Document 5kkaJ4gJopBG5521XDxqqG8v4

FILE NAME: Saranac 7th Symposium (SSY) DATE: 1952 DOC#: SSY054 DOCUMENT DESCRIPTION: Text of Presentation by Dr. Lynch - Carcinoma of the Lungs in Asbestos Weavers RECEIVED F.HI.H&S DATE: J U L 3 i 1S 7S K.E.N' 1_*a r-, lOt (Ko response), l*ov, IT those of you who arc is the tack, could you cose forward 6 0 that we car* really cet a picture. There are ft lot of seats up forward end it will orly take a fev minutes, I nir.ht say thatthe photo^repher will print these pictures and you nay buy one from hir. if you rc v-sh; on the bulletin board outside will be a paper where you rJLcht indicate whether you. want one or a doten, (Photograph vas taken, after which too -,se tin; was adjourned, feosior* reconvened at 2 ;u7 *' **) o t> ?-idr::D ci:;:osii a::d ?\l:'D..a?i * c ^ c ih ^Continued) 2 o * 50 Chronate Workers fU. | - *\T-*, T u^-- wU, 1.*i# r-- Discussion Experimental I-ulnontry Cancer - General Review G u'urrou-ns .lia c r , Discus cion Pulmonary Cancer in Experimental Exposures to Coronate Anna D a e tje r, -Sc.D, Discussion pirsconary Cancer in Experiments! Zr.reeurcs to b a r y lliu Arthur J . Vorvaic, D, Discussion, ' 5047 CABCIFOKA OF TEE LUF3S IK ASEESTCS VLASIES RECE.i ** DATE.- KZNKETE K. LYNCH, K. D. W Professor of Pathology Kedical College of South Carolina Charleston (Summary o f presentation at the Seventh Saranac Symposium, Saranac, Kev Tork, September 2V, 1952) Perhaps the main ju s t ific a t io n fo r ay acceptance of the in v it a tio n to discuss the subject of th is paper in th is company rests in my in te r e s t in the questions concerned more than in any sp ecial con trib u tio n th at I might, make out o f a rather sketchy and spasmodic indulgence in e ffo r ts to solve then. I an sure tr.at others vhc are present here are better q u a lifie d , and my purpose is to gain from tbeE rather than to expect then to b e n e fit from any o fferin g c f m-.-e Vben in 19*L I had the opportunity tc examine by necropsy the case o f carcinoma of the lung that vas tc become apparently the f i r s t o f such an occurrence in a ease c f asbestosis tc be fo r c a _.y set in to published records^-, there immediately arose the questmen cf a possible causal relationship in the prior state c f chronic lung d ise a se . We had for several years been deeply interested in asbestos and th is nev occurrence produced an ad d ition al question for thought and in v e s tig a tio n . At le a s t up to that time chronic inflammatory disease, cr ehroni i r r i t a t i o n , p a rticu la rly with fibrous production and disarrangement * concerning the o f stru ctu re , vas the main anchor in speculations / etiology of KtutiVLU KH.H&S ' DATE; Jill J i 1973,: 5043 M.E.M , cancer, p a r tic u la r ly o f e p ith e lia l typ es. In advanced asbestos.s an opportunity fo r the occurrence o f carcinoma o f the lung on th at b asis seemed to be good. A ctually nothing has yet occurred to cast out that p o ssib ility . In the intervening tim e, during which ve were to encounter two other lik e cases, there appeared scattered reports of the sane occurrence in other lo ca tio n s ; u n t i l , by compilation in 19^7 Herevether2sta tes that there were then recorded at le a s t 31 in stances o f cancer o f the lung in 235 cases o f a sb e stc s is , an autopsy pulmonary cancer incidence of 13.2* la persons su fferin g fron as- b e s to s is . For a f u l l y acceptable comparison of th is incidence of course one would be lim ited to the use o f an autopsy series fron a clo se ly , sim ilar, group in age and sex and at le a s t in lik e environment for T 's i^ ila r period o f time except for exposure to asbestos in h a la tio n . Even these rather loosely set c r it e r ia could hardly be met where numbers would be large enough to providers''fcinimal chance of error in s ta tis tic ia n -ty p e '-calculation . The most that can be done at the present is to take vhst is a v a ila b le as evidence for or against an e tio lo g ic a l basis for cance: o f the lung in a sb e sto sis, at the sane time recognizing that the la rg e chance o f s t a t is t i c a l error does not allow proof tc be claime but merely suspicion to be supported or not supported. At present such evidence as is availab le appears to support the suspicion and to Ju s t ify further in v e stig a tiv e e ffo r t of what ever nature may be s c ie n tific a liy o revicsTf.ly At le a s t the a v a ila tle evidence does not a lla y the suspicion. receded f.h.h&s date.j u ^ j ^ oj3 In South Carolina the autopsy service that has furnished the kuoaii m aterial fo r our studies in asbestosis is in a general h o sp ita l that through the years might be expected to produce a cross section o f the run o f serious diseases o f the community of lo c a tio n . For such value as i t may have ve have analyzed the findings in the 39^3 autopsies occurring in th at service from 1926 to 1950 in the age period of twenty years or over, the purpose being to cover a span o f tvB nty-five years t h a t corresponds roughly to the period o f observation of asbestosis and an age group that would also cover the occurrences of that condition. In that t o t a l autopsy series were found instances of a diagnosis of asbestosis by microscopic evidence, including a l l cases regardless o f degree, and among these ^6 were three with advanced carcinoma of the lung, an incidence of 6 .5 . In a l l others carcinoma o f the lung occurred 56 tim es, an incidence c f 1. Obviously such a comparison i s of lim ited valu e, as are a l l others from which the question has been posed, although taken as a whole they are at le a s t in agreement that carcinoma of the lung ha been co n sisten tly more common than was to be expecteo in reports o a sb e sto sis. Our incidence of th *t order is le ss than in some otke re p o rts, while our general incidence o f carcinoma of the lung is comparable to some (Homburger) but le ss then others (Rigdon & K ir c b o ff) . Our incidence in asbestosis would approach tr.at given in other reports i f the ca lcu la tio n were made within the group of medium and advanced grades of a sb e sto sis, in which area the three instances o f pulmonary carcinoma occurred. In thaw group ve he- 28 cases, and the incidence within the group would te 10 . nUEiVED F.H.H&S DATE: J L i L - L t - l 2a ' 5050 M.E.M In c id e n ta lly , fo r such support as i t asp ElTe tc ^ eocEon report o f growing prevalence of earcinone o f the long, we fin d th a t in the f i r s t th ird of the tine period cohered in ear se rie s the incidence o f cexcinoae o f the lung was 0 . # , in the second third l . l j t and in the la te s t third 2 .2 * . apparent ly a steady increase daring the tw enty-five year period, even though s t i l l not as high as reported fron sone other areas. hEiEIVLD F.H.H&S niro. JUL 3 i 1575 S 0 5 -1 K.E.M Without, a t th is tin e attempting to sake a thorough eoalysis of the published papers snd records, a le v recent pertinent reports are noted* . in one o f the l a t e s t , S t o l l , Bass and to s ris t-r e p o r t an ad d if.o n - H ease o f cancer of the lung in asso ciatio n v itk astestcsis^ end cast np the lite ra tu re as of 1951. refer to Kerevether's 19-s re p o r t, as previously noted herein , and also re fe r to a report by Vyers in 1 * 9 recording a series o f 115 cases of ashestosis in i c there v . r . 17 instances o f associated pulnonary carcinona, an autopsy se rie s incidence of * . W , a compared to Kerevether-s 1 3 .2 ,. lonhurge^ reported three edditional cases of associatien of pulnonaxy carcinona and asbestosis in his autopsy se rv ice . In h i . se rie s o f autopsies from 1918-1938 there vere h5 cases of r - ^ = ^ y carcinona, an incidence o f 1 .0 W . Ashestosls vas diagnosed 8 tines sn4 m W of the 8 cases pulnonary carcinona vas also found. " C yor such comparison as nay he a lle v a b le , Rigoon and K ir c h o .. reported in 1951 pulmonary cancer incidence of 7.5? (67 in 8=2) in an autopsy series in individu als 30 years o f a g ^ d * . ' Z They suggest "th at frequency c f cancer of the lung/be e s ta :--s .e o . . . a se rie s of au to p sies," on account o f the u n r e lia b ility c f c e . . - c e r tific a te s . Counterbalancing a t le a s t some of the veigh t of evidence of reports of cancer of the lung associated v itb asbestosis is t_e widespread increase of pulnonaxy cancer in the general population th a t has been recognised during the sane period o f t in e , i references w ill serve to focus that tremendous problem. - 5- RECEIVED F.H.H4S CATE: -II li V j 1079 a0 - M.E.M _ Graha/,in 1951, says, "Eronchogenlc carcinoma d iffers from other ceneere In two important respects: (1 ) i t has shows an enormous increase in the la s t 35' years5 (2) there has been a progressively larger incidence in the male sex." He states that id ler in 1912 could co lle ct only 371* eases of cancer of the lung from the world's litera tu re , while individual ' experiences in th is country greatly exceed that to ta l of reported eases from the whole world, and that cancer of the lung has ad vanced to a position of f i r s t place in men from one of 8th place in frequency - and this a ll within the la s t 35 or **0 years. D e ll and H i l f refer to a B r it is h government report which shows th a t fo r the 25 year period from 1922 to 1 * 7 the incidence of lung cancer in autopsies in England and Wales Increased fifte e n times over vhat i t bad been previously* in e d ito r ia l note in The la n ce t in January, 1952, strikes a timely note in referrin g to H i l l 's report th at "in a t le a s t 17 cut of 29 Boroughs (m etropolitan), deaths from neoplasm of the lung and Bronchus vere more numerous than deaths from tuberculosis" end in remarking, "This is something quite nev." Smitt^ in 1952, states th at lung cancer has shown an increase ever and above what could be expected as a re su lt of increases in number, o f e ld e rly persons. He sta tes U s e that high lung m ortality has been recorded fo r both men and women patients with asbestcsls in England. -- -------------- " Perhaps ."person al note is permissible to illu s t r a t e the ap parently universal"experience in autopsy services during the la st ^ fo r ty years th a t carcinoma of the lung has changed from a r a r ity U . commonplace. As a resident in the Philadelphia General Hospital Rl'JElVED f.h .h &s DATE: JUL 3 i 1979 . 5053 M.E.M I had done as autopsy on vhat I took to be a case o f tu b ercu lo sis, and had discarded a l l organs and tissu es except the small pieces from vhicb I prepared microscopic s e c tio n s. Vhen I shoved the resultin g s lid e s o f carcinoma o f the long to my ch ie f and had to acknowledge th a t I had throve the lung's^ avay, he arose stern ly from his mic roscope and l i t e r a l l y booted,*6 down the s t a i r s . Perhaps I may also note that the sca rcity o f residents in pathol- \ their ogy nowadays has e3*e brought about a differen ce in /treatment, a l though possibly not so much d ifferen ce in th e ir desert's . EXPERIMENTAL STUDIES Because o f the question raised by autopsy observation of associated asbestosis and cancer o f the lu n g, anc among the many apparently experimental studies that/have been done and lo r . are now going on by subjection of experimental animals to respiratory exposure to a v a rie ty o f suspected substances, I have unoertaken to see whether evidence of carcinogenic action on the part c f asbestos or o f the condition of asbestosis might be gotten in this vay. Hov in the third year, we have such a project under vay, supported in part by a Rational Cancer In s titu te grant. In devising such an experiment, one i s , of course, faces with many questions, among which are the choice c f experimental anim als, the methods c f exposure, the mechanical questions in volved in methods, the p ra c tic a l matters o f time and h elp , e t c ., e tc . Because, ao far as I an avare, no animal except man has shown bronchogenic carcinoma of the lung n aturally(or experimentally for that matter) 7- ; 5054 ve chose to work v ith a stra in o f mice known to develop adenom atous tumors o f the lung in regular p re-calcu lab le occurrence. In th is animal we have one o f abort l i f e span, o f known lung tumor productiveness th at might be susceptible to influence in th a t natural occurrence, and at the same tin e as good as any other prospect for bronchogenic carcinoma so fa r as is known. The str a in chosen i s the AC^ hybrid (A Bale and C fenale) f i r s t generation from breeding stock obtained from the Koscoe E . Jackson Memorial Laboratory. Approximately equal numbers o f mice are being exposed and kept as c o n tro ls. Exposure chambers are o f our own d e v isin g . B_gular dust counts are made, v ith concentrations e . obtained _ o f dust as high as may be/vithout risk of k i lli n g the anim a.s. As near as fe a s ib le , the sane asbestos as our human cases ex perienced i s being used as d u st. . As the animals are s a c r ific e d they are autopsied and the number, s iz e , and d istrib u tio n o f lung tumors recorded. An attempt to grade these w ill also be made. I t would be premature to give any an alysis o f th is date as y e t . Ecvever, no epidermoid c a r c i noma has yet been observed. - Because ve wished to also use another and larger animal, a number of dogs are a tin being subjected to sim ilar dusting in s p e c ia lly constructed chambers. This i s , o f course, a much longer term experiment, and no report can be made upon i t at this tim e. One o f the reasons the dog was selected is that observation c f the occurrence o f asbestosis bodies in the lung of a dog exposed in an asbestos factory is recorded. So fa r as I am aware, there is only one published report c f an in h aletio n experiment exposing mice to asbestos dust as a te st - 8. ' RDECAL.TVtED: JFk.HL.Hi&lSi i 2 it . 505::' 9 o f eaneerigenie a c tio n . Hals rep o rt, by Fordmann and Sorge, by the authors vas elaimed/as p o sitiv e evidence of such a relatio n sh ip and has p been eited to that e ffe c t by o th ers. Smith, however, analyzes I t to the conclusion that i t not only produces no proof of a causal relationship of asbestos In cancer of the lung but actu ally to the contrary. In that report ill-d e fin e d e p ith e lia l changes vere thought to have resulted in the lungs o f 9 a rie a ls out o f an o r ig in a l 100 n ic e , squamous metaplasia vas found In 6, adenocar cinoma in one and squaaous c e ll carcinoma in one. Smith questions whether the interpretation vas correct as tc the demonstration of a ctu a l squamous c e ll carcinoma and c a lls attention to the common occurrence o f squamous c e ll metaplasia In old rats with chronic pulmonary in fe ctio n s and in animals d e fic ie n t in vitamin A. The only other experiment o f w hich.I am aware where animals under exposure to in h alation of asbestos dust developed tumors o f the lung in a way suggestive o f a relatio n sh ip occurred in an uncompleted experiment o f the l a * I . V. Gardner that came to my a tte n tio n through a courtesy from the Saranac Laboratory. In one o f Gardner' s experiments in asbestosis he found e high incidence o f the type of lung cancer to which mice are disposed. Since the stra in he vas using vas unknown as to tumor s u s c e p tib ility and since the experiment vas uncontrolled from that standpoint, he stopped i t , apparently intending to set up a proper experiment to fo llo v up the suggestion la t e r . A t le a s t i t does not appear th at any repo.ted experiment can be accepted as conclusive, and I am in clin ed to the same view as expressed by Smith, that up to the present no experimental proof th a t the in h alation o f asbestos or any other m aterial w ill cause REwEiVtD F.H.H&S _o_ ntTr. JUL 3 1 bronchogenic carcinoma has been presented. As the matter nov stands, i t appears that v h ile additional ridence of the same sort has been collected in the meantime, the question that vas raised with our f i r s t V & * in 1925 as to vbether asb esto sis can act as a producer of cancer of the lung in human beings remains as open as i t vas vhen ra is e d . So fa r as ve are concerned,`"tEe'conditions in the industry are so much improved th at even the problem o f asbestosis has be come g re a tly lessened. The grade o f exposure to the dust has been so reduced in our te r r ito r y o f experience that ve no .longer ex pect to see the extreme of the disease that e a rlie r uncontrolled conditions caused. medium to Even so , and although our cases vere those cf/advaneed a sb e s to s is , i f tie exposure may be eancerigenic i t could not nov be ce rta in ly said that le sse r grades of the primary disease vculd be immune to the tendency. In *11 respects, th erefo re, the problem remains with us and should be subjected to continued in v e stige tio n on i t s ovn m erits, aside from any advantage th at would accrue t c the in vestigatio n of malignant n eop lastic disease as a whole i f such en .t lo lo g ie fa c to r were uncovered. JUL M.E.M - 10- ' RECEIVED F.H.H&S 1 references M.E.M 3 1 197S 1 Lvnch. I . H. and Smith, V . A .: Pulmonary Asbestosis I I I : Car * cinosa of Lung in A s b e s to -S ilic o s is . An. J . Cancer, F e l. XX^ , Ko. 1 , Hay, 1935* c vT#u#ther E . R . A .: Annual Report o f the Chief Inspector 2` o f m t o r li s T l^ndtn; K s M a je sty '. Stationery O ffic e , 19*7.. 3 . S t o l l , Roger: B ass, Richard; and A n g rist, A lfred A. s **|bes| e il-n J Associated with Bronchogenic Carcinona. Arch. I n t . H ed., 8- 831 (Dec.) 1951* V . KoEbureer, F .i The Coincidence o f and Pulmonary A sb estosis. An. J * P a th ., 19*19*3 (?( ^ ' r Riedon. R . E . and K ir c h o ff, Helen: Frequency o f Cancer of the * Lung in A ll Malignancies Studied at Autopsy. Sou. Med. J . M r!506, June 1951* 6* sife S iio n r f'it^ fS lS o iT ^ ta ll! " ^ l a ^ M e d M ^ '^ 7- i" l J c` 8. Sm ith, V. E .i LnnE Cancer VI th Sp ecial Reference to Experimental A spects. Arch. In d . Eye. 4 Oceup. M ed., V o l. 5, S o . 3 , <w,, March"1952. 9 Kordmann, M ., and Sorge, A .: Lungenkrebs durch Asbeststaub la T i" er*neh, Z tsch r. Erebsforsch. 51:168-182, 19-1. - 11-