Parole chiave: mesotelioma, pleura, amianto, epidemiologia, autopsia, cantieri navali, corpi dell amianto, placche pleuriche.

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1 Malignant mesothelioma of the pleura in Monfalcone, Italy: a 23-year monitoring in an area at high incidence Il mesotelioma maligno della pleura a Monfalcone: 23 anni di monitoraggio in un area ad alta incidenza Claudio Bianchi*, Alessandro Brollo**, Lucia Ramani**, Tommaso Bianchi* * Centre for the Study of Environmental Cancer, Italian League against Cancer, Monfalcone (GO), Italy ** Laboratory of Pathological Anatomy, Hospital of Monfalcone, Monfalcone (GO), Italy Summary The incidence of pleural mesothelioma and the relationship mesothelioma-asbestos were investigated in the Monfalcone area, a small industrial district (population about 60,000), with large shipyards. All the cases of pleural mesothelioma (215) diagnosed at the Monfalcone Hospital in the period October June 2002 were examined. The pathological diagnosis was based on, or confirmed by necropsy findings in 169 cases, on surgical biopsies in 41 cases, and on cytological findings in 5 cases. Occupational histories were obtained from the patients themselves or from their relatives by personal or telephone interviews. In 132 cases asbestos bodies were isolated after chemical digestion of lung samples (Smith-Naylor method). The series included 182 men and 33 women, aged between 44 and 91 years (mean 69.7 years, median 70.0). All the cases were asbestos-related. About 80% of the male patients had worked in the shipyards. Among women, the most frequent source of exposure to asbestos (51.5%) was the cleaning of work clothes polluted by the mineral. The latency periods (time intervals between first exposure to asbestos and diagnosis of the tumour) ranged from 21 to 72 years (mean 50.2, median 53.0); in about 80% of the cases latency periods were longer than 40 years. At necropsy, pleural plaques were found in 90.4% among men, and in 72.4% among women. Asbestos bodies were seen on routine lung sections in 71.9% of men, and in 46.6% of women. After isolation, lung asbestos bodies ranged between 0 and about 10 millions of bodies/gramme dried tissue. Burdens higher than 1,000/g were found in 86.3% of men, and in 36.3% of women. The mean annual number of cases was 6.8 in the period , and 12.5 in the period The peculiar features of this series were a high rate of necropsy examinations, a high percentage of people with objective signs of exposure to asbestos, a very high prevalence of shipyard workers, and very long latency periods. The marked rise in incidence observed during the Address/Indirizzo: Dr. Claudio Bianchi, Centre for the Study of Environmental Cancer, Lega Italiana per la Lotta contro i Tumori, Sezione di Gorizia, Ospedale di Monfalcone, Via Galvani 1, Monfalcone (GO), Italia - Tel. 0039/0481/ Fax 0039/0481/ legatumori1@interfree.it 49

2 Eur. J. Oncol. Library, vol. 3 study period plausibly reflects the increase in the workforce of the Monfalcone shipyards which had occurred some years previously. Key words: mesothelioma, pleura, asbestos, epidemiology, necropsy, shipbuilding, asbestos bodies, pleural plaques. Riassunto Sono stati analizzati l incidenza del mesotelioma della pleura e il rapporto amianto-mesotelioma nell area di Monfalcone, un piccolo distretto industriale (popolazione di circa abitanti), sede di grandi cantieri navali. Sono stati esaminati tutti i casi (215) di mesotelioma pleurico diagnosticati all Ospedale di Monfalcone nel periodo ottobre 1979-giugno La diagnosi patologica è stata basata su, o confermata da reperti autoptici in 169 casi, da biopsie chirurgiche in 41 casi e da reperti citologici in 5 casi. Le storie lavorative sono state ottenute dai pazienti stessi o dai loro parenti per mezzo di interviste personali o telefoniche. In 132 casi i corpi dell amianto sono stati isolati dopo digestione chimica di campioni di tessuto polmonare secondo il metodo Smith-Naylor. La serie comprendeva 182 uomini e 33 donne, di età tra 44 e 91 anni (media 69,7 anni, mediana 70,0). Tutti i casi erano amianto-correlati. Circa l 80% dei pazienti maschi aveva lavorato nei cantieri navali. Nelle donne, la fonte più frequente di esposizione ad amianto (51,5%) era la pulitura di abiti da lavoro inquinati dal minerale. I periodi di latenza (intervalli di tempo intercorrenti tra la prima esposizione ad amianto e la diagnosi del tumore) variavano da 21 a 72 anni (media 50,2, mediana 53,0); in circa l 80% dei casi i periodi di latenza erano maggiori di 40 anni. All autopsia, placche pleuriche furono trovate nel 90,4% degli uomini e nel 72,4% delle donne. Corpi dell amianto furono osservati nelle sezioni di polmone di routine nel 71,9% degli uomini, e nel 46,6% delle donne. Dopo isolamento, i corpi dell amianto nel polmone variavano tra 0 e circa 10 milioni di corpi per grammo di tessuto secco. Quantità superiori a corpi per grammo furono trovate nell 86,3% degli uomini e nel 36,3% delle donne. Il numero medio annuo di casi è stato di 6,8 nel periodo e 12,5 nel periodo Gli aspetti peculiari di questa serie erano l alto numero di esami autoptici, l elevata percentuale di persone con segni obiettivi di esposizione ad amianto, l elevatissima prevalenza di lavoratori dei cantieri navali, ed i periodi di latenza estremamente lunghi. È plausibile che il marcato aumento di incidenza osservato durante il periodo dello studio rifletta l incremento nella forza-lavoro dei cantieri navali di Monfalcone verificatosi anni prima. Parole chiave: mesotelioma, pleura, amianto, epidemiologia, autopsia, cantieri navali, corpi dell amianto, placche pleuriche. Introduction The Monfalcone area is a small industrial district (population about 60,000), located in Northeastern Italy at the border with Slovenia. Shipbuilding is the principal industry in the area. The Monfalcone shipyards began their activity in In the following decades they 50

3 C. Bianchi, A. Brollo, L. Ramani, et al: Mesothelioma of the pleura in Monfalcone, Italy became the most important shipbuilding installation in the Mediterranean region. The workforce of the Monfalcone shipyards reached a peak in the late 1930s with some 6,000 workers. Moreover, at that time, about 4-5,000 workers were employed in the aeronautic works and in electro-mechanic shops, included in the shipyards. The analysis of the mortality data in Italy in the period showed high mortality rates for pleural cancer in seven Provinces, including the Province of Gorizia, in which Monfalcone area is comprised 1. Since October 1979, investigations have been conducted at the Hospital of Monfalcone (Laboratory of Pathological Anatomy), aimed at monitoring the mesothelioma incidence in this area, and analysing the relationships between mesothelioma and asbestos. These studies have been the object of numerous reports 2-8. In the present paper, the findings obtained over approximately 23 years are reported and discussed. Methods All the cases of malignant pleural mesothelioma seen at the Monfalcone Hospital in the period October 1979-June 2002 were collected and analysed. The pathological diagnosis of the 215 cases included in the study was based on, or confirmed by necropsy findings in 169 cases, and on surgical biopsies in 41 cases. In the remaining 5 cases, in which material for histological examination was not available, the diagnosis was based on clinical, radiological, and cytological findings. Occupational histories were reconstructed by interviewing the patients themselves or their relatives, generally by personal consultation, and in a few cases by telephone. In many cases the employment card (a personal document in which all the occupations and the employers are listed) was consulted. In parallel with the above interviews, a series of enquiries were conducted aimed at identifying the features of the work in the various occupational settings. In the necropsies carried out at the Monfalcone Hospital, the thoracic cavities were carefully explored to detect even minimal pleural plaques. These were classified in three classes on the basis of their size: unilateral or bilateral plaques, not larger than 4 cm across the major axis were classified as class 1 (small); plaques larger than 4 cm but involving less than 50% of the thoracic cavity were defined as class 2 (intermediate); plaques involving more than 50% of the thoracic cavity were labelled class 3 (large). In all necropsy cases routine lung sections were histologically examined for asbestos bodies. In 132 cases, samples were obtained at necropsy from the base of the right lung (or from the base of the left lung if the right one was largely involved by the tumour); such samples were digested in hypochlorite solution after the Smith-Naylor method 9, and the asbestos bodies were isolated and counted. Results The annual number of cases showed considerable variations in the study period (Table 1). The series included 182 men (age range years, mean 69.1 years, median 69.0), and 33 women (age range years, mean 72.8 years, median 73.0). The sex and age distribution of the patients is reported in fig. 1. There were 196 subjects resident in the Monfalcone area, and 19 persons resident in other parts of the Province of Gorizia. A large majority of patients had worked in the shipyards (Table 2). Asbestos exposure at home, caused by the cleaning of work clothes polluted by asbestos, was the second source 51

4 Eur. J. Oncol. Library, vol. 3 Table 1 - Annual number of pleural mesotheliomas, Monfalcone, October 1979-June 2002 Year Men Women Total 1979 (Oct-Dec) (Jan-June) Total Fig. 1. Sex and age distribution in 215 cases. of exposure in frequency. A number of occupations appeared in the other work histories (Table 3). Of the women with probable environmental exposure, one patient had spent the first 20 years of her life in a coastal city, where she lived near a large dockyard. The second patient lived near the Monfalcone shipyard. 52

5 C. Bianchi, A. Brollo, L. Ramani, et al: Mesothelioma of the pleura in Monfalcone, Italy Table 2 - Occupational data in 215 cases Men Women Category N. cases % N. cases % Total Shipbuilding Domestic exposure Maritime trades Insulation Other Total Table 3 - Occupations in the cases classified as other Category Men Women Total Textile industry 3 a 4 b 7 Construction industry 4 4 Brickyard Environmental exposure? 2 2 Railways 2 2 Sodium carbonate factory 2 2 Bakery 1 1 Chemical industry 1 c 1 Distillery 1 1 Foundry 1 1 Machinery industry 1 1 Paper mill 1 1 Total a Two patients had worked in cotton mills; one patient had worked in a dye works in which fire-proofing tissues were manufactured b The patients had worked in cotton mills; two of them had also histories of domestic exposure c The source of exposure was a small chemical factory the family had at home. A majority of patients had their first exposure to asbestos before 1960 (fig. 2). The latency periods, defined as time intervals between first exposure to asbestos and diagnosis of the tumour, ranged from 21 to 72 years (mean 50.2, median 53.0). In about 80% of the cases the latency periods were longer than 40 years (fig. 3). Asbestos bodies were observed on routine lung sections in 71.9% of men and in 46.6% of women. Asbestos body burdens higher than 1,000/g were found in 86.3% of men, and 36.3% of women (fig. 4). Pleural plaques were found in 90.4% of men and 72.4% of women (fig. 5). Among the patients classified as other, 19 were examined for the presence of pleural plaques and lung asbestos bodies; of these 16 cases showed pleural plaques and/or asbestos bodies on routine lung sections; in a further two cases, amounts of about 600 bodies/g were observed. Discussion In the present series malignant pleural mesothelioma was a condition mainly involving men, aged years, with histories of working in shipyards. The relationship between 53

6 Eur. J. Oncol. Library, vol. 3 Fig. 2. First exposure to asbestos in 185 cases. Fig. 3. Latency periods in 185 cases. shipbuilding and mesothelioma is one of the most investigated topics in mesothelioma epidemiology Asbestos use in shipbuilding began as far back as the last decades of the 1800s 16. A number of studies have indicated the shipyard areas as those mostly heavily affected by mesothelioma 11, The maritime trades have been recognized, only with some delay, as occupations at risk for asbestos disease. Some years ago mesothelioma among merchant seamen was still considered as a strange event 20. However, the relevance of asbestos exposure among sailors is well ascertained Apart from shipbuilding, maritime trades and insulation, a variety of other occupations were encountered in the Monfalcone series (Table 3). In the past, asbestos risk in many of such occupations has scarcely been recognized. For instance, the (non-asbestos) textile 54

7 C. Bianchi, A. Brollo, L. Ramani, et al: Mesothelioma of the pleura in Monfalcone, Italy Fig. 4. Lung asbestos body burdens (log 10) in 132 cases) Fig. 5. Pleural plaques in 160 cases. In a further 5 patients (4 men and 1 woman) pleural plaques were observed but they had not been classified industry seems to be a new branch at risk 27. However, the cotton mills of the Province of Gorizia have already been indicated as workplaces in which relevant exposure to asbestos has occurred 7. The well known importance of asbestos exposure in the construction industry has recently been emphasized 28. Railway work is a classical occupation at risk Data from the literature, as well as findings obtained at the Monfalcone Hospital, documented asbestos exposure in sodium carbonate factories 31, bakeries 28, 32, brickworks 2, 28, foundries 28, 33-35, distilleries 36, and paper mills 37, 38. Asbestos exposure in the above cases is not only suggested by the occupational data, but also frequently corroborated by objective signs, such as the presence of pleural plaques and the presence of asbestos bodies in the lung tissue. The proportion of mesotheliomas attributable to asbestos ranges strongly from one series 55

8 Eur. J. Oncol. Library, vol. 3 to another. Some researchers have stated that 90% or even higher percentages of the investigated cases had been caused by asbestos 15, 28, 39, 40. In the present group all the cases were categorized as asbestos-related. In other series the percentages were lower. In a study about malignant pleural mesothelioma conducted in Spain (Provinces of Barcelona and Cadiz), occupational histories indicating asbestos exposure were obtained in 62% of the cases 41 ; in an investigation conducted in Romagna, Italy, 45% of the cases were considered as asbestos-related on the basis of occupational data 42. In another series of pleural mesotheliomas examined in the Varese area, Italy, 12% of the cases were considered as due to occupational exposure to asbestos 43. These low percentages may be explained by several reasons. Major difficulties are not rarely encountered in obtaining a complete lifetime occupational history. In addition, many occupations at risk for asbestos have only recently been recognized or remain yet misevaluated. Finally, occupational and environmental data taken alone sometimes do not allow the identification of exposure sources. In this context, the data recently reported by Leigh et al 28 are paradigmatic. When the cases defined as negative, on the basis of occupational and environmental data, were examined for the lung asbestos content, high amounts of asbestos fibres were found in 80% of the cases. The data obtained on the latency periods in the Monfalcone series are at variance with those reported in the literature. It is currently stated that mesothelioma development requires incubation periods of some years. In the present series, latency periods were longer than 40 years in about 80% of the cases. The mean latency period was about 50 years. Latency periods show substantial variations from one occupational category to another 44. The groups with heavy exposure to asbestos, such as insulators, show latency periods of about 30 years 44. At the other extreme, categories with lower exposures, such as sailors, show longer latency periods 25, 44. The increase in the number of cases observed in Monfalcone since 1989 plausibly reflects the variations in the workforce of the Monfalcone shipyards which had occurred some years previously; in fact in the 1930s the number of the shipyard workers rose from about 2,500 to about 6,000. Finally, in the Monfalcone area, asbestos exposure occurred at least until the 1980s. Given the long latency periods documented in the present study, it is predictable that a high mesothelioma incidence will continue to characterise this area over the next decades. References 1. Facchini U, Marcazzan MG, Camnasio M, et al. Studio sulla mortalità per mesotelioma della pleura del decennio con riferimento alle province italiane. Med Lav 1986; 77: Bianchi C, Brollo A, Bittesini L. Mesotelioma da asbesto nel territorio di Monfalcone. Pathologica 1981; 73: Bianchi C, Brollo A, Bittesini L. Malignant mesothelioma of the pleura in Monfalcone (Italy). In Caldarola L, Pocchiari F, Minardi F, et al. Epidemiologia in Oncologia. Bologna: Monduzzi Editore, 1986, Bianchi C, Brollo A, Bittesini L, et al. Mesotelioma pleurico da asbesto nel territorio di Monfalcone. In Parolari G, Gherson G, Cristofolini A, et al. Il rischio neoplastico da amianto nei luoghi di lavoro e nell ambiente di vita. Verona: Bi & Gi Editori, 1987, Bianchi C, Brollo A, Ramani L. Malignant pleural mesothelioma in Monfalcone, Italy. Proceedings of the VII International Pneumoconioses Conference, Part II. US Department of Health and Human Services, 1990, Bianchi C, Brollo A, Ramani L, et al. Mesotelioma maligno asbesto-correlato nel territorio di Monfalcone. In Buselli R, Cristaudo A, Ferrante S, et al. Atti del Convegno Nazionale Mesoteliomi maligni ed esposizioni professionali ad amianto. Sarzana: Epigrafica snc, 1992,

9 C. Bianchi, A. Brollo, L. Ramani, et al: Mesothelioma of the pleura in Monfalcone, Italy 7. Bianchi C, Brollo A, Ramani L, et al. Asbestos-related mesothelioma in Monfalcone, Italy. Am J Ind Med 1993; 24: Bianchi C, Brollo A, Ramani L, et al. Malignant mesothelioma of the pleura in Monfalcone, Italy: trend of an epidemic. In Moraes M, Brentani R, Bevilacqua R. 17 th International Cancer Congress. Bologna: Monduzzi Editore, 1998, Smith NJ, Naylor B. A method for extracting ferruginous bodies from sputum and pulmonary tissue. Am J Clin Pathol 1972; 58: McDonald JC, McDonald AD. Epidemiology of mesothelioma from estimated incidence. Prev Med 1977; 6: Giarelli L, Bianchi C, Grandi G. Malignant mesothelioma of the pleura in Trieste, Italy. Am J Ind Med 1992; 22: Kishimoto T. Intensity of exposure to asbestos in metropolitan area Kure City as estimated by autopsied cases. Cancer 1992; 69: Kurumatani N, Natori Y, Mizutani R, et al. A historical cohort mortality study of workers exposed to asbestos in a refitting shipyard. Ind Health 1999; 37: Jemal A, Grauman D, Devesa S. Recent geographic patterns of lung cancer and mesothelioma mortality rates in 49 shipyard counties in the United States, Am J Ind Med 2000; 37: Bianchi C, Brollo A, Ramani L, et al. Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases. Ind Health 2001; 39: Harries PG. Asbestos dust concentrations in ship repairing: a practical approach to improving asbestos hygiene in naval dockyards. Ann Occup Hyg 1971; 14: Damhuis AM, Planteydt HT. Trends in incidence of pleural mesothelioma in the Rotterdam area (letter). Int J Cancer 1995; 60: De Vos Irvine H. Mesothelioma (letter). Lancet 1995; 345: Puntoni R, Merlo F, Borsa L, et al. A historical cohort mortality study among shipyard workers in Genoa, Italy. Am J Ind Med 2001; 40: Varouchakis G, Velonakis EG, Amfilochiou S, et al. Asbestos in strange places: two case-reports of mesothelioma among merchant seamen. Am J Ind Med 1991; 19: Bianchi C, Brollo A, Bittesini L. Patologia da asbesto nei marittimi. Atti della Sezione Studi, Centro Internazionale Radio-Medico, 1983, Velonakis EG, Tsorva A, Tzonou A, et al. Asbestos-related chest X-ray changes among Greek merchant marine seamen. Am J Ind Med 1989; 15: Selikoff IJ, Lilis R, Levin G. Asbestotic radiological abnormalities among United States merchant marine seamen. Br J Ind Med 1990; 47: Bianchi C, Brollo A. Mesoteliomi maligni della pleura e del peritoneo: tumori professionali dei marittimi. Atti della Sezione Studi, Centro Internazionale Radio Medico, 1991, Rafnsson V, Sulem P. Cancer incidence among marine engineers and machinists, a population based study (abstract). Med Lav 2002; 93: Saarni H, Pentti J, Pukkala E. Cancer at sea: a case-control study among male Finnish seafearers. Occup Environ Med 2002; 59: Colli G, Terzi M, Vinci L, et al. Un caso di mesotelioma pleurico da inusuale esposizione professionale ad amianto nell industria della lana. G Ital Med Lav Erg 2001; 23: Leigh J, Davidson P, Hendrie L, et al. Malignant mesothelioma in Australia, Am J Ind Med 2002; 41: Merler E. Identificazione dei casi di mesotelioma insorti in Italia per l esposizione all amianto usato nella coibentazione di mezzi ferroviari. RMDL 1990; 5: Maltoni C, Pinto C, Mobiglia A. Mesotheliomas following exposure to asbestos used in railroads: the Italian cases. In Mehlman MA, Upton A. The identification and control of environmental diseases: asbestos and cancers. Adv Modern Environ Toxicol, XXII. Princeton, NJ: Scientific Publishing Co. Inc., 1994, Bianchi C, Brollo A, Ramani L, et al. Exposure to asbestos in Monfalcone, Italy. A necropsy-based study. In Riboli E, Delendi M. Autopsy in epidemiology and medical research. Lyon: IARC, 1991, Ascoli V, Calisti R, Carnovale Scalzo C, et al. Malignant pleural mesothelioma in bakers and pastry cooks. Am J Ind Med 2001; 40:

10 Eur. J. Oncol. Library, vol Dodson RF, O Sullivan M, Corn CJ, et al. Analysis of ferruginous bodies in bronchoalveolar lavage from foundry workers. Br J Ind Med 1993; 50: Rosenman KD, Reilly MJ. Asbestos-related x-ray changes in foundry workers. Am J Ind Med 1998; 34: Mattioli S, Nini D, Mancini G, et al. Past asbestos exposure levels in foundries and cement-asbestos factory (letter). Am J Ind Med 2002; 42: Robotti M, Fasciolo PG, Bonsignore AD. Su di un caso di asbestosi pleuro-polmonare in addetto alla chiarificazione di alcoolici in distilleria. G Ital Med Lav 1982; 4: Bianchi C, Brollo A, Bittesini L, et al. Esposizione all asbesto nel territorio di Monfalcone. Riv Inf Mal Prof 1986; 73: Carel R, Boffetta P, Kauppinen T, et al. Exposure to asbestos and lung and pleural cancer mortality among pulp and paper industry workers. J Occup Environ Med 2002; 44: van Gelder T, Hoogsteden HC, Versnel MA, et al. Malignant pleural mesothelioma in the Southwestern part of the Netherlands. Eur Respir J 1989; 2: Chailleux E, Pioche D, Chopra S, et al. Épidémiologie du mésothéliome pleural malin dans la région de Nantes-Saint-Nazaire. Évolution Rev Mal Resp 1995; 12: Agudo A, Gonzalez CA, Bleda MJ, et al. Occupation and risk of malignant pleural mesothelioma: a case-control study in Spain. Am J Ind Med 2000; 37: Gruppo di Lavoro per la Sorveglianza del Mesotelioma in Romagna. Analisi dell esposizione professionale ad asbesto dei casi di mesotelioma registrati in Romagna ( ). Med Lav 2000; 91: Tiso C, Bagaglio A, Castoldi MR, et al. Analisi dei casi di decesso per mesotelioma pleurico occorsi nel quinquennio in Provincia di Varese. Conferenza Nazionale sull Amianto, Roma 1-5 marzo 1999, Bianchi C, Ramani L, Bianchi T, et al. Latency periods in asbestos-related mesothelioma of the pleura (abstract). Med Lav 2002; 93: