Assessment of Global Trends in the Diagnosis of Mesothelioma From 1990 to 2017.

Importance: It is difficult for policy makers and clinicians to formulate targeted management strategies for mesothelioma because data on current epidemiological patterns worldwide are lacking. Objective: To evaluate the mesothelioma burden across the world and describe its epidemiological distribution over time and by sociodemographic index (SDI) level, geographic location, sex, and age. Design, Setting, and Participants: Annual case data and age-standardized rates of incidence, death, and disability-adjusted life-years associated with mesothelioma among different age groups were obtained from the Global Burden of Disease 2017 database. The estimated annual percentage changes in age-standardized rates were calculated to evaluate temporal trends in incidence and mortality. The study population comprised individuals from 21 regions in 195 countries and territories who were diagnosed with mesothelioma between 1990 and 2017. Data were collected from May 23, 2019, to January 18, 2020. Main Outcomes and Measures: Primary outcomes were incident cases, deaths, and their age-standardized rates and estimated annual percentage changes. Secondary outcomes were disability-adjusted life-years and relative temporal trends. Results: Overall, 34 615 new cases (95% uncertainty interval [UI], 33 530-35 697 cases) of mesothelioma and 29 909 deaths (95% UI, 29 134-30 613 deaths) associated with mesothelioma were identified in 2017, and more than 70% of these cases and deaths were among male individuals. In 1990, the number of incident cases was 21 224 (95% UI, 17 503-25 450), and the number of deaths associated with mesothelioma was 17 406 (95% UI, 14 495-20 660). These numbers increased worldwide from 1990 to 2017, with more than 50% of cases recorded in regions with high SDI levels, whereas the age-standardized incidence rate (from 0.52 [95% UI, 0.43-0.62] in 1990 to 0.44 [95% UI, 0.42-0.45] in 2017) and the age-standardized death rate (from 0.44 [95% UI, 0.37-0.52] in 1990 to 0.38 [95% UI, 0.37-0.39] in 2017) decreased, with estimated annual percentage changes of -0.61 (95% CI, -0.67 to -0.54) for age-standardized incidence rate and -0.44 (95% CI, -0.52 to -0.37) for age-standardized death rate. The proportion of incident cases among those 70 years or older continued to increase (from 36.49% in 1990 to 44.67% in 2017), but the proportion of patients younger than 50 years decreased (from 16.74% in 1990 to 13.75% in 2017) over time. In addition, mesothelioma incident cases and age-standardized incidence rates began to decrease after 20 years of a complete ban on asbestos use. For example, in Italy, a complete ban on asbestos went into effect in 1992; incident cases increased from 1409 individuals (95% UI, 1013-1733 individuals) in 1990, peaked in 2015 after 23 years of the asbestos ban, then decreased from 1820 individuals (95% UI, 1699-1981 individuals) in 2015 to 1746 individuals (95% UI, 1555-1955 individuals) in 2017. Conclusions and Relevance: This cross-sectional study found that incident cases of mesothelioma and deaths associated with mesothelioma continuously increased worldwide, especially in resource-limited regions with low SDI levels. Based on these findings, global governments and medical institutions may consider formulating optimal policies and strategies for the targeted prevention and management of mesothelioma.

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

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

Experimental asbestos studies in the UK: 1912-1950.

The asbestos industry originated in the UK in the 1870s. By 1898, asbestos had many applications and was reported to be one of the four leading causes of severe occupational disease. In 1912, the UK government sponsored an experimental study that reported that exposure to asbestos produced no more than a modicum of pulmonary fibrosis in guinea pigs. In the 1930s, the newly established Medical Research Council, with assistance from industry, sponsored a study of the effects of exposing animals to asbestos by injection (intratracheal and subcutaneous) and by inhalation in the factory environment. Government reports, publications, and contemporary records obtained by legal discovery have been reviewed in the context of the stage of scientific development and the history of the times. Experimenters were engaged in a learning process during the 1912-1950 period, and their reports of the effects of asbestos were inconsistent. Pathologists who studied the effects of asbestos experimentally, at whole animal, tissue and cellular levels, advanced experimental methodology and mechanistic knowledge. In the hands of public relations experts, however, research was exploited to preserve an industry and perpetuate preventable diseases, a practice that continues to this day.

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic.

Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.

Rarity of malignant mesothelioma prior to the widespread commercial introduction of asbestos: the Mount Sinai autopsy experience 1883-1910.

BACKGROUND: Most malignant mesotheliomas are related to asbestos exposure. Whether malignant mesothelioma occurs in the absence of asbestos exposure remains unsettled. To address this question we reviewed a series of 2,025 autopsies performed at the Mount Sinai Hospital between 1883 and 1910, prior to the widespread commercial introduction of asbestos. METHODS: Retrospective autopsy review. RESULTS: No cases of malignant mesothelioma were identified in 2,025 autopsies performed between 1883 and 1910. CONCLUSIONS: Malignant mesothelioma was rare prior to the widespread commercial introduction of asbestos.

Epidemiology of mesothelioma and historical background.

Mesothelioma is a "new" malignant disease strongly associated with exposure to amphibole asbestos exposure (amosite and crocidolite) environmentally and in the work place. Nonetheless, in recent years, we have learned that many cases of mesothelioma are idiopathic, while some are caused by therapeutic irradiation or chronic inflammation in body cavities. This paper reviews the key epidemiological features of the malignancy in the context of the biological and mineralogical factors that influence mesothelioma development. These tumors challenge the diagnostic pathologist's acumen, the epidemiologist's skill in devising meaningful and definitive studies, the industrial hygienist's knowledge of environmental hazards in diverse occupational settings, and the clinician's skill in managing an intrepid and uniformly fatal malignancy.

Mesothelioma and asbestos, fifty years of evidence: Chris Wagner and the contribution of the Italian occupational medicine community.

BACKGROUND: One of the first studies that "convincingly" described the relationship between pleural mesothelioma and asbestos was made by Wagner, Sleggs and Marchard in 1960. This article, published fifty years ago, contains much of what we still know to-day about malignant mesothelioma. OBJECTIVES: The aims of this article were to analyze the historical and scientific developments that led to the publication of Wagner's paper, to critically examine its contents and to consider the contribution to the initernational debate on the carcinogenesis of asbestos fibres made by occupational medicine in Italy in that period. METHODS: A thorough analysis ofscientific and historical literature on the relationship between asbestos exposure and tumours was conducted, with special regard to the articles by Italian authors in the 1960's. RESULTS: The decisive role of Wagner's paper in understanding the aetiopathogenetic mechanisms of asbestos-related tumours is inconfutable. In particular, his article clearly demonstrated the existence of a typical cancer of the mesothelium, expressing three fundamental principles of the epidemiology of occupational cancer: association with the carcinogen, latency and individual susceptibility. Enrico Vigliani, then director of the "Clinica del Lavoro" in Milan, made important contributions to this debate, also through the collection of data regarding mortality among Italian asbestos workers. CONCLUSIONS: Wagner's 1960 paper can be considered as a milestone not only in the history of occupational and environmental health, but also in the evolution of other medical disciplines such as epidemiology, pathology and oncology. A re-appraisal of the Italian contributions to the international debate on this subject should be considered.

Recent advances in mesothelioma staging.

Lack of a consensus staging system for malignant pleural mesothelioma has had a profound impact on clinical practice and research, which necessarily relies on comparison of outcomes across multiple institutions and studies for reliable prognostic information. Some lack of agreement arises from the difficulty of conforming this particular cancer to existing staging systems because of its unique biology. The heterogeneous prognosis of patients with differing tumor histology and constant search for new more effective therapies also play a role. Periodic data-driven refinement of staging criteria, based on careful pathologic analysis of histologically homogeneous cohorts, is mandated to provide clinicians with the optimal ability to stratify patients according to survival and select treatments most appropriate for the patient's individual tumor biology.

Asbestos and ship-building: fatal consequences.

The severe bombing of Belfast in 1941 had far-reaching consequences. Harland and Wolff was crippled. The British Merchant Ship Building Mission to the U.S.A. was being constrained by the U.K. treasury. On being told of the Belfast destruction, the British Mission and the United States Maritime Commission were emboldened. The result was 2,710 Liberty Ships launched to a British design. The necessary asbestos use associated with this and other shipbuilding, after a quarter century or more latency, is a genesis of malignancy killing thousands. Reversal of studies on asbestos limitation of fire propagation was crucial to Allied strategic planning of mass-fires which resulted in the slaughter of one to two million civilians. Boston and Belfast institutions made seminal discoveries about asbestos use and its sequelae.

Shooting the messenger: the vilification of Irving J. Selikoff.

Dr. Irving J. Selikoff (1915-1992), a New York physician based at Mount Sinai Hospital, was the leading American medical expert on asbestos-related diseases between the 1960s and early 1990s. In a country that had been the world's greatest consumer of asbestos, he was also at the center of the key controversies connected with the mineral. In these controversies, Selikoff was consistently demonized as a media zealot who exaggerated the risks of asbestos on the back of bogus medical qualifications and flawed science. Since his death, the criticism has become even more vituperative and claims have persisted that he was malicious or a medical fraud. However, most of the attacks on Selikoff were inspired by the asbestos industry or its sympathizers, and for much of his career he was the victim of a sustained and orchestrated campaign to discredit him. The most serious criticisms usually more accurately describe his detractors than Selikoff himself.

[Asbestos: a long lasting tragedy. Useful considerations for a historical reconstruction of the most remarkable facts]. / Amianto: una tragedia di lunga durata. Argomenti utili per una ricostruzione storica dei fatti più rilevanti.

A thought back on the "epic of asbestos" scanning the fundamental steps, from the "discovery" of the adverse effects for the workers. A first phase, the "asbestosis one" concluded in Britain in the early thirties with the issue of a technical legislation is described. It was the first regulation shared by the Unions and the asbestos companies, some of which were or will then become leaders all over the world. The main effect of this legislation enforcement is the reduction of the exposure in some units of the asbestos textile industry; no effects were observed instead in other asbestos industrial divisions where it's consumption for insulations and asbestos cement increased massively. The second phase lasting approximately thirty years next sees together to a formidable diffusion of all the asbestos fibres including the crocidolite ones, advertised and accepted like "indispensable" for the economical and social development, an absolute leadership of the companies in the management of health effects information for the workers and therefore also those on the pulmonary cancerogenicity. Such selfish and aggressive leadership, receives in return from government, labour and consumers organizations just inertia, impotence and incredulity. This attitude will also continue in the third phase, beginning in the early sixties of the last century. The time period will be dominated by mesothelioma with all its new and terrible meanings, the dangerousness of asbestos exposure especially to the blue one even at lower levels than those observed in the past for other pathologies and the long latency before the appearance of the effects. Discussing about asbestos substitutes was out of the agenda, indeed just in the period where the mining and the consumption of asbestos touched the highest levels. The initiatives assumed in some countries like the auto limitation of the use of crocidolite and a more rigorous reduction of the occupational exposures will only turn out useful in order to lower the risk for asbestosis and, probably, the one for pulmonary tumour. In the United States, the judicial litigation for compensation between the workers and the companies begins. The same phenomenon will characterize also in the other countries industrializes the fourth phase of the epic, until our days; it is just in these years, and especially during the eighties, that industry starts thinking about the substitution of asbestos; the lively public debate will favour initiatives oriented to obtain economic compensation for damages caused by past occupational and environmental exposures. These legal actions will carry to bankruptcy all the asbestos companies and later to the ban of asbestos. The judicial debates will also uncover "confidential" information useful to better reconstruct the epic, to formulate more dispassionate historical judgments and to allow everyone on answering to more complex questions and more important than how much generally it was previously believed; all this should happen contextualizing the ages in which the scientific acquaintances on the effects of asbestos have been published and disproving prejudgments, able to affect some conclusions of the past.

The Rochdale asbestos cancer studies and the politics of epidemiology: what you see depends on where you sit.

The history of the exploitation of epidemiology by the U.K. asbestos industry and the subsequent obscuring of the disastrous results of exposures is presented, exploring in particular the roles of Sir Richard Doll and his colleagues. Epidemiology, often regarded as a neutral science, is susceptible to socio-political influences.

Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis.

BACKGROUND: The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos. METHODS: We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex-specific national populations. FINDINGS: Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero. INTERPRETATION: Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos.

Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor.

Diffuse malignant mesothelioma (DMM) is a distinctive tumor which provides an uncommon opportunity to observe the gradual appreciation and increasing incidence of a new disease. DMM is a new disease. One cannot comment intelligently about the pathology of sporadic cases that might have occurred before the beginnings of anatomic pathology, but we do know that there were so few cases before 1930 that the very existence of the disease was not accepted in general before 1930 and not accepted by all pathologists even up until 1960. Because DMM is increasing on a worldwide basis and is making its appearance in the developing world, where it has not previously been diagnosed, appreciation of how the disease came to be noticed sheds light on its causation. As a signal tumor for exposure to asbestos, and knowing that all special exposures contribute to the development of the disease, knowledge of its continuing escalation underscores the importance of recognition of previously unimplicated or occult exposures for reasons of public health in both developed and developing countries.