Document 0gxekwKEOYov8Q1o22G6ObgBx

Special Communication ,<if Angiosarcoma of Liver in the Manufacture of Polyvinyl Chloride Three reported cases of angiosarcoma of the fiver serve as an alert to Ihe probability that this condition may, in some instances, be causally related to employment in the manufacture of polyvinyl chloride resins. |. L Creech, Jr., M.D. and M. N. Johnson, M.D. On lanuary 22-23. 1974, a manufacturer of polyvinyl chloride and copolymers notified it's employees, the National institute of Occupational Safety and Health, she Kentucky State Department of Labor, and the public, that three workers had died of angiosarcomas of the liver. These cases had as a common denominator employment in the manufac ture of polyvinyl chloride resins. A patient of one of the authors (I.I.C., lr.) died on Sep tember 27, 1971 2'om an angiosarcoma of the liver. At that time the potential causal relation to the manufacture of polyvinyl chloride resins was not realized. Although other clinical manifestations of exposure to VCM were known (acroosteolysrs), only one experimental paper1 indicated that vinyl chloride may be a carcinogen. The tumors in rats that he described occurred primarily in the skin and were epidermoid in origin. Eighteen months later on March 3, 1973. a second former employee in the Louisville plant died. Srncc he was no! under our care, no connection was marie that the two cases may have had a common origin. When ,i thirr! [Mtiout lin'd on December 19, 197 i, iIk- jkilholegisl on gross examination diagnosed an angiosarcoma of the liver Since all thru* patiems were ircaicd by different physicians, no relationship to ex posure to polyvinyl chlonde was surmised until the authors, recognizing the rarity of the tumor, and learning thal all three had worked in the PVC plant, brought (he matter to the at- Dr Clt'fhi'lljiU I'fusnijn, Ihrttt (lOKltar It C tu-iir .it ( I >mhs alii . Xv t > M>nwiii as I h'<\ ku til trrvaliMUtii-iH.it t Ii-mIiIi. ll- II I ( hI'I< Ii ( >vti|k><>v. Aknifl. OtUit (Uiwini ri-rnn-K in rV| 0020. Prig S-H. SIX) South Mvin Si . Akron. (tarn 44 11ft 40' Inhnson) tention of the company. Further search indicates that a fourth death from angiosarcoma may have occurred ftve years ead.r-r (19f>8), but the death certificate shows primary liver tumor as the cause of death. (Clinical, epidemiologic, toxicological and occupational investigations are being vigorously pursued with regard to other employees svho may have been similarly ex posed.) A brief resume of the first case under our care is presented The history, clinical course, and pathologic findings are con sistent with the others who died of angiosarcoma. These cases wilt be presented in a group and in more detail at a future date. Case Report Patient one. a 36-year old white male, was hospitalized January S, 1970 because of tarry itools. Occupational History.-- The patient had been employed from NnvemfMT 1999 until his illness, except for two lay-ntfs of nine months m 19911 aim! mx months in 1999, as a rhemu.il Ih-I{h-r ,kkI opcr.ilnt in llu' Louisville pl.ml ol II l. (iiiiahith Chemical Comiwny in the manufacture <ii polyvinyl chloride resins Present Illness.-- A! the lime of admission the patient hid no complaints except passage of l.irry stools I'.isi Insloiy -.vjs negative except for an operation for hemorrhoids lour years earlier Physical examination snowed pallor, and black stool on rort.il examination. Liver and spleen wr*re not paljiahle. Although upper C-l series was inicrprrtcd as normal, a ten tative diagnosis was made of blooding duodenal ulcer On diet and medication, the patient had no recurrence of 0ISO r rrJ,C 11,(3) rf-fy RSV 0016560 <wi*l Mivding until M.iy I. Iink iitonllts wlnsi W4s uuiImiiUiiI M Miry sl*ds Agam lt<` w.is MmmnI lir Iwve HMrkiil (Mttur, rfdfl Miry mii n-rl.il mimiuliiHi A( litis lime ific liver w.is fkiiiomiialily eiUatg<'<l and lltrr s)>lix'ti was palpable. Blood chemistry studies (5MA-I2) wkc not significantly abnormal; total biliruInn, alkaline phosphatase, IDH, and SCOT were only slightly elevated. G-l sork-s showed only anterior displaermc ti of the stomach, but barium swallow suggesirri esophrgral varices. Intravenous pyelogram was normal; barium enema was normal except for displacement of the splenic flexure by an enlarged spleen. Liver scan on May 4,1970 vas interpreted as bong compatible with a large lesion in the left lobe of (he liver, extending into the right lobe. Operative Procedure and Findings.-- On May 7. 1970 an exploratory laparotomy was carried out. Under anesthesia, the abdomen was entered through a vertical incision. Marked enlargement of the liver and spleen were noted, and the liver was adherent to the anterior surface of the stomach. The liver capsule was quite thickened and lough. TherlT was a gelatinous-tike- material at the |unction of the liver and the stomach. Retroperitoneal nodes were very soft, enlarged, and succulent in apfjearance. A biopsy ol 1h liver was performed. There was marked degree of hemorrhage following this which was controlled with large sutures through the fiver. Report of Pathologic Findings Gross.-- Specimen is a portion of soft gray and light brown tissue that is 2.2 x 1.9 x 1 cms. at the present state. In some ansis it i|i|'.irs l*i Ik- t uti|Msst ol |tvr-i .mil m i.Hh-is MMNk-ialHy turn lissm- with <rrrus ot s|HHi|;iiir-\s mxt V ll|W*a>S Microscopic. -- Most of (Ite tissue pati*n of liver is replaced by luxuriantly growing cells forming irregular spates These .spaces display many irahtirulaiions in their lumina anri are lined by pleomorphic malignant emlixhelul cells. Mere anri there those cells grow in nearly solid sheet'. tlsewficre they line capillaries. There is a newly formed stroma with various degrerrs of hyalinuaiion here and there. Diagnosis. -- "Liver, biopsy of, angiosarcoma malignant hemangioendothelioma)." Clinical Course Following the laparotomy and biopsy the patient was given 3600 R cobalt and several intra-arterial infusions of S FU. During this time there was marked distortion of his blood chemistry with severe diminution of albumin, and marked in crease in total bilirubin, alkaline phosphatase. IDH. and SCOT. After a stormy course and several months of con valescence, including several abdominal paracenteses lor recurrent ascites, he recovered sufficiently to return to work for a short lime He succumbed toihe liver tumor fourteen months posi-ofK'ratively and died on Scptemlxjr 27. 1971. Reference 1 Viola PL. Ri^oiii A and Caiiuio. A Oncog-nic response of ra> skin, lungs, and bones 10 vinvl chloride. Cancer Research 3V.5lh-5lS. 1971 Special Communication Editor's Note Professor Ccsare Maltoni, Director of the Institute of Oncology of the University of Bologna Italy, presented ihe results, of his unpublished experiments with vinyl chloride on February 15,1974 at the U.S. Dept, of Labor hearing in Washmgion, D C. on "Possible Hazards of Vinyl Chloride Manufacture and Use". His work, which is obviously original and innovative, demonstrated angiosarcoma of the liver and other tumors to experimental animals ai atr concentrations of vinyl chloride which are known to be present at times in workroom atmospheres. Professor Maltoni describes his methodology as predichvc of the carcinogenic potential of airborne chemical contaminants. Professor Moitoni is apparently the first to show ihe relationship be tween exposure to vinyl chloride and the appearance of angiosarcoma in mammals --fRT fi'htu.ity Jl, Y)74 Journal of Occupational Medicine/Vol. 16, No. 3/March 1974 151 RSV 0016561