Feb. 2011, Volume 8, No. 2 (Serial No. 75), pp. 84-91 Journal of US-China Medical Science, ISSN 1548-6648, USA

Mesothelioma in Russia: Review of 3603 Published Cases Sergey V. Kashansky Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia Abstract: True incidence rates of mesothelioma in Russia are unknown. We reviewed 889 works of Russian-speaking scientists published from 1881 till 2006. For the 126 years (1871-2006) 3,603 mesotheliomas were diagnosed in Russia. 1,348 (37.4%) were male and 1,125 (31.4%) were females. In 1130 (31.4%) the sex is not specified. The age of cases varied from 6 months to 93 years (meaning, 48.3). 3,494 (97.0%) cases were malignant and 109 (3.0%) were benign mesotheliomas. 3,040 (84.4%) were pleural mesotheliomas, 366 (10.2%) were peritoneal, 162 (4.5%) were pericardial, 29 (0.8%) were mesotheliomas of tunica vaginalis testis, 5 other localizations, and 1 was unspecified mesothelioma. 51 (1.4%) mesotheliomas were diagnosed in XIXth century. 223 (6.2%) cases were diagnosed in first half of 20th century, 2,995 (83.1%) in the second half, and in the beginning of the 21st century it was 334 (9.3%) cases. For period of observation mesotheliomas were diagnosed in 64 (71.9%) of 89 areas of the country. First 17 mesotheliomas were registered 16 years before the modern mining of asbestos in Russia (1886). Asbestos exposure was reported only for 56 (1.6%) cases. Not a single case of asbestosis cases develop mesothelioma, congenital or familial mesothelioma has been described in Russia. During the XXth century only 6 epidemiologic studies of mesothelioma were carried out in Russia: local in towns Asbest, Ekaterinburg and St. Petersburg, and regional in Republic of Karelia, Sverdlovsk Region and Altaysky Krai. In 1990s mesothelioma morbidity in Russia was in the range of 0.2 (Ukraine) to 4.2 (Altaysky Krai) cases per million a year. Key words: Mesothelioma, Russia, a system review, reported cases.

to include most of the pleura [3]. Pleural mesothelioma

1. Introduction Mesothelioma is a rare malignancy of the pleura, peritoneum, pericardium, and other large cavities of the body [1]. The diversity of histological structures constituting serous cavities determines a wide specter of tumors that might develop in them. Cells of the mesothelial layer are the source of malignant mesotheliomas and those of the submesothelial connective tissue layer are the source of fibrotic mesotheliomas

[2].

Malignant

mesothelioma

is

generally divided into three histological categories, or types of cells: epithelioid, sarcomatoid, and mixed (biphasic) mesothelioma. Other histological variants are much rarer. Depending on their growth mesotheliomas may be diffuse and localized. Diffuse forms are usually malignant, and they spread rapidly as whitish tubercles Sergey V. Kashanskiy, MD, research field: epidemiology of asbestos-related diseases. E-mail: [email protected].

represents about 75% of all mesotheliomas, peritoneal and pericardial mesotheliomas are 5-6 and 10 times rarer, respectively [4]. Mesotheliomas of other sites (testicles, liver) are extremely rare. The median latent period of the disease is 32 years, and this is the reason why mesotheliomas are usually diagnosed in older people; yet, the disease may develop at any age [1, 5]. In 1933, S. Gloyne first noticed the association between mesotheliomas and asbestos [6], in 1943 Н. Glatzel paid attention to a higher mesothelioma incidence in seaports [7], and in 1954 F. Leicher found a higher mesothelioma risk in asbestosis cases [8]. Results of a later acknowledged as classical study by J. Wagner et al. relating mesothelioma to crocidolite were published in 1960 [9]. Later there appeared reports on the role of asbestos in the etiology of mesothelioma of the peritoneum [10], pericardium [11], and testicles [12]. Since the beginning of 1970s Western scientist

Mesothelioma in Russia: Review of 3603 Published Cases

have attributed the development of mesothelioma exclusively to inhaling asbestos-containing dust, amphibole asbestos in the first place, especially crocidolite and tremolite which are now considered to play the primary role in the etiology of the disease [1, 2, 13, 14]. At first in Germany, later in France, Japan, Finland, the United States and other countries, and in 1996 in Russia mesotheliomas were included in the list of occupational asbestos-related diseases. Many countries develop national mesothelioma registers and there exist numerous federal institutions and public societies studying various aspects of this pathology. Much evidence of polyetiology of the disease has been accumulated lately. Many publications show that chemical (nickel, beryllium, soot, polyurethane, ethylene oxide, and almost all types of natural and man-made fibrous minerals and products: man-made mineral fibers, vollastonite, erionite, etc.), physical (radioactivity), biological (MC 29 and SV 40) agents, and genetic factors may cause the disease [1, 15]. The incidence rate of mesothelioma varies from 0.6 per million a year in Tunis [16] to 35 in Australia [17]. The background incidence rate is 1-2 cases per million a year [15]. Despite the asbestos ban, only for Member States of the European Union J. Peto et al. predicted the rise in mesothelioma mortality from 5 thousand cases in 1998 to 9 thousand in 2018, and the death from mesotheliomas of about 250 thousand people in the following 35 years [18]. The

Russian

Federation

has

no

national

mesothelioma register, and the disease is not included in official statistics. Only the population cancer register of St. Petersburg allocates mesotheliomas in a separate group [19]. A system review of publications by Russian authors has been made to study the state-of-the-art of the problem in Russia. Some histological descriptions provided in the publications were reevaluated. Additional information has been collected since publishing the first interim results and considered while preparing this review [20].

85

2. Result and Discussion For the period of 126 years (1881-2006) Russian scientists published 889 works describing 3,603 mesotheliomas, including 3,040 (84.4%) cases of pleural mesothelioma, 366 (10.2%) – of the peritoneum, 162 (4.5%) – of the pericardium, 29 (0.8%) – of the testicles, 2 (0.06%) – of the atrioventricular node, 1 (0.03%) – of the posterior mediastinum, 1 (0.03%) – of the valve of the pulmonary artery, and 1 (0.03%) – of the vermiform appendix (Table 1). In one publication the site of the tumor is not specified. Of all 3,603 cases 3,494 (97.0%) mesotheliomas were malignant and 109 (3.0%) – benign. In 1,130 (31.4%) cases the sex of patients is not specified, whereas 1,348 (37.4%) mesotheliomas were diagnosed in men and 1,125 (31.4%) – in women. Mesothelioma of the right pleura was more prevalent than that of the left (52.4% and 47.6%, respectively). Table 2 shows the time of diagnosing the first case of mesothelioma of various sites, sex and age of patients reported by Russian authors. Fig. 1 shows distribution of cases by sex and age. There are no significant differences in the size of male and female cohorts in all age groups in contrast to foreign publications indicating a higher incidence of the pathology in men [1, 2]. The disease rate in men and women is the highest in the age group of 51-60 years. Eighty-two (2.3%) cases of mesothelioma, especially that of the pleura (61 cases), were younger than 20. The age of cases ranged from 6 months to 93 years, the average being 48.3±0.5 years. The mean age was 48.4±0.7 years for men and 49.1±0.7 years for women. There were no significant differences between men and women suffering from mesothelioma of different sites. The study of age of cases in dynamics showed no distinctive features either. During the 20th century the mean age of cases was 48.5±2.6 years that indirectly indicates the possible role of endocrine pathology or hormonal dysfunction (climacteric period), which increase the risk of malignancies in the etiology of mesotheliomas.

86

Mesothelioma in Russia: Review of 3603 Published Cases

Table 1 The total number of reported mesothelioma cases. Sex Male Female Undefined sex Total

Pleura 1117 878 1045 3040

Peritoneum 121 185 60 366

Mesothelioma Tunica vaginal testis 29 – – 29

Pericardium 77 61 24 162

Other 4 1 – 5

Undefined site – – 1 1

Total 1,348 1,125 1,130 3603

Table 2 The year of diagnosing the first case, sex and age of cases of mesothelioma of different sites reported by Russian authors. Mesothelioma Pleura

Year of diagnosing the first case/sex/age, year 1871/M/Non stated 1871/F/Non stated 1896/М/50 1896/F/46 1882/М/34 1922/F/38 1928/М/10 1986/М/3.5 2003/F/18 1979/М/23 1959/М/65 1954/M/27

Peritoneum Pericardium Tunica vaginal testis Atrioventricular node Posterior mediastinum Valve of the pulmonary artery Vermiform appendix

Reference [15] [58] [59] [60] [61] [62] [63] [64] [65] [66] [66]

30 % - Males, N = 598 - Females, N = 518

25,3

23,7 20,4

21,2

20,3 20,6

20 15,1 12,6 9,9 7,9

10

6,2

4,9 3,7

4

1,41,7

0,6 0,7

0 0-10

11-20.

21-30

31-40

41-50

51-60

61-70

71-80 more 80

Fig. 1 Distribution on a sex and age of patients with mesothelioma in Russia, %.

Due to the absence of reliable clinical and radiological criteria of diagnosing mesothelioma in Russia, we observe under- [21-24] and overdiagnosis [22, 23, 25-30] of the disease reaching 26.7% and 74.0%, respectively, in some regions of the country. Nowadays, histological methods of diagnosing mesothelioma in typical cases are the most reliable [1]. Nevertheless, according to data of the population

cancer register in St. Petersburg, the number of morphologically verified mesothelioma cases in 1990s decreased by almost 20% [19]. As for histological categories, of all 232 reported cases epithelioid mesothelioma was most frequently observed (67.2%) followed by sarcomatoid (12.5%), biphasic (11.2%), and fibrotic (9.1%) mesotheliomas (Table 3). The first two cases of mesothelioma in Russia was

Mesothelioma in Russia: Review of 3603 Published Cases

Table 3

87

Histological variants of reported mesothelioma cases.

Histological variant Epithelial Sarcomatous Mixed Fibrous

Pleura 138 21 22 21

Peritoneum 8 3 3 –

Mesothelioma Pericardium 10 5 – –

registered in 1871 [15], a year after its first convincing morphological description by E. Wagner in 1870 [31]. By the end of the 19th century Russian authors had published 51 (1.4%) case reports. In the first half of the 20th century their number grew to 223 (6.2%), in the second half–to 2,995 (83.1%), and in the beginning of the 21st century it was 334 (9.3%) cases. It should be noted that the first 17 observations, including one in a 14-year-old boy [32], were published 16 years before the development of Russian chrysotile-asbestos industry in 1886 [33]. Although many scientists in their reviews of Russian data constantly underline the leading role of asbestos in the etiology of mesotheliomas [34-39], only 7 clinical studies reported unsuccessful attempts to determine asbestos exposure of patients. In the reviewed literature only 56 (1.6%) people had a definite occupational exposure to asbestos [26, 28, 30, 35, 36, 40-51]. The first case of pleural mesothelioma in a 41-year-old man, which can be considered as asbestos-related, was published in 1928 [51], and the first case of mesothelioma of the pericardium in a 70-year-old man, an ex-inspector of boilers, - in 1959 [36]. We found neither reports of Russian authors describing asbestos-related mesotheliomas of other sites, nor clinical descriptions of mesotheliomas developing in asbestosis cases, nor “congenital” or “familial” mesotheliomas, which some authors pay big attention to due to the supposed “obligatory” role of asbestos in the etiology of the disease [1, 2, 17]. For the whole observation period mesotheliomas were registered in 64 (71.9%) of 89 regions of the Russian Federation (Fig. 2). The cartographic analysis of the disease incidence showed no geographical link

Total, absolute data Tunica vaginal testis / % – 156 / 67.2 – 29 / 12.5 1 26 / 11.2 – 21 / 9.1

between the excess number of cases and the location of asbestos mines and mills, and in sea ports. The major number of cases was diagnosed in specialized medical institutions. Only three local studies of mesothelioma epidemiology in the towns of Asbest [35], Yekaterinburg [45] and St. Petersburg [19], and three regional studies in the Republic of Karelia [49], Sverdlovsk Region [26] and Altai Krai [52, 53] were conducted in the 20th century (Fig. 3). We managed to estimate the mesothelioma incidence in the Kuybyshev and Perm Regions. The figure also shows data on mesothelioma incidence in such ex-republics of the Soviet Union as Byelorussia, Latvia, Lithuania, Estonia, and the Ukraine [54, 55]. The regional studies conducted by Russian researchers showed that occupational asbestos exposure might account for only 12.0-29.4% of all mesothelioma cases [26, 45, 49]. Three cases of mesothelioma were found among other tumors in two studies of cancer epidemiology in printing [42] and rubber [50] industry: that of the pleura and peritoneum in the first study and pleural mesothelioma in the second study. By Order 90 of the Ministry of Health and the Ministry of Industry from March 14, 1996 mesotheliomas were included in the list of occupational asbestos-related diseases in Russia. In 1996-2006, during 11 years since the introduction of this Order, mesothelioma was considered occupational only in 4 of 907 reported cases (