Document MJv9X768rwOK63450doGw9Zv9
R&S 106053
BIO-MEDICAL.RESEARCH DOCUMENT DESCRIPTION FORM
6368 6976
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I 1 0000033
year as-1961- File number
[Right justify
[Numeric only]
77 78
Sub-Index Code
Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space
1 20 2140
41__________________________ 60
L/r'ZsKn.f?
0. .47VtCdT /l
{f7Y, J
61 62
Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms, separated from each other with comma-space. Avoid other punctuation;
Source (Journal, Vol., Number, Pages, Date) 12
Yiv' YY?f
Brief Summary
12
10
SUMMARY:
61 62 31 32
61 62 61 62 63 64
'ir^ypo Box No 6
-v
.Bessemer Road
" i" Welwyn Garden City Hertfordshire AL7 1HD
VV- '
iV
Telephone Welwyn Garden 23400 (STD Code 07073)
Telex 264251
Imperial Chemical Industries Limited
From
J Stafford Division Manager
Health & Environment Protection
Plastics Division
To Dr W G F Adams Dr D P Duffield Dr J T Carter Dr D W Plester Mr G J Sleddon Dr F W Best Dr G Paddle JS(6)
Copies to
Dr D Douglas, EMAS Dr P Baxter, EMAS Dr T R Torkelson, Dow Dr M N Johnson, BFG
Your ref.
Our ref
Tel ext
Date
JS/MJE/DS0-107
3162
2 February 1979
FRENCH ASL CASES
With my letter of 1 November 1978 I gave some of you a photocopy of a paper by the French Works Medical Officers of the ten ASL cases so far encountered in France. I said that when things were a bit quieter I would do some rough translation. Now the French are up to eleven ASL cases I thought I had better get on with it. I do apologise, it is a very rough translation and probably medically inexact. X did not translate the tables which I think will be quite clear to all of you.
!I
R&S 106054
Encs ' J?^ ` "
R&S 106055
000003Q
TEN CASES OF LIVER ANGIOSARCOMA EXPERIENCED IN WORKERS EXPOSED TO VCM
******
PAPER PRESENTED TO THE 19TH INTERNATIONAL OCCUPATIONAL MEDICINE CONFERENCE AT DUBROVNIK ON 28 SEPTEMBER 1978 BY : DRS J BERROD - P LAZARD - C PIERRE -AM PUECH - E RAVIER -
J RETY - G SMAGGHE -
******
V; 1
At the end of the Viola and Maltoni experiments the publication of the^ evidence of the carcinogenic action of VCM and particularly the induction of ASL by this chemical agent led, as one might expect, to a large number of studies, particularly experimental studies.
The Works Medical Doctors found themselves, however, confronted in their factory activities by practical problems of surveillance and prevention.
It seemed likely that a worker newly recruited into the factories would be exposed only to a very small risk as a result of the effective technical measure taken during the past few years. But a considerable number of workers still employed in the factory or retired had been exposed for a number of years to concentrations of VCM which in former times seemed harmless but which in the light of recent information seemed possible agents for the induction of angiosarcomas.
Knowing the evolution of this disease, it can seem fruitless to interest oneself in finding means of early detection of ASL.
Nevertheless, we have been able to observe the case of a patient having undergone a surgical intervention with a survival of about two years, although the diagnosis had only been taken to the stage of clinically detectable lesions.
Without ignoring the many fold and well known difficulties of cancer therapy, we consider that it is not useless to try to discover as early as possible an ASL lesion and allow the different skilled specialists to give an efficient therapy.
With this in mind we have applied ourselves to the detailed study of the ten cases of ASL diagnosed in France in workers exposed to VCM.
It is not possible for us, of course, in the time available to look in detail at the observations which consist of the precise data on previous occupation, clinical history, the results of various practical examinations, therapies, the results of anatomo-pathological examinations, etc. We can communicate these data to anyone in the audience interested if they should wish.
We have assembled in the tables the principal elements in our observations to try to display the relevant data leading up to our surmise of a diagnosis.
We hope that these tables will be sufficiently legible and we will comment on them briefly.
Table No 1
Table No 1 shows that the ten cases studied were all exposed for a long time at high concentrations (11 years minimum and most of the time cleaners of autoclaves or polymerisation workers) the youngest case being 38 yrs and the oldest case 62 yrs : in processes of making emulsion, suspension and mass PVC).
It should be noted that case no 1 was diagnosed in 1967 and that tie was found again as a result of an epid miological study conducted in our ; factories;- :Th ^-diagnosis has-beenconfirm d histo-pathologically ini--the t n^cases*
30
Ui
a
at
0 01 O)
Table No 2
In Table No 2 we have gathered together previous history and tried to enumerate clinical symptoms from the first appearance.
We would point out in this comparison one case only (No 4) with a record of alcohol intake and consequent hepatic troubles(?), one case (No 7) with an indisputable acro-osteolysis one year before the discovery of the ASL, one case (No 9) which presented itself after biological tests 4 years previously had shown a transitory increase of alkaline phosphatase and jaundice. Finally, in Case No 5 it was the fortuitous discovery of an angiosarcomatose costal tumour which led the works doctor to ask a specialist to look systematically for an ASL.
This table displays the poverty of clinical signs of the initiation of trouble, the initial symptoms often being either an acute or haemorrhagic phenomenon or a rapid loss of weight accompanied by debility.
In the majority of cases at the time of diagnosis the liver appears augmented in volume (8 times out of 10) and the spleen was also clinically enlarged (7 cases out of 10).
Table No 3 37 --------------------
to Table No 3 lists the complementary practical examinations, eg scintigraphy laparoscopy and arteriography. In most cases the appearance of abnormal pictures of the right lobe and the good reproducability of these examinations which are in a good state of practical evolution reinforces clinical suspicions which are already strong.
^S090i
Table No 4
Table No 4 indicates to us that in a number of cases the haemorrhagic symptoms are a characteristic of the evolution of the disease (6 out of 10). Th treatment has been surgical in all the cases.
In one case there was an exploratory laparotomy; in the other cases a s gmentary hepatectomy, a multi segmentary hepatectomy or right lobe. tw nty month survival in Case No 9 is to be noted.
A
Furthermore one must note that Case No 7 survived thirteen months aft r the removal of a hematsmisis(?) resulting from a local haemorrage near th angiosarcoma.
Radiotherapy was used in association with surgical treatment in one cas only (No 8). In Case No 5 radiotherapy was done locally near the bony lesion.
Table No 5
Table No 5 gives the histopathological data. One must note the spongy aspect of the lesions in five cases, sinusoidal in four cases, papillary in two cases and massive in two cases.
Th non-cancerous fibrosis of .the parenchyma is weak in five cases, much
mor marked in one case (No 4), The xtent of the lesion is in general very local (Nos 1,3,6, 7 and 8) it is bony (costal) in Case No 5 which is
th only case in our obs rvations wh r on has had any vidence. of
metastasis.
^
' y-\ ,
3
Table No 7
Table No 7 is confined to Case No 10. This case was found diagnostically at the beginning of this year. His medical dossier comprises a series of examinations which we have displayed.
It is notable that the alkaline phosphatase is raised (10.4 units against a normal of 3 units) and a bilirubin of 12 mg/litre (N 10 mg) only one
month after hospitalisation with normal transaminases and normal alpha-foeto protein (6.5 - N 15). The alkaline phosphatase stayed high on 3 January 1978 (one month afterwards) the transaminases were always normal and stayed so three days before surgical intervention. They only seemed high (15/ and 113 units against a normal 40) on the day of the surgical operation.
Anaemia with 3.4m hematocytes appeared only on the 7th January with a normal number of thrombocytes (day of operation).
At this time arteriography had already shown an irregularity on the right lobe and scintigraphy had shown three very sharp lacunae. The slides which we will now show you show the extent of the lesions in some sections from the operation.
This example highlights the difficulty if not the impossibility of early diagnosis solely by biological investigations and the study of the ten cases has served to reinforce this impression.
Scintigraphy, arteriography, laparoscopy, even laparotomy are certainly more precise techniques, but in the range of our diagnostic tools can only be the exceptional method of investigation and not without risk.
That is why we are now turning our studies towards ultrasonography.
This test, which has the merit of being well accepted by the patients, does not carry any additional risks and seems to be capable as the technique progresses to disclose abnormal pictures with good resolution in the liver parenchyma, and seems to us capable of giving valuable information to a early diagnosis and in conjunction with biological examinations limits the number of patients who must be exposed to diagnostic techniques which are more invasive and risky.
31 (/) o oo> U1 00
J Stafford
JS/MJE/DS0-107 2 February 1979
Tableau I
CA3 DATE DF NAISSANCE
N 1 15.4.24
EXPOSITION
ANNEES
AU C.V.M. lcre EXPOSITION ANNEEIj
DEC RE
DATE DU DATE DU
DE A AU DIAGNOSTIC EXPOSITION' EXPOSITION DIAGNOSTIC DECES
1946 19 67
21
19
+++
19.2.67 19.2.67
(etude dpi
ddmi o.
anr.path.)
ACS ET SITUATION AU DECES
43 (a)
ENPLOI Conducteur-ddcroQtcur
fN0 2 i i-------Is" 3
1
3.6.11 6.1.20
i | N 4` 27.1.27
1959 197 1 194 6 1975 1949 1975
N*> 5 29.1.38
1965 1976
16 29
26 11
12
-H-+
1975
24.1.75 63 (r)
Polymerisation
(anapath.)
29
+++
15. 1.75 26.6.75 55 (a)
Decroutcur (JO ana)
(anapath. )
Synthesc cu CV (16 ans)
Compounds (3 ans)
26
+-H-
'16.1.76 3.1.76
49 (a) Synthase du CV (3 ans)
(autopsie)
Filtration du PCV (18 ar.s)
"rfTtaJT
11
+++
autopsie 13.5.76
Conducteur (10 ans)
j
DdcroGceur (1 an)
N 6 26.4.27
1950 1972
26
22.
+-H-
autopsie
2.7.76 49 (m)
Polymerisation
(Agent de Maitrise)
N<> 7 14.4.34
1958 1971
18
13
-H-
12.9.76
12.9.76 42 (a)
Polymerisation
(autopsie)
N 8 1.4.34
, _____^ N 9 8.10,14
1957 197 6 1943 1976
N10 24.5.19
1956 1977
19 28 ' 21
19
++
1. 12.76 30.1.7/ 43 (a)
DecroQteur
(anapath.)
Conducteur
28
+++
26.4.76 25.12.7 ,7 62 (a)
Polymerisation
(anapath.)
2: T++
1.73
20.1.78 | 58 (a)
Decroutcur
(anapath.)
Conducteur
a = activitd
r = retraitd m = m
gg090L S'SU
Tableau II : antecedents .S^^^DRiatologic initlalc
DU SEE CAS O'
EXPOSITION
ETHYLISHE
OLf
. ANTECEDENTS
ANTECEDENTS
IlEPATLQUES
MODE DE DEBUT S ynp t otre rave1 aLcur
AUTS.ES ST.CNES FONCTIONNELS
FOIE
RATE
STONES PUYSTOUES 1
ASCITE ICTE^
TUT: EUR PALPABLE
1 19
0
Cephalccs Hepatomjgalie
llcmoper Itoune
Murphy +
-
+ --
-
2 12 .
3 29
4 26
i 4...
5
11
6 12 7 13 8- 19 9 28
10 2S
0
Castrectomie
Douleur hypo-
(u Lcus)
dre droit
Ecctorragics
Anemic
T 4-
+
0 \ Ulcere duodenal ........................1
Masse doulourcusc epl-
gastrique
Amal gr i s s craer. t 12 Kg cn 6 mois
JL
-
-
++ i' Etat genera'
Douleur hypo-
-
-4-
+
condrc droit
a un oxam.cn
systenatique
Accident de
A.n"i osaeccmc
trav.
os seux
311. 12 a 15mg/
1 un an avant
-
--
-
0
FibrLllatLon Tableau de ventriculairc cholecystite
Amaigrisscmcnt Anorexic.Astheni e
+
--
T a 3S
- Ac r o - os t e o ly r. e Syndrome dou Defense cpigas-
inclocnas 1 an loureux nscu- trique.
- --
avant
do perforatif T a 378
-
Valvulltc mitrt Nauseas post
a or t it[uc
prandlalcs
-
+ *T -
,1 Contusion hypo- Douleur hypo-
chondrc drt.
chondre droit
Atnaigrlssenent T a 37 5-3S
+
' i subicterc PA
A ans avant
--
0
Cure de hernia Asthenic
Amaigrisscmcnt
+
+
0
inguinale g.
3 Kg en 3 sc::i.
HTA (1976)
Pcsantcur epiga 5
Taenias
trique.
090901 SSU
-
-+
+
Subictcre au debut
--
0 Hcpa tome galic rdguliere.
SCINTIGRAPHIC
- LAPAROSCOPIC
arteriqcraphie
F0I K
:------------------(
CAS
FIXATION
MAS si:
F.EPATO HTP RATE
N Local is a Li. on SPLEN IQUE TUMORALE Mi:CALIE
1 M'. lade decade avant tout cxnme comp lorficntaire
2 ..IC'J ncs Lobe droit + Foie masque par das
ir,u Iti-
ndhcrcnccs
11 c r,
3 2 La- Lobe droit cures
Non faite.
SW DROME TUMORAL
HYPER VASCULA
GENE AU RETOUM
ARTECL DILATA HEPATI TION AR
RATE
LOCALISATION RISATICN VEINEUX QUE
TERE S?LE
+ Lobe droit
1
issue dt 1 'AMS
4
+
4
Lobe droit
4
+ D^N
-f-
C=CrSlc
A K on f a i t c
' 5 1 la cuna
Lobe droit
+
+
4
+
+ diffus
-F 1 +
dilatee
!+
+
-
-
+
- Lobe droit
Jl.
44
0* 1 la cuna
Lobe droit
4 +-
(masse)
+
Lobe droit
+
7 Nor. faite
Non faite
+
Lobe droit
+
4+
S Hetdroger.e
DiEfus
9 2 la Lobe droit cunas
+++
Pas dc doruices
+
JL.
Lobe droit
+ +
10 3 la Lobe droit cunas ,
+4
+ Lobe droit
Tableau I [I : cxnr ens c TOD ICD entaircs
i
0
4
I
1.90901 S'SH
Tableau-IV '.evolution
CAS EVOLUTION 1
TUAITDIENT
Chtrurgic llepat.eecomic droitc
Chi r.viothernpic!
Radiotnernolc
SURVIE 1 j ou r
DECES post-operatorre
2 Hemopcrltolnc
Ilepatectomic droitc Sp k'.ncctomle
3 mois
Hemorragrcs digestives Coma hepatique
3 Me locnas
1) L.eeresc tumeur 2) Resection duodena-
lc et antrectomic
A 11 erne to me sc
Hep.itcctomlc droitc
Syndrome oedema to S p lencctomic
asciiiquc
Cool eey:; t cc t o;:iie
5 l'.cr.opu r i t olnc
Keparcccomic droitc S plencctomic Cholecysccc Cotale
6 Teat general Masse droitc Septicemic
Hcpatcctomlc segr.'.entnirc
7 Etat general Amaigrissemcnt Evacuation hematome 0 ou 1 on r s a bd er.'.i I'.alcs violences Hemorragies digestives
8 Ascrtc-Uenor-
Laparotomic
ragics (rector- exploratrice
ragies)
Denutrition
9 Fistulc biliairt Ilepatectomic pluri-
a la pcau puis
segmentaire
fistulc bilio-
brcnchiqwe
10 EmboLte pultno- Ilepatectomic droitc
naire
Cholecystectomic
Surrcnalectomic
droitc
+ + +
6 mois 1
3 mois
Coma hepatique Hcr.orragles digestives
4- pour
8 nois
tumeur osscusc
6 mois
Choc Heir.orragies internes
Coma hepatique Septicemic
13 mois
Remorragics digestives Fistulisation a la pcau
+ ( 1 OCO rads)
3 mois
20 mois
Hemcrragie digestive
Post-operatoire apras fistulc bilio-brcnchique operce 20 mois cores la lere intervention.
10 Jour- ; Embolic pulmonairc
! | 29090. s?y
Tableau V : Anut-rno-pathologic
.. A*) 10 L E JO Poles
TUMEllR ( f ocner, )
i inus oi
C*1 *.i Li ij J.
dale
La ire neu r,cr. VC5
1
2 16l0g +
++
PARHNCHYM
tumoral
F.paissis-serpent cap * ibrosc
IK Lata- Cellules tion si- ondothelie
s ill--lire
.ni: 3 ol des ) f* ~ f* vn i f
RATO
.EXTENSION
\/cinc cave
+
+ HT?
0
G. CHI RLT.GICALE AUTO ?3 IE diagnostic pr: sitif -f-r
-H-
+"f +
3 <4 2230c
+
+
+
++
+
+
++ +
Duodenum
+ HTP
0
400g
4-r
+
"f-r
5 COO g lobe droit
6
+ + + + HT? 0 s s eu r, e +4* 650c surrerta le
t gauche
h + +
peu
+
Grcle
+
-H-
irr.portantc
7 1750E
++
+ PeLiose +
HTP '
Oiaphragr.e colon paroi abdominale
++
8 3000c
donnecs insufflsanLcs
270S Ganglions aortiques
++
+
9 'y. +
10 V
;-1p5ieCcOeg
oxeresc )
s>
-+
(+)+ +
+
+
-H-
++ H-
90901 SSU
DATES 21.11.79
Tableau VI : Surveillance h^matologiquc CAS N 10 (do I979al97S)
CR Hgb VCfl LEUCO PN
EO
BASO
LYiSPKO
MONO ' KYELO
META MYELO
TR0M20 CYTES
VS 1 K
9,2 13,9 93 5 300 29
6
0 99 12
'I 0 215 CCO
6
19.1.76
9,59 19,9 99 5 700 54 i
0 39 11
- - 160 000 2
26.10.76
9,36 13.8 99 6 700 9 8
3
0 39 10
- - 220 OCO 3
1.12.77 '
9,29 13,5
- 10600 51
2
7.1.78
3,6
(3 jours avant intervention)
l
10,3
10900
0 j 39 1
13
--
-
-
fr90901- S$a
DATES
Tableau VII : Surveillance Eiologique CAS N 10 (de 1974 a 1978)
-------------
TOTALE .ILIRUBIK : p.a.
ir-g/l
-----
S.C.O.T S.G.P.T.
ELECTROPFiORESE PROTEINES
LDH
--
i
GT
OCT
FOE TO PROTEIMES
21'. 11.74
7
-
28'
16
Norma *.e
-
-
-
N 19
N 19
19.1,76 7 66 10 7
- ---
N 85
N 19
N 19
-
-
26.10.76
1.12.77 3.1.78 7.1.78 10.1.78
6
68 6
-
162 15
11
-
N 65
N 19
N 19
K:
96/240 N 28
N 10
i
12
10,4 UB
29
34 CONSULTATION- noui . .
6,5 ~.g
N3
N 40
N 40
svr.nto::: ; r. o l os i c <. le debut aoparent
N 15
____________________________
4
11.2 UB
17
21
-
N3
N 40
N 40
4
t
-
-
1 i
i.
!
--
21 23
KB : 3 jours avc nt inter vention cl 'irurgicale
1
N 40
N 40
i
i
i
-
157 .
113
KB : Joe r de l'in terventi on chirur;,'icale
N 40 N 40
S9090I. S$d