Document mBXnM2On7Dgz2mEaVMmBv0Q70

* to * ?*****>. r- o s ; iy r r -/ j , 4 \ ' THE NEW ENGLAND JGLANAL OF MEDICINE \% 1565 '.S>l'.cor:.e s.'.rf Company, for assis:.-.:.'- and for nir.tnv'r,: iv<], arid to Drs. M in-own S i'r.v_rcr ur.d M. Kerstcin for p'-r:o.'i.;.nc trie ' * . -downs. R eferen ces D r .-k IV. v* c *9SC. M S-. a n d S .-"'! P . D . B acterial c >: : irr <na; on of c .-tra v e r.o u j j/y ^ c u iy ie ric c a tD e trrj J A M . A . <25 9v>- il S.. lic l^ rr A. N., 3 'e\in s. A., a rd O-'rb'-T? O coccai bactertz--la . A *n. M a? York A c a d . S c. ii: c .2 - - 2 S i. Mor.rrirf, J. A . r^rr/oral'catoet^rv Awn S v r - 147 ' '''172 IVk 4. A'rS'-j J K, Is s .? ) tt>ur,>. ci%*.,`n \ a-, j *' * , T ' - * catr.ctrrt. , (*,T.ec. ^ 11 5. Bcn^/ l:J2. iVr..2. w2,tT-'3:99if9.-untrer, ? . M y >rArta>4 Area /rrf6. D j Iv. A . K , P c iu r. B , and r'a** 3 . H <r:*r*. f-r? ijiiS'r. t,{ 7*~i n a : 5 W kvo 3 . a :..ira te ..j. d ue tn .*jcd. no v-i9i, y.2. 7. P / Bury. D . M .. S.V *y. W . a - p X /j'?T; .r,,, A l iJrrmt- 'log,- 1331 p p . Prw.aCclph.a: S - .r .o e n . i9y> Bp. 2- r>.r, P ., S r r i'k 'e r, J - H ., arc A .r t C . O. L*v- o: in ir.rra%erjOU therapy for pat-ents. . a*"tUu.|rT^< fct:C/3-oB0, 13-3. RELATION BETWEEN EXPOSURE TO ASBESTOS AND MESOTHELIOMA* I r v in g J. S e l ik o f f , M .D .,f J acob C h u r g , M .D.:j a n d E. C u y l e r H a m m o n d , Sc.D.^ N E W Y O RK CITY T x i960 Wagner, Sleggs and Marchand1 reported -* 33 ca>es of diffuse pieural mesothelioma from the North Western Cape Province of South Africa. The co'.lectio:. of such a large number of cases of a rare tumor within a short time (1956-1960) in one area was considered unusual enough. Even more striking was the fact that close questioning and investiga tion revealed that 32 patients had evidence, admit tedly circumstantial in most cases, of some potential or actual contact with asbestos by virtue either of residence in mining areas or in industry twenty to f o r ty years before. . This remarkable concentration of cases in one area of South Africa seas explained by the hypothesis that mesothelioma was the result of exposure to one special tyoe of asbestos (crocidolite'., mined almost entirely ir. that region. The report of a mesothe lioma associated wide asbestosis in Western Austra lia." or.e of the few other regions of the world in which crocidolite is mined, was consistent with this hypothesis. Similarly, the occurrence of other cases of mesothelioma, including several of the perito neum, in Great Britain3'4 was not disturbing since British asbestos companies have long been intimately related in ownership and management with the South African asbestos industry and the largest por tion of crocidolite mined in South Africa had in previous years been imported into Great Britain.5'* P r e s e n t I n v e s t ig a t io n We undertook to study the question whether mesothelioma of the pleura and peritoneum had an important relation with asbestos exposure in the United States. We had previously found that lung cancer and possiblv gastrointestinal cancer were markedly increased in incidence among asbestos-in- Fm n ibe Section on Environmental H ealth, D fjurtnw ut o i M edicine, and the I>e*\*rtment o f PjcSoiO^v, M ount r.ai iios*Aitai. ^^ >u,,x,*r` ea hv the Hca'.:h Research C ouncil the C*tv o i N ew York. tU e s J . Scct.oo on Environmental H ealth, l>efvarunent ot M edicine. M ount Sinai Htapiial. A*>c<iaie a tte n d in g paiho4ot*t. D ep artm en t o i Pathology M o u n t S in ai Hco^Mia*. D irector, S tatistical R esearch Section, A m erican C ancer Society. sulation workers/ The investigation was p.armed to demonstrate whether another potential r/op!ast.c hazard of asbestos exposure existed in the United States. Secondly, data developed in the investiga tion would have epidemiologic and patuo/enetic bearing on the problem since the concution ot American asbestos utilization differed to some ex tent from British and South African experier.ee in at least one important respect. Crocidolite is a relative newcomer to the American asbestos-indus try Scheme. Thus, American' imports of crocidolite (none is mined here; were less than 5CG tons tn 1935 and had reached a level of only 20.0CG tons even in 1962. In contrast, chrysotile. the type o: asbestos fiber widely used in the Americnr. asbestos industry, was imported at a level of 165.COj tens ir. 1935 and 650.000 tons in 1962/ Our investigations sought to determine whether mesothelioma is more common amor.? peop.e c\- ing with asbestosis than those without tr.Ls disease in the United States, conversely, whether proof o: asbestos inhalation can be found among cases c: mesothelioma and whether an estimate of the inci dence of this neoplasm can be made among worker- with known exposure to asbestos. The answers to these questions are poier.ua..-. of considerable practical importance. Ii the r.vpothe- sis that mesothelioma associated with asbestos con tact is a special case of asbestos cancer, caused b; exposure to one kind of asbestos fiber (crocidolite' is correct the problem is a rather limited or.e. Al though it would be important in the areas :n whir;, crocidolite is mined, and to those working with it the United States asbestos industry could be advisee to avoid this type oi fiber in favor of other tonus ot asbestos. ' Our investigations could serve to test this hy pothesis. Crocidolite has had a small role in the United States asbestos indust in ar.d that but recent!' Neoplasms associated with aseostos expos..:;' ce.ie;- ally occur only iwvmv to forty years after exposure If mesothelioma could be found with increased fre quency in association with asbestos *: :his coar.tr, Ll.U ; ..cr ;.rue n i^tic '*k; ">05*. ,A J \ \ J-.;- ^ :\c :o u. 1 *D iy 65 , Vd 272 No. 1! M ESOTHELIOM A AND ASBESTOS -- SELIKOFF ET AL. ma. e to In t. i5vu.ernfe l to istic ited igaetic of ex in sa lus in ons : of stos . in her dyase of of id ler? i* x K l-\:- i5h00 of V \ L-. t wou'd demonstrate that this tumor was another ,r'o!ast:c hazard of asbestos exocsure in general and -j? h r to one area or to one type of fiber. among persons exposed to asbestos, we undertook a survey of 1522 members of the Asbestos Workers union m the New Vork metropolitan area, rrem | M aterials and M ethods bers of New York Local 12 and Newark, New Jer-ev. Local 32 of the Internationa! Association of Heat ' F:rv. of all, since diffuse p'eural and peritonea! : uesotheliomas are fata! conditions we decided to I =rjdv their relation to asbestosis in autopsy series. for this purpose, we analyzed 2509 consecutive , ratopsies, which comprise the persona! autopsy ex erience from 1953 to 1954 of two pathologist memat-rs .of our investigative T r o w * A!! natients show- % characteristic asbestos bodies and pulmonary `-frosts were accepted as having had pulmonary as estosts, and the cause of death was reviewed. Al! :i;es of diffuse mesothelioma were also selected, and tumors carefully restucied to verifv pathological , -assihcation and histologic characteristics of the tumor. and Frost Insulators and Asbestos Workers. These men are msulation workers, or.marilv engaged - building, powerhouse and shipyard construction work in which they have relative's- light, intermittent exposure to asbestos-containing insulation materials. Some of the insulation materials used bv these men. such as fibrous glass. cork and hair felts, con tain no asbestos, whereas others, such as matrnesi2 or calcium silicate insulation block and insulation cements, may contain 10 to 15 per cent asbestos.Exposures are therefore to a number of dusts, but asbestos appears to be the onlv biolosfcallv active r.brogemc material present in significant amounts. Little free silica is found, and histologic studv in ` Secondly, even if mesotheliomas were frequently ' round in patients dying with asbestosis, this would ' c -- not prove whether or not the tumors were cornonly caused by asbestos inhalation since few pa tents are known to die with asbestosis. To studv v.:s second question, we reviewed a:! cases of pleura! -~c peritonea! mesotheliomas in the files of the our laboratory of lung tissue of 45 of these insula tion workers showed diffuse interstitial fibros's char acteristic of asbestosis and no evidence of the whorlec nodular fibrosis of silicosis.11 Our survey covered everv man who was a mem ber of either o: these locals at anv time from. De cember 31. 1942, to December 31. 3962. Six hun- Armed Forces Institute of Pathology, in co-operaon with. Dr. S. Rosen of the Institute. Forty-five ses (1 9 'pleural and 26 peritoneal) of diffuse pleu- crec and thirtv-tvvo men were enrolled in these local? m 1942, and 899 men subseauent'v :oined in the vears between 1942 and 1962.7 On January 1. 1963. 254 -* ot peritoneal cancer were found in which the o: these men were dead, 1258 were alive, and. e: tiagr.osis of mesothelioma had been stronelv con- these, 111? have been examined bv us. From. Janu edered although in some cases alternate diagnoses rich as peripheral bronchogenic carcinoma, fibroi sreoma and metastatic carcinoma of undetermined origin were entertained. In addition, each of these ary 1, 1963, to August 31, 1954, 43 men died. Tim?, from January 1. 1943. to August 31. 1954. there have been 307 deaths among this group of asbestos workers. Each death has been investigated, ar.c! totes had available at least a small portion of lung th.e cause ascertained. Copies of death certificates or histo'ogic study (sometimes verv small, such as were obtained in al! but 1, autonsv protocols were 1 tag of lung at the border of tuinor tissue'' . Other reviewed i69 cases', histologic specimens were ex cases of diffuse mesothelioma are present in the files amined (71 cases', and hospital records were obtained of the Institute, but since lung tissue was not ava.l- and reviewed in the deaths (165 in number' in which thle. they were not studied. the terminal illness had occurred in a. hospitak Each cam was careful'y restudied. both to verifv The types and intensity of exposure to asbestos pathological dingnoris and histologic character- were studied in several wavs, including a.na.'.vsis of arcs of the neoplasm' and to search for asbestos the occupational histories detailed during the inter --es in t'ie lung tissue available. We appreciate views with the examined men. review of trade prac at any attempt to ev aluate the presence or absence tices with union and industry sources, ama'vses of ' asbestos b, rs in tissues, limited to identification materials retrieved during repair work and rev ew of 't asbestos bodies, m.iv grosslv underestimate th.e pei merit published data in this field. Final -.. work trequcncy of the p-escnce of asbestos. In other mstortes o: the men were obtained from the ex 'takes, we have demonstrated that in workers ex- arm ed men when available and from undo" 'ceorris 't'sed to ns'x-stos. asbestos fibers mav be present tor the others. These data gave the he.<e':r-' fo- .apgr mmilx'rs in the .u>MWce of asbestos bodies. calculation of the onset and duration of extv?-:iv '-rich, are nN-red and. enured fibers. Urfortunatelv. I n th e g ro u p o f ? o : c o n 5 t\'is :iw c e .v ''* 'W 'C '"fe in most cases tissue was not available for T 'teso a sb o tp s -m .s n '. \ \ O! k l'rS n o 1* .' ri - 'dditiora! sttidies 'x-cessarv. it was not txvssible m e s o th e l io m a w a s a c i't'n ttx i ;i : v \ ; " 1<- ' '`mate th.e problem m this material tuvrer. t o l o g i c m a t e r i a ' a r.ri \ o r : n e a t to n o f *->at''o 'o . 0 1i'.irvlly. to studv the incidence of mesothelioma s it- c a tio tir i I t b p,,>sS'N Ja t h a t m o s o th e 'lo - - . \W !V present in tx-rsons who died and in who-" had tin. J, CSurf and S. Mi'o'lfn. no CPixirtunitv to examine histologic mat-" ar.ri l-y> THE NEW ENGLAND JOURNAL OF MEDICINE Mar. i 3, :%i , ; ,..,r .',!! ,,, - '.it nil unfii'rr-tiliiritc oi mo . , . ..........; .im.**![.< .pi.'*!!" .1 i*\ ........ ... .. . . , , 1 !, - . .1 1. Iil'.lnlr, 1. ,.i.\ \ . . .. .. ui i.o i <;***il. r . | M ' Rr.sn.TS M r -ntlieiiomn in A uto p sies w ith A sb esto sis in tlir .miopw s,-; :rs suufii 25t\'i cases wen' rx,i!.. I.,,-,i ;i i i'. 6 i. iin'liHiir.p (''JO adult iria.es. Among these ashcsiosis was recorded in 26 c a s e s . The causes of death in these eases are summarr/ea in Table 1. Mesothe.ioma of the p.eura was present in 4. mesothelioma of the peritoneum in 3. and broT.c'nocenic carcinoma in 7. This frequency'of 4 pleural mesotheliomas amons 26 autopsies (15 per cent) with asbestosis may be contrasted with the frequency of pleural mesothe lioma in a general autopsy scries. Hochbcrtr2 col lected 43.732 reoorts of autopsicc cases from the literature, with 36 mesotheliomas recorded, for an autopsy incidence of 0.07 per cent. He added 7 mesotheliomas among 16.310 autopsies studied by him. an incidence of 0.04 per cent. Knig13 found 102 pleural mesotheliomas among 13.307 consecu tive autopsies without asbestosis at the St. Georg Hospital in Hamburg (0.77 .per cent1. but 4 of 26 autopsies with asbestosis (15.4 per cent).12 In the same study he reported 22 "peritoneal carcinomas'' among the 13.307 autopsies without asbestosis (0.16 per cent) and 3 among 26 autopsies with asbestosis ( 11.5 per cent). In this autopsy series we found no case of meso thelioma in the absence of asbestosis. Asbestosis among C ases of M esotheliom a* A search for asbestos bodies demonstrated them to be present in 12 of 45 cases of pleural and peri toneal mesothelioma in which lung tissue was avail able for study: in 5 of 19 pleural mesotheliomas and in 7 of 26 peritoneal mesotheliomas \Table 21. In 2 cases asbestos bodies were already known to be present. In the other 10 the present review first brought them to notice. The discovery of previously undetected asbestos bodies on re-examination of lung tissue in these cases of mesothelioma parallels the experiences of McCaughey. Wade and Elmes14 and of Houri'nane.4 It reflects the rarity of these bodies in lung sections, easily missed on random scanning and often found only with difficulty on prolonged examination even when deliberately sought. How often such diligent search of histologic lung sections would uncover asbestos bodies in routine autopsy material has not yet been completely stud ied. The negative results of ordinary autopsy ex;x'rience should not be accepted as an answer to this T a ;ii r 1. M c t o lk e lio r n a in ' V / i C o n t e e u t i: e A n ! ',; ; > j , /Co ? to 1 'jO i* i `j \sH in < a T ' i ** t'jo-* v. nh -4'f IVura! tnr~\y>>r, ., c.i? ir/ii't/ifiiO fn a iir<.r ca.'cinoruii Vi -Gier N o 0 7 C *r*. 2 'S / j 25 4 3 7 12 'I Litri, vr; of C'lurjf I k M ' . ' - V T 2 5 O f 25 r ^ -V sto lti ,i` ,t ; ii.'J a'.'j.t r. j.cv w.jti i rj'i s-xr<jat t-a vs.'n ._-r **.>'-r * wiaaa; n o ii.rvjtheiiomaj otrier t .Z t ir tr r - e asiOCia'ea ^s 'n V rv ri, question since detailed, prolonged review of luno sections is usually not undertaken in the ao-ence of special indications. However, in one study, in an institution in which mesotr.ehomas were iour.d to be frequently associated with asbestos bodes in lung sections. 50 consecutive autopsy cases exclud ing chest tumors) were studied specifically to dem onstrate asbestos bodies in lung sections. In none were they present.4 Tine results of our review of this group c; meso theliomas may well represent an underestimate o: the true incidence of asbestosis among cases o: mesothelioma in the United States. In tr.e r.rs: place, as noted, verv little lung tissue was avai.ao.e tor scanning in many cases since the submission o; the material to the Institute had been for review o: the neoplasm, with the status of the iur.g not o; immediate concern. This was particularly true of biopsy specimens. Secondly, no information was available concerning the portion of the iur.g from which the specimen was taken. In the search for asbestosis the lung bases are preferred, since these areas are more heavily involved. Thirdly, see r.zz to be satisfied with a review ot sections tor rbestos bodies as a diagnostic criterion. 5 ec in sotr-* cases of asbestosis. these may be virtual.v absem despite the presence of many unaltered asbestos nbers. which usually require special technics :cr dem onstration. These were not available in tins srucy. Incidence of M esotheliom a among Asbestos Workers We have analyzed 307 consecutive deaths arr.cn: asbestos-insulation workers. These comprise a., ceatrs of members of the Xew York City ana New ark, New Jersey, locals of the insulation workers' union from January 1, 1943, to August 31, Ibol T a b l e 2. Presence of Asbestos Bodies in L u n g S ' : 4 ' among 45 Cases of Pleural ar.j Peritoneal .\!esof.e.:.->-n' T OCATtON o r P '.c u r * IV riiootum Touh No. or C vsss 19 26 __ 45 A d u st i Bc k is K K 'N P J*CT POI NT * - # / f t H i K*. <f' -tt* 3 7 ---- 12 33 "A rm ed Fore Im cutc o< Pathology m aterial. "A rm ed Forces Iniirute o{ m itert*!. -c -D :.r r .; m u _ :.o r. n et o ... i A et ikT.fvH T i car. err v a r.c er i isra:: * : u V '.r ' .v v I th ii 272 No. U M ESOTHELIOM A AND ASBESTOS -- SELIKOFF ET AL. tr_E 3. Underlyin g C a m e of D e a th in 307 Consecutive t;:hs among Asbestos Insulation Workers, January 1, 1943, to Avgust 31, 1904. Cause. o r D eath Brc-ncHogcn'C ca re nom * C-auroInt^ na! cancer y.t-jra! m esot' e l.o n a Peritoneal rr.etotSeLiora AJ other neop'asics A.VfUos'-i Al other ca-rses Total* N o. of D eaths 53 34 4 6 27 17 166 307 P l*E.VTAGE 17.3 11.1 1.3 1.9 ZZ 5.5 M .l 1o o . o "tble 3 summarizes the causes of death among these Ten mesotheliomas, 4 of the pleura and 6 of the -dtoneum, were found. This incidence of more than wr cent of deaths is remarkably high for a tumor knarilv so rare that neither mesothelioma of the t'jta nor mesothelioma of the peritoneum is sep.jtelv classified in the International Classification Diseases used by health departments for report- causes of death. In the absence of data segregated by such cod ; of recorded deaths it is difficult to ascertain the noarative incidence of mesothelioma among -rhs in general. V.'e have been able to obtain v.e information, however, that emphasizes the frequence of this r.eoolasm in the general popuricn of the Unitec States at the present time. Between October 1. 1959. and February 15, 1960, .. 16 volunteer workers of the American Cancer '::;tv enrolled 1.078.894 men and women in a tractive stuev. The subjects are traced annually ' i once every two years are requested to fill out a -ef Questionnaire. Whenever a death is reported tapv of the death certificate is obtained, and when incer is mentioned on tire certificate, inquiry is trie of the certifying phvsician concerning diag'ls and h.istologic type of the neoplasm; 1,048, ' men and yvomen 'retyveen the ages of thirty 1 ettriitv-r.m.e vears yvere traced throv.g.r Septemr 3 5 . i r o n . 11 of yvhom 81,652 yvere dead. Only 3 died of mesothelioma of the pleura, and none "esothel'oma of the oeritoneum. la addition to the neoplasia among the recorded nits of trie asbestos yvorkers. 3 men are alive with ' ".71 r.ecu)!asms (1 lung cancer and ! pleural and "ritoneal mesothelioma', 1 is apparently cured of -'ior of the colon and 1 of tongue cancer, and 3 alive after successful resection of localized lung `err discovered in the examinations. been proposed'"' such considerations faced the dif ficulty of the infreo'iency of reported cases and the absence of pooulatlon and epidemiologic studies. Similar difficulties plagued the question of the rela tion betyveen lung cancer and asbestos exposure until their resolution bv adequate crudemto.ogtc in vestigations, yvhich confirmed the accurate but un verified pathological and clinical studies. It appears that a similar process is being completed regarding the complication of mesothelioma. Lung cancer has nreviously been demonstrated to be a frequent complication of asbestos exposure among insulation yvorkers in the United States.7 The data in Table 3 may be considered an extension c: previously reported observations, which yvere based uoon age-specific death rates among 632 men yvith. at leas: tyyentv years' elapsed time from onset o: first exposure to asbestos and yvhich yvere concerned yvith 255 consecutive deaths. There yvere 42 deaths due to lung cancer at that time (16.5 per cent'. In the 52 additional deaths 11 have been due to lung cancer (21.2 per cent;. Originally, there v.-ere 4 mesotheliomas among the 255 deaths: there are r.ow 10. Ten deaths from mesothelioma among 307 consec utive deaths is an extraordinarily high rate and per mits the conclusion that this disease :s an important complication of asbestos exposure. This conclusion, moreover, refers to such exposure in the Unitec States, under working conditions of the recent past, yvith relatively light and intermittent asbestos ex- i>-y*- D tscrsstox ternil tenor's of rronlasia of the o'rural and su: aces in ass.v'ation yvith asbestos:* var- iv la'vled "midit'c'entiated carcinoma." "endo"t-a eua" h.ave Iven avadable years. Alt gh a special relation had F w.I 'rf F i l s the C h e s t a t an AF-cr.'^-ln.o. V : :r r v f v V \' r " * < : * . : "'.r . 'vu rLL>v:r.\:ur;*: <c\g. 3 , " * TU E NEW ENGLAND JOURNAL OE MEDICENE r * A f- i a, F igvre 2. Microsc opical App ea ra n ce of the T u m o r ( X 7 5 ) There are compressed, tubules of epithelial-like cells in dense connective-tissue stroma. F igvre 3 Peritoneal Merctheliyrr.c in an A <be to'-In'ulut'-W'orker zvith *M inimal P ulm onary Fibrozi; rX 75). T his is a biopsy of one o: m any noduies that ::uddrd : p e rito n e u m , showing papillary and solid areas of epithet:: like cells. postirc. It indicates, too, that mesothelioma may not necessarily be entirely a problem of only one from fifteen to forty-three years faverage, thirti- kind of asbestos (crocidolite) and that it is surely one and four tenths), but there was no man > not limited to South Africa. whom this neoplasm developed in less man thirr.- We undertook three different types of investiga two years from the onset of exposure faverage, th.ra- tions because each is subject to the difficulty of eight and five tenths . Sever, of the men were woff small numbers of cases of mesothelioma available ing as insulation workers at the time o: onset , for study, and with small numbers, there is a danger the fatal illness, and 2 .at other occupations Or that findings may be due to chance. Autonsy series was retired. The 3 no longer exposed to asbesa are selected: they exclude the patients with a disease had left insulation work three, fiitecn and fiftee 1 L .' who do not die, and carry the risk of including an vears before. There was no evident corre.anor. be undue proportion of the more unusual ana com tween the occurrence of mesothelioma ar.n the se plicated cases. Thus, the finding of 7 cases of verity of asbestosis {Fig. l-3ff mesothelioma in the autopsy series of 26 cases of Six of the 7 men with, mesothelioma in tr asbestosis cannot be interpreted as necessarily indi autopsy series also had histories of prolonged em cating the true incidence of this neoplastic com ployment in the asbestos industry ahhct.rh in n- plication although it does point to its significant ire- bestos-factory work rather titan insulation work. Tv. quency. Secondly, the search for asbestos in cases of mesothelioma, as in the Armed Forces Institute of Pathology material, carries the hazard of underrc.iding because only small specimens of lung paren of the 6 had left such work five and fifteen year before their fatal illness. The seventh man in the autopsy series raises potentially important problem. He was seen by or chyma are available and it is simultaneously difficult of us in 1961, and the diagnosis of mesothelioma v to demonstrate scant asbestos bodies. On the cider hand, there is the risk of overemphasis of the im f --,ii i <*** m i . y i w -- i ni -f h . ' '1 ' ' portance of such bodies since they are occasionally \ -' found in "normal'' lungs without asbestosis. owing to chance environmental contact.17 Analysis of the results of our clinical study, with review of 307 consecutive deaths among 1522 asbestos insulation workers, has the advantage of suggesting an estimate * ' ' /V * _ of the incidence of mesothelioma. However, even this estimate may underevaluate the incidence since, ' \ '* whereas each of the 10 mesotheliomas was confirmed ' }' V ^ by histologic examination of operative or autopsy material, only 110 of the remaining 297 deaths had such confirmation. We have analyzed the work experience of the 10 i \ \ 1 '' -- -- - -- 3 men in the union group who died of mesothelioma. Age at death varied from fifty to seventv-five vears F igure 4 . Thoracotomy S ^ecimen. Demonstrating n Extr sit* I'nilaJerel Pleural Tumor in a - C a rp en ter. {average, fifty-nine). Exposure to asbestos varied A u to p sy confirm ed th e diagnosis o f pleural mesothelioma 1207 272 No. 11 M ESOTHELIOM A AND ASBESTOS -- SELIKOFF ET AL. ./ > "I ieti aif f/ic v.rty- n in jirtv- V'Oik- Oivie?'o< i u,, the e:ni 2s- Two ear' es a one a of " vre 5. A sbestos B o d y (A r r o w ) in an A re a o f P u lm o n a ry Fibrosis (X 4 4 0 ). u pleura was made clinically and by biopsy (Fig. Because of the suspected association with as- es'.os exposure, he was closely questioned with re nte to such exposure. This questioning was par.ularlv thorough because he was employed as a "ttpenter 'employment in the construction industry i suspect). This man denied ever having seen, -ed or handled any asbestos product. He later -td, and on post-mortem examination, both assstos bodies and fibers were found in the underlyN lung IFig. S'1. In another case we found asv.os fibers in the lung of a man who died of '.feral mesothelioma and who had worked in a -'v-cleaninsr nlant as a "sootter." This observation 'tils to mind the fir-dint: of asbestos bodies and li fts in the sputum of neonle employed in a dryiar.ir.g works in South Africa in an area 100 miles :'-av from the nearest m:ne.is as well as cases of ' nlhos's caused bv handling contaminated work e s .'" These examples o f indirect occupational '-'%asv.re a"d community exoositre raise the invtor- ovestion wh.etlier mesothelioma will be fou.n.d ` be a community problem in addition to th.\ nesting with industrial exoosure to asbestos. SUM M A RY AND CO N CLU SIO N S Our study of 207 consecutive deaths '1040-1007 among asbestos-insulation workers in New York and New Jersev disclosed 10 deaths caused by mesotnelioma of the pleura '4 cases] or uerltoneum '5 cates). This is an extraordinarily high incidence for a tu mor generally so rare that it is not separately coded among causes of death. In contrast, in a prospec tive study of the general population, among 31.652 deaths 'in patients thirty to eighty-nine years of age), only 3 were due to mesothelioma. In 2 additional studies, the association of meso thelioma with asbestos was further indicated by the finding of 4 mesotheliomas of the pleura and 3 mesotheliomas of the peritoneum among 25 consec utive autopsies of cases of asbestosis and, also, by the finding of asbestos bodies in lur.g sections in more than 25 oer cent of cases of mesothelioma. It appears that mesothelioma must be added to the neoplastic risks of asbestos inhalation, ar.c joins lung cancer (53 of 307 deaths' and probably cancer of the stomach and colon (34 of 307 deaths' as a significant complication of such industrial exposure in the United States. We are indebted to the A FIP for m aking available col lected cases of m esotheliom a for our review and, in p articular, to D r. S. H. Rosen, of the Institute, for co-operation. R eferen ces I . W a rn e r , J . C ., S'eRCT, C . A ., a n d M a re h a n d , P . D i f f e r p le u ral m esotheliom a and asaestos cynosure :n N nrdi W estern C ane Pros- nce. /?'if / . / id i . ; ; . M e d . ! 7 . - ' i ' - J i , reO. e M cX u itv T C . -V 1 n: D 'eural m eso th elio m a in asses' ; w o rk er. / . A w i'c H a 2 ,? :e ;-l-;5. '.h i-'. . 3 F.nf 'ck n ap 1 hi., n "<: S-n.'r'ier. W . T. P erito n ea] tu m o u rs :n as- `,,-stosis. i n - . I l - d m : . M e d . 2 1 :2 .'-3 I. 1904. _ t'4. H o n rih a n e , D . O '2 P a th o 'oev of n e s o th e 'io m atn a - c anaV sis o f assoc-ation w ith asbestos cyn o su re. g - o 'e r 19 " - - ' '. '. . 5. M av . T . C . E \te n s h ,t. .. st-U-sT ca! tab .es In Bowies.* 6. Bowies, O . Asbestos, m aterials survey. A n n . S e w > e ' i A end. S c . (in p ress'1. 7. S c''k*iT. 1. J . C Ku r r . J ., an d H x n v 'io n d , E. C . A sbestos e \ - jHsurc an ti n e o n 'asia. ISS I?o4. 8. C 'luir. J . M o o l'o n . S .. a n d R osen. S. IlA '.o'o c 'e a l cS ar-icteristics cf m o o th eh o m a associated w ith asbestos, ir . . AfU' Y ork A .'iJ . Sc. 'm press'. 9. F!c'<-cact, W . E . V iles. F . J ., J r . , C a d e . R . L .. a n d P r n l f r . P. H e .i'th s-irxev of p i ^ co x e rin c ope^at-ons in c o n u r u c : nax-a' vrx>ca. ) . in d v si. H vg. 2 8 9 -I b . ! ^ . ' 19 M a rr. \N . T A sbestos r \ 'x>sure durw 'C na\-al xesae' o x erh au i. A n / / i f . A J . 1 S . ^ - A S . I mM. !1 . Se) ko'T. I. J ,. C H urc. J ., and H .in u u o n d . E. C . O ccu rren c e of a d v su x is an io n t ir.<u'ation workers in U nited States. .' *. S c u F o rk .1 sw4. vin ore-hs'. ! J . H fo h S c re L . A . E r d s 't^ e 'io tn a (n > ev 'tb e'io n \a ^ of r V u r a - m i o ' $3 . ^v\ I 'm re*-*ort of 7 ca^e 4 of w hiclt w e re e x tT p a te d su re i pm .{**. 13. K vmuc. 1 l V r t'.e Vsbr^tose. A r c k . f. C cu 'erb cp eth . . few i s ' r.?-. 'r*\ ' 14. M< t'.u -c b e x , W T . E . 3\*ade. O . L .. a n d E 'mes. P . C . F .\^w u * e to j d e c . t t ib.rst ansi dtfTnse p le u ra l nw-sothenoma. B * i` . -Vf. K i '.-'97. !3. H .v i" 'vxmi. F. C . S n K 'k 'n c in r e 'atio rt to m o rtaiirv a n d ''wr^'-ViTN I'm ii'iex *> :f'rxt o4 o ' lo hi T'rv"TNec*'\e :-i V' .li \ - f . C t.v * / **.. !L-4. W w A. '!"i-i b e' l.' n ce".xs'e> 'v'!w*, in xixo Cv< C 1r * 3 4 : jx* . i c, o. o i ' ' k ; >' "l"*) .v*W ii K..w-'v ' A. R- O .' C . a'd N 'aciX '- . / RR f is as :">v e m L-',> n haaarxl. 'w: t 3/. / ^ "-7 s* e ":*'aC .*n A. So . r \ - ! b u A '-d. A :- v-a. P.. a - d 3A.' c - e - . T. A M. C. '. 35 *-- - *o?. v . n ' MN! . r t al. Non'OCCUVNitioiw*'. S-r.as^wjs. j , . . . : ;0