Document kggLr45rEeX9KZkRZQO31qLB

/ / ANGTO?:\RCOMX OF THE HUMAN LIVER 4 i`or tne sains xuinor are to be found in tr.e literature. <7* 1. Keinan^io-enciothelial Sarcoma 2. r^tiigiiano vdsouuar tumor oi the liver 3 Kupffer Cell Sarcoma 4. Hemangioendothelioma 5. Hemangioblastoma 6. Endothelioblastoma 7. Reticuloendothelicra (Purdy Stout) 8,. Aneiopla'slic Sarcoma 9. Primary Hepatic Sarcoma 10. Angioblastic Sarcoma 11. Endothelioma, grades,-undifferentiated, veil different! and anaplastic. 12. Hemangiosarcoma 13# l&lignant Hemangiosarcoma 14. Malignant Hemangioendothelioma 15*lfetastasizing Hemangioma c Historically there'are many reasons for the above fence sitting type of terminology. In 1940 James Ewing reports in his textbook an "Neoplastic Disease" quote: "I do not believe, therefore,, that the existence of a true angiosarcoma arising from bleed vessels of the liver has been satisfactorily demonstrated." As late as 1948, Rupert A. Willis in his textbook on PATHOLOGY OF TUMORS states. " We cone now to a difficult question;, Bo truly neoplastic angiomatous growths occur? They are very rare and most supposed examples are either multifocal hamartomas or vascular tumors.of other kinds, ! VVC 000006350 / jr _xy. oxX_ -------- -lU^OI'a Ol LliO j-U vC-T 1-*0j*_-n^-. x*'i^ j*;--^ ---<--. u. ^ c^**^ / Thor&trast. Suckow, E.G*, Kenegar, G.S., and Baserza^ R. Am. Journal ol' pathology* vol. 50: acj--o/ / due to thoraurast used intravascularlly. The latency perrcus were 3 vo <c~r vs^.is with the average 15 years. 1965 ''-- Malignancy hD other Late Effects Following the Administration of Thor^trast. Da Silui Horta, J. et al: Lancet 2: 201--205. 22 Additional cases of Angiosarcoma 22a of the Liver were'reported in this article. 3y this time hundreds of cases of angiosarcoma, of the liver have been produced from this radioactive substance* It was aJs first clained there was no danger because thorctrast 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 12* 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 busn^ a storage point in the lirer one can easily see the damaging effect of radiation. t` r V' <' VVC 000006351 TKCRtfrRAST AMD ANGICGARCCI'A OF Hl'I'AM LIVES l. ly^.j --------iii<3.0 i-iuiiiz. ci rranee fix's L >^.v2ituanwr<.tLi .C -*. bwUO active material in the form of colloidal Thorium dioxide could be used in cerebral vessel visualization* distrioution in Europe and the United States for use vascular visuaiization-arLeriogrupxiy-hepaaospicriograpiiy- and cerebral graphy. 1932- - The Council of Pharmacy of the American. Medical Association took a stand against its use* 1940-- -Thorotrast was still in use although animal experimentation had-demonstrated the formations cf c.wrcinomaG and in the lively angiosarcomas. 194-7-- -Finally discontinued when the human cases of angiosarcomas tsere reported. It was K.H. Bauer of Germany who compared the time of appearance of neoplasms after the injection of thorotrast, experimentally ; i produced in animals, with their average life expectancy and the average span of life in man* Ke came to the conclusion that such c/* _ tumors sould appear between the 12th and the 18th year after the injection into the vascular system of max* Qoerc) 194-7----Endothelial Cell Sarcoma of the Liver following Thonatrast Injection, h&.clfe.han, H*.t Murphy, A.S., 1961- and Bates, M. I. American Journal of Pathology 23: 535--611. The first case of angiosarcoma from 1hor*trast was reported in the U.SJl. The latent period vas 17 years# 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 angiosarcoma of the liver due to thorotrast. The latency pericd. vas 16 years. VVC 000006352 iLjiianHJ aNu aUF ih^ nuKAn Liva-t More than any other element of*metal carcinogenesis, arsenic remains one of the enifnras, It is corm-vr-lv referred to in human RwwiroiTCTixx cancer formations . One group an Chicago-'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 anifoal models have been found.- . 1947--.Arsenical Cancers --a Review, Neubausr,' 0,: British Journal of Cancer 1: 192--251. The authors estimated the latency of arsenical cancer to be 18--20 years. P 1953,,hhltiple Arsenical Cancers of the Skin and Internal Organs. Sommers, S. C., aND McHanus, R. G.. Cancer 6: 3^7"~359* The estimated latency of arsenical cancer was 13 to 50 years 1956 ---- Roth, F.: Zeit Krebforsch 61: 287--319. 1957 ------Roth, F.,: Zeitschrift Krebs Forschung, Bd. 61(s): ^8--503.B. Three hcmangioendothelial Sarcomas of the liver were described from 2? autopsies in vinters. Latency in the German Vineyard workers was 12 to 17 years Estimated intake of Arsenic was 53*7 Gris over a 12 yr. period. 1959_-- Roth, F.j Zentrelblatt Alleg, Pathol. 100: 529--530. Eight harvingiosarconas 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. vvc OOOOO6353 iUuJ -U--- l C/i' LltZs ilUlvT.i< j_yoo.. i -- One case of KeTnangioendothelial Sarrrona of Liver Fowler*s Solution. Regelson, w#t Kin, V., Ospina, - - iioi iana, J.F. Cancer 4Li 5L+--vll. Latency period of 17 years plus 7* The amount of arsenic ingested vas estimated to be 50 grans b 1 j (,/KT An Environmental and Industrial Chemical Registry, is needed to face our evu^^ffiy Environmental chemical exposure. Most recently another case of Angiosarcoma has been reported, with no history of thorium dioxide or arsenic* ucctcbb* the case was from the New York Hospital, Cornell I'fedical Center and was in a 16 year old white male* 1974---- One Case Report of Hemangioendcthelial Sarcoma of Live^r and Hemochromatosis. (With widespread metastasis) Sussm^n, E. B., Nydick, l/i and Gray, O. F., A.M.A. Archives of Pathology 97:39--^2* In summary we have histologically angiosarcomas from thorotrast, arsenic and vinyl chloride which have the sane morphological appearances VVC 000006354 / / Dv tu *, / W L' SPONTANEOUS ANGIOSARCOMAS OF TITS LIVER EULS 5- < A. /.----- / ^ * l^,r5 T" +t-.-k +Vi-i r ie n *t i m Ir-'i r*.rvi n''.* t +* T'It* , 1 anireals has never seen this lesion. I have in my files rooerds of c")r 10,000 rats v.'if:. r.vy different strains and have never seen this lesion. itlCS------- In nice Angiosarcoma does spontaneously occur. This is iaxiha in the Haired and Hairless strain H.2.. mouse. Kemangio- endothelianas (Angiosarcomas) were observed in 45 out of 251 id the control groups. <v- ( Ir ape Deringer, M. K.t J. of the National Ctncer Institute. Vol: 12: 437^45, Oct. 1951. As would fcs be expected when (C--areiinazotoluene) was subcutaneously inoculated the ixcideme of angiosarcomas increased. -------;-Ibid; 17: 533-53?3-956 Swiss Albino mice have a spontaneous 3. $ occurrence of angiosarcoma of the liver. <y EXPERIMENTAL ANDIGSARCC! AS IN ANIM\L3 DUE TO AHCROIRAST c 1936--Capillary angiosarcomas were produced in mice by RXXS Selbie, F.# Experimental Production cl 5arcoma with iix Thorotrast. lancet 2: 847. I938------- Reticulosarocmas(angiosarcomas) of the Liver was produced by intraveous injections. Onufrio, Su di un caso di Reticulosarcoma sperimentale do Thorotrast. Folia med. 24: 12^5- (probably used different speies) ARSENIC EXPERIMENTAL IN A. MIMILS A?n ITS EFFECT ON MAN An excellent monograph on Arsenicals, has been written by A. Furst and will be published in the future by the World Health Organigation working group on Evaluation of Carcinogenic Fisks of Chemicals to fen. I VVC 000006355 r --.T/','T V' .. -,-p- . p p- *< | jcx'i\, j :i.,. ar1 uasn .-- i "> . n>i to r" .< Urethane-- Herr old, K. M., Joum?] of the NaticnAL Cancer o ; , about. 'idrdr.is traticn to Syrian Hamsters . Otsuka, H. and Kuwahara., A*, Gann 62:147-156,1971* By oral ad-ranistration and subcutaneous injection to DDD & 3AL b/c strain mice. tz> N&ert 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 %x ^ female and 0.161 mg. to the male. 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 Albino strain mice. 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 HOUSE IS 5;S. Me thylhydrazine--- (A rocket fuel component)^jyrian Golden Hamsters received 0.01 in drinking water. Angio sarcoma of the liver (Kalignant Histiocytoma) (Kupffer Cell Sarcoma)- was produced in 32 % of the females and 5^ $ of the males. 000006356 Latency period 70 and 78 weeks,. No such tumor was seen in the controls, \ '} / Toth. B.. and Shi, F. Crir*'e-- Research Jj: T _o --v-^- or--i- , ^ ^^ ^ ^ |. t ., a v*-> ^u^ui/x^a xu i-u. u_iir>.i_i lg t> ' * . * o * f'- rr r - ^ Swiss mice. Angics**rcrr.as of the liver ':-:c-'.rr.''; ir: 3 cuL ;_' \'lr, a;:d in t:n controls 4 out of 44, Toth, B. ind SkaKxxax Shimizu. H# Journal of the National Cancer Institute, 52: 241-251, 1974. ARB ENTOC-n-SNTAL HAZARDS IN TIH5 GROUP? Hydrazines are used in industry as a rocket propellent, Mbnomethylljydrazines are used as corrosive aosnts. V/ ^/ >feleic hydra2ide used as a herbicideThydrolyred to hydrazines, 2- Hydroxysthylhydrazine is used to nicer. pineapples and is sprayed C Fhenylbydrazine is used in medicine for polycythemia vera. NEPHROBLASTOMA Since Professor C, tfeltoni mentioned the high incidence of nephroblastoma in rats treated with Vinyl Chloride, a brief statement if included for the Interagency groip 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(19c0--19&9) A review on Cancer of the Kidney-Etiology, Epiiemiology, and Pathology is recently published by J,L. Benninjton in Cancer Vol 32: 1017--1029, Nov, 1973. In view of Dr~ Maltcnifs experiments should not the Vinyl Chloride workers and families be studied with this lesion in mind^ 4-S' /u VVC 000006357 itvy