Document x5DYZvLZdEZ4j4YKnjLqE42zQ

Ten Cases of Angiosarcoma of the Liver in Shawinigan, Quebec Fernand Delorme, M.D., and Gille* Theriault, M.D. Ten cases of angiosarcoma of the liver have been diagnosed in Shawinigan, Quebec since 1955. All have occurred in men who worked in a vinyl chloride polymerizing plant. Cigarettes and alcohol do not seem to be associated with this tumor. The amount of vinyl chloride to which these people were etposed, according to information obtained through questionnaires, ap pears elevated. Angiosarcoma of the liver is accompanied by a fibrosis of the liver which may precede its appearance. In de scribing the Canadian case* of angiosarcoma, this study at tempts to shed more light upon the causal relationship be tween vinyl chloride monomer and angiosarcoma of the liver and thus to provide some dues to understanding the patho genesis of this disease. In January 1974. three cases of angiosarcoma of the liver were discovered among workers of a chemical plant.' This finding ap peared abnormal and the agent suspected of being responsible for the disease was identified as vinyl chloride monomer (VCM). Since then, many reports on the occurrence of this cancer among vinyl chloride workers have appeared around the world'" and the Unit ed States Occupational Safety and Health Administration has enacted a new threshold limit value for concentration of this chemical in the air of the working environment* Ten cases of angiosarcoma of the Ever were diagnosed among workers of a vinyl chloride polymerizing plant in Shawinigan. Quebec. This is the largest number of rases ever to take place in a single plant. The pri-sent study dew rihes n<t iip.ilmn.il history, drinking and smoking habits and some histological features of these Canadian cases Data on some nf these Canadian cases jointly with cases of angmsari him from tls* United States have al ready Invn dcscnticd in another arts le by one of the aullmrs' Since more accurate and complete information was retrieved on the Canadian cases, it is being presented separately in the present article._______ tto QsflAitmrfW rrf Pitfotagy OrtMt HtVfMUW* 4* U QsJrhrr Of CVWw**1 And fVftArtmrfti ml Stirfrrwnw ffW IjVil (MntffUy. ()np(t Of fhrrutiifl 338 Methods Case Finding. -- A seart li fm i asi-s of angiosari miu of tlv> User Ivy,inning .is t.u |i. k .is |'iv, and evleitdiitg u\et two dis.ules was earned out hv scrutinizing files of (he regional hospitals in the Shawinigan vicinity. All cases of primary tumors oi the liver were collected and the histological material (slides, biopsy reports, autopsy reports) were reviewed for the present e of angiosarcoma. To confirm the diagnosis of jngiosarenma of the liver, the cases were submitted to consultants from the United Stales familiar with this disease. Occupational History. -- The questionnaires used to obtain a detailed occupational history nf each case culled information i on coming past and present residence, medical history, smoking and drinking liabits along with |iat decollations anti employers in chronological ordec The answers to most of questionnaires \\ ern given by spouses ot the men who died Invn the disease. In one in stance. however, the answers were given bv the sister and brother-in-law. and in another, hy the worker himself. Two former co-workers of fhe men who died of an angiosart oma of the liver confirmed and completed the ^formation obtained through the families. Plant Description. -- The Shawinigan vinyl chloride plant start ed operating m 1943. At that time, it produced and polymerized vinyl chloride monomer, later m the 1950s. it slopped producing VCM and In-pi operating Its- polymeri/alton unit, fist- wmUoue varied InMO 1(g) to 150 winkers Al da- uvunent. n employs 250 men. Prnduc lion of PVC has due tibiled with turn- Present prndorIhhi is rsl Iinalisl at 50 million pounds annuallv I spo-ure to VCM m thp working atmosphere, though not documented, is believed to have been very high m the past Sharp improvement has taken pin e in us enl yeais .mil it is estimated at k*ss thin 1 p|mi at tin* moment. Result* Table 1 show* the age at death, the smoking habits and alcohol consumption lor the ten rases of angiosarcoma ot the liver diag nosed m the Shiwinigan region over On- last two dis .ides All ucc 006428 were male*, the ape at death ranging front 41 In f>1 year* with an averape of SO 5 year*. It is somewlul doubtful llvtt smoking Isas huh It tn do with llns type of tumor. Out of the ten cases, one man was a nonsmokcr. five were moderate smokers, smoking an average of 20 cigarettes or less per day. and the remaining four smoked one pack of cigarettes per day or more. The tumor appeared earlier in tlte moderate and nonsmokers lit age 47 years) than in the heavy smokers ix 54 years'. The men who developed an angiosarcoma of the liver were very light drinkers. Only two men out of ten drank more than one bottle of brer |>er day. None of it*' ten men drank wine nr luymr regularly. As with cigarette smoking, drinking does not appear to be associated with an angiosarcoma of the liver in vinyl chloride workers. Past diseases of the liver mav also be ruled out as potentiating the development of angiosarcoma of the liver since the medical history of the ten cases showed no previous liver diseases nor hepatic troubles. Table 2 shows the length of time the men were exposed to vinyl chloride oitlx'r hv working in |U> polymerization unit or by being directly exposed to vinyl chloride. It also shows the occupa tions they performed and whether they worked overtime. They worked for (Winds ranging from 11 to 20 years in the plant with an average of 21 years and 4 monlln Direst exposure In vinyl ihlnride monomer w.w obviously Oioftcr lunging Horn 4 \i\irS \ mooli*, lo 2t< seals wills an .isei.ige ol In sc.ii- 10 moollsv. i f t >in I In |uts ill*i options n i an he seen Out most of die men worked either as operators or maintenance workers, or both. Seven men worked as "reactor cleaners." an operation which seems to have been the worst in exposing people to vinyl chloride monomer. One svom.es said ol let Isusls.usd's expunge. 'He svent down into the autoclaves nvmy limes. Once, they Iwd to fake him out unconscious." It is difficult to get a fair idea of I he amount of vinyl thloride monomer to which these |ienpk' were exposed. Many spouses (six no! iif hut insishxl u|xhs uexilHHiiog lliil llvir leisKeids worlu-d overtime. As shown in Table V liv' time elapsrxf between the first ex* isosure to vinyl chloride monomer and (he diagnosis ol tlx* disease ranges from 11 years to 28 years svilh an average of 20 5 years. This concurs with previous findings that .in angiosarcoma ol the liver can develop after a minimum exposure of four years, but that actual manifestation does not occur for at least ten years * Residence Ixxtnrv rcie.tkxf tlvit .ill winkers lived wiilnn a bvo mile radkis id llie VCM plant sime tlx- liegumiug ui llx-ir empluyment at tKlt plant. Ilnwex-er. no particular p.utixn in the residen tial history could be idixitified that could lead to finding environ mental factors common to everyone I'.wt iKiupation.il Ixxlixv xlxmixl iKlI all llx-se woikeis s|hxi( ucc 006429 the greater part of tlx'ir active lives working (or tlx' same em ployer. The longest period anyone worked outside the plant was four years. Once the tumor is diagnosed, the survival period is very short. In the present study, the longest survival period was eight months, the average 4,1 months. It must be painted out that angiosarcoma is not the only liver pathology found in vinyl chloride monomer workers.' 10 There are two types of benign lesions -- sclerosis and cellular transforma tion. Sclerosis manifests itself bv a thickening of the capsule of the liver, a portal fibrosis with proliferation of the hilo ducts and lym phocytic infiltrate, a sclerosis of the wall of the portal vein and centrolobular veins and a perisinusoidal fibrosis with sinusoid dila tation. Cellular transformation shows a sinusoidal cell proliferation with atypic, dysplasic and reactional liver cells. The tumor itself is a malignant angiosarcoma type tumor appearing in four definite histological patterns: a cavernous pattern, a sinusoidal pattern, a nodulo-papillar pattern and a sarcomatous pattern. In our exper ience. the cavernous pattern is the most constant and frequent one (Table 3). Discussion The present study is an epidemiological and a histokigical de scription of the ten cases of angiosarcoma of the liver found in the region of Shawinigan. Quebec. Although the selection of cases was made from hospital records, it happened that all were men who worked in the same factory -- a vinyl chloride polymeriza tion plant. This type of tumor being very rare, a causal relationship between tlx? exposure to vinyl chloride and rivet development of an angiosarcoma of the liver is established. The prescml study reveals (hat the exposure necessary to develop the cancer must be relatively high. Cleaning reactors and operating production units were occupations carried out in an en vironment with a High concentration of vinyl chloride monomer. Furthermore, it is possible that io tlx* 1040's, tlx- men worked more than 40 hours a sveek. To this, one must add overtime wink, another contributing factor It will be necessary to assess with as much accuracy as possible the exposure of these people to vinyl tliloikfe monomer to discover a dose-response rclationsixp be tween the chemical and the disease. It seems that benign noo-tumoral reactions are the first re sponse of the liver to I lx- iIximicAl. Eventually 11x7 give way to malignant transformations''" Obviously, more studies will he necessary to discover wlx'ther the benign and malignant lesions are two steps of a unique phenomenon or two different diseases. Reference* I Creech It and kihrise MM: AixtitixarnxiM d Nwr in (hi- manufasture <4 pnlwtnvl rhlixxte HIM 1* 19(1-191 l'>74 4. I is- (I ,iixl limy MS' AngHuuistia x tlx- liver m a vim-l t UikmIt Wtxkis I,unit IIlieIIIX. Iixx- 29. 1974, 3. (Dock, Bradford |: Angiosarcoma n< the liver fnllnwmg vinyl chloride e\|Mo MW-t 229 91-94 |*r,| 4. Kcty I, Sairv.ige, ruailksv ,xxt Maltrarrl A: le tx'mc ias tram .its dangiosarcnme hepatxyje ehei os nuvoer du chlorure de vinyle. Arch Wal Prnt 9*1-**$, 12 Afe, 197V V Center ft# Oisrsise Conlrtl. Mndxrfciy .uxl MlI,liny, Weekly Xc|xxl. 2*011:1-2. Feb 197b 6. Department of labor. Oi rupalitcMl Safeiv and Health Administration.' Exposure of vinyl chloride Federal Aeipurr 2*11941:3*890-1*898. Part II. Oct 4. 1974. 7 Makk l. Delorme F. et .4 Ctirxrai and mrxphuhigH' kiXins (4 hefMtic angmsautxna m viiwl ihliitik- ssixkcrx ( .tutu 37 | I'l IM, 19*11 8, (as/lst M. IkSrite I h al ( linn at aixl m.-Iliv4-VM le.ilixi-s -a hr|Mln angirnau nma hi vinvl iiarvek- wiHkrss (ansis 37111 kin 197b. 9, Di-iivmo f ,xxl hlakk I Angm-aii ixne du fine i he/ ho ixnrx-rs avanl etc on contact pn4nnge avis- le i hlerixe ik- vtnvte Oescri|Xmn mnrpholoRiiyie til's tesmns I'rwrvi Ml-'a C.mj'ii 104 814.841 t97* 10 Delivme F and M.ikk I - Angtosau ixne rlst true i hr/ ho ixivrx-tx avant cte en contact prefnnge aver te chlrrure de vmvle Descupunn morpbohigiryx' rk`S lesxxH Kniir bant g.nirr-nt It* May t97b It tlwnnax Ift ,irxl PisSvi It r.itU4i gy '* angHtsarriHna r4 itx> Itvrs among vinyl < l4<Kh"|4yviiiyl . 14-vvh- wuhi-fs Arm NY Ai mI In 24V2bH-277, 1979 12 ilvvnas 18. Piygns It el al1 V.nvi-thbvvir-HxiiH111 faset disease New Fngl / \fcyf 292 17-22. 197* II Orhgh P. Muller 8. et al Motf4x4<x;y t4 liws damage among poly- vinvl i Minnie |viskx Ihhs wiskiss A itpri m 91 i JM' .Suit M Aialki 24* 3*8.289. 19*9 14 Mi lVuki KK I'intM'V t Ait *4 tW kwi \< H JtM U'<( W JWv 27*1. 15 r(|fi|irr H sirtri rhiwM.w IH i* In** ,iml *|iU**> |fi vinvl chlnrwV Ann M\ 4.rl Si 246 I47S 340 Angiosarcoma of the liver in Shavnmgan. Quebec/Deiorme and Theriault ucc 006430