Bray SE, Kernohan NM, et al (2023)

The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.

BJC reports, 1(1):4.

BACKGROUND: Malignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes. A large proportion of mesotheliomas have been shown to be arginine auxotrophic, leading to new research for therapeutics which might exploit this potential vulnerability.

METHODS: We measured the levels of General Control Non-derepressible 2 (GCN2) protein in malignant mesothelioma tumour samples and determined whether these levels correlate with clinical outcomes.

RESULTS: We observed that the expression levels of GCN2 correlated with patient survival and was an independent prognostic variable in pairwise comparisons with all available clinical data.

CONCLUSION: These findings suggest that GCN2 levels provides prognostic information and may allow for stratification of care pathways. It may suggest that targeting GCN2 is a viable strategy for mesothelioma therapy development.

RevDate: 2024-11-07

Lief S, Patibandla S, Ansari AZ, et al (2024)

Ascites as a Rare Manifestation of Malignant Peritoneal Mesothelioma: A Case Report.

Cureus, 16(10):e70982.

Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that originates from the mesothelial cells lining the parietal peritoneum or visceral peritoneum and extensively spreads within the abdominal cavity. It is a rare malignancy characterized by an insidious onset and poor prognosis. We present the case of a 79-year-old Caucasian male who experienced escalating abdominal pain for six weeks and acute abdominal distension. His medical history was significant for hypertension, gastroesophageal reflux disease (GERD), hypercholesterolemia, and prior coronary artery bypass grafting (CABG). The patient had a 30-pack-year smoking history and worked as a plumber and roofer until retirement. We also confirmed with the patient that he has never been diagnosed with asbestosis. He reported no family history of mesothelioma or related conditions. A computed tomography (CT) scan revealed a prior sternotomy, mild pleural calcifications, mild hepatic steatosis, diffuse peritoneal ascites, diffuse omental edema, and pelvic phleboliths. MPM was confirmed through histopathological examination, which revealed atypical mesothelial cells with high nucleus-to-cytoplasm ratios, prominent nucleoli, and irregular nuclear membranes. It also revealed tumor cells positive for p53, calretinin, WT1, and podoplanin (D2-40). This case highlights the importance of considering MPM in the differential diagnosis for patients with ascites and possible asbestos exposure, particularly with respect to occupational hazards, as it is a rare manifestation of the disease.

RevDate: 2024-10-31

Gilbert A, Wieland R, Zacher N, et al (2024)

Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.

The American Journal of dermatopathology pii:00000372-990000000-00439 [Epub ahead of print].

Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

RevDate: 2024-10-30

Behrouzfar K, Mutsaers SE, Chin WL, et al (2024)

Mesothelioma survival prediction based on a six-gene transcriptomic signature.

iScience, 27(10):111011.

Mesothelioma is a lethal cancer. Despite promising outcomes associated with immunotherapy, durable responses remain restricted to a minority of patients, highlighting the need for improved strategies that better predict outcome. Here, we described the development of a mesothelioma-specific gene signature that accurately predicts survival. Comprehensive gene expression analysis of asbestos exposed MexTAg Collaborative Cross mouse tumors revealed distinct tumor clusters characterized by epithelial mesenchymal transition/extracellular matrix, or immune infiltrate related gene expression profiles. Weighted gene co-expression network analysis (WGCNA) identified 20 hub genes that drove differential gene expression. Human homologues of these 20 hub genes were refined through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to identify a six-gene mesothelioma-specific prognostic signature that accurately predicted patient survival across four independent human mesothelioma datasets. Furthermore, this six-gene signature demonstrated the potential to predict treatment response, thus advancing the management of this challenging malignancy.

RevDate: 2024-10-29
CmpDate: 2024-10-29

Mei W, Yang SJ, YP Zhang (2024)

[Establishment and research progress of early diagnosis system for pleural mesothelioma].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases, 42(10):793-800.

Pleural mesothelioma (PMe) was associated with asbestos exposure.The Diagnosis of PMe is difficult due to the lack of specificity of clinical signs and symptoms, although there are many tools available for early diagnosis of mesothelioma. Most PMe patients are diagnosed at an advanced stage. This article reviews advances in strategies for early diagnosis of mesothelioma, focusing on breath analysis, early diagnosis of pleural effusion cytology in patients with mesothelioma, serum biomarkers and miRNA.

RevDate: 2024-10-29

Santos C, Sacadura-Leite E, Feijó S, et al (2024)

Translation, Cultural Adaptation, and Content Validation of a Pleural Mesothelioma Questionnaire to Portuguese Context - A Key Tool for Epidemiological Surveillance.

Portuguese journal of public health, 42(2):101-110.

OBJECTIVE: The main objective of this study was to describe the translation, cultural adaptation, and content validation process of the French National Surveillance Programme for Pleural Mesothelioma (FNSPPM) questionnaire for the Portuguese context.

METHODS: A search was conducted in the PubMed database and Web of Science, in the period from January 1, 1960, to December 31, 2022, to select the questionnaire. Forward and reverse translations, calculation of the content validity index (CVI) by a panel of experts (n = 9), and cognitive interviewing with individuals with at least one exposure to asbestos (n = 10) were performed. Experts rated items on a Likert scale (1-4) based on their relevance. The item-level content validity index (I-CVI), scale-level content validity index based on the average method (S-CVI/Ave), and scale-level content validity index based on the universal agreement method (S-CVI/UA) were calculated.

RESULTS: The final version of the FNSPPM questionnaire for the Portuguese context resulted from a translation and content validation process. The panel of experts considered the questionnaire relevant, with an I-CVI of up to 0.78 in 68 of 69 of the questions, an S-CVI/Ave of 0.98, and an S-CVI/UA of 0.90. The participants in the cognitive interviews reported an understanding of the questionnaire.

CONCLUSION: A validated FNSPPM questionnaire for the Portuguese context is now available to study individuals with pleural mesothelioma (PM) and asbestos exposure.

RevDate: 2024-10-29

Santos C, Dixe MDA, Sacadura-Leite E, et al (2023)

Asbestos Exposure and Malignant Pleural Mesothelioma: A Systematic Review of Literature.

Portuguese journal of public health, 40(3):188-202.

BACKGROUND: The relationship between exposure to asbestos and malignant pleural mesothelioma (MPM) is already well established. Nevertheless, much remains to be known about exposure thereto and the incidence and mortality from MPM.

OBJECTIVE: This systematic review aims to map the relationship between asbestos and MPM by studying the exposure to asbestos and the incidence and mortality of MPM.

METHODS: A systematic review was conducted relating asbestos and MPM. Exposure to asbestos, incidence, and mortality by MPM was reviewed. PubMed, Web of Science, Cochrane Library, RCAAP, DART-Europe, and the reference lists of included studies were searched, from January 1, 1960, to December 31, 2020. Methodological quality was checked, the risk of bias analysis was performed, a level of evidence grade was assigned, and descriptive data analysis was performed.

RESULTS: 3,484 unique citations were identified, which included seventeen observational studies that met inclusion criteria with a total of 1,104 patients. Heterogeneity is present between the included studies which range from a case series of 16 retrospective studies and 1 prospective study. Studies were mostly conducted in Europe, particularly in Italy (6), and were published between 1969 and 2020. The mean age of patients is approximately 66 years with a latency period between the first exposure and diagnosis of approximately 42 years. 14 studies present data regarding the occupational context and chrysotile and crocidolite are the most studied types of fibre. The incidence of cases occurred between the interval 1966 and 2014 and in 9 studies the mortality rate was 100% of patients.

CONCLUSION: There is high evidence to support the relationships between asbestos and MPM. However, the relatively scant information provided by the studies reinforces the need for well-conducted research and implementation of National Mesothelioma Surveillance Centres at a global level.

RevDate: 2024-10-24

Stevens ME, Tuttle BP, Brew DW, et al (2024)

An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).

Toxicology and industrial health [Epub ahead of print].

Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.

RevDate: 2024-10-24

Paremuzyan A, Onwubuya E, J Mathews (2024)

A Case of Malignant Pleural Mesothelioma With Unknown Asbestos Exposure.

Cureus, 16(9):e69966.

Malignant pleural mesothelioma (MPM) is a rare, locally invasive tumor that develops from mesothelial cells lining the lung's pleura. It is mostly associated with prolonged asbestos exposure. The long latency period between asbestos exposure and clinical symptoms makes diagnosing MPM challenging. This report describes a 57-year-old Hispanic female who presented with a persistent nonproductive cough and was ultimately diagnosed with advanced-stage pleural mesothelioma after extensive work-up. It highlights the difficulties in diagnosing MPM in patients without apparent asbestos exposure independent of age or gender.

RevDate: 2024-10-23

Suehiro T, Ahmad KM, Hoang NTD, et al (2024)

Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.

Journal of biochemistry pii:7833210 [Epub ahead of print].

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

RevDate: 2024-10-23

Guerra J, Pina JM, Andrade V, et al (2024)

Malignant Mesothelioma of the Tunica Vaginalis: About a Rare Clinical Case.

Cureus, 16(9):e69897.

Malignant mesothelioma (MM) of the tunica vaginalis is an exceedingly rare neoplasm, with fewer than 300 cases reported in the medical literature. Due to its rarity, epidemiology, and risk factors are still unclear, and it is unknown whether asbestos or chronic inflammatory conditions play a role in etiology. This case study presents a 70-year-old male patient with MM of the tunica vaginalis, detailing the diagnostic challenges, treatment procedures, and eventual progression to palliative care. The study underscores the importance of accurate diagnosis and the aggressive nature of the disease despite treatment efforts.

RevDate: 2024-10-22
CmpDate: 2024-10-22

Visonà SD, Pace MC, Consonni D, et al (2024)

Accuracy of the Lombardy Mesothelioma Registry: comparison with the autopsy database of Pavia University (Lombardy Region, Northern Italy).

Epidemiologia e prevenzione, 48(4-5):320-325.

OBJECTIVES: to evaluate the accuracy (completeness of case recording and diagnostic quality) of the Lombardy Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) through a comparison with the autopsy database of Pavia University (years 2000-2016).

DESIGN: validation study.

SETTING AND PARTICIPANTS: all mesothelioma records with incidence date between 01.01.2000 and 16.09.2016 were extracted from the RML. They were cross-referenced with deaths from any asbestos-related disease subjected to a forensic autopsy extracted from the archive of the Department of Public Health, Experimental and Forensic Medicine of Pavia University.

MAIN OUTCOMES MEASURES: using the postmortem diagnosis by Pavia University as the gold standard, RML sensitivity and specificity and their 95% confidence intervals (95%CI) were calculated using the Agresti-Coull formula.

RESULTS: based on 141 deaths, the RML showed very good accuracy: specificity was 100% (95%CI 87%-100%; 32/32 deaths) and sensitivity 94% (95%CI 87%-97%; 102/109 deaths). The 7 false negative cases either were missed by the RML (N. 4) or had been wrongly classified as non-mesotheliomas (N. 3) because the diagnosis was made or confirmed only postmortem after a forensic autopsy.

CONCLUSIONS: RML accuracy (completeness and diagnostic quality) was very high. No false positive was found and the few false negatives were due to lack of notification of mesotheliomas diagnosed postmortem to the registry. Forensic pathologists should be made aware that mesothelioma notification to the regional mesothelioma registry is important and compulsory.

RevDate: 2024-10-21

Ye L, Ryu H, Granadier D, et al (2024)

Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.

Translational lung cancer research, 13(9):2352-2372.

BACKGROUND: Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8[+] T cells include less differentiated stem-like exhausted T (Tex[stem]) cells and terminally exhausted T (Tex[term]) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort.

METHODS: Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Tex[stem] and Tex[term] CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire.

RESULTS: Higher frequency of Tex[stem] was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Tex[term] was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Tex[stem], median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Tex[stem] cells also contained 'bystander' virus-specific T cells.

CONCLUSIONS: This study demonstrates that PE CD8 Tex[stem] cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.

RevDate: 2024-10-16

Stella GM, Lisini D, Pedrazzoli P, et al (2024)

Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design.

Cancers, 16(19): pii:cancers16193391.

Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well.

RevDate: 2024-10-16
CmpDate: 2024-10-16

Chiec L, DS Bruno (2024)

Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies.

International journal of molecular sciences, 25(19): pii:ijms251910861.

Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.

RevDate: 2024-10-16

Jain M, Crites MK, Rich P, et al (2024)

Malignant Pleural Mesothelioma: A Comprehensive Review.

Journal of clinical medicine, 13(19): pii:jcm13195837.

Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.

RevDate: 2024-10-14

Arrandale VH, Berriault C, Song C, et al (2024)

Surveillance of asbestos related disease among workers enrolled in an exposure registry.

American journal of industrial medicine [Epub ahead of print].

INTRODUCTION: Contemporary asbestos exposure occurs during construction, remediation, and maintenance involving asbestos-containing materials (ACM), as compared to the historical exposure scenarios of asbestos mining and milling. The Ontario Asbestos Workers Register (AWR) was established in 1986 to track asbestos exposure among construction workers. This study reports on the risk of asbestos-related diseases (ARD) among workers in the AWR.

METHODS: AWR registrants were linked probabilistically with administrative health databases (1986-2019) to identify cases of ARD including both cancer and chronic respiratory disease. Follow-up began at AWR enrollment and continued prospectively. Incidence rates were compared to the general population using standardized incidence ratios (SIRs). Associations between ACM exposure and ARD were estimated among AWR registrants using Poisson regression.

RESULTS: In total, 26,204 (81%) registrants were linked successfully. Common industries of employment were construction (62%), manufacturing (19%) and education (8%). Among men and women mesothelioma (M:SIR 6.83 [95% CI = 5.56-8.31]; W:SIR 19.2 [3.86-56.1]) and pulmonary fibrosis (M:SIR 14.1 [12.2-16.2]; W:SIR 9.25 [2.49-23.7]) rates were higher than the general population. Asbestosis risk was elevated among men (M:SIR 11.2 [9.59-13.1]). Workers with longer reported exposures (≥140 h) had increased rates of lung cancer (RR 1.34 [1.10-1.63]), mesothelioma (RR 2.83 [1.75-4.58]), asbestosis (RR 3.07 [2.12-4.43]), chronic obstructive pulmonary disease (RR 1.42 [1.29-1.57]), and pulmonary fibrosis (RR 1.88 [1.35-2.62]).

CONCLUSION: Exposure to asbestos in construction and building maintenance continues to contribute to ARD incidence. Despite a Canadian ban on asbestos in new products, exposures to existing ACM will persist from construction activities. The AWR offers an opportunity for ongoing surveillance of resulting ARD in Ontario.

RevDate: 2024-10-12
CmpDate: 2024-10-12

Li R, Yu WK, Wang Q, et al (2024)

[Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases, 42(9):668-672.

Objective: To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells. Methods: In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm(2) chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet-t test. Results: Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased (P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Conclusion: Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

RevDate: 2024-10-09

Rezvani A, Shahriarirad R, Jahanshahi S, et al (2024)

The aftermath of asbestos prohibition in industry and its association with malignant mesothelioma in the south of Iran: An enduring predicament yet to be resolved.

Health science reports, 7(10):e70117.

PURPOSE: Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure.

METHODS: In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow-up of the patients' disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non-MM patients.

RESULTS: Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post-diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM (p = 0.028; OR: 14.602; 95% CI: 1.328-160.499).

CONCLUSION: Both occupational and para-occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at-risk groups.

RevDate: 2024-10-08

R PD, Grace Priyadarshini S, J P (2024)

Malignant Mesothelioma: Overcoming Diagnostic Hurdles.

Cureus, 16(9):e68718.

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.

RevDate: 2024-09-30

Porzio A, Feola A, Salzillo C, et al (2024)

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

Healthcare (Basel, Switzerland), 12(18):.

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.

RevDate: 2024-09-29
CmpDate: 2024-09-27

Roca E, Aujayeb A, P Astoul (2024)

Diagnosis of Pleural Mesothelioma: Is Everything Solved at the Present Time?.

Current oncology (Toronto, Ont.), 31(9):4968-4983.

Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.

RevDate: 2024-09-24
CmpDate: 2024-09-24

Pacella A, Ballirano P, Di Carlo MC, et al (2024)

Geological and mineralogical characterization of fibrous tremolite from Iacolinei quarry (Basilicata, Italy).

Environmental geochemistry and health, 46(11):429.

Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications. A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress.

RevDate: 2024-09-25

Khosla D, Singh PK, Chhabria BA, et al (2024)

Malignant pleural mesothelioma: The disdained member of thoracic oncology!.

World journal of experimental medicine, 14(3):91739.

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure. The ban on asbestos has helped to lower the incidence, but in developing countries like India, it is expected to rise. It has an extended latency period usually progressing over decades and presents with nonspecific symptoms. It has a median survival ranging between 10-22 months. The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT, with the last two predicting the resectability of the tumor better than CT alone. A pleural biopsy along with an array of immunohistochemical markers, such as p16, BRCA1 associated protein 1, and claudin-4, are required for a definitive diagnosis. Several genetic alterations have prognostic significance as well. The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored. The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. However, the latter continues to be a robust treatment option for patients with the epithelioid subtype. Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant, adjuvant, and palliative settings along with systemic treatment. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc.) that have led to significant developments in recent years with clinically meaningful results.

RevDate: 2024-09-19

Reddy S, M G K, Gattu R, et al (2024)

Challenging the Norm: Occurrence of Synchronous Pleural and Peritoneal Mesothelioma in a Female Patient.

Cureus, 16(8):e67118.

Here, we present a unique case involving a female patient in her 40s with synchronous malignant pleural and peritoneal mesothelioma, despite lacking a history of asbestos exposure. The patient's initial symptoms included dyspnoea, chest pain, cough, fever, appetite loss, and weight loss over a month. Clinical evaluation led to the identification of right-sided pleural effusion, prompting consideration of differential diagnoses, such as tubercular or malignant pleural effusion. A thoracoscopy-guided biopsy, followed by histopathological examination and immunohistochemical staining, confirmed the diagnosis of mesothelioma. Chemotherapy was initiated as part of the treatment plan. The prognosis for this condition is generally bad; however, unusual cases of extended survival have been documented. The complexities of our case underscore the critical necessity for a thorough and aggressive evaluation of pleural effusion cases to unveil rare underlying causes, such as mesothelioma.

RevDate: 2024-09-18

Huang Q, Chen Y, Lian L, et al (2024)

Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029.

Journal of the National Cancer Center, 4(3):214-222.

OBJECTIVE: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China.

METHODS: Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.

RESULTS: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.

CONCLUSION: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.

RevDate: 2024-09-13

Sheema AN, Naiki-Ito A, Kakehashi A, et al (2024)

Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration.

Archives of toxicology [Epub ahead of print].

Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.

RevDate: 2024-09-14

Feng L, Li T, Xu B, et al (2024)

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.

Environmental pollution (Barking, Essex : 1987), 362:124928 pii:S0269-7491(24)01642-7 [Epub ahead of print].

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.

RevDate: 2024-10-07
CmpDate: 2024-10-01

Kinsman N, Del Monaco A, Dimitriadis C, et al (2024)

Bauxite mine and alumina refinery workers: mortality and cancer risk.

Occupational medicine (Oxford, England), 74(7):508-513.

BACKGROUND: Aluminium industry workers are at risk of long-term health consequences.

AIMS: To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers.

METHODS: A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment.

RESULTS: Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11-4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60-3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06-1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66-6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36-3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02-3.65]. Overall cancer incidence was otherwise similar to the general Australian population.

CONCLUSIONS: Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation.

RevDate: 2024-09-05
CmpDate: 2024-09-06

Duraffour F, Ramos-Bonilla JP, B Lysaniuk (2024)

Use of agent-based modeling to analyze potential non-occupational exposures to asbestos of the general population of Sibaté (Colombia).

Environmental monitoring and assessment, 196(10):900.

Previous studies conducted in the municipality of Sibaté (Colombia) have revealed alarming findings regarding asbestos exposure in the region, as it is the site of the country's first mesothelioma cluster. Non-occupational asbestos exposure events were identified in this population, and the young age of the mesothelioma cases at the time of diagnosis suggests that asbestos exposure occurred during their childhood. The creation of landfilled zones in the 1980s and 1990s, utilizing friable asbestos among other disposed materials, may have been a significant asbestos exposure event contributing to the elevated number of mesothelioma cases. The objective of this study was to model various historical exposure scenarios related to the creation and interaction of the population with asbestos-contaminated landfilled zones, in light of the absence of asbestos monitoring in the region. The models utilized a multi-agent simulation process, focusing on a 10-year period (1986-1995). Various relevant variables were incorporated into the modeling process, including, for example, the number of children playing in the landfilled zones and the percentage of children carrying asbestos fibers on their clothes to their homes. A range of values for input data for the models were utilized, spanning from very conservative numbers to exposure-promoting values. The average number of exposed individuals estimated over 750 simulation runs, considering all scenarios, was 571, with a range between 31 and 3800 exposed individuals. The use of multi-agent simulation models can assist the understanding of past asbestos exposure events, especially when there is a lack of environmental surveillance data.

RevDate: 2024-09-03

Favaron C, Gaiaschi L, Casali C, et al (2024)

Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound.

Pharmaceutics, 16(8):.

Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma.

RevDate: 2024-09-27
CmpDate: 2024-08-27

Giacomino F, Marinelli F, Bisceglia I, et al (2024)

Trends in Asbestos Exposure and Malignant Mesothelioma Incidence in Emilia-Romagna Italy: A Retrospective Study 1996-2023.

La Medicina del lavoro, 115(4):e2024028.

Malignant mesothelioma (MM) is a rare but lethal cancer strongly associated with asbestos exposure. This retrospective study examines trends in asbestos exposure in Emilia-Romagna, Northern Italy. Between 1996 and 2023, 3,513 cases of MM were recorded, predominantly in males (72%) and in older than 65 years (79%). Occupational exposure accounted for 82% of cases, with a significant increase observed over time from 71% to 88% in the most recent period. A greater definition of professional exposure indicates that certain exposure has gone from 49% in the first period to 62% and 58% in the last two periods; probable exposure showed a decrease from 21% to 16% while possible exposure decreased from 16% to 13%. Familiar exposure remained relatively constant at around 8%, environmental exposure showed a slight decrease from 4% to 2%, while non-occupational exposure remained stable at 2%. Among patients with exclusively occupational exposure (1,826 cases), 87% were male and aged between 65 and 75 years (36%) and 75+ (41%). The exposure rates for the province of residence see the province of Reggio Emilia with the highest occupational exposure rate (2.5 x 100,000 residents), followed by Ravenna (2.3 x 100,000 residents) and Parma and Piacenza which have similar exposure rates with 2.2 x 100,000 residents. Professional sectors such as construction, railway maintenance and metalworking are identified as high-risk industries. Despite efforts to mitigate exposure, non-occupational and environmental exposures persist. The study highlights the importance of continuous surveillance and exposure monitoring to guide effective interventions and legal recognition of MM.

RevDate: 2024-09-13

Kindler HL, Rosenthal A, Giroux DJ, et al (2024)

The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer pii:S1556-0864(24)00777-9 [Epub ahead of print].

INTRODUCTION: The International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations.

METHODS: Cases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM. The presence and number of metastases (single versus multiple) in each of eight organ systems were reported for patients with M1 disease at diagnosis. Overall survival (OS) was calculated by the Kaplan-Meier method. Differences in OS were assessed by log-rank test.

RESULTS: Of 7338 submitted cases, 3598 were eligible and 3221 had sufficient data for clinical staging; 228 cases (7%) were M1. Median overall estimated survival was inferior for M1 compared with M0 patients: 10.5 months versus 21.5 months, respectively (p < 0.0001); estimated 1-year survival was 46% versus 71%, respectively. OS differences between M categories were preserved within histologic subgroups. Among 158 patients with organ-specific documentation of M1 disease, there was no statistically significant difference in OS between those with intrathoracic versus more distant metastatic disease (14.4 mo versus 10.9 mo, p = 0.64). No significant survival difference was detected between patients with metastatic disease in a single-organ system versus multiple-organ systems (12.6 mo versus 8.8 mo, p = 0.45).

CONCLUSIONS: This evidence-based analysis of the M category for PM conforms with the eighth edition M descriptors. No changes are proposed in the ninth edition of the mesothelioma M category.

RevDate: 2024-08-24
CmpDate: 2024-08-21

Zhang M, Bzura A, Baitei EY, et al (2024)

A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.

Nature communications, 15(1):7187.

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68[+] monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8[+] T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68[+] monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

RevDate: 2024-09-14
CmpDate: 2024-09-11

Little LD, Barnett SE, Issitt T, et al (2024)

Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts.

Journal of breath research, 18(4):.

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies. Volatile organic compounds (VOCs) have previously shown diagnostic potential as biomarkers when analysed in MPM patient breath. In this study, chorioallantoic membrane (CAM) xenografts of MPM cell lines were used as models of MPM tumour development for VOC biomarker discovery with the aim of generating targets for investigation in breath, biopsies or other complex matrices. VOC headspace analysis of biphasic or epithelioid MPM CAM xenografts was performed using solid-phase microextraction and gas chromatography-mass spectrometry. We successfully demonstrated the capture, analysis and separation of VOC signatures from CAM xenografts and controls. A panel of VOCs was identified that showed discrimination between MPM xenografts generated from biphasic and epithelioid cells and CAM controls. This is the first application of the CAM xenograft model for the discovery of VOC biomarkers associated with MPM histological subtypes. These findings support the potential utility of non-invasive VOC profiling from breath or headspace analysis of tissues for detection and monitoring of MPM.

RevDate: 2024-08-14

Mayoral M, Araujo-Filho JAB, Tan KS, et al (2024)

Are there features that can predict the unresectability of pleural mesothelioma?.

European radiology [Epub ahead of print].

INTRODUCTION: The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM.

METHODS: Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling.

RESULTS: Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879).

CONCLUSION: Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM.

CLINICAL RELEVANCE STATEMENT: A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments.

KEY POINTS: About half of pleural mesothelioma patients are reported to receive an incorrect disease stage preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.

RevDate: 2024-08-13

Nash J, Stone E, Vinod S, et al (2024)

Lung cancer (internet-based) Delphi (LUCiD): A modified eDelphi consensus process to establish Australasian clinical quality indicators for thoracic cancer.

Respirology (Carlton, Vic.) [Epub ahead of print].

BACKGROUND AND OBJECTIVE: Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand.

METHODS: Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting.

RESULTS: The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking.

CONCLUSION: Twenty-seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia.

RevDate: 2024-08-12

Thunold S, Hernes E, Farooqi S, et al (2024)

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

European journal of nuclear medicine and molecular imaging [Epub ahead of print].

PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.

METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response.

RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5.

CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response.

STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic.

CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

RevDate: 2024-08-12
CmpDate: 2024-08-12

Delhaise J, M Gustin (2024)

[Erionite, an exposure factor linked to pleural mesothelioma].

Revue medicale de Liege, 79(7-8):478-484.

Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.

RevDate: 2024-08-09

Al-Moussally F, Alamin F, Khan S, et al (2024)

Sarcomatoid Mesothelioma With New Pancreatic Lesions Presenting As Acute Pancreatitis: A Case Report.

Cureus, 16(7):e64088.

Sarcomatoid mesothelioma is a rare, aggressive malignancy that usually follows asbestos exposure. It is the least common subtype of mesotheliomas, following epithelial and biphasic subtypes. Pleural mesothelioma can metastasize, with the liver, kidneys, adrenal glands, and opposite lungs being the most commonly reported sites for metastasis. Metastasis of the pancreas is extremely rare, which is why the authors of this case report intend to present the case of a 78-year-old male who was found to have acute pancreatitis, most likely secondary to metastatic lesions.

RevDate: 2024-09-06
CmpDate: 2024-09-06

Otte N, Fraune E, Cetiner Y, et al (2024)

Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers.

Lung cancer (Amsterdam, Netherlands), 195:107899.

BACKGROUND: The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos.

RESEARCH QUESTION: How does asbestos exposure patterns affect cancer mortality and the duration of latency until death?

METHODS: A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis.

RESULTS: The mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62-29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89-1.17). Median latency until death was 46 (15-63) years for mesothelioma and 44 (15-70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking.

CONCLUSION: Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.

RevDate: 2024-08-23
CmpDate: 2024-08-23

Kraus T, D Jonigk (2024)

[Mesothelioma-30 years after the asbestos ban in Germany].

Pathologie (Heidelberg, Germany), 45(5):305-308.

In 1993, a total asbestos ban was introduced in Germany. Thirty years later, mesothelioma is still one of the most frequent occupational diseases. Recent data on incidence, mortality, recognized occupational diseases, early detection, and assessment are presented in this article.

RevDate: 2024-08-27
CmpDate: 2024-08-25

Gislard A, Gramond C, Clin B, et al (2024)

[Compensation of occupational diseases during monitoring of the ARDCO cohort].

Revue des maladies respiratoires, 41(7):472-487.

INTRODUCTION: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases.

METHODS: OD recognition - and possible compensation - was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005.

RESULTS: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs.

CONCLUSIONS: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved.

RevDate: 2024-07-18

Neilly MDJ, Pearson J, Thu AW, et al (2024)

Contemporary management of mesothelioma.

Breathe (Sheffield, England), 20(2):230175.

Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets.

RevDate: 2024-07-18

Cravero JC, Yakubik T, Wahab L, et al (2024)

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

Case reports in oncology, 17(1):596-601.

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.

RevDate: 2024-08-09
CmpDate: 2024-07-17

Khan S, Malik A, Qureshi S, et al (2024)

Incidental Diagnosis of Malignant Peritoneal Mesothelioma During Liver Transplantation Surgery: A Case Report.

The American journal of case reports, 25:e943787.

BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare, lethal tumor of serous membranes. The most common factor reported in association with MPM is asbestos exposure, while viral infections, genetic predisposition, paraneoplastic syndrome, and altered immunity have been described as well. The diagnosis can be challenging among those with lower tumor burden as well as nonspecific symptoms, and it is not unusual to discover the diagnosis incidentally. CASE REPORT A middle-aged woman with decompensated cirrhosis underwent extensive pre-transplant workup, showing no evidence of malignancy. She had a personal history of asbestos exposure and family history of MPM in the extended family. During transplant surgery, a few peritoneal nodules were noted, leading to termination of the procedure. Pathological analysis confirmed malignant MPM. A multidisciplinary discussion led to following a conservative treatment approach without any intervention, due to higher risk of worsening hepatic decompensation associated with peritonectomy and intraperitoneal chemotherapy. The patient's hepatic decompensation resolved 6 months after the aborted liver transplant operation. Since the diagnosis of MPM, positron emission tomography scans have shown no recurrence of MPM for 3 consecutive years. CONCLUSIONS This is the first case of MPM diagnosed incidentally during a liver transplantation surgery. This case highlights the challenges in the diagnosis and management of MPM in a patient with decompensated liver disease. A multidisciplinary approach and following a consensus decision led to prolonged survival in the described patient.

RevDate: 2024-07-17

Costa A, Forte IM, Pentimalli F, et al (2024)

Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.

Frontiers in oncology, 14:1418951.

INTRODUCTION: Diffuse pleural mesothelioma (DPM) of the pleura is a highly aggressive and treatment-resistant cancer linked to asbestos exposure. Despite multimodal treatment, the prognosis for DPM patients remains very poor, with an average survival of 2 years from diagnosis. Cisplatin, a platinum-based chemotherapy drug, is commonly used in the treatment of DPM. However, the development of resistance to cisplatin significantly limits its effectiveness, highlighting the urgent need for alternative therapeutic strategies. New selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have shown promise in various malignancies by inhibiting cell cycle progression and suppressing tumor growth. Recent studies have indicated the potential of abemaciclib for DPM therapy, and a phase II clinical trial has shown preliminary encouraging results.

METHODS: Here, we tested abemaciclib, palbociclib, and ribociclib on a panel of DPM cell lines and non-tumor mesothelial(MET-5A) cells.

RESULTS: Specifically, we focused on abemaciclib, which was the mosteffective cytotoxic agent on all the DPM cell lines tested. Abemaciclib reduced DPM cell viability, clonogenic potential, and ability to grow as three-dimensional (3D) spheroids. In addition, abemaciclib induced prolonged effects, thereby impairing second-generation sphere formation and inducing G0/G1 arrest and apoptosis/ necrosis. Interestingly, single silencing of RB family members did not impair cell response to abemaciclib, suggesting that they likely complement each other in triggering abemaciclib's cytostatic effect. Interestingly, abemaciclib reduced the phosphorylation of AKT, which is hyperactive in DPM and synergized with the pharmacological AKT inhibitor (AKTi VIII). Abemaciclib also synergized with cisplatin and reduced the viability of DPM cells with acquired resistance to cisplatin.

DISCUSSION: Overall, our results suggest that CDK4/6 inhibitors alone or in combination with standard of care should be further explored for DPM therapy.

RevDate: 2024-07-16

Sonobe H, Omote R, Habara T, et al (2024)

A Rare Case of Pleural Epithelioid Mesothelioma With a Prominent Myxoid Stroma Reported With Morphology, Fluorescent In Situ Hybridization, and Ultrastructural Findings.

Cureus, 16(6):e62212.

Herein, we report a rare case of pleural epithelioid malignant mesothelioma with a prominent myxoid stroma. To date, detailed morphological or molecular pathological findings have not been reported for this type of tumor. Hence, we aimed to describe the cytological, histological, immuno-cytohistological, electron-microscopic, and molecular pathological findings using fluorescence in situ hybridization (FISH) in such a case. The patient was a male in his mid-sixties with a history of asbestos exposure and had originally visited the hospital with a persistent cough and fever. Chest radiography revealed left pleural effusion, and laboratory examination revealed a high titer for hyaluronic acid in the effusion. Additionally, computed tomography revealed diffuse multinodular or cystic lesions in the left parietal pleura, and pleural effusion cytology revealed large epithelioid cells with mild nuclear atypia, which were considered reactive mesothelial cells. Cytologically, Giemsa staining revealed that these cells harbored variously sized intracytoplasmic vacuoles that were Alcian-blue-positive, suggesting hyaluronan production. Biopsy revealed large epithelioid cells that loosely proliferated against a prominent myxoid background. These cells were immuno-positive for calretinin, Wilms' tumor 1, D2-40, vimentin, and cytokeratin AE1/AE3 but not for carcinoembryonic antigen, Ber-EP4, or desmin. BRCA 1 associated protein 1 immunostaining showed nuclear loss, and FISH showed homozygous deletion of cyclin-dependent kinase inhibitor 2A (p16) on chromosome 9p21. Based on these findings, the lesion was diagnosed as an epithelioid mesothelioma with a prominent myxoid stroma. Electron-microscopy demonstrated a dense microvillus pattern on the surface of the tumor cells, indicating a mesothelial cell origin, and variously sized vacuoles in the cytoplasm, confirming the presence of intracytoplasmic vacuoles demonstrated on cytology. The tumor tissues obtained during surgery harbored prominent myxoid stroma, which proved that the present tumor was consistent with this type of mesothelioma. After informed consent was obtained, the patient and family wished for total resection of the tumor and postoperative chemotherapy, and the patient eventually died eight months after surgery.

RevDate: 2024-08-07
CmpDate: 2024-08-07

van Zandwijk N, Frank AL, Reid G, et al (2024)

Asbestos-Related lung Cancer: An underappreciated oncological issue.

Lung cancer (Amsterdam, Netherlands), 194:107861.

Asbestos, a group of class I (WHO) carcinogenic fibers, is the main cause of mesothelioma. Asbestos inhalation also increases the risk to develop other solid tumours with lung cancer as the most prominent example [91]. The incidence of asbestos-related lung cancer (ARLC) is estimated to be to six times larger than the mesothelioma incidence thereby becoming an important health issue [86]. Although the pivotal role of asbestos in inducing lung cancer is well established, the precise causal relationships between exposures to asbestos, tobacco smoke, radon and 'particulate' (PM2.5) air pollution remain obscure and new knowledge is needed to establish appropriate preventive measures and to tailor existing screening practices[22,61,65]. We hypothesize that a part of the increasing numbers of lung cancer diagnoses in never-smokers can be explained by (historic and current) exposures to asbestos as well as combinations of different forms of air pollution (PM2.5, asbestos and silica).

RevDate: 2024-07-19
CmpDate: 2024-07-12

Mirabelli D, B Terracini (2024)

Carcinogenicity of asbestos-free talc and talcum powder: A systematic review of the epidemiological evidence after the 2006 monograph of the International Agency for Research on Cancer.

Epidemiologia e prevenzione, 48(3):220-232.

BACKGROUND: in 2006, the International Agency for Research on Cancer (IARC) concluded that the evidence of carcinogenicity for asbestos-free talc was inadequate (group 3), whereas perineal use of talcum powder was classified as possibly carcinogenic (group 2B).

OBJECTIVES: to assess whether later studies provide more solid information on the carcinogenic risk from asbestos-free talc and talcum powder and a better characterization of exposure.

DESIGN: systematic review.

METHODS: cohort studies of talc miners and millers exposed to asbestos-free talc, as well as cohort and case-control studies reporting cancer risk in talc powder consumers published from 2006 onwards were identified through PubMed and reference lists. Pooled analyses were included, but not reviews and meta-analyses. In the case of repeatedly reported studies, the article with the longest follow-up or the largest number of observed cases was selected for data abstraction. Notice was taken of studies which were both reported individually and included in pooled analyses.

RESULTS: publications meeting inclusion criteria were: 2 cohort studies on talc miners and millers, 10 cohort studies on talcum powder users (4 of which estimated ovarian cancer risk), and 14 case-control studies (13 on ovarian and 1 on endometrial cancer) on the risk from talcum powder use. No excess cancer mortality has been reported among asbestos-free talc miners and millers. Case-control studies consistently led to estimates of ovarian cancer excesses associated with the use of perineal talcum powder (odds ratios up to 1.5). Most studies quantifying exposure also provided evidence of a dose-response relationship. Individual cohort studies estimated hazard ratios (HR) just above 1. In an analysis of pooled cohorts for a total of 3,112 cases, the HR for women with patent reproductive tract was 1.13 (95%CI 1.01-1.26) with a correlation between HR and frequency of use (p for trend 0.03). In all cohort studies, the perineal use of talcum powder was measured only once in the early phases of follow-up, thus producing an inaccurate measure of cumulative exposure. Results of epidemiological studies regarding cancer risk in other organs are limited and inconsistent.

CONCLUSIONS: epidemiological studies updated or published after IARC 2006 evaluation indicate that: no increase in cancer risk is apparent among miners and millers of asbestos-free talc; risk for ovarian cancer increases following the perineal use of commercial talcum powder. A correlation between indicators of quantity of use and cancer risk is suggested by a number of studies. The composition of talcum powders considered in such studies is not known.

RevDate: 2024-08-07
CmpDate: 2024-07-11

Novelli F, Yoshikawa Y, Vitto VAM, et al (2024)

Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.

Proceedings of the National Academy of Sciences of the United States of America, 121(29):e2405231121.

We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1[V523A] mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.

RevDate: 2024-07-06

Cedres S, Calvete J, Taylor-Stokes G, et al (2024)

Treatment patterns and humanistic burden of malignant pleural mesothelioma in Spain.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Epub ahead of print].

PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here.

METHODS/PATIENTS: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life.

RESULTS: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being.

CONCLUSIONS: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.

RevDate: 2024-08-05
CmpDate: 2024-08-05

Andersson EM, Barregard L, Akerstrom M, et al (2024)

Cancer incidence in Swedish oil refinery workers exposed to benzene.

International journal of hygiene and environmental health, 261:114420.

BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma.

AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries.

METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated.

RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1-31.1).

DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure.

CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.

RevDate: 2024-08-16
CmpDate: 2024-08-16

Berge LAM, Shala NK, Barone-Adesi F, et al (2024)

Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.

Occupational and environmental medicine, 81(7):331-338 pii:oemed-2024-109424.

OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers.

METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure.

RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma.

CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.

RevDate: 2024-07-02

Zhao Z, Li J, Tan F, et al (2024)

Assessing the global burden of mesothelioma: trends, socioeconomic influences, and asbestos exposure: a retrospective cohort study.

International journal of surgery (London, England) pii:01279778-990000000-01752 [Epub ahead of print].

INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level.

METHODS: The Global Cancer Observatory in 2022 and 2019 Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. Multivariable linear regression analyses was conducted to explore the associations between mesothelioma incidence and key predictors including Human Development Index (HDI), Gross Domestic Product (GDP) per capita, and occupational asbestos exposure, adjusting for age and sex across global regions.

RESULTS: This study identified 30,870 global cases of mesothelioma in 2022, with a higher age-standardized incidence rate (ASR) in males (0.25 per 100,000) compared to females (0.39 per 100,000). Geographical analysis indicated the highest disease burden in Northern Europe, with particular prevalence in more developed regions. The incidence was also significantly associated with higher Human Development Index (HDI), with a beta coefficient of 0.133 overall, and Gross Domestic Product (GDP) per capita, with a beta coefficient of 0.101. These socioeconomic factors exhibited stronger associations in the elderly population, especially with HDI (β=0.512) and GDP (β=0.389), than in adults. Additionally, occupational exposure to asbestos remained a significant risk factor across all groups, except for the younger adult population, with an overall beta of 0.122 for incidence. The temporal trend analysis revealed a general decrease in mesothelioma incidence, particularly in the 15-49 years age group.

CONCLUSIONS: The analysis indicates a higher mesothelioma incidence in males and in developed regions, with marked disparities noted particularly in Northern Europe. Significant correlations with socioeconomic indicators-HDI and GDP-and occupational asbestos exposure were identified, particularly affecting the elderly. Despite a decline in global incidence, especially among younger individuals, persistent cases in females highlight the need for continued public health measures addressing both occupational and environmental exposures.

RevDate: 2024-07-03
CmpDate: 2024-07-02

De Maria L, Pentimone F, Cavone D, et al (2024)

Clinical investigation of former workers exposed to asbestos: the health surveillance experience of an Italian University Hospital.

Frontiers in public health, 12:1411910.

BACKGROUND: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992.

OBJECTIVES: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari.

MATERIALS AND METHODS: We adopted the health surveillance protocol, which was validated at the national level in 2018.

RESULTS: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%.

CONCLUSION: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.

RevDate: 2024-07-04
CmpDate: 2024-07-01

Sherborne V, Ejegi-Memeh S, Tod AM, et al (2024)

Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers.

BMJ open, 14(6):e075071.

OBJECTIVES: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.

DESIGN: Systematic review.

DATA SOURCES: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA.

ELIGIBILITY CRITERIA: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002.

DATA EXTRACTION AND SYNTHESIS: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews.

RESULTS: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support.

CONCLUSIONS: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma.

PROSPERO REGISTRATION NUMBER: CRD42022302187.

RevDate: 2024-08-01
CmpDate: 2024-08-01

Girardi P, Rigoni S, Ferrante D, et al (2024)

Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.

American journal of industrial medicine, 67(9):813-822.

OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks.

METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death.

RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death.

CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

RevDate: 2024-06-28
CmpDate: 2024-06-26

Zhand S, Liao J, Castorina A, et al (2024)

Small Extracellular Vesicle-Derived Circular RNA hsa_circ_0007386 as a Biomarker for the Diagnosis of Pleural Mesothelioma.

Cells, 13(12):.

Pleural mesothelioma (PM) is a highly aggressive tumor that is caused by asbestos exposure and lacks effective therapeutic regimens. Current procedures for PM diagnosis are invasive and can take a long time to reach a definitive result. Small extracellular vesicles (sEVs) have been identified as important communicators between tumor cells and their microenvironment via their cargo including circular RNAs (circRNAs). CircRNAs are thermodynamically stable, highly conserved, and have been found to be dysregulated in cancer. This study aimed to identify potential biomarkers for PM diagnosis by investigating the expression of specific circRNA gene pattern (hsa_circ_0007386) in cells and sEVs using digital polymerase chain reaction (dPCR). For this reason, 5 PM, 14 non-PM, and one normal mesothelial cell line were cultured. The sEV was isolated from the cells using the gold standard ultracentrifuge method. The RNA was extracted from both cells and sEVs, cDNA was synthesized, and dPCR was run. Results showed that hsa_circ_0007386 was significantly overexpressed in PM cell lines and sEVs compared to non-PM and normal mesothelial cell lines (p < 0.0001). The upregulation of hsa_circ_0007386 in PM highlights its potential as a diagnostic biomarker. This study underscores the importance and potential of circRNAs and sEVs as cancer diagnostic tools.

RevDate: 2024-06-20
CmpDate: 2024-06-20

Couchman E, Ejegi-Memeh S, Mitchell S, et al (2024)

Rethinking continuity in primary care for people with mesothelioma.

The British journal of general practice : the journal of the Royal College of General Practitioners, 74(suppl 1): pii:74/suppl_1/bjgp24X737373.

BACKGROUND: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma.

AIM: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use.

METHOD: Realist case studies of patient journeys through the healthcare system (involving longitudinal interviews with people with mesothelioma, their close persons, and HCPs; and exploration of the organisational context). Data analysis allowed understanding of hidden mechanisms (resources and reasoning), triggered in certain contexts, leading to specific outcomes.

RESULTS: Forty-eight interviews (involving 9 patients, 8 close persons, and 12 HCPs) were undertaken (totalling 30.8 hours/1848 minutes). Context-Mechanism-Outcome configurations related to: challenges unique to mesothelioma; capacity of patients/close persons/HCPs to facilitate continuity; multidisciplinary (MDT) approach differs from the family doctor model; and 'the NHS primary care system is broken'.

CONCLUSION: Patients perceive their continuity needs to be unmet by the inflexible primary care system, which needs to adapt to a society in which people receive increasingly novel treatments and live longer with complex healthcare needs. A societal perspective shift is required to understand that an MDT now shares responsibility for care, rather than an individual family doctor. Policy documents continue to focus on access, and still do not advocate strongly enough for continuity, despite unequivocal evidence demonstrating its worth.

RevDate: 2024-06-20

Santos C, Sacadura-Leite E, Ferreira J, et al (2024)

The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.

Healthcare (Basel, Switzerland), 12(11):.

BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.

OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.

METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.

RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).

CONCLUSION: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.

RevDate: 2024-08-22
CmpDate: 2024-08-14

Lin RT, Boonhat H, Lin YY, et al (2024)

Health Effects of Occupational and Environmental Exposures to Nuclear Power Plants: A Meta-Analysis and Meta-Regression.

Current environmental health reports, 11(3):329-339.

PURPOSE OF REVIEW: Numerous epidemiological studies have shown increased health risks among workers and residents living near nuclear power plants exposed to radiation levels meeting regulatory dose limits. This study aimed to evaluate the association between radiation exposure and disease risks among these populations exposed to radiation levels meeting the current regulatory dose limits.

RECENT FINDINGS: We searched four databases (Cochrane Library, PubMed, ScienceDirect, and Web of Science) for studies published before August 2023, screened eligible studies (inclusion and exclusion criteria based on population, exposure, comparator, and outcome framework), and collected data on exposure indicators and disease risks. We applied random-effects models of meta-analysis to estimate the pooled effects and meta-regression to assess the dose-response relationship (radiation dose rate for workers and distance for residents). We identified 47 studies, 13 with worker and 34 with resident samples, covering 175 nuclear power plants from 17 countries, encompassing samples of 480,623 workers and 7,530,886 residents. Workers had a significantly lower risk for all-cancer and a significantly higher risk for mesothelioma. Residents had significantly higher risks for all-cancer, thyroid cancer, and leukemia. Notably, children under 5 years old showed the highest risk for all-cancer. Our meta-regression showed a significantly positive dose-response relationship between cumulative dose of radiation exposure and risk for circulatory disease among workers. Our findings demonstrated higher risks for mesothelioma for workers and all-cancer, thyroid cancer, and leukemia for residents exposed to low-dose radiation from nuclear power plants. Some included studies did not adjust for cancer risk confounders, which could overestimate the association between radiation exposure and cancer risk and increase the risk of bias.

RevDate: 2024-06-20
CmpDate: 2024-06-16

Fu F, Zhang Y, H Shen (2024)

[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].

Zhongguo fei ai za zhi = Chinese journal of lung cancer, 27(5):391-398.

Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .

RevDate: 2024-06-13
CmpDate: 2024-06-11

Huh DA, Choi YH, Kim L, et al (2024)

Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.

Environmental health : a global access science source, 23(1):56.

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer.

METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality.

RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30).

CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.

RevDate: 2024-08-13
CmpDate: 2024-08-13

Chornkrathok S, Carbone M, Yang H, et al (2024)

Mineralogical investigation of asbestos contamination of soil near old vermiculite processing plant in Honolulu, Hawai'i.

Environmental pollution (Barking, Essex : 1987), 356:124350.

From 1954 to 1983, a vermiculite processing facility operated near the Honolulu airport and processed raw material from the Libby, Montana mine, which is now well known for the high asbestos content of its clay deposits. The factory was closed in 1983 due to health hazard concerns, and remediation was performed in 2001 as part of the Libby mine superfund project. However, because of close proximity of the closed-down facility to residential areas of metropolitan Honolulu, some concerns remain regarding the possible environmental persistence of the harmful contaminant. To assess the dispersion of asbestos-contaminated vermiculite and explore the impact of trade winds on its distribution, air samples, and soil samples were collected from multiple locations near the former vermiculite plant. Polarized light microscopy was employed to identify elongated minerals, including potential asbestos. Quantitative mineralogical analysis utilizing X-ray powder diffraction and Rietveld refinement revealed an average content of approximately 7% vermiculite and 4% tremolite at the site. The asbestiform nature of tremolite was confirmed through X-ray micro-diffraction. Detailed analysis of airborne samples using transmission electron microscopy revealed no detectable levels of asbestos fibers in the vicinity of the former processing facilities, but the possibility of asbestos fibers becoming airborne due to mechanical disturbance during dry weather cannot be ruled out.

RevDate: 2024-06-11

Potesta MA, Guld E, J Laman (2024)

Dual Malignancies Discovered: A Rare Case of Malignant Peritoneal Epithelioid Mesothelioma and Lung Adenocarcinoma.

Cureus, 16(5):e59962.

Clinicians diagnosing malignant peritoneal epithelioid mesothelioma (MPM or MPeM) have historically had challenges due to the low incidence of the disease, as well as the often vague symptomatology that patients present with. Newer advances in technology, specifically in immunocytochemistry, have provided a clearer path to diagnosis. Additionally, malignant mesotheliomas must be differentiated from carcinomas. This is done via histology, immunocytochemistry, as well as a careful incorporation of the patient's clinical history. In this case, we present an asymptomatic 73-year-old non-smoker female with no past medical history of asbestos exposure. She was diagnosed with MPM following a routine abdominal hernia repair. Subsequent workup revealed a lung infiltrate that was successfully biopsied and resected, evidently found to be adenocarcinoma. A careful review of the resulting pathology, as well as the interpretation of immunocytochemistry, supported the notion that the patient had two independent malignant processes occurring at once. This case underscores the rarity of two similar, yet distinct cancers, as well as epidemiology, symptomatology, histology, immunocytochemistry, and prognosis.

RevDate: 2024-06-09
CmpDate: 2024-05-29

Chen Z, Cai Y, Ou T, et al (2024)

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

Journal of cancer research and clinical oncology, 150(5):282.

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.

RevDate: 2024-05-28

Albano GD, Rodolico V, Di Franco S, et al (2024)

Asbestos exposure determined 357 days after death through autopsy: a report of a multidisciplinary approach.

Forensic science, medicine, and pathology [Epub ahead of print].

Asbestosis is an interstitial lung disease caused by the inhalation of asbestos fibers and poses a significant risk to individuals working in construction, shipping, mining, and related industries. In a forensic context, postmortem investigations are crucial for accurate diagnosis, for which the gold standard is the histopathological examination. This case report describes the autopsy and related investigations conducted on an 84-year-old man, nearly one year (357 days) after his death. After a post-mortem CT scan, an autoptic investigation was performed, followed by histopathological, immunohistochemical, and scanning electron microscopy examinations. The integration of the evidence from these examinations with previously available personal and clinical information conclusively confirmed the diagnosis of asbestosis. We demonstrated the efficacy and reliability of our diagnostic protocol in detecting asbestosis and asbestos fibers and excluding mesothelioma even in decomposed tissues. According to our findings autopsy remains the diagnostic gold standard in cases of suspected asbestosis within a forensic context, even 1 year after death, therefore it is always highly recommended, even in cases where the body has decomposed.

RevDate: 2024-08-29
CmpDate: 2024-08-08

Yaşar S, Yılmaz F, Utkan G, et al (2024)

Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.

Annals of surgical oncology, 31(9):6228-6236.

BACKGROUND: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population.

METHODS: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study.

RESULTS: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason.

CONCLUSIONS: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.

RevDate: 2024-08-12
CmpDate: 2024-05-28

Altshuler PC, Newman AL, JA Garibay (2024)

Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.

The American journal of case reports, 25:e942948.

BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.

RevDate: 2024-05-28

Singh R, AL Frank (2024)

Analysis of mesothelioma cases and National Cancer Registry data to assess asbestos exposure in India.

Public health action, 14(1):30-33.

SETTING: Asbestos exposure can cause mesothelioma, a form of cancer which should be recorded by cancer registries. However, such registries currently cover only a small fraction (16%) of the population in India. Because India still uses asbestos, it is important to understand its health impact, especially the number of mesothelioma cases.

OBJECTIVE: To assess the number of mesothelioma cases in India and compare these to the number reported to the National Cancer Registry.

DESIGN: We used the Right to Information Act 2005 to gather data for 83 hospitals across India from 2012 to 2022-2023.

RESULTS: From a total of 83 hospitals, there were 2,213 cases of mesothelioma from 2012 onwards. During the 2012-2016 period, the number of reported cases in the Cancer Registry was 54, whereas 1,126 cases were reported by these hospitals for this period. Only 21 (25%) of the hospitals assessed in this study were part of the population-based national cancer registry programme. Overall, cases of mesothelioma occur far more frequently than are reported in cancer registries.

CONCLUSION: National record-keeping is inadequate and the system needs to be expanded and improved across all of India. This will provide more effective reporting and help to highlight the risk of exposure to asbestos.

RevDate: 2024-05-27

Hintermair S, Iser S, Varga A, et al (2024)

Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis.

Cancers, 16(10):.

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5-55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7-14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy.

RevDate: 2024-07-15
CmpDate: 2024-07-05

Hassan A, Prabhakaran S, Pulford E, et al (2024)

The significance of BAP1 and MTAP/CDKN2A expression in well-differentiated papillary mesothelial tumour: a series of 21 cases and a review of the literature.

Pathology, 56(5):662-670.

The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/CDKN2A expression loss. Two tumours with MTAP/CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.

RevDate: 2024-05-25

Testa JR, Kadariya Y, JS Friedberg (2024)

Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma.

Oncoscience, 11:53-57.

Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.

RevDate: 2024-06-27
CmpDate: 2024-06-14

Broggi G, Massimino M, Failla M, et al (2024)

Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.

Pathology, research and practice, 259:155350.

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

RevDate: 2024-05-19

Takata A, Yamauchi H, Yamashita K, et al (2024)

Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat.

Industrial health [Epub ahead of print].

Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.

RevDate: 2024-05-14

Hong Lee AH, Macalister SJ, KK Yap (2024)

Pleural small cell lung cancer masquerading as malignant mesothelioma: A case report.

Radiology case reports, 19(8):2969-2972.

Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials. We present the case of a 71-year-old male who presented with acute worsening of shortness of breath associated with a recurrent left pleural effusion post-pleurocentesis. He was an ex-smoker with previous asbestos exposure. Computed tomography performed demonstrated left-sided pleural thickening in the hemithorax and hemidiaphragm with complex pleural effusion. [18]F-2-deoxy-d-glucose whole body PET scan revealed extensive uptake throughout the left hemithorax in multiple pleural masses. The imaging findings and clinical case were typical of malignant mesothelioma. However, histopathology results revealed small cell lung cancer. We need to be cognisant of this atypical presentation of a common disease entity. Even when all clinical and imaging findings point towards a certain diagnosis, histopathological assessment cannot be ignored.

RevDate: 2024-05-14

Lapidot M, Mazzola E, R Bueno (2024)

Prolonged survival and novel prognostic factors in women with pleural mesothelioma treated with extended pleurectomy decortication.

Translational lung cancer research, 13(4):811-820.

BACKGROUND: Pleural mesothelioma (PM) is an uncommon and extremely aggressive malignancy associated with past exposure to asbestos. The low representation of women among PM patients is likely due to differences in occupational asbestos exposure. Due to the controversial role of female sex as a prognostic factor in PM, the study aims to evaluate the survival of females treated with lung-sparing surgery. We present a cohort of 114 consecutive female patients with PM who underwent intended extended pleurectomy decortication (ePD) over 11 years in a high-volume single institution.

METHODS: All women from 2007-2017 who underwent intended ePD were enrolled in the study. Data on clinical, operative, and outcome were collected. Kaplan-Meier estimators and log-rank tests were employed to assess the overall survival, and Cox regression models were utilized to analyze prognostic factors.

RESULTS: During the study period, 454 patients underwent thoracotomy with intended ePD in a single institution. There were 114 females (25%), and macroscopic complete resection (MCR) was achieved in 97 (85.1%). The median age was 65 years, histology was epithelioid in 81 (71.0%), biphasic in 31 (27.2%), and sarcomatoid in 2 (1.8%). The 30- and 90-day mortality were 3.5% and 6.1%, respectively. Median survival in females was 38 months, and 5-year survival was 28.2%. The median survival and 5-year survival rate for patients with epithelioid histology and MCR were 44.4 months and 36.4%, respectively. In a univariate analysis, several factors were found to be associated with patient overall survival including MCR [hazard ratio (HR): 0.3, P<0.001], early T status (HR: 1.6, P=0.03), adjuvant therapy (HR: 0.5, P=0.006), intraoperative heated chemotherapy (IOHC) (HR: 0.8, P=0.03), age (HR: 1.02, P=0.03) and epithelioid histology (HR: 0.5, P=0.009).

CONCLUSIONS: For women with epithelioid PM undergoing intended ePD within a multimodal setting, prolonged survival is anticipated.

RevDate: 2024-09-10
CmpDate: 2024-09-06

Bille A, Ripley RT, Giroux DJ, et al (2024)

The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the "N" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 19(9):1326-1338.

INTRODUCTION: The International Association for the Study of Lung Cancer developed an international database to inform potential revisions in the ninth edition of the TNM classification of diffuse pleural mesothelioma (PM). This study analyzed the clinical and pathologic N categories to determine whether revisions were indicated relative to the eighth edition staging system.

METHODS: Of 7338 PM cases diagnosed from 2013 to 2022 and 3598 met all inclusion criteria for planned analyses. Data on 2836 patients without metastases were included in this study. Overall survival (OS) was measured from date of diagnosis. Patients were included regardless of whether they received neoadjuvant treatment. For the pathologic N analysis, patients who underwent resection (extrapleural pneumonectomy or pleurectomy/decortication) were included. N subgroups were analyzed and OS assessed by the Kaplan-Meier method.

RESULTS: The existing eighth edition N categories were performed adequately in the ninth edition data set. A median OS advantage was noted for clinical and pathologic N0 versus N1 patients: 23.2 versus 18.5 and 33.8 versus 25.0 months, respectively. Patients with resected pN0 had a 3-year OS of 48%. No difference in OS was noted for single- versus multiple-station nodal metastases. The number of nodal stations sampled at the time of resection was not associated with a difference in OS.

CONCLUSIONS: Data regarding clinical and pathologic N categories corroborate those used in the eighth edition. No changes in the N categories are recommended in the ninth edition of PM staging system.

RevDate: 2024-06-08
CmpDate: 2024-05-24

Gugnoni M, Lorenzini E, Torricelli F, et al (2024)

Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma.

Cancer letters, 592:216950.

Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function.

RevDate: 2024-05-09
CmpDate: 2024-05-09

Bluhm M, Atmeh B, Boehm S, et al (2024)

Pleural Effusion Caused by an Unusual Mass in the Right Hemithorax.

Chest, 165(5):e151-e155.

An 80-year-old woman presented with complaints of weakness and dizziness. She had a medical history of subacute cerebral ischemia, vertigo, hypertension, and thalassemia minor. The patient was born and raised in Turkey and has lived in Switzerland for 50 years. Her sister died of a mesothelioma caused by asbestos exposure at the age of 60 years but had lived in Turkey until her death. The patient had neither a history of TB nor B symptoms. She has never smoked.

RevDate: 2024-05-09

Stirpe E, Bardaro F, J Köhl (2024)

Gluteal muscle metastases from malignant pleural mesothelioma: a case report.

Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the mesothelial or subthelial layer of the pleura, and it has increased in recent decades, mainly associated with asbestos exposure. Sarcomatoid mesothelioma is the second-most common subtype of MPM. It is usually difficult to differentiate MPM from benign mesothelial pleural proliferations or other cancers. Because of its nonspecific symptoms, MPM is often diagnosed at a late stage with distal metastases. However, it is extremely rare to see a metastatic lesion within subcutaneous tissue and muscles, which is most likely caused by hematogenous spread. We present a case of sarcomatoid mesothelioma with a metastatic lesion of the right gluteal muscles.

RevDate: 2024-05-08

Syed Ahmad SD, Kirk F, Wijesinghe W, et al (2024)

A peculiar presentation of tamponade: pericardial mesothelioma.

Journal of surgical case reports, 2024(5):rjae279.

Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour, behind angiosarcoma and rhabdomyosarcoma. PM incidence increases with age, typically incidentally diagnosed between 50 and 70 years, with a 3:1 male predominance. Occasional PM can cause chest pain, dyspnoea, cough and even dysphagia. PMs are often misdiagnosed with only 25% of cases being antemortem diagnoses. Unlike pleural mesothelioma, the link between asbestos exposure and malignancy is less convincing, with only 20% of cases having known exposure. 6 There are three histological types: epithelioid, fibrous (spindle cell), and biphasic (mixed). The average life-expectancy post diagnosis is 3-10 months. Due to the heterogeneity of the presentation and rarity there is no standardized management algorithm, and the diagnostic imaging or laboratory investigations are scarcely described. We are presenting one of the cases diagnosed in our unit here in the Gold Coast.

RevDate: 2024-05-13
CmpDate: 2024-05-03

Chin WL, Zemek RM, Tilsed CM, et al (2024)

Time-course RNAseq data of murine AB1 mesothelioma and Renca renal cancer following immune checkpoint therapy.

Scientific data, 11(1):448.

Time-critical transcriptional events in the immune microenvironment are important for response to immune checkpoint blockade (ICB), yet these events are difficult to characterise and remain incompletely understood. Here, we present whole tumor RNA sequencing data in the context of treatment with ICB in murine models of AB1 mesothelioma and Renca renal cell cancer. We sequenced 144 bulk RNAseq samples from these two cancer types across 4 time points prior and after treatment with ICB. We also performed single-cell sequencing on 12 samples of AB1 and Renca tumors an hour before ICB administration. Our samples were equally distributed between responders and non-responders to treatment. Additionally, we sequenced AB1-HA mesothelioma tumors treated with two sample dissociation protocols to assess the impact of these protocols on the quality transcriptional information in our samples. These datasets provide time-course information to transcriptionally characterize the ICB response and provide detailed information at the single-cell level of the early tumor microenvironment prior to ICB therapy.

RevDate: 2024-05-24
CmpDate: 2024-05-03

Lombardo C, Maugeri G, D'Amico AG, et al (2024)

Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.

European journal of histochemistry : EJH, 68(2):.

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.

RevDate: 2024-05-03

Fisher SA, Patrick K, Hoang T, et al (2024)

The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.

Frontiers in toxicology, 6:1373003.

Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model. Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets. Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets. Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.

RevDate: 2024-05-16
CmpDate: 2024-05-01

Li H, Husain AN, Moffat D, et al (2024)

Nonmesothelial Spindle Cell Tumors of Pleura and Pericardium.

Surgical pathology clinics, 17(2):257-270.

Spindle cell lesions of the pleura and pericardium are rare. Distinction from sarcomatoid mesothelioma, which has a range of morphologic patterns, can be difficult, but accurate diagnosis matters. This article provides practical guidance for the diagnosis of pleural spindle cell neoplasms, focusing on primary lesions.

RevDate: 2024-06-02
CmpDate: 2024-06-02

Nuvoli B, Sacconi A, Bottillo G, et al (2024)

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 175:116662.

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.

RevDate: 2024-04-29
CmpDate: 2024-04-27

Gogou E, Hatzoglou C, Siachpazidou D, et al (2024)

Asbestos ban policies and mesothelioma mortality in Greece.

BMC public health, 24(1):1177.

BACKGROUND: Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece's mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.

METHODS: Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).

RESULTS: From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males' ASMR and the whole population's ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000-2009 and 2010-2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000-2009) to 0.31/100000person-years (2010-2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.

CONCLUSIONS: In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.

TRIAL REGISTRATION: Not applicable.

RevDate: 2024-08-23
CmpDate: 2024-08-23

Feder IS, Fruth E, A Tannapfel (2024)

[Asbestos: detection and characterization in tissue].

Pathologie (Heidelberg, Germany), 45(5):333-338.

BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.

OBJECTIVES: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods.

MATERIALS AND METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented.

RESULTS: Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM).

CONCLUSION: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.

RevDate: 2024-04-22
CmpDate: 2024-04-22

Gómez Herrero H, B Álvarez Galván (2024)

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

Radiologia, 66 Suppl 1:S3-S9.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography.

MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis.

RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%.

CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

RevDate: 2024-06-06
CmpDate: 2024-06-06

Ejegi-Memeh S, Sherborne V, Mayland C, et al (2024)

Mental health and wellbeing in mesothelioma: A qualitative study exploring what helps the wellbeing of those living with this illness and their informal carers.

European journal of oncology nursing : the official journal of European Oncology Nursing Society, 70:102572.

PURPOSE: Mesothelioma is an incurable, asbestos related cancer with a poor prognosis. Little is known about how patients and carers living with the condition manage their mental health and wellbeing needs. This paper reports findings on interventions being used by patients and informal carers living with mesothelioma and those which they find most helpful.

METHODS: In-depth interviews with patients (n = 10) and (informal) carers (n = 11) living with mesothelioma in the UK. We analysed our data inductively using a reflexive thematic analysis approach.

RESULTS: Participants described the importance of both smaller and larger actions and strategies which helped with their mental health. This included spending more time with family and friends and going on holidays. Professionals who participants said supported their mental health journey included not only specialist nurses and mental health professionals but also legal and Asbestos Support Group professionals. The latter demonstrates the unique needs and support required for this population. Exposure to asbestos as the cause of mesothelioma, has led to a social justice aspect of the experience of living with this cancer. Participants reported the importance of collective action to their mental health and wellbeing. The data indicate that patients and carers may have distinct mental health and wellbeing requirements and need to manage these in different ways at different times.

CONCLUSIONS: Findings have implications for nurses and other key professionals working in healthcare, community and legal settings supporting this client group, and for those living with mesothelioma who want to understand ways to enhance their own wellbeing.

RevDate: 2024-05-30
CmpDate: 2024-05-23

Liu RA, Wang BY, Chen X, et al (2024)

Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Genetic testing and molecular biomarkers, 28(5):189-198.

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

RevDate: 2024-07-03
CmpDate: 2024-07-01

Yang SR, Jayakumaran G, Benhamida J, et al (2024)

Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features.

Clinical cancer research : an official journal of the American Association for Cancer Research, 30(13):2780-2789.

PURPOSE: Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined.

EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm.

RESULTS: A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across >80% of the genome, was detected in 10 cases (4.8%). Compared with 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, whereas 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. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response.

CONCLUSIONS: 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 immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

RevDate: 2024-04-17

Mirra L, Beretta GL, Lisini D, et al (2024)

Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.

Current medicinal chemistry pii:CMC-EPUB-139795 [Epub ahead of print].

Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated with asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.

RevDate: 2024-08-27
CmpDate: 2024-08-23

Gibson AEJ, Ahmed W, Longworth L, et al (2024)

Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.

The patient, 17(5):551-563.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers.

METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models.

RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving.

CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.

RevDate: 2024-06-05
CmpDate: 2024-05-20

Miller E, Beckett EM, Cheatham D, et al (2024)

A review of the mesotheliogenic potency of cleavage fragments found in talc.

Toxicology and industrial health, 40(7):398-424.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

RevDate: 2024-04-12
CmpDate: 2024-04-10

Kadariya Y, Sementino E, Ruan M, et al (2024)

Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment.

Cancer research communications, 4(4):1004-1015.

UNLABELLED: Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.

SIGNIFICANCE: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.

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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.

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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.

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