Document KGnEpyr8NRXVD7BQ7J0BB3w5r

/y f rjx AWGi03,iaco;-:v of tee human liver Similar Terrrinolorv or Semantics used for the same tumor are to be found in tne literature. / '' 1. Kwmangio-endoihelial Sarcoma 2. i^a.iig?ianL vascuar tumor of the liver 3. Kupffer Cell Sarcoma ' 4. Hemangioendothelioma 5* Hemangioblastoma 6. Endothelioblastoma 7. Reticuloendothelioma (Purdy Stout) 8*. Angioplastic Sarcoma 9. Prinary Hepatic Sarcoma 10. Angioblastic Sarcoma 11. Endothelioma, grades,-undifferentiated, well differentiated and anaplastic. 12. Heraangiosarcoma. 13* Malignant Hemangiosarcoma 14, Malignant Hemangioendothelioma 15.Metastasizing Hemangioma C 1 Historically there'are many reasons for the above fence sitting type of terminology. In 1940 James Ewing reports in his textbook xn "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 textbook on FATK0L0GY OF TUMORS states. " V* cone now to a difficult question;. Do truly neoplastic angiomatous growths occur? They are very rare and most supposed examples are either multifical hamartomas or vascular tumors of other kinds. ! V UCC 083296 V / } /' xyol- --- linuord oi Luti 1 .i/ig .....,'xj'tr'G.ticns ofi Ifconatrast. Suckow, E.G., Kenegar, G.E., and Baserza/ R. An. Journal ol' pathology. Vol. >o: ocj--0/7. !& C*Cs2~C.3 --- /*+*-* l << due to tnoratras.t used intravas culorl/. The latency perious were 3 to i-r yexrs with the average 15 years, I965-- fJalignaricy SKD other Late Effects Following the Administration of Thorp trast. Da Sil-ai Horta, J* et al.: Lancet 2: 201--205* 22 Additional cases of Angiosarcoma 2* of the liver 4* were'reported in this article. 3y this time hundreds of cases of angiosarcosa of the liver have been produced from this radioactive suqsfcance. It was 1)/ if/ tx 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 radium. The half life of thorium is 1,39 x years, and the radioactivity of thorium dioxide rises after 5 yearsj the breakdown products are active and reach a peak after 15 years. With the Kupffer cells bien^ a storage point in the liner one can easily see the damaging effect of radiation. UCC 083297 V Aajis.rtlC AnJ AliiUiAAbU A UF 'inF nu.-n.ri Liv^it / rI I vV More than any other lenient of*metal carcinogenesis, arsenic hremains one of the enigmas. It is conrv'nlv referred to p*. in human cancer formations. One group in Chicago'Claixns 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 anjfoal 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. I953-----Miltiple Arsenical Cancers of the Skin and Internal Organs. Sommers,' S. C., aND McManus, R. G.. Cancer 6: 347--359. '- * The estimated latency of arsenical cancer was 13 to 50 years. 1956---- Roth, F.: Zeit Krebforsch 61: 287--319. 1957--Roth7 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 53*7 Qns over a 12 yr. period. 1959---- Rothj F.: Zentrelblatt Alleg. Pathol. 100 : 529--530. Eight hesnnziosarcoras 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. UCC 083298 (i**(,e-2) _ _/ ^ u C* / "*' <" ,^t " // bJ lyod---- Une case of hemangioenaothelial Sarcoma of Liver dL*r~c. ; i /./^ ,' ^ Fowler's Solution. Regelson, w., Kin, V., Ospina, J., 1 - - -awi Holland., J /. oancer Zl: 5I*+--j'j 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 evci igity environmental chemical exposure. Most recently another case of Angiosarcoma has been reported with no history of thorium dioxide or arsenic. Sncv the case was from the New York Hospital, Cornell Medical Center and was in a 46 year old white male. 1974------ one Case Report of Hemangioendcthelial Sarcoma of LiveTT and Hemochromatosis.(With widespread metastasis) Sussmgn,' E. B.V Nydick, 1/, and Gray, Q. F., A.HJU Archives of Pathology 97:39--42. In summary we have histologically a ngiosarcomas from thorotrast, arsenic and vinyl chloride which have the same morphological appearances. UCC 083299 SPONTANEOUS ANGIOSARCOMAS OF THE LIVER IN ANI'ALS iJUr~ A* --------T" +fr T-* 4,h*y Is an vn'm'W' emtr ty, Dr, v.n. Snell J,cL /icl JSCtriL^ ^ animals has never seen this leaden. I have in my files '`OCC T'* 3 Of PY "*I* 2.0 t 000 *,'5 0*\ r.r different strains and have never seen this lesion. TUGS--------In mice Angiosarcoma does spontmsoisly occur. This is xxxikB in the Haired and Hairless strain HJ!L mouse. Hemangio endotheliomas (Angiosarcomas) were acserved in 45 out of 251 iii the control groups. tv-- / f apo Deringer, M. K., J* of the National Sincer Institute. Vol: 12: 437-445, Oct. 1951. As would fasst be expected when (C-ardraazotoluene) was subcutaneously inoculated the incidezce of angiosarcomas increased. ------:-Ibid; 17 : 533-53SU956 Swiss Albino mice have a spontaneous 3. i occurrence of angiosarcoma of the liver. sr EXFERI2-SNTAL ANGIOSARCOMAS IN ANIMALS DTE TO IHCROmAST I936------ Cappllary angiosarcomas were produced in mice by HA2S Selbie, F.# Experimental Production df Sarcoma with 4x Thorotrast. lancet 2: 847. I938----- Reticulosarcomas (angiosarcomas) of the Liver was produced by intraveous injections. Onufrio, Q., Su di un caso di Reticulosarcoma sperimentale do Thorcrirast. Folia med. 24: 12^5 (probably used dif ferent speies) ARSENIC ECPEEIIENIAL IN ANIMALS AND ITS ErTECN ON MIN An excellent monograph on Arsenicals, has been written by A. Furst and will be published in the future by the Waxld Health Organisation working group on Evaluation of Carcinogenic Risks of Chemicals to Man. | UCC 083300 \ ') / Tot>n B., T. vi A/fl-t** Swiss "ice.> AngiecT-*-'rcvcas of the liver f*f ~ A--' ' * 4 out of 44. Toth, B. and afcfrjcixaji Shimizu. H, Journal of the National Cancer Institute. 52: 241-251, 1974. Hydrazines aife used in industry as a rochet propellent. Monomethylliydrazines are used as corrosive agents. Maleic hydrazide used as a herbicideT'hydrolyiEd to hydrazines. 2- Hydroxyethylhydrazine is used to ripen piieapples and is sprayed. G Phenylhydrazine is used in medicine for polypjthernia vera. NEPHROBIA5TOMA ! Since Professor C. Maltoni mentioned the high incidence of nephroblastoma in rats treated with Vinyl Chlxride, a btief statement if included for the Interagency grotp and the Environmental Protection Agency Task Force. Renal Adenocarcinoma in our population ias shown a rapidly increasing incidence with age in both sexes. This is well documented by the State of California, Alameda County, Department of Public Health, California Tumor Registry(19S0--1969) A review on Cancer of the Kidney-Etiology, Epidemiology, and Pathology is recently published by J.L. Benninjton in Cancer Vol 32: 1017--1029, Nov. 1973* In view of Dr- Maltoni*s experiments should not the Vinyl Chloride workers and families be studied with this lesion in ndndj TM ^ *,o UCC 083301 IT--' \ --T T*-- NitrosodimiStiylaiuins--------, ? *, uamt&a, J.^.,. Drltisn t_________ .r ~------------------ ... *1 'N . yyh r\r C Urethane-- Herrold, K. M., Journal of the NationAL Cancer Tr.r titutc. 3.1: IT?-, lr',7. Sibcut. administration to Syrian Hamsters. Otsuka, H. and Kuwahara, A., Gann 62:147-156,1971. By oral administration and subcutaneous injection to DDD & BAL b/c strain mice. ^-<C/riCtg -- faiax:iiix3xratsxxpggira.ra . Dercnger, M. K., Journal of the National Cancer Institute 34: 841-847, 1965 Cave intraperitoneal injections to D3A/2eBDe 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. V Angiosarcomas occurred in 89 of the females and 82 % in the males. The tumors were in the livers, lings, 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 Albipo strain mice. Toth, B., Scientific Proceedings, AJl.P.B. San Fran 1974. n,Butyl-hydrazine HCL--only lung cancer. . l-carbajiyl-2-phenylhydrazine--only lung cancer. CONTROL INCIDENCE OF ANGIOSARCOMA IN THE SWISS ALBINO MOUSE IS 5%. Methylhydrazine---- (A rocket fuel component)^Syrian Golden Hamsters received 0.01 # in drinking water. Angio sarcoma of the liver (Lalignant Histiocytoma) (Kupffer Cell Sarcoma) was produced in 32 1* of the females and 54 % of the males, latency period 70 and 78 weeks,. N such tumor was seen in the controls, ; UCC 083302 TK0PJ7TRA5T AMD ::9ICS.\?.CCI'A OF THE LIY53 active material in the form of colloidal Thorium djoxide could be used in cere oral vessel visualization* distribution in Europe and the United States for use vascuiar visualization-axi^riorapv-hepatospicno^npiiycerebral graphy. I932------ The Council of Pharmacy of the American. Medical Association took a-stand against its use* 1940------ Thonatrast was still in use although animal experimentation had d* e* monstrated the formati one of cnrffinemnff and in the live`s angiosarcomas. 1947------ Finally discontinued when the human cases of angiosarcomas (sere reported. It was K.E. Bauer of Germany who compared the time of appearance of neoplasms after the injection of theretrast, experimentally , produced in animals, with their average life expectancy and the average span of life in man. He came to the conclusion that such tumors ^sould appear between the 12th and the 18th year after the injection into the vascular system of max. -C?* *TGife/rJ 1947----Endothelial Cell Sarcoma of the liver following tha Thomtrast Injection. MacMahan, HU., Murphy, A.S., and Bates, M. I. American Journal of Pathology 23 : 585--611. The first case of angiosarcoma from dhoretrast was reported in the U.S.A. The latent perird was 17 years. 1961--Neoplasms of the Liver following Injection of Thoratrast. Nettleship, A., and Fink, W. J. Am. Journal of Clinical Pathology Vol 35 : 422--426* This was the 8th reported case of anjiosarcoma of the liver dMcdbaxtharatmt due to thoretrast. The latency perird was 16 years. UCC 083303