Document M44YQM4g7z1popkKwJGBwev9

ANGIOSARCOMA OF THE HUMAN LIVER i'or tr.e same tumor are to be found in the literature. 1. Hbmangio-enuothelial Sarcoma * 2. raiignant vasouxar tumor of the liver 3. Kupffer Cell Sarcoma ' 4. Hemangioendothelioma 5. Hemangioblastoma 6. Endothelioblastoma 7. Raticuloe ndothelicra (Purdy Stout) 8,. Angioplastic Sarcoma 9. Primary Hepatic' Sarcoma 10. Angioolastic Sarcoma 11. Endothelioma, grades,-undifferentiated, well differ'ar,4`'? and anaplastic. 12. Hemangiosarcoma 13. t&lignant Hemangiosarcoma 14. Malignant Hemangioendothelioma 15.Metastasizing Hemangioma C Historically there`are many reasons for the above fence sitting type of terminology. In 1940 James Ewing reports in his textbook nn "Neoplastic Disease" quote: "I do not believe, therefore* that the existence of a true angiosarcoma arising from blood vessels of the liver has been satisfactorily demonstrated." As late as 1948. Rupert A. Willis in his texibook on FATHOLOGY OF TUMORS states. " We cone now to a difficult question;, Do truly neoplastic angiomatous growths occur? They are very rare and most supposed examples are either irxLtifrcal hamartomas or vascular tumors of other kinds. ! i DTH 00001 ( f I' iyol- Tu.'iiijrrf of Li.u Li\ viaulw.ij Wx t Thoratrast. Suckow, E.G., Henegar, G.E., and Baserza_, R. Am. Journal oi' i-atnology. Vol. ju: acj--oV y. due to thoratras.t used intravascular!!./. The latency periods were 3 to It yeais with the average 15 years. I965----- Malignancy XnD other Late Effects Following the Administration of Thoratrast. Da Silva Horta, J. et al.: . Lancet 2: 201--205. 22 Atd'ditional cases of Angiosarcoma tii of the Liver were'reported in this article. 3y this time hundreds of cases of angiosarcona of the liver have been produced from this radioactive substance. It was ais first claimed there was no danger because thorotrast was 'an alpha emitter. However'the standard dose of 75 ml. ordinarily used gives a gamma radiation equivalent of 1.37 micro-gram of 1 radium. The half life of thorium is 1,39 x U years, and the radioactivity of thorium dioxide rases after 3 years; the breakdown products are active and reach a peak after 15 years. With the Kupffer cfells bsn\r a storage point in the liter one can easily see the damaging effect of radiation. DTH 00001381; ( (' THCftflTRAST AMD ANOICGAP.CCrA OF ..-S LIVES lyUj" -- Mouis of r feUlCd lira l vACliiciio LTil.c J u. IMdlO / active material in the form of colloidal Thorium dioxide could be used in cereoral vessel visualization. distribution in Europe and the United States for use vascular visualization-a-rLeriograpry-hepatospicnograpiiy- and cerebral graphy. I932------The Council of Pharmacy of the American. Medical Association took a stand against its use. 1940----- Thorotrast was still in use although animal experimentation . .' i had demonstrated the formation* of ciir7inows and in the live`s angiosarcomas. I947------Finally discontinued when the human cases of angiosarcomas lyere reported. It was K.H. Bauer of Germany who compared the time of appearance of neoplasms after the injection of thorotrast, experimentally t produced in animals, with their average life expectancy and the average span of life in man. Ke came to the conclusion that such tumors ^sould appear between the 12th and the 18th year after the injection into the vascular system of naa. (Ts /CT I947------Endothelial Cell Sarcoma of the Liver following thw Thoratrast Injection. tkcMahan, Eds., Murphy, A.S., 1961- and Bates, M. I. American Journal of Pathology 23: 585--611. The first case of angiosarcoma fi*om dhoretrast was reported in the U.S Jl. The latent period was 17 years. -Neoplasms of the Liver following Injection of Thoratrast. Nettleship, A., and Fink, W. J. Am. Journal of Clinical Pathology Vol 35s 422--426. This was the 8th reported case of angiosarcoma of the liver due to thorotrast. The latency pericd was 16 years. DTH 000013812 AtoaulU KMJ AUlUiA^UOM UK lha nu.-'Aii Livart /r I I Ji / \ 'More than any other element of*metal carcinogenesis, arsenic remains one of the enigmas. It is cornmnnlv referred to r^. _ --W W in human r.xr.r.ixjr.xaaxx cancer formations . One group in Chicagor'claims it is a producer of angiosarcoma of the human liver* It is for this reason a shot brief literature review is made. Complicating the interpretations of studios dealing with arsenic is the fact that, no satisfactory animal models have % been found.-. . 1947----Arsenical Cancers--a Review, Neubauer, 0,: British Journal of Cancer 1: 192--251. The authors estimated the latency of arsenical cancer to be 18--20 years. 1953----Multiple Arsenical Cancers of the Skin and Internal Organs. Somers, S. C.,' aND McManus, R. G.. Cancer 6: 34?--359. The estimated latency of arsenical cancer was 13 to 50 years. 1956-- Roth, F.: Zeit Krebforsch 61: 28?--319. 1957------Roth,' F.,: Zeitschrift Krebs Forschung, Bd. 6l(s): 468--503.B. Three hemangioendothelial Sarcomas of the liver were described from 27 autopsies in vinters. latency in the German Vineyard workers was 12 to 17 years. Estimated intake of Arsenic was 537 Gms over a 12 yr. period. 1959-- Roth7 F.: Zentrelblatt Alleg. Pathoi. 100: 529--530. Eight har-angiosarcomas of the liver were reported in a study from 82 autopsies. These were vineyard workers exposed to chronic arsenic intoxication in the form of oral ingestion via insecticides, sprays, and dust. L'" r DTH 00001381c lUuJ.i.i aU (p'ite") l/l1 iiuli ^lUV\<^Jj^ ' rb) lyod------ One case of Hemangioendothelial Sarcoma of Liver Fowler's Solution. Regelson, W., Kin, V., Ospina, J., --a*tu noi iana, J.F. Cancer idlj --idl. 1r Jij Latency period of 1? years plus 7. The amount of arsenic ingested was estimated to be about 50 grams. An Environmental and Industrial Chemical Registry, is needed to face our evo^jiay environmental chemical exposure. Host recently another case of Angiosarcoma has been reported, with no history of thorium dioxide or arsenic. u&Hjsae the case was from the New York Hospital, Cornell Msdical Center and was in a 46 year old white male. 1974---- One Case Report of Hemangioendcthelial Sarcoma of LiveTi* and Hemochromatosis.(With widespread metastasis) Sussmgn,' E. B.^ Nydickj i/ and Gray* G* F., A.M.A. Archives of Pathology 97:39--4-2. In summary we have histologically a^ngiosarcomas from thorotrast, arsenic and vinyl chloride which have the same morphological appearances. I r f r i i dth 00001361" SPONTANEOUS ANGIOSARCOMAS OF THE LIVER \i aeimals > O* rPCJ___wn +* + Vim e nc n i tr 1/ rr.m onAi T>r , V . H . f>no1 T_ animals has never seen this lesion. I have in my files records of o"cr 10,000 rats v;iii r.-~;r~ different strains and have never seen this lesion. MICE-----In mice Angiosarcoma does spontanroaly occur. This is ixxJtks in the Haired and Hairless strain H.2. mouse. Hemangio endotheliomas (Angiosarcomas) were observed in 45 out of 251 iri the control groups. *r- / f cj a Deringer, M. K., J. of the National Ctncer Institute. Vol: 12: 437-445, Oct. 1951. As would fctia be expected when (C-amirnazotoluene) was subcutaneously inoculated the incidence of angiosarcomas increased. ----- ;-Ibid; 1?: 533-53HA-956 Swiss Albino mice have a spontaneous 3- % occurrence of angiosarcoma of the liver. \T j . <^ / V 1 V\ <r-- EXPERIMENTAL ANGIOSARCOMAS IN ANIMALS DUS TO UHCROTRAST C 1936---Cappllary angiosarcomas were produced in mice by EOS Selbie, F., Experimental Production al Sarcoma with tx Thorotrast. Lancet 2: 847. 1938------Reticulosarocmas (angiosarcomas) of the Liver was produced by intraveous injections. Onufrio, Q., Su di un caso di Reticulosarcoma sperinentale do Thorotrast. Folia med. 24: 12^5- (probably used different spcies) ARSENIC ECPSRIH5NHL IN ANIMUS AND ITS EFFECT ON MAN An excellent monograph on Arsenicals, has been written by A. Furst and will be published in the future by the V/oiid Health Organigation working group on Evaluation of Carcinogenic Risks of Chemicals to Man. i 1 DTH 00001381! \ r r- tt--ti -- laxtl*0S0dxi?u3 tiXajr ia*iU.UO | F a* f ijtXM ila^O | J al l* , a Bl'JalaXoll _________1 n______________ 1 i'i . nil Trtrr.< Urethane Herrold, K. M , Journal of the NationAL Cancer Tr.r- tituto. ?/ 1C?-?, !?'?. Sibcut. adninistra tier. to Syrian Hamsters. Otsuka, H. and Kuwahara, A., Gann 62:147-156,1971. By oral administration and s ubcutaneous injection to DDD & BAL b/c strain mice * J}a> NCtti, Deronger, H. K., Journal of the National. Cancer Institute 34: 841-847, 1965 Gave intraperitoneal injections to D3A/2e3De strains of nice. 1,2-Dimethylhydrazine Dihydrochloride------Syrian Golden Hamsters were given in water daily 0.156 mg. to the female and 0.161 mg. to the male. Angiosarcomas occurred in 89 $ of the females and 82 % in the males. The tumors were in 4 the livers, lungs, muscle, heart, and pancreas No such .tumor is seen in the control. Toth, B,, Cancer Research, 32: 2818-2827, 1972 Ethylhydrazine hydrochloride---- -o.ol25 # was given in drinkihg water and 38 $ vascular tumors were produced in Swiss Albino strain nice. Toth, B., Scientific Proceedings, A.A.P.B. San Fran 1974. n,Butyl-hydrazine HCL--only lung cancer. - l-carbamyl-2-phenylhydrazine--only lung cancer CONTROL INCIDENCE 0? ANGIOSARCOMA IN THE SWISS ALBINO MOUSE IS 5jS. Methylhydrazine--(A rocket fuel component)-^Syrian Golden Hamsters received 0.01 $ in drinking water. Angio sarcoma of the liver (Dxlignant Histiocytoma) (Xupffer Cell Sarcoma)- was produced in 32 $ of the females and 54 $ of the males. . latency period 70 and 78 weeks,. No such tumor was seen in the controls, t r` \ -- i' DTH 000013816 1 --f"N --'-`I -3 ' \ t) / "\ Toth. B., and Sbi^rn, F. Cenr''"t" Research 33: 2744---2733, 1973* ~ --- -- S. C--_/ ,, Juxuuj.uii J-u UJ. JJU\.J_Ug 1 " ' *"' - V*v > Swiss rn.ee. Angics^rccnas of the liver cccvirr.:"' in 3 out cf ar.d in the controls 4 out of 44. Toth, B. aid Skiucixax Shimizu. H. Journal of the National Cancer Institute. 52 : 24-1-251, 1974. ARE EinoaCNI-SmL HAZARDS IN THIS GROUP? Ifydrazines are used in industry as a rochet propellent. !> Ifonomethylhydrazines are used as corrosive agents. / Maleic hydrazide used as a herbicidePhydrolyned to hydrazines. %/ 2- Nj'droxyethylhydrasine is used to ripen pareapples and is sprayed. Phenylhydrazine is used in medicine for polycythemia vera. NEPHROBLASTOMA Since Professor C. Maltoni mentioned the high incidence of nephroblastoma in rats treated with Vinyl Chliride, a brief statement if included for the Interagency groin and the Environmental Protection Agency Task Force. Renal Adenocarcinoma in our population las shown a rapidly increasing incidence with age in both sexes. This is well documented by the State of Californiat Alameda County, Department of Public Health, California Tumor Registry(19S0--1969) A review on Cancer of the Kidney-Etiology, Epiieniology, and Pathology is recently published by J.L. Benninjton in Cancer Vol 32: 1017--1029, Nov. 1973* In view of Dr- Maltcni's experiments should not the Vinyl Chloride workers and families be studied with this lesion in mind^ 4-? rt> Tf+Lr L , % ..O . DTH 000013817