Document ZJdbYVwDaLkM6Vp40bjX8Jw88

3-, ..;v ' Sciences 1 M ilan, carcinom a of the scrop.'ies 15.3 p er cent of th e ra te found am ong all am ong those who came to were found in 76 out of a jects over 40 years of age. ;re found am ong the 172 s of m esotheliom a of the 1 to asbestos d u st; three of i besides chrysotile. In 10 ;ed to asbestos dust, w here sbestos bodies w ere found. i ! ! | jt j i \ id aetiology. B rit. Med. J . 2: plasie polmonari. Ulteriore 15:276. rcinoma polmonare. Minerva iso di associazione asbestosid. Lavoro. : 376. Rome, Italy, puth Wales coal w orkers w ith <. -bepath. Gewerbehyg. 18: 159. mmoconiosi in Italia. Istituto tica dell'asbestosi polmonare Med. Ind u str. 10: 321. ologica e patogenesi della as- la pneumoeoniosi da amianto, ituto Poligrafico dello Stato. azione asbestosi e cancro pol ire in una filatrice di am ianto, xilosi. A tti 17 Congr. Soc. It. 4. Asbestos exposure and neo . Relation between exposure to ed. 272: 560. osi polmonare. Rass. Med. In- m anifatture di amianto. Ed. -Ann_._N.Y. Acad. S c i . . 1 3 2 : 5 7 5 - 5 / 0 , 1965> t EPIDEMIOLOGY OF DIFFUSE MESOTHELIAL TUMORS: EVIDENTE OF AN ASSOCIATION FROM STUDIES IN SOUTH AFRICA AND THE UNITED KINGDOM J . C. W agner Pneumoconiosis Research. Unit, Medical Research Council Llandougii Hospital, Penarth, Glamorgan, Great Britain The first South A frican case of diffuse m esotheliom a of the pleura w ith asbestos bodies in th e lung was diagnosed a t the Pneum oconiosis R esearch U nit in Jo h a n n esb u rg in 1956. E a rlie r th an th is C. A. Sleggs, S u p erin te n d e n t/o f th e Vc-it .End .T.nrj'-r!. u'o-i-s H o sp ita l in K im b erley , h ad o bserved an increasing num ber of cases adm itted to his hospital w ith the diagnosis of pleural tuberculosis, who did not respond to antituberculous therapy. These cases subsequently died from pleural m alignancy which, Sleggs was inform ed, was secondary to some other internal neoplasm . He was puzzled by this, as the incidence of m alignancy am ong his patients was in general su rp risin g ly low. A few m onth? a fte r the o rig in al case, a num ber of p atien ts from Kim berley were tran sferred to Johannesburg fo r investigation, and specim ens taken at thoracotom y showed histological features sim ilar to those seen in the original m esotheliom a. Paul M archand, a thoracic su r geon, w ent down to K im berley to biopsy the rem ainder of Sleggs' cases and w ith in a y ea r 16 cases o f diffuse m esotheliom a had been diagnosed histologically. In try in g to explain this m ysterious epidemic we suggested th a t asbes tos m ight play some p art in the etiology. The grounds for th is w ere ex trem ely flim sy; asbestos bodies had been found in the lungs of the first case, and large crocidolite asbestos desposits were 200 miles w est of K im berley a t the nearest point. A t first, this hypothesis received little support since none of th e original cases had been referred from the asbestos fields. T heir occupations were housewives, shepherds, farm ers, lawyers, and in su r ance agents. None of them adm itted to m ining asbestos. In the m eanwhile, other cases w ere occurring both in K im berley and elsew here In South A frica. From one of these. M archand established th a t although he was not a m iner, his fath e r had been m anager of a small asbestos m ine, and he had played around the m ine and on the dum ps as a boy. Sleggs and M archand then requestioned all the surviving patien ts and relatives of the others, and obtained detailed life histories. By 1959. they had been able to establish an association w ith the Cape A sbestos fields o r the in d u strial use of asbestos in 32 of 33 p atients w ith histologically proven pleural mesotheliomas. The m ajority of these patients had not actually worked w ith asbestos but had lived in the vicinity of the m ines and mills, and some had left th e asbestos fields as young children, o r in th e ir teens. The average P mm VUMNJVP juw y"'"'" '*1.........! UJipfPWIBf iUIljP_llll.il/lliPjiJ,fflljpi. I" L. i " ) i- il'fl'M M ltt1 mm 576 Annals New York Academy of Sciences \Yan period betw een first exposure and development of the tum ors w as 40 years. tion. T his is particul As a consequence of this the investigation was intensified, w ith the ; m ining area, crocidol support of the South A frican Government, the asbestos producers, and j m ining and m illing n the South A frican Cancer A ssociation. The findings of the epidemiological j exposure seems to be t surveys of th is area have been presented by G. K. S luis-C rem er and C. P. j There are two poss; T heron. Ian W ebster, who has been in charge o f th e Pathology D ivision i started in 1S90. w her of th is U nit throughout these investigations, will describe some o f the j cant extent 30 years problems of diagnosis and the experim ental work. j more than 40 years, t A t the end of 1961 we had diagnosed a total of 87 pleural and tw o peri- ! m atic hydrocarbons ; toneal m esotheliom as. In only tw o cases had it not been possible to estab- j significant factor. Iish a history of exposure to asbestos dust and only in one of the cases w as j W ebster has diagn th e re no d efin ite ex p o su re to cro cid o lite. T h is w as a m an w ho h a d m ad e ! well o v er 100. T h e n fireproof clothing w hile serv in g in the South A frican A ir Force d u rin g j years ago. at a tim e th e last w ar. The youngest case diagnosed, aged 21. gave a h isto ry of a ( the annual production very b rief exposure as an in fan t when he was taken to a "cobbing'' site by j more than 80.000 tom h is m other fro m the age of six weeks until he was weaned. O f the 87 cases, sively milled to produc 12 had had industrial exposure and the rest came from the region of th e f W hen I came to tl Cape A sbestos fields. M ore th an h alf of these people had not been em - ! investigations at the ployed by th e asbestos in d u stry . A few of them had-had occupational ex Unit, in o rd er to see posure -- two men had been road w orkers in an area w here before 1940 | and m eso th elio m as co many of the roads were surfaced w ith m aterial from the asbestos dum ps, j and long-established iV and one man had worked in a railw ay yard w here the sam e m aterial had j ducted in cooperation been used as ballast fo r the rails. A nother m an had been employed dig- j Gloyne's first observ; ging wells in the vicinity of the asbestos m ines. j w orkers, the Inspectc The rem ainder of the people had had environm ental exposure due to f lem. W. D. B uchanan living in the vicinity of the mills and dum ps in an arid, w indsw ept region. 1 Annal. An example of th is w as a woman who was born in a tow n on the asbestos j To find out if case fields in 1900. S he le ft th e re a t th e ag e o f five, an d w as in good h e a lth u n til >. had been exposed to i she w as 55 w hen she developed a pleural effusion. She died from a pleural | thoracic surgery and m esotheliom a eighteen m onths later. D etailed questioning on her childhood j of these tum ors. We revealed th at she attended an In fan ts School near to an asbestos dum p. j their cases had been . The children used to enjoy sliding down this on th e ir way home. Two of : for this could be e^ta h er playm ates at this school have subsequently died of the sam e condition. . a i exam ination of f Even am ong those w orking in the asbestos m ines, the actual exposure i bodies and fibers, 5 seems to have been slig h t -- a num ber of them cobbed und er relatively j b; in the case of d u st-free conditions. In these cases, th ere was no evidence of asbestosis in ; . bodies and fibers, the lungs, but only a few a.-bestos bodies and fibers in the a ir spaces. ; ci by o b ta in in g df Therefore, the association appeared to be with exposure to asbestos dust the patients or the rath er than a sequelae of asbestosis. ; The excellence o f t. ; A puzzling fea tu re o f the .South A frican investigations is th a t alth o u g h * Belfast and Liverpoc the country produce- approxim ately the same am ount of crocidolite, am osite gation w ere not pres- a n d c h ry so tile <if S w azilan d is in c lu d e d ;, no case o f m eso th elio m a h as been v.-ell re p re se n te d . I reported from eith er of the other areas in spite of an intensive investiga- in C ard iff, N'ev-ca.^t! bf of Sciences t of th e tu m o rs w as 40 year-.. ,n was intensified, w ith the th e asbestos producer.-, am: in,jings of the epidem iological G- K. S lu is-C rem e r and C. P. Ke of th e Pathology- D ivision !.s w ill d escrib e som e o f the '' w ork. . tal of 87p leu ral and tw operi- 1 it not been possible to estab- id only in one of th e cases was h is w-as a m a n w ho h ad m ace ith A frican A ir Force during , aged 21, gave a history of a as taken to a "cobbing" site by ,e w as w eaned. O f th e 87 cases, it cam e fro m th ereg io n of th e .hese people had not been emthem had had occupational ex in an area w here before 1940 erial from the asbestos dumps, d w here the same m aterial had r m a n h ad been em ployed d ig lines. environm ental exposure due to ps in an a rid , w in d sw ep t reg io n . ; born in a town on the asbestos rive, an d w as in good h e a lth u n til ffusion. She died from a pleural iled questioning on h er childhood ;hool n ea r to an asbestos dum p. this on th e ir way home. Two of ently died of the same condition. estos m ines, the actual exposure of them cobbed under relatively ; w as no evidence of asbestosis in ies and fibers in the a ir spaces, e w ith exposure to asbestos dust . 1 ' : ; i j J j I j f | j | 1 < j . an investigations is th a t although im e am ount of crocidolite. am osite . no case of m esotheliom a has been in spite of an intensive investiga- Vagr;er: Diffuse Mesotheirei Tumors -577 - r.. T p a r t i c u l a r . ; . " re m a rk a b le t-ecause .-.j-, - e dge o f th e arc-: - : v- a , a r a re a , c ro c ic o u te also occurs, .-orr.et.rr.e? in th e sa m e seam s. Tr.-e a t.t m l.jr.g rr.etr.ods are sim itar and th e chance of environm ental t \ ; y - ..- c-err..- to be th e .-ame. Tnere are tw o po-~:o.e explanations fo r this. F irstly , crocidolite m ining --.artea in 1890. w hereas the o th er two areas w ere only m ined to a signifi cant extent 30 years -ater. N evertheless tr.ey have been operational to r more m a n 40 y e a rs, se co n d ly . H a r in g to n 's d isco v ery o f th e polycyclic a r o matic hydrocarbons ad-orbed onto th e croc-idoli;e fiber. T his m ay be th e -.'gr.ificant factor. W ebster has diagnosed fu rth e r cases since 1961. and th e total is now V...11 v - r 10. T he nr.-st d is' u rb in g mc-t o f th is in v e s tig a tio n is th a t 40 years ago. at a tim e when most of these cases had th eir initial exposure, the annual production of crocidolite was ess th an 10.000 tons a year. T ccay more th a n SO.000 to n s a r e produced an d a la rg e p ro p o rtio n o f th is is in te n sively milled to produce short clean fibers. W hen I came to the U nited K ingdom it was decided to continue these investigations a t the Medical Research Council's Pneum oconiosis R esearch Unit, in o rd er to see w hether th is association betw een asbestos exposure and m esotheliom as could be confirmed in B rita in -- a country w ith a large and long-established asbestos industry. The investigations are being con ducted in cooperation w ith the industry and the M inistries concerned. Since Gioyne s first observations in 1935 o f pulm onary m alignancy in asbestos workers, the Inspectorate of Factories has been concerned w ith this prob lem. W. D. B uchanan has rep o rted th e ir findings up to date ea rlie r in th is Anna!. To find out if cases of m esotheliom a w ere o ccu rrin g am ong people who had been exposed to asbestos, we approached the problem through those thoracic surgery and pathology departm ents who had published accounts of these tum ors. We asked people to cooperate in finding out how m any of their cases had been associated w ith asbestos dust exposure. The evidence for th is could be established in the follow ing w ay s: a > exam ination of lung tissue, if available, for the presence of asbestos bodies and fibers. b l in the case of living patients by exam ining the sputa fo r asbestos bodies and fibers. c) by obtaining detailed occupational and environm ental histories from the patients or th eir relatives. The excellence of th e ir response you can read in th e papers from London. B elfast and Liverpool. L 'nfortunately. all those concerned in th is investi gation w ere not present at the Conference, although we w ere uncommonly well represented. I will, th erefo re, add briefly an account of the findings in Cardiff. X wcastle and Portsm outh. Some of these rep o rts are of a ,)f1 J l.w->wlA "-JU-pgji11 WBP I ' t i - I 57S Annals Xew York Academy of Sciences ( prelim inary n atu re and the investigations in B ritain are fa r from com pleted. However, we have been able to show evidence of asbestos exposure j EPIDEMIOLC IX in at least as m any cases of m esothelioma of the pleura and peritoneum as have been diagnosed in South A frica. The South A frican finding has been confirm ed th a t th e association is w ith asbestos exposure, and not necessarily w ith asbestosis. In a num ber I i ! M uriel I Department of O London Sclu of cases the actual exposure has been slight, in one case three m onths of boiler lagging, and the latent period between initial exposure and diagnosis of tum or is again about 40 years. A t Sully H ospital near Cardiff. Roger Seal has diagnosed six cases of j In recen t y ears, th e a. pleural m esotheliom a. The histo ries of these patients have been followed ; cancer of the lung, and o t 1i in d e ta il by m e m b ers o f P ro fe s s o r A. L. C o c h ran e's E p id em io lo g ical U n it, and in five of th e six cases, th e re h as been a definite h isto ry o f asbestos ; much research (B rit. Me ^ ( I9 6 0 ' d escrib ed th e oc> exposure. In N ew castle-upon-T yne, T . A sh c ro ft o f P ro fe s s o r A. G. H ep p lesto n 's j exposed to crocidolite as ! and have stim ulated fu rt D ep a rtm en t, h as found 13 histologically diagnosed cases, and evidence of \ (Glyn Owen, 1964; Fowl asbestos exposure in 11. In P o rtsm o u th . R. D. Clay has found evidence of j The present investiga i asbestos exposure in two out of his th ree cases. O f B r ita in 's m a in s h ip -b u ild in g a re a s -- B e lfa st, T y n esid e, M erseyside, ! m esothelioma had been n i and biopsy sp ecim en s he] and Clydeside -- we have not yet investigated Clydeside but tw o cases have i nosis of m esotheliom a ht been referred by P. D. S tew art at D unbarton. The most disturbing fact * viewed by H o u rih a n e f 19 is th a t d u rin g the investigation new cases in increasing num bers have j series consists of 41 met been reported from all these areas. In B ritain, it has not been possible to obtain positive, clear evidence im 1 mors, and 42 women of j The aim of this study ha plicating a single type of asbestos as in South A frica, since the m ajority i these patien ts and to trac of cases have been exposed w here several types of asbestos were used. How ` There were four survr ever, definite evidence of crocidolite exposure has been established in a but these have subsequen m ajority of cases, and no indisputable case of pure chrysotile exposure has was 1917, 10 died b efo re yet been discovered. ing 40 in th e past fo u r at 33 an d n e a rly h a lf w ere c: ' The w ard notes of 6o o i1 *uro o f a- d ise ase w ith a , pleural tum ors, the comn l 1 extreme shortness of bre effusion. P ain was a pro: Ii ' som etim es d u e to in v a sio 1 radiating, suggesting ner. uncommon, occurring eitf vasion of th e chest wall. T more varied. In some pati ration o r m ic tu ritio n ; di and sw elling of the abdorn Tr.e tre a tm e n t w as v a rie d ; I { ! I" A