Document MGDB1YLZxrekx1kbeEqXXeXvy
177 r
RECEIVED JUN^r 197Q
Wt C KURYLA
RSCEIVED JUN 0 8 1978 R. N, WHEELER, jRm
Ten Cases of Angiosarcoma of
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the Liver in Shawinigan, Quebec
Fernand Delorme, M.D., and Gllles Thdrlaull, M.D.
Ten cam of angiosarcoma of the liver have been diagnosed in Shawinigan, Quebec since 1955. AU have occurred in men who worked in a vinyl chloride polymerizing plant. Cigarettes and alcohol do not seem to be associated- with tMs tumor. The ^amount of vinyl chloride to which these peoplg-were exposed, ' ^according to information obtained through questionnaires, ap> - pears elevated. Angiosarcoma of the liver.ls accompanied by a
4 "f fflbrosis of the liver which may precede Hs appcarance. In de scribing the Canadian cases of angiosarcoma, tMs study at/ '?v`tempts- to shed more light upon the causal relationship be^tween vinyl chloride monomer and angiosarcoma of the Hver - '"-andthus to provide some clues to understanding the patho genesis of this disease.
\ " Itv January 1974, three cases of angiosarcoma of the liver were
discovered among workers of a chernic^ plant,' This finding ap> ' peered 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 world1** 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 liver were diagnosed among workers of a vinyl chloride polymerizing plant in Shawinigan. Quebec. This is the largest number of cases ever to take place in a single plant The present study describes occupational history, drinking and smoking habits and some histological features of these Canadian cases. Data on some of these Canadian cases jointly with cases of angiosarcoma from the United States have al ready been described in another article by one of the authors.1 , Since more accurate and complete information was retrieved on the Canadian cases, it is being presented separately in the present article.
From tht Ofpvtmtm of Fithotogy, Cemi* HofpiuSar xvfiwva dt Is Mint Stuwvilgin. Quatuc Pf Dtfcnm) mi tho Ovpiftnwm of Socaf xnd PnunUw MwS. cino. tavaf Unfnnfcy. Sttdoy. Qusbac Dr. ThoriMU.
Methods Case Finding. -- A search for cases of angiosarcoma of the liver
beginning as far back as 1955 and extending over two decades,\
was carried out by scrutinizing files of,the raaionatbosp'*-1"**--- Shawinigan vicinity. All cases of primary tumwTofrine tiverwere
collected and the histological material (slides, , biopsy-reports.,
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autopsy reports) were reviewed for the presencootangiosarcoma^, K, . To confirm the diagnosis of angiosarcoma oftlw liver;. th|asees^y .
were submitted to consultants from the United States'familira^ith&y.
this disease. Occupational History, -- The questionnaires used- to obtairva^v-
detailed occupational history of each case culled information'eon-*-.%
cerning past and present residence. medicai history..SrT>oking andVV drinking habits along with past occupations^andsemployjgs^jni chronological order. The answers to most-of questfennaireswveft*, given by spouses of the men who died from thedisease.In' cineip-H
stance, however, the answers were given by the sistew and-0, brother-in-law, and in another, by the worker himself.-Two former co-workers of the men who died of an.angiosarcoma of the'liver
confirmed and completed the information obtained-through:the families.
-
Plant Description. -- The Shawinigan vinyl chloride plant start ed operating in 1945. At that time, it produced and polymerized vinyl chloride monomer. Later in the 1950s, it stopped producing VCM and kept operating the polymerization unit. The workforce . varied from 100 to 350 workers. At the moment it employs 250 men. Production of PVC has fluctuated with time- Present/productkm is estimated at 50 million pounds annually. Exposure to VCMin the working atmosphere, though not documented, is believed - :-
to have been very high in the past. Sharp improvement has taken
place in recent years and it is estimated at less than 3 ppm at the
Results Table 1 shows the age at death, the smoking habits and alcohol
consumption for the ten cases of angiosarcoma of the liver diag nosed in the Shawinigan region over the last two decades. All
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were males, the age at death ranging from 41 to 61 years with an average of 50.S years.
It is somewhat doubtful that smoking has much to do with this type of tumor. Out of the ten cases, one man was a nonsmoker, 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 the moderate and nonsmokers (x 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 beer per day. None of the ten men drank wine or liquor 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 may 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 either by working in the 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 periods ranging from 11 to 29 years in the plant with an average of 21 years and 4 months. Direct exposure to vinyl
chloride monomer was obviously shorter, ranging from 5 years 3 months to 26 years with an average of 16 years 10 months.
From the job descriptions, it can be seen that most of the 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 woman said of her husband's exposure. "He went down into the autoclaves many times. Once, they had to take him out unconscious."
It is difficult to get a fair idea of- the amount of vinyl chloride monomer to which these people were exposed. Many spouses (six out of ten) insisted upon mentioning that their husbands worked overtime.
As shown in Table 3. the time elapsed between the first ex posure to vinyl chloride monomer and the diagnosis of the disease ranges from 11 years to 28 years with an average of 20.5 years. This concurs with previous findings that an angiosarcoma of the liver can develop after a minimum exposure of four years, but that actual manifestation does not occur for at least ten years.*
Residence history revealed that all workers lived within a two mile radius of the VCM plant since the beginning of their employ ment at that plant. However, no particular pattern in the residen tial history could be identified that could lead to finding environ mental factors common to everyone.
Past occupational history showed ttat all these workers spent
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** TabU 3. -- Flnt Exposure, Yoor of Witwoilx, SurvHrel Timo, Typo of Tumor, Accompanyinf Booty Uvor Lotiom, tod
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the greater part of their active live* working for the 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 pointed out that angiosarcoma is not the only liver pathology found in vinyl chloride monomer workers.1 ,# There are two types of benign lesions -- sclerosis and cellular transforma tion. Sclerosis manifests itself by a thickening of the capsule of the liver, a portal fibrosis with proliferation of the bile 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 histological de
scription of the ten case* 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 the exposure to vinyl chloride and the development of an angiosarcoma of the liver is established.
The present study reveals that 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 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 with as much accuracy as possible the exposure of these people to vinyl
chloride monomer to discover a dose-response relationship be tween the chemical and the disease.
It seems that benign non-tumoral reactions are the first re sponse of the liver to the chemical. Eventually they give way to
malignant transformations.''" Obviously, more studies will be
necessary to discover whether the benign and malignant lesions
are two steps of a unique phenomenon or two different diseases.
References
1. Creech |L and Ichnson MN: Angiosarcoma of liver in the manufacture of polyvinyl chloride /OM 16:150-151. 1974.
2. Lee FI and Harry OS: Angiosarcoma of the liver in a vinyl chloride worker, tancor 1J16-1.118. luno 29, 1974
3. Sock. Bradford I: Angiosarcoma of the liver following vinyl chloride exposure. IAKIA 229:51-54. 1974.
4. Rfty I. Sauvage. Tuaillon. and Habrard A: Le lieme cas francais d'angiosarcome hepalique chez un owner du chlorure de vinyle. Arch Mil Pro) 551-555, 12 die, 1975.
5. Center for Disease Control. Morbidity and Mortality. Weekly Report. 25(81:1*2. Feb 1976
6. Department of Labor. Occupational Safety and Health Administration: Exposure of vinyl chloride. Fedpraf Register 3911941:35890-15898. Part II. Oct 4, 1974.
7. Makk L Delorme F. et al: Clinical and morphologic features of hepatic angiosarcoma m vinyl chloride workers. Cancer 37-149-163. 1976.
8. Laszio M. Delorme F. et al: Clinical and morphologic features of hepatic angiosarcoma in vinyl chloride workers Cancer 3711). Ian 1976
9. Delorme F and Makk L: Angiosarrome du foie chez les owners ayant 4t4 en contact prolong^ avec le chlorure de vinyle. Description morphoiogique del lesions. Urnan Med Cimdl 104 834-841. 1975.
10. Delorme F and Makk l: Anginsarcnme du fne chez les owners ayant etrf en contact prolong^ avec le chlorure de vinyle. Description morpholagique des lesions. Revue franc gasimenr 119 May 1976,
11 Thomas 18 and Popper H- Pathology of angiosarcoma of the liver among vinyl chlonde-pnlyvinyl chloride workers Ann NY Acid Sri 246:268-277. 1975.
12. Thomas LB. Popper H. et al: Vinyl-chlonde-mduced liver disease. New Fngl I Ucd 292:17-22. 1975.
13 Cedigk P. Muller R. et al: Morphology of liver damage among poly vinyl chloride production wcxkers. A report on 51 cases. Ann NY Acid So 246:278-285. 1975.
14. McDonald RB: Primary carcinoma of the liver. Arch Ini Med 99:266279. 1957.
15 Popper H and Thomas LB- Alterations ol liver and spleen among workers exposed to vinyl chloride Ann NY Acid Sri 246-172-194. 1975
340 Angiosarcoma of the Liver in Shawinigan. Quebec/Delorme and Theriault
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