Document dMQk3MgEogj8NGe7qrv4JbO0

A ftt f 4. * j .,.* -.'.rv v jtf .yv 4 H &*! ; .. - I `.v. UN1Vr.P.C-lTY Cr - J1 Hr.HM t-ALirOPWA vChOOl Or LC-.A^CiUi.fAWfC! VIA An*, t`:t *i* .**. 7 Clark W. Heath Hr, Mb - Chief Career U Birth Defects Division building .1, Room 520 Center for- Disease Control .- . ATLANTA, GA *30333 Special Delivery ** -------------------------D----------------SUBJECT; - Review and Recommendations ,, ____________ concerning Hepatic Angiosarcoma ^ apparently related to vinyl chloride exposure (Conference of 3/2/1974) ' ___... Dear Dr. Heath: At the conference at the NIH on March 2, 197-4, data was presented concerning 6 proven cases of angiosarcoma of the liver (possibly a seventh case) occurring at the 13. F. Goodrich plant at Louisville, Ky. On the basis of the exposure there to vinyl chlor- - Idc* the cases presented by Dr. .Vopper from Germany and the animal studies mentioned, it seems essentially inescapable that the f lesions occur incident to the exposure to vinyl chloride. There were a number of similarities among these cases. The tumor pathology was identical and the tumor behavior seemed to be one of local extension rather than widoly metastatic. Case #1 might be tumor of multicentric origin. The liver lesion in the non-tumor portions a2 the liver was Was of great interest. Material from four cases without known tumor wa.*> reviewed, presenting similar pathology. Primarily, there was widening and fibrosis of the portal areas, some collaccm in the sinusoid near the periphery of the lobule and peculiar sinus" `oitirti-lining cells, presuncibiy -the prccor;;or*- of tho-angiesarcor.-.a cells. It would appear that the portal fibrosis, or, m&ybe, more 2/ *\ V'J u. c;h sW 1376 pr. Clark !'<--a'th Jr ( page - } March 7. 197} important!-/, the s'.nu-.oidtl fibrosis leads to fairly early portal hypertension, hemcrh'-'riTnica Uv '>milar to idiopathic portal hyper tension {Rant:*s difeav-cj. Esophageal varices and marked spleno megaly .were present i:i some, of the cases. Unfortunately, neither the tumor nor the liver lesion preced ing it provoke very ii-arked alterations iu the hepatic tests. -the most consistent app-nrs to. be small to moderate increases in the SCOT* some increase in scrum alkaline phosphatase and sometimes small rises in the scrum total bilirubin. Other tests seemed to be variably abnormal (JLDH, serum globulin). Coupled with the mild test abnormalities was increased- spleen ssr.e in a number ok the , cases, > The central problem is that of how to monitor exposed work ers for early evidence of hepatic toxicity-. It would appear that the hepatic lesion precedes tumor formation, as a rule, by some years. Also that there is some relationship to a long duration of exposure for both lesions. It is recognized that rather large numbers of workers arc involved for screening purposes. My suggestions are as follows: 1. Biochemical screening at the time of new employment (base line) and for all workers, then once per year, I .would suggest this be increased to every six months after the 10th year of exposure. 2, Preferably tit* biochemical tests should be those able to be done by the ShlA {or other automated means). 3, It might be of use - experience would tell - to pro-' gram the MA for the SGPT {as well as SCOT) and possibly for the GGTP. This type of liver lesion appears to produce little hepatocyte injury and thus transaminase-type tests are going to be of limited value, but there may be nothing cur rently better. ,,, 4. More intensive investigation could then b done on the cases that drop >ut with test abnormalities. I would suggest repeat tests in one month, possibly again in another month. Hopefully the abnormalities will be modest in number and therefore practically could be investigated more thoroughly. 3/ W 1377 Dr. Clark Heath Jr [pn Se 3) March 7, 1974 The hepatitis B i-eti pr.u:-.b!y should be done when the enzyme test3 are elevated ru help clear the picture oi un- r^'hiied viral kepaitiis. ** a ^normal1.*)*'- persist one nrenth, j v, .`Mrr.in'i'Vi, hs;-t.>ry takinc (alcohol, medications, . recent transfusion or hepatitis con tacts, etc.) (! 5, If the cnui>.` of the h.eun+ic test abnormalities is not clear, i.e. now possibly vinyl chiorivie-reiatcc liver disease, a liver tear, with techmeium would seem indicated and useful. As discussed at the conference, at this point practicably it is likely the patients would be referred to private physicians or clinics for further work-up. #6. There are a number of other considerations. The proline hydroxylase tesc might be of interest and utility in screening. - The BSP test-seems not to be <not surprising, in light of the* Banti-Hke disorder). It remains uncertain u the hepatic le sion might still advance to tumor with withdrawal from vinyl chloride exposure. I doubt this tumor will be associated with alpha-fetoprotein, but this should be determined, especially by* radioimmunoassay. * # 7, I doubt that unusual biochemical tests will turn out to be of much value over customary hepatic tests, since the hep atic tests are usually based on reduction of functional mass, hepatocyte injury or bile duct obstruction, none being prom inent here. Nonetheless some rather intensive investigation of a tumor case and a few* of the ''liver disease" cases might provide useful information applicable to screening. #8, J_ivcr scan features showing some degree of splenomeg aly or "spotty" hepatic uptake probably should bo arbitrarily interpreted in this setting as vinyl chloride toxicity. #9. Liver biopsy, when indicated as considered by physicians caring for these patients, can be very helpful, it appears, and should be encouraged. However, if the scan suggests tumor type of defects, needle biopsy might be somewhat hazardous with this vascular type of tumor. ,, ** 4/ f Dr. Glark'-Heath jr (page 4) March 7, 197*1 / 10. The idea-of monitoring a `'control1' population, was raised and is attractive it ieasible. sf 11. An effort should be made to follow up former exposed em ployees to see v.hat has occurred after leaving exposure areas. *? 12, for wnrk.*rs in high exposure work (autoclaves), some of the techniques used in the lead industry (air currents, gas ..masks, showers, etc.) might be of value in reducing the de gree of exposure, ,' h 13. There seems to bn urgent reed for data rd the biology of vinyl chloride (metabolism, excretion, tissue levels, etc. ) Vary truly yours, ""T.........Q .' LU^.~ jah Allan G. Redeker, MD Prof, of Medicine Director, JLivor Unit, , John Wesley Kocpital h- D OoV 1379