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Ten Cases of Angiosarcoma of the Liver in Shawinigan, Quebec Fernand Delorme, M.D., and Cities Theriault, M.O. Ten case* of angiosarcoma of the liver have been diagnosed in Shawinigan, Quebec since 1955. All have occurred in men Methods Case Finding. -- A starch i * i'.'m*'* oi irt. rn i inekver who worked in a vinyl chloride polymerizing plant. Cigarettes nog'nntng av (.: o.u k ,is I9"i nd exN-nd over two .loc.idei and alcohol do not seem to be associated with this tumor. The v,uru'd mil bv scrutinizing ii e- i: the rvg ^ vi-: i u-m the amount of vinyl chloride to which these people were etposed, Sh.iwimgan vn. mtv All uses i^r.nurv to'"'-rv ot ;hr were according to information obtained through questionnaires, ap u^ected anc the h:vtnlng eat mater: il '-'..ae* biops. sports pears elevated. Angiosarcoma of the liver is accompanied by a autopsy r^port^' were reviewed :<' the pres* m ot mg vircoma, fibrosis of the liver which may precede its appearance. In de "0 t onttrm the diagnosis of .to^i ^arcorru * ;ho ve' fv scribing the Canadian cases of angiosarcoma, this study at wTr submitted to consultant* >m :ne l r1.:*- '! v.tif- > - ar with tempts to shed more tight upon the causal relationship be disease tween vinyl chloride monomer and angiosarcoma of the liver Occupational History. -- TN* .'luestionn.i.r*-. UM*rj .btam a and thus to provide some clues to understanding the patho derailed ott unatmnal h -rorv - ,r- u A , a\t . t. em , ,n rnrv I genesis of this disease. k or ; ng past an i present :evci r< e medica1 sji>rv sii is. ng and drinking run t> along with rust .u < upi*nvi% inn em*s r* in In lanuary 1474. three cases of angiosarcoma of the liver were i hronologxal order The artswi'f' to must .ue^t-t vt x were given hv spouses ot the men a *v . from t> d i*e - ,ne in discovered among workers of a chemical plant.' This rinding ap stance, however the answers* were' even n\ trv - ier and peared abnormal and the agent suspected of being responsible for orother-in-law and .n another bv :ne vvnrkef ^ m*e( T\\nv>rmer the disease was identified as vinyl chloride monomer (VCM Since co-wo'kers 01 the men who diec o? an angiosarcoma he liver then, many reports on the occurrence of this cancer among vmvl confirmed and completed the .nrormation .blamed mr.nj^n :ne i chloride workers have appeared around the world''' and the Unit families ed States Occupational Safety and Health Administration t\ts Plant Description. -- the 5nawin.qjnv.n. . hionce *..m`start enacted a new threshold limit value for concentration ot this ed operating in 1945 At that t.me t oroOw* *d arn o-menaed chemical in the air of the working environment." vmvl chloride monomer later .n the 1950s -r stopped "due ng Ten cases of angiosarcoma of the liver were diagnosed among VCM and kept operating the pnlvmernat jmi *h* vs rk:rrte workers of a vinyl chloride polymerizing plant in Snavsmig.tn tried from 10') to 550 worker* As 'he moment as 250 Quebec. This is the largest number of cases ever to take oi.k e m a men Prr>ducl'on ot PVC has iluc tuated with P-.-v.-'it .ir xlug* single plant. The present study describes occupational history on .s >stimated M 50 million pfxjnd'* annual \ fcvn surt- *o VCM ! drinking and smoking habits and some histological features oi m the working atmosphere, though not dociment**d - 's.'-is-ved i these Canadian cases. Data on some of these Canadian saves to have been very high .n the p^ist sharp improvement has taken jointly with cases of angiosarcoma from the United States have al pl.ue m recent years and ft is estimated at loss thm * o.en at the ready been described m another article by one of the authors ` moment. Since more accurate and complete information was retrieved on the Canadian cases, it is being presented separately in the present article. Result! Table 1 shows the age at death the smoking habits and alcohol From th* 0p*rtment otf Pathology, Cemr* MotpiUler Regional (V u Shawinigan Quebec ;Qr 0*k*m*l an<j the Department of Social and Pr*v*mv* one Laval Uflfvewty. Ste-foy. Quebec (Or Theriault; consumption for the ten cases or angiosarcoma of the io,u diag nosed in the Shawinigan region over the last two decach" Alt 338 THIS PHCTC ' " v/iTH .THE 1973 u:.\-.._r.i lAW OL1 7016 * 1 t wore mile', the age at death ranging from 41 to 61 vears with an chloride moot .me' was unv.'iash -.noMer 'mg'ig :r r ^ average ot 50 5 vears months to Jh soars with an average ,e\rx lit n. m;rs ^ It is somewhat doubtful that smoking has much to do with this from the joo ot*s< r-ptions ; < an ne ,'\t' most . >* *-ri**n * type of tumor Out of the ton cases one man was a nonsmokor. worked either as operators or mamten.m* e workers . r h<-:n ` five were moderate smokers smoking an average of JO cigarette f* Of Ins per dav and the remaining tour smoked one pack or 'xeven men w'rkei| as re.u t >r , ItMners in pcrar -n ,\h*i h s. vms to nave htvn the wirs*. m e\r> s,ng >\ <<ii* jj Cigarettes per dav or more The tumor appeared earlier in the monomer One woman said >t her husband s o;)->sM'e H* .\mi er ^ moderate and nonsmokers -x age 47 vears than in tne heaw down into the au'oclaves manv times Once t-rv had to ,ake nim ies f* smokers x 54 years* out unconscious *he The men who developed an angiosarcoma or the liver were !( is d'Ouult t*> get a fair dea nr tne amnt*i t or x.rv. ` i rSonde v very light drinkers Only two men out or ten d'ank more than one monomer to whi* h these ,i-,ii;)ic were exp- vM Manv *-[><i_.-.es isn, bottle of beer per dav None of the ten men drank wine or liquor Kit or ten ns-ted upon mentioning that "Vir husoano worked regularly As with cigarette smoking, drinking does not appear to overtime be associated with an angiosarcoma ot the liver n vmvl chloride As mown n Table > ;he t*me oiaosec r,t.\een the r *st ex workers posure to vmv c hlor.de mon-'.mer and the oiavzn. w > or ttv i Past diseases ,>t the Ivor mav also be ruled out as potentiating `anges from 11 -ears to 28 vea*s wtn ar ,,..e'age nr JO 5 veVv the development or angiosarcoma or the liver since the medical This concurs w,tn previous r.ndmgs that an ar,^rearc ma v `nr history ot the ten cases showed no previous liver diseases nor - ser can develop after a minimum exposure .r * )Ur vo v' n^t ;hot hepatic troubles actual manifestation do*1* not -k j: r.r r -ms( ten '.ear*. Table 2 shows the length ot time the men were exposed to Ros.fleo;p rtistorv revcAx; that ai worst*'-, .ei: witn * ;w<, vinyl chloride either bv working in the polymerisation unit or bv mile Mihus ot tee VCM p.am s.m e me hea "t r' * fiei --mpi... being dir tiv exposed to vmvl chloride It also shows the ocs upa- men: at that p'ant However nopartui.ur *i::>'n m ih' 'os.n* e lions thev performed and whether thev worked overtime Thev t. al hisforx iMu-ci he loentif *\i (hat mu'd : tnd n^ .-in,* m worked tor periods ranging from 11 to 29 years in the plant with mental tacvors tomrnon to over .one an average ot 21 years and 4 months Direct exposure to vmvl Past (KCuoat-'nal h.storv -.^-.wed that s. "i*-e w-*.* ee-rv TiM* 2. -- Occupational HMoiy at Tm Catat at Anjlotarcoma at tfia livar m a Canadian Community. 7 Cm m. TiMB CxpM^ Wwttf W tta ftaW WftM ta Crntnat vttfe VC Ymi mam Vf* tfwtow OcCMMtlM w C#Nt*ct with Vidyt OWfWl 1 11 11 tact* cwm pd*ym*nrjt'0" umt 2u 3 20 7 14 ft 20 2 Mjmftrttfa oomV<M mtiiif*i(W ;<{ titter ft OfWitor tveiyn 4 22 17 22 ft ft Ucjrxr cpmurn larwrwt *a(r eoolint un>t 3 id* dtww (* rd<nt j*t V6 >1 2ft 4 21 ft 2ft 4 fteadw eitMr fnBwnM> m.,'i|N >cj|r ft faictor dunar oowitw VCM m <ntyrnri(M<ft 1 . ww itHdM WWB ft ftft: t 2i 1 Radar dunv. mmiiMM. mtdM J9 29 2ft 10 IS 10 14 .> apvMar. Mt itawmins ft wta. Annn ta udu(<| I 21 4 1ft 10 All L Journal of Occupational Mtdicine/Vol 20. No 5/May 1978 Oveifv m vex .rs n m OLI 7017 f CMi *> 1 l l 4 5 ft 7 l 9 10 T Ttbu }. -- First Ejioosur*, Y*r ot Oiagnoin, Survival Tiido, Tyo* of Tumor Accompanying flon<gn livor L*5iom and Moans of 01a(nosn of Ton Cosot of Anfiourcami of (ho Livor m 4 Canadian Community Tup* < Olhor LOHflS AccompOrtyuif J Tumor 5 .* _a * 1 ! Fif Expettr* OlHBI Found Survmod Months 4 -ill 1 iI I 1 * 2 Z <3 ? 1J 5 ; h X Is 11 ji is 1! S 1 i1 I 1 at> - <5 >* *01 3,,,PSW 1344 1943 1941 194S 1944 1955 1997 1962 1967 1966 l i 4 8 3 i i .* |3 ii i i 1(t1 1 1 ! 4. v^y . 1 1 * 1 1 4.--^, ii * 1 1 < * 1 iS ,, tot *TOugh fyjn jnefi. i 1. `.csr 13 1947 1946 1961 1946 1993 1971 1977 1973 1974 1976 2 7 8 2 aim* 4 41 1 . 1 1 1 1 i * j 4ta;-cv In 1 i 1 * 1 j = XI. 1 1 1 l 1 > 1 | 4b*xs* I 1 1 1 * 1 i <1 | tu Xll | 1 i 1 i 1 1 * 1 ! 9'OOty 1 the greater oart ot their active iwes working tor the -ame emplover Tne longest period anvone worked outside the plant was four years Once the tumor o diagnosed, the survival period is very short in the present studv, the longest survival period was eight months the average 4 1 months It must he pointed out that angiosarcoma is not tin1 on'.v User pathologv tound in Vinvl chloride monomer workers,1 ' There are two types ot benign lesions -- sclerosis and cellular o.instnrmation Sclerosis manifests itselt by a thickening of the capsu'e of the liver, a portal fibrosis with proliferation of the pile durts and lym phocytic intiltrate a sclerosis or the ss.oil ot the ports1 vein and centroioouiar veins and a pensmusoidai iibrosis with sinusoid dila tation, Cellular transformation shows a sinusoidal cell proliferation with atvpn rissplasu and rear (tonal iiver relk The tumor itclt is a malignant angiosarcoma type tumor appearing in tour dc'inne histological patterns a cavernous pattern, a sinusoidal pattern, a noduio-papiilar pattern and a sarcomatous pattern. In ojr exper ience, the casernous pattern is the most constant and trequent one (Table 3 Discussion The present study is an epidemiological and a histological de scription of the ten cases of angiosarcoma of the liver found in the region of fshawinigan. Quebec. Although the selection ot cases was made from hospital records, it happened that all were men who worked in the same factory -- J vinyl chlorine pi ilymenration plant. This type of tumor being very rare a causal relationship between the exposure to vinyl chloride and the deve ooment or an angiosarcoma of the liver is establisned The present study reveals that the exposure ni-cessarv to develop the cancer must be relatively high. Cleaning reactors and operating production units were occupations carried out m an en vironment with a high concentration of vinyl chloride monomer Furthermore, it is possible that in the 1940's, the men worked more than 40 hours a week. To this, one must add overtime work another contributing factor. It will be necessary to assess witn as much accuracy as possible the exposure of these people to vmvl chloride no-irmer to d:s. over j dose-u*. ji.-v .it .-i-no h tween the chemTal and tee d^ease It seems th.it benign non-:..moral mart nns ,i.-e :v -i'-i . .p.mse ii* liv liver to live ihwnua! fve:' . lilv :h.*v g w iv malignant tran'tormaton' Onv.ouvlv more. a: wit necessarv To iusi over whetner me benig-1 .vorf mal'gnarr: Irs.i are twu -li'iis .a a unique :itvirv ,'nennn .u 1 w. e, 1 * -e .i-i'i.i References I h !( ,, .h .'r 1 .r ;v.!vink *. * or >' i* ` 1ft "x. -1 J Ifi ! : H.trrv H' V ^ I "1 I > H: - -i' .n, *- ' 229 i -"i 4\ 7' ,< : ihl;" '- if! f't '"1,< ittr i i> . `>"1 V.' ,'V) -I '* .......... * i , ' ` Cvni" 3 'f.isr C-'n** #M ' ... 25 rt Cr- i Wft > * 0 m - fi.ioti/.- , nv ^1. /,Q| f 1 ' , _ i9 . I' - ' - , - ) 4 `,<4'4 " M.hkk nrmi- F i>` i ', *i . ( i >ci *vift > :n. ,rt v.nv1 'f3lfi<ji 37 M l.is^ln M ,">!'< ini'f l , 1 t *'l< 'll * " ,, u**-yih* nfn,i \ nv > '* - ' *i* i" i-i" 4 Dfi i/mr f ,ind M<lk< i *'* Ot'.nMs* ;)rr.|imy*- him v itT;, i ,tt .jc . ' -i i'. ci.'lul lil-h i'sn ills f ' *T V- I, I t04 - ' '1 1' > ill'' ' Ilf f .lift! M isk l ' - ,i up- c , o .h rn c'F!ta : p'-rfh**i '>!''.j'i- >*. t. < - < >JQ<` dl'x I's /is V ,ut 119 .`t. ` " ir.i- II Thond' *,8 Ptiprii*' m P'.rnn'.^j *>*;. .oiixm \'Ovi filof \io, K ii t;, * '"s.1 246 _'M-2" ' f`3 12 ThoiTVH lB P**p>-r hl i * ti ^ it>., ^ ' i1 V'st i v- 292 r-22 i- 11 j* Mullpf R *! ,W Ms vrj)f)f lit njv , i-r * * , *- - ^ ,> i t hlofiOt* pfodui tmn am4 246 :ra*:8^ 19-5, -tf*. '' m * 14 M< OondJ.'i R0 PffTWifv c.Kc nnma f) .hf . v' r* 19,7 * 99 *5 M \n<1 rhom,H 18 i.s.s* o\pi)<t*d to vmvl chf/w Vm \ V f >. 24ft "'*4 - 340 Angiosarcoma of the Liver m Shawimgan, Quebec/Ds'crne Tr- ac. OLI 7018