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Original Article

Mesothelioma among shipyard workers in Monfalcone,

MATERIALS AND METHODS Claudio Bianchi, Abstract Tommaso Bianchi Background: The high mesothelioma incidence The Monfalcone shipyards roll was Center for the Study of Environmental Cancer, in Monfalcone, Italy, is mainly attributable to examined to identify the persons hired shipbuilding activity. Mesothelioma risk among Italian League against in the period 1950-1959. Available Cancer, Monfalcone, shipyard workers in Monfalcone is poorly defined. data were registered including: Name Italy Materials and Methods: Workers hired at the and family name of the worker, birth Monfalcone shipyards in the period 1950-1959 were year (or complete birth date when For correspondence: identifi ed by surveying shipyard roll. The list of the reported), employment date, trade Dr. Claudio Bianchi, workers was coupled with the archive data of Monfalcone at the hiring time. The list of hired Center for the Study of and Hospitals. Mesotheliomas diagnosed workers was coupled with archive Environmental Cancer, in the above people were reexamined. Results: Of Italian League against data collected at the Pathological 1,403 workers hired in 1950-1959, 35 were diagnosed Cancer-Hospital of Anatomy Units of the Monfalcone with mesothelioma (34 pleural, one peritoneal) between Monfalcone, and Trieste Hospitals. Mesothelioma 1978 and 2012. Latency periods exceeded 40 years in Via Galvani 1-34074 cases diagnosed in the workers 31 cases. The highest percentage of mesotheliomas Monfalcone, Italy. hired in 1950-1959 were reexamined. was observed among people aged 14-19 years at hiring E-mail: legatumori1@ interfree.it time (3.4%). Four mesothelioma patients had a blood In particular we reviewed the relative with the same tumor. Conclusions: The present pathological diagnosis (type and fi ndings show high mesothelioma percentage among date), occupational history, latency shipyard workers hired at young ages. The effects of period (time intervals elapsing asbestos exposure begun in 1950-1959 cannot be between hiring year and mesothelioma considered as exhausted. diagnosis), and markers of asbestos exposure (presence/burden of asbestos bodies in lung tissue). In Key words: Age, asbestos, asbestos bodies, familial many cases asbestos bodies had mesothelioma, latency period, mesothelioma, peritoneum, pleura, shipyards been counted after isolation from lung tissue, following Smith-Naylor method.[6]

INTRODUCTION The Chi-square and the Student’s t-test were used to compare the AAccessccess thisthis articlearticle onlineonline Monfalcone, Northeastern Italy, is the site of large shipyards. prevalences of mesothelioma in the WWebsite:ebsite: www.ijoem.com These began their activity in 1908. The Monfalcone district various age groups at hiring time. DDOI:OI: has been characterized as an area at high incidence of 10.4103/0019-5278.111753 QQuickuick ResponseResponse Code:Code: malignant mesothelioma and shipyard work has emerged RESULTS as the principal cause of mesothelioma in Monfalcone.[1,2] Studies conducted on a series of 3,640 consecutive necropsies In the period 1950-1959, 1,403 workers showed that in the Monfalcone shipyards, asbestos exposure (1,375 men, and 28 women, aged was an ubiquitous phenomenon, often reaching high levels.[3] between 14-59 years) were hired at Recent studies have been conducted, aimed at obtaining data the Monfalcone shipyards. The age on the magnitude of mesothelioma risk in the Monfalcone distribution of the male workers is shipyards as well as the features of such tumor in different reported in Figure 1. The Figure 2 periods. In a series of 2,776 persons hired in 1942, 18 pleural shows the principal trades of the male mesotheliomas were diagnosed in the period 1981-2005.[4] Of workers. Of the 28 female workers, 1,637 workers hired in the period 1960-1969, 17 had a diagnosis 21 were hired as canteen employees. of pleural mesothelioma.[5] In the present study, people hired at the Monfalcone shipyards in the period 1950-1959 were Thirty-five cases of malignant investigated. mesothelioma (34 pleural, one

Indian Journal of Occupational and Environmental Medicine - December 2012 - Volume 16 - Issue 3 119 Bianchi and Bianchi: Mesothelioma in shipyard workers peritoneal) were diagnosed among people hired in the period plumber (11 cases), carpenter-shipwright (ten cases), and 1950-1959. Mesothelioma patients included 34 men aged welder (six cases) being the more frequent. Two men had between 47 and 82 years and one woman aged 88 years. histories of asbestos exposure prior to the employment The age distribution of the patients with mesothelioma is in 1950s. The woman with mesothelioma had worked as a showed in Figure 3. The tumors were diagnosed between canteen employee. She had also a history of exposure to 1978 and 2012. The pathological diagnosis was based on or asbestos at home, having cleaned the work clothes of her confirmed by necropsy findings in 27 cases. In the remaining husband and of her son, occupationally exposed. cases, mesothelioma was diagnosed on biopsy or surgical material (seven cases), or on cytological findings (one case). Of 29 patients for whom data on the employment duration were available, 28 had worked in the shipyards for more than Figure 4 shows the age distribution of the mesothelioma patients at the employment time. Mesotheliomas were Table 1: Percentages of mesotheliomas after the age at hiring time among male workers hired at the Monfalcone shipyards concentrated among persons aged 14-33 years at hiring date. in 1950-1959 The highest prevalence was observed among people aged Age No. of Mesothelioma Mesothelioma 14-19 years at hiring time [Table 1]. The differences among (years) people cases percentages the various groups did not reach the statistical significance. 14-19 667 23 3.4 20-29 382 8 2.0 The trades of the workers with mesothelioma were various. 30-39 179 3 1.6 40-49 112 0 Not rarely, the patients had worked with more trades, with 50-59 34 0

Figure 1: Age distribution at hiring time in 1,374* male workers, hired at the Monfalcone shipyards in the period 1950-1959. *In one Figure 2: The most prevalent trades at hiring time in 1,375 male case the age of the worker was not reported workers hired at the Monfalcone shipyard in the period 1950-1959

Figure 3: Age distribution at the time of diagnosis in 35 Figure 4: Age distribution at hiring time in 35 mesothelioma cases, mesothelioma cases, diagnosed among people hired at the diagnosed among people hired at the Monfalcone shipyards in the Monfalcone shipyards in the period 1950-1959 period 1950-1959

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10 years, and 25 for more than 20 years. The latency periods cases have been observed even in 2012, suggests that further calculated in 34 cases ranged between 25 and 68 years (mean cases have to be expected as effects of shipyard work in 48.3 years) [Figure 5]. Monfalcone in 1950-1959. Finally, archive data of Monfalcone and Trieste Hospitals do not cover all cases, especially in Asbestos bodies isolated in 22 cases ranged between 1,000 case of people migrating to other areas. Despite to these and 886,000 bodies per gram of dried tissue [Figure 6]. In a limitations, the prevalence of mesothelioma among shipyard further six cases, the presence of asbestos bodies on routine workers was high. lung sections was reported. The relative rarity of peritoneal mesothelioma in the present Four men with pleural mesothelioma had a blood relative study corresponds to that seen in more large series examined with the same tumor. Familial mesotheliomas included one in Monfalcone.[1,14] couple father-son, one couple of brothers, and two couples brother-sister. Of the blood relatives, three had histories of A relevant factor in determining the risk of mesothelioma occupational exposure to asbestos and one had a history of is the age at the hiring time. In the present series, nearly domestic exposure. 50% of people hired in 1950-1959 were aged 14-19 years at the time of employment. In this group, the prevalence DISCUSSION of mesothelioma reached the highest values. This fact is not difficult to explain. People hired at young age may The cancer geography clearly shows the relationship have experienced longer exposures to asbestos. Moreover, between shipbuilding activity and development of malignant the development of mesothelioma generally requires mesothelioma. Since the 1950s, the sites with largest very long latency periods. The studies conducted in the shipyards have been identified as areas at high mesothelioma Trieste-Monfalcone area[1,15-18] showed mean latency periods [7,8] incidence. Some cohort studies showed high mesothelioma close to 50 years among shipyard workers. Similar values, [9-12] incidence/mortality among shipyard workers. somewhat higher than those currently reported, were also observed in other shipyard areas.[19] Older people at hiring After the destruction caused by the raids in World War II time die before they might reach mesothelioma age. It should (WWII), the Monfalcone shipyards had an intense activity be noted that asbestos exposure represents a risk factor in the decade 1950-1959 and in the following years. Units of for a wide spectrum of pathological conditions, that are various types were produced; including passenger motorships not entirely known. Besides the malignancies certainly or and turbine steamships, turbine tankers, and warships (air possibly related to asbestos,[20] some studies indicate also carrier cruiser and many submarines). a higher risk for cardiovascular diseases among asbestos exposed persons.[21] In the Monfalcone district, studies on mesothelioma began [13] in 1979. This means that mesotheliomas developed prior The latency periods observed in the present mesotheliomas to this date may be remained undetected or unregistered. showed extreme variations, from 25 to 68 years. The mean Consequently, the data emerged from the present study may latency period was superimposable to that observed in large be underestimated. Moreover, the fact that mesothelioma

Figure 5: Latency periods in 34 mesothelioma cases, diagnosed Figure 6: Asbestos body burdens in 22 mesothelioma cases, among people hired at the Monfalcone shipyards in the period diagnosed among people hired at the Monfalcone shipyards in the 1950-1959 period 1950-1959

Indian Journal of Occupational and Environmental Medicine - December 2012 - Volume 16 - Issue 3 121 Bianchi and Bianchi: Mesothelioma in shipyard workers series of mesotheliomas among shipyard workers in the 5. Bianchi C, Bianchi T. Shipbuilding and mesothelioma in the Monfalcone Trieste-Monfalcone area.[18] area, Italy. Trend of the epidemic. Eur J Oncol 2012;17:43-8. 6. Smith MJ, Naylor B. A method for extracting ferruginous bodies from sputum and pulmonary tissue. Am J Clin Pathol 1972;58:250-4. Lung asbestos bodies isolated at necropsy in 22 mesothelioma 7. McCaughey WT. Primary tumours of the pleura. J Pathol Bacteriol cases showed wide variations in number. In 14 cases, 1958;76:517-29. high burdens (more than 10,000 bodies per gram of dried 8. Bianchi C. Mesothelioma and naval work. Eur J Oncol 2002;7:159-60. tissue) were found. In evaluating these findings, it should 9. Kolonel LN, Yoshizawa CN, Hirohata T, Myers BC. Cancer occurrence be remembered that clearance of asbestos fibers from the in shipyard workers exposed to asbestos in Hawaii. Cancer Res 1985;45:3924-8. lung tissue represents a mechanism by far more efficient 10. Danielsen TE, Langård S, Andersen A, Knudsen O. Incidence of cancer [22] than believed in the past. Clearance involves, although at among welders of mild steel and other shipyard workers. Br J Ind Med different degrees, both chrysotile as well as amphiboles. If 1993;50:1097-103. long time intervals have elapsed from the end of asbestos 11. Puntoni R, Merlo F, Borsa L, Reggiardo G, Garrone E, Ceppi M. exposure, the number of lung asbestos bodies reflects A historical cohort mortality study among shipyard workers in , only partly the intensity of occurred exposure. Moreover, Italy. Am J Ind Med 2001;40:363-70. 12. Krstev S, Stewart P, Rusiecki J, Blair A. Mortality among shipyard asbestos body burdens in the lung tissue may differ from Coast Guard workers: A retrospective cohort study. Occup Environ Med those of pleura. Studies conducted on lung and pleural 2007;64:651-8. tissues obtained at necropsy in a small group of Monfalcone 13. Bianchi C, Brollo A, Bittesini L. Mesothelioma caused by asbestos in shipyard workers showed that the number as well as the the Monfalcone area. Pathologica 1981;73:649-55. type of asbestos fibers in the pleura differed markedly from 14. Bianchi C, Bianchi T. Malignant mesothelioma of the peritoneum and those found in the lung.[23] Even with these limitations, lung heavy exposure to asbestos. Eur J Oncol 2007;12:255-8. 15. Giarelli L, Bianchi C, Grandi G. Malignant mesothelioma of the pleura asbestos body burdens offer relevant data on the entity of in Trieste, Italy. Am J Ind Med 1992;22:521-30. exposure. 16. Bianchi C, Giarelli L, Grandi G, Brollo A, Ramani L, Zuch C. Latency periods in asbestos-related mesothelioma of the pleura. Eur J Cancer In general, asbestos is the cause of mesothelioma in Prev 1997;6:162-6. nearly 100% of the cases. Nevertheless, the percentages of 17. Bianchi C, Brollo A, Ramani L, Bianchi T, Giarelli L. Asbestos exposure in malignant mesothelioma of the pleura: A survey of 557 cases. Ind exposed people who develop mesothelioma are relatively Health 2001;39:161-7. low. This indicates the role of cofactors in the genesis of 18. Bianchi C, Bianchi T. Malignant pleural mesothelioma in Italy. Indian [24,25] asbestos-related mesothelioma. Such cofactors are J Occup Environ Med 2009;13:80-3. poorly known. A lot of investigations have been devoted 19. Hilliard AK, Lovett JK, McGavin CR. The rise and fall in incidence of to familial mesothelioma.[26-29] The meaning of familial malignant mesothelioma from a British Naval Dockyard, 1979-1999. aggregations in malignant mesothelioma has been Occup Med (Lond) 2003;53:209-12. 20. International Agency for Research on Cancer. IARC Monographs variously interpreted. After the data recently reported on the Evaluation of Carcinogenic Risks to Humans. A review of [30] by de Klerk et al., from Wittenoom, Australia, familial Human carcinogens: Metals, arsenic, dusts, and fi bres. Lyon: World aggregations in mesothelioma occur more frequently than Health Organisation, International Agency for Research on Cancer; expected. This suggests an important genetic component 2012;100C. in mesothelioma.[30] The presence of four cases of familial 21. Harding AH, Darnton A, Osman J. Cardiovascular disease mortality mesothelioma in the present series agrees with the view that among British asbestos workers (1971-2005). Occup Environ Med 2012;69:417-21. genetic susceptibility has a relevant role in asbestos-related 22. Barone-Adesi F, Ferrante D, Bertolotti M, Todesco A, Mirabelli D, mesothelioma. In conclusion, the current results indicate Terracini B, et al. Long-term mortality from pleural and peritoneal a high mesothelioma risk among workers hired at the cancer after exposure to asbestos: Possible role of asbestos clearance. Monfalcone shipyards in 1950-1959. A further observation Int J Cancer 2008;123:912-6. period is needed to evaluate the entire impact of asbestos 23. Dodson RF, Williams MG Jr, Corn CJ, Brollo A, Bianchi C. Asbestos exposure begun in the Monfalcone shipyards in the above content of lung tissue, lymph nodes, and pleural plaques from former shipyard workers. Am Rev Respir Dis 1990;142:843-7. decade. 24. Giarelli L, Bianchi C. Host factors in asbestos-related mesothelioma. Eur J Oncol 1999;4:541-3. REFERENCES 25. Bianchi C, Bianchi T. Susceptibility and resistance in the genesis of asbestos-related mesothelioma. Indian J Occup Environ Med 1. Bianchi C, Brollo A, Ramani L, Zuch C. Asbestos-related mesothelioma 2008;12:57-60. in Monfalcone, Italy. Am J Ind Med 1993;24:149-60. 26. Bianchi C, Brollo A, Zuch C. Asbestos-related familial mesothelioma. 2. Bianchi C, Brollo A, Ramani L, Bianchi T. Malignant mesothelioma of Eur J Cancer Prev 1993;2:247-50. the pleura in Monfalcone, Italy. A 23-year monitoring in an area at high 27. Bianchi C, Brollo A, Ramani L, Bianchi T, Giarelli L. Familial incidence. Eur J Oncol Library 2004;3:49-58. mesothelioma of the pleura--a report of 40 cases. Ind Health 3. Bianchi C, Brollo A, Ramani L. Asbestos exposure in a shipyard area, 2004;42:235-9. Northeastern Italy. Ind Health 2000;38:301-8. 28. Bianchi C, Nemo A, Bianchi T. Familial mesothelioma: A puzzling issue. 4. Bianchi C, Bianchi T. Shipbuilding and mesothelioma in Monfalcone, Eur J Oncol 2008;13:181-6. Italy. Indian J Occup Environ Med 2012;16:14-7. 29. Ascoli V, Cavone D, Merler E, Barbieri PG, Romeo L, Nardi F,

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et al. Mesothelioma in blood related subjects: Report of 11 clusters Cite this article as: Bianchi C, Bianchi T. Mesothelioma among among 1954 Italy cases and review of the literature. Am J Ind Med shipyard workers in Monfalcone, Italy. Indian J Occup Environ Med 2007;50:357-69. 2012;16:119-23. 30. de Klerk N, Alfonso H, Olsen N, Reid A, Sleith J, Palmer L, et al. Familial Source of Support: Cassa di Risparmio di Foundation, aggregation of malignant mesothelioma in former workers and residents Confl ict of Interest: None declared. of Wittenoom, Western Australia. Int J Cancer 2013;132:1423-8.

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