Document KJRMMVyym2XrKvQD7j1G2KDb6

FILE NAME: Neighborhood Exposures (NE) DATE: 1965 DOC#: NE007 DOCUMENT DESCRIPTION: Journal Article - Epidemiology of Diffuse Mesothelioma Tumors V'lzi- ht, s' 74 Annals New York Academy of Sciences f age in Turin, Milan and Pavia. In Turin and Milan, carcinoma of the mg accounts roughly for 4 per cent of the necropsies (5.3 per cent of len and 1.8 per cent of women); this is half the rate found among all ubjects with asbestosis and one-fourth the rate among those who came to ost-mortem. Mesotheliomas, either pleural or peritoneal, were found in 76 out of a Dtal of 24,700 necropsies (0.3 per cent) of subjects over 40 years of age. 'hree cases of mesothelioma (all pleural) were found among the 172 atal cases of asbestosis. Altogether, six cases of mesothelioma of the leura occurred in people occupationally exposed to asbestos dust; three of hem had worked with crocidolite and amosite besides chrysotile. In 10 ases of mesothelioma, not occupationally exposed to asbestos dust, where lung specimen was available for study, no asbestos bodies were found. R eferences )0LL, R. 1953. Bronchial carcinoma: Incidence and aetiology. Brit. Med. J. 2: 524. ''arina, S. & G. Mazzanti. 1963. Asbestosi e neoplasie polmonari. Ulteriore contributo su di un caso clinico. Lavoro Umano 15: 276. 'rancia, A. & G. Monarca. 1956. Asbestosi e carcinoma polmonare. Minerva Medica 47(2) : 1950. .'rancia, A. & G. Monarca. 1958. Un nuovo caso di associazione asbestosicancro polmonare. A tti XXII Congr. Naz. Med. Lavoro. : 376. Rome, Italy. Tames, W. R. L. 1955. Primary lung cancer in South Wales coal workers with pneumoconiosis. Brit. J. Industr. Med. 12(1) : 87. Koenig, J. 1960. Ueber die Asbestose. Arch. Gewerbepath. Gewerbehyg. 18: 159. jOViSETTO, D. 1930. Asbestosi. In Studi sulla Pneumoconiosi in Italia. Istituto Poligrafico dello Stato. Rome, Italy. tfottura, G. 1939. L'interpretazione patogenetica dell'asbestosi polmonare sulla base del reperto linfoghiandolare. Rass. Med. Industr. 10: 321. Cottura, G. & G. F agiano. 1940. Anatomia patologica e patogenesi della as bestosi polmonare. Rass. Med. Industr. 11: 233. tfussA, G. 1930. Note cliniche e radiologiche sulla pneumoconiosi da amianto. In Studi sulla Pneumoconiosi in Italia. Istituto Poligrafico dello Stato. Rome, Italy. ?0RTIGLIATTI, M. 1955. Considerazioni sulla associazione asbestosi e cancro pol monare. Giorn. Accad. Med. Torino, fase. 1: 6 : OMBOL, G. 1955. Asbestosi e carcinoma polmonare in una filatrice di amianto. Med. Lavoro 46:242. Scarpa, M. 1908. Industria dell'amianto e tubercolosi. Atti 17" Congr. Soc. It. Medicina Interna. : 128. 5EUKOFF, I. J., J. Churg & E. C. Hammond. 1964. Asbestos exposure and neo plasia. J.A.M.A. 188: 22. Jelikoff, I. J-, J. Churg & E. C. Hammond. 1965. Relation between exposure to asbestos and mesothelioma. New Engl. J. Med. 272: 560. / igliani, E. C. 1940. Due casi mortali di asbestosi polmonare. Rass. Med. In- dustr. 11: 26. 7IGLIANI, E. C. 1940. Studio sull'asbestosi nelle manifatture di amianto. Ed. E.N.P.I., Capella, Ciri. EPIDEMIOLOGY OF DIFFUSE MESOTHELIAL TUMORS: EVIDENCE OF AN ASSOCIATION FROM STUDIES IN SOUTH AFRICA AND THE UNITED KINGDOM J. C. Wagner Pneumoconiosis Research Unit, Medical Research Council Llandough Hospital, Penarth, Glamorgan, Great Britain The first South African case of diffuse mesothelioma of the pleura with asbestos bodies in the lung was diagnosed at the Pneumoconiosis Research Unit in Johannesburg in 1956. Earlier than this C. A. Sleggs, Superin tendent of the West End Tuberculosis Hospital in Kimberley, had observed an increasing number of cases admitted to his hospital with the diagnosis of pleural tuberculosis, who did not respond to antituberculous therapy. These cases subsequently died from pleural malignancy which, Sleggs was informed, was secondary to some other internal neoplasm. He was puzzled by this, as the incidence of malignancy among his patients was in general surprisingly low. A few months after the original case, a number of patient,s from Kimberley were transferred to Johannesburg for investigation, and specimens taken at thoracotomy showed histological features similar to those seen in the original mesothelioma. Paul Marchand, a thoracic sur geon, went down to Kimberley to biopsy the remainder of Sleggs' cases and within a year 16 cases of diffuse mesothelioma had been diagnosed histologically. In trying to explain this mysterious epidemic we suggested that asbes tos might play some part in the etiology. The grounds for this were ex tremely flimsy; asbestos bodies had been found in the lungs of the first case, and large crocidolite asbestos desposits were 200 miles west of Kim berley at the nearest point. At first, this hypothesis received little support since none of the original cases had been referred from the asbestos fields. Their occupations were housewives, shepherds, farmers, lawyers, and insur ance agents. None of them admitted to mining asbestos. In the meanwhile, other cases were occurring both in Kimberley and elsewhere in South Africa. From one of these, Marchand established that although he was not a miner, his father had been manager of a small asbestos mine, and he had played around the mine and on the dumps as a boy. Sleggs and Marchand then requestioned all the surviving patients and relatives of the others, and obtained detailed life histories. By 1959, they had been able to establish an association with the Cape Asbestos fields or the industrial use of asbestos in 32 of 33 patients with histologically proven pleural mesotheliomas. The majority of these patients had not actually worked with asbestos but had lived in the vicinity of the mines and mills, and some had left the asbestos fields as young children, or in their teens. The average rrrr 576 Annals New York Academy of Sciences period between first exposure and development of the tumors was 40 years. As a consequence of this the investigation was intensified, with the support of the South African Government, the asbestos producers, and the South African Cancer Association. The findings of the epidemiological surveys of this area have been presented by G. K. Sluis-Cremer and C. P. Theron. Ian Webster, who has been in charge of the Pathology Division of this Unit throughout these investigations, will describe some of the problems of diagnosis and the experimental work. At the end of 1961 we had diagnosed a total of 87 pleural and two peri toneal mesotheliomas. In only two cases had it not been possible to estab lish a history of exposure to asbestos dust and only in one of the cases was there no definite exposure to croeidolite. This was a man who had made fireproof clothing while serving in the South African Air Force during the last war. The youngest case diagnosed, aged 21, gave a history of a very brief exposure as an infant when he was taken to a "cobbing" site by his mother from the age of six weeks until he was weaned. Of the 87 cases, 12 had had industrial exposure and the rest came from the region of the Cape Asbestos fields. More than half of these people had not been em ployed by the asbestos industry. A few of them had had occupational ex posure-- two men had been road workers in an area where before 1940 many of the roads were surfaced with material from the asbestos dumps, and one man had worked in a railway yard where the same material had been used as ballast for the rails. Another man had been employed dig ging wells in the vicinity of the asbestos mines. The remainder of the people had had environmental exposure due to living in the vicinity of the mills and dumps in an arid, windswept region. An example of this was a woman who was born in a town on the asbestos fields in 1900. She left there at the age of five, and was in good health until she was 55 when she developed a pleural effusion. She died from a pleural mesothelioma eighteen months later. Detailed questioning on her childhood revealed that she attended an Infants School near to an asbestos dump. The children used to enjoy sliding down this on their way home. Two of her playmates at this school have subsequently died of the same condition. Even among those working in the asbestos mines, the actual exposure seems to have been slight -- a number of them cobbed under relatively dust-free conditions. In these cases, there was no evidence of asbestosis in the lungs, but only a few asbestos bodies and fibers in the air spaces. Therefore, the association appeared to be with exposure to asbestos dust rather than a sequelae of asbestosis. A puzzling feature of the South African investigations is that although the country produces approximately the same amount of croeidolite, amosite and chrysotile (if Swaziland is included), no case of mesothelioma has been reported from either of the other areas in spite of an intensive investiga Wagner: Diffuse Msothlial Tumors 577 tion. This is particularly remarkable because on the edge of the amosite mining area, crocidolite also occurs, sometimes in the same seams. The mining and milling methods are similar and the chance of environmental exposure seems to be the same. There are two possible explanations for this. Firstly, crocidolite mining started in 1890, whereas the other two areas were only mined to a signifi cant extent 30 years later. Nevertheless they have been operational for more than 40 years. Secondly, Harington's discovery of the polycyclic aro matic hydrocarbons adsorbed onto the crocidolite fiber. This may be the significant factor. Webster has diagnosed further cases since 1961, and the total is now well over 100. The most disturbing fact of this investigation is that 40 years ago, at a time when most of these cases had their initial exposure, the annual production of crocidolite was less than 10,000 tons a year. Today more than 80,000 tons are produced and a large proportion of this is inten sively milled to produce short clean fibers. When I came to the United Kingdom it was decided to continue these investigations at the Medical Research Council's Pneumoconiosis Research Unit, in order to see whether this association between asbestos exposure and mesotheliomas could be confirmed in Britain -- a country with a large and long-established asbestos industry. The investigations are being con ducted in cooperation with the industry and the Ministries concerned. Since Gloyne's first observations in 1935 of pulmonary malignancy in asbestos workers, the Inspectorate of Factories has been concerned with this prob lem. W. D. Buchanan has reported their findings up to date earlier in this Annal. To find out if cases of mesothelioma were occurring among people who had been exposed to asbestos, we approached the problem through those thoracic surgery and pathology departments who had published accounts of these tumors. We asked people to cooperate in finding out how many of their cases had been associated with asbestos dust exposure. The evidence for this could be established in the following ways: a) examination of lung tissue, if available, for the presence of asbestos bodies and fibers. b) in the case of living patients by examining the sputa for asbestos bodies and fibers. c) by obtaining detailed occupational and environmental histories from the patients or their relatives. The excellence of their response you can read in the papers from London, Belfast and Liverpool. Unfortunately, all those concerned in this investi gation were not present at the Conference, although we were uncommonly well represented. I will, therefore, add briefly an account of the findings in Cardiff, Newcastle and Portsmouth. Some of these reports are of a 578 Annals New York Academy of Sciences preliminary nature and the investigations in Britain are far from com pleted. However, we have been able to show evidence of asbestos exposure in at least as many cases of mesothelioma of the pleura and peritoneum a have been diagnosed in South Africa. The South African finding has been confirmed that the association is with asbestos exposure, and not necessarily with asbestosis. In a number of cases the actual exposure has been slight, in one case three months of boiler lagging, and the latent period between initial exposure and diagnosis of tumor is again about 40 years. At Sully Hospital near Cardiff, Roger Seal has diagnosed six cases of pleural mesothelioma. The histories of these patients have been followed in detail by members of Professor A. L. Cochrane's Epidemiological Unit, and in five of the six cases, there has been a definite history of asbestos exposure. In Newcastle-upon-Tyne, T. Ashcroft of Professor A. G. Heppleston's Department, has found 13 histologically diagnosed cases, and evidence ttf asbestos exposure in 11. In Portsmouth, R. D. Clay has found evidence of asbestos exposure in two out of his three cases. Of Britain's main ship-building areas -- Belfast, Tyneside, Merseyside, and Clydeside -- we have not yet investigated Clydeside but two cases have been referred by P. D. Stewart at Dunbarton. The most disturbing fact is that during the investigation new cases in increasing numbers have been reported from all these areas. In Britain, it has not been possible to obtain positive, clear evidence im* plicating a single type of asbestos as in South Africa, since the majority of cases have been exposed where several types of asbestos were used. How* ever, definite evidence of crocidolite exposure has been established in a majority of cases, and no indisputable case of pure chrysotile exposure hits yet been discovered. EPIDEMIOLOGY OF MESOTHELIAL TUMOltH IN THE LONDON AREA Muriel L. Newhouse and Hilda Thompson Department of Occupational Health & Applied PkuMouy!, London School of Hygiene and Tropical Medicine, London, England I ntroduction In recent years, the association between exposure to nub!'* dui enneer of the lung, and other malignant neoplasms has boon tlm suh|i much research (Brit. Med. Journal, 1964). Wagner, Hleggs mi Mine ( I960) described the occurrence of mesothelioma of the ileum til exposed to crocidolite asbestos in the mining districts of Hoot It AI and have stimulated further studies of patients suffering froth thin t (<!lyn Owen, 1964; Fowler e al., 1964). The present investigation concerns patients ip whom it dhtunee mesothelioma had been made at the London Hospital. All the mot on and biopsy specimens held in the Pathology Department in which h minis of mesothelioma had been made in the past. 50 year Imvo httti Viewed by Hourihane (1965). In 83 cases the diagnosis woo ooffittieil series consists of 41 men of whom 31 had pleural luitl it) puHhnmi mors, and 42 women of whom 25 had pleural and 17 peril oneI Ipj The aim of this study has been to establish the oeeupaMunitl hinfttii these jiatients and to trace any other possible exposure to hm1>(oh There were four surviving patients at the outset of tit invent tgi hut these have subsequently died. The earliest date of death Ip ilia * was 1917, 10 died before 1950, 33 between 1950 and 1959 amt Ilia Wt| log 40 in the past four and a half years. The youngest died lit the a 13 and nearly half were dead before the age of 55 (TAIll.K J), The ward notes of 65 of these patients were available; they give j tore of a disease with a consistent symptomatology. Among liman pleural tumors, the commonest symptom present was the rapid Him extreme shortness of breath due to the formation of a massive jd effusion. Pain was a prominent feature, either described an a dull Sometimes due to invasion of ribs or vertebrae, or sometimes sliiU ) Militating, suggesting nerve involvement. Tumors in the chest wall wet inieenimon, occurring either in previous operation scars op by tllri* vaaiori of the chest wall. The symptomatology of the peritonea! imnut more varied. In some patients the presenting symptom was Jittifi oil Hun or micturition; diffuse upper abdominal pain was very eitf ltd swelling of the abdomen due to ascites was always present term) Tim treatment was varied; pneumonectomy, decortication of Ihe lung! rrn\