Document g0nBOmJk4rdokkjQE4ZNpKmL

Progression of vinyl chloride induced hepatic fibrosis to angiosarcoma ofthe liver 307 varices to be the source of haemorrhage, and these were treated by injection sclerotherapy. The serum alkaline phosphatase and y-glutamyl transpeptidase levels rose over the next three months to 334 1U/1 and 106 1U/I respectively. Radioisotope liver scan showed multiple rilling defects consistent with tumour deposits. Ascites and ankle oedema developed, and he died suddenly in January 1980 from an intrapcritoneal bleed after a liver biopsy. Necropsy showed that a large haemorrhagic tumour, occupying most of the right lobe of the liver, had ruptured into the peritoneum. Several smaller haemorrhagic tumours were found elsewhere in the liver. An enlarged spleen (wt 760 g) and thrombosed oesphageal varices were also noted. Histology showed the tumours to be angiosarcomas, with areas of sinusoidal dilatation and portal fibrosis in unaf fected areas of the liver. absence of portal hypertension, und may then be difficult to detect. It docs not lead to a disturbance of liver function tests and may even be missed on needle biopsy of the liver.2 Greyscale ultrasonogra phy a useful diagnostic aid,11 but it has yet to be used in a large industrial survey, and there are prob ably several unrecognised affected VCM workers. Stringent measures to control levels of exposure should lead to eventual disappearance of non cirrhotic fibrosis. Those patients who already have the condition, however, arc still at risk of developing hepatic angiosarcoma m the future. A problem highlighted by the second case is that angiosarcoma is, by definition, a vascular lesion, and there is u risk of uncontrolled haemorrhuge after blind liver biopsy. We believe, therefore, that the diagnosis should be sought cither by laparoscopic biopsy or by hepatic angiography. Dhoudos Vinyl chloride monomer is transformed by hepatic microsomal enzymes to toxic metabolites that coval ently bind to DNA.' After exposure to VCM hepatocytic proliferation, sinusoidal lining cell pro liferation, and focal sinusoidal dilatation occur4 and angiosarcoma may later develop from the sinusoidal lining cells. Enlarged lipocytes may be seen in the space of Diasc*; time cells are fibroblast precursors and can lay down collagen.* Hepatic fibrosis results and may be associated with presinusoidal portal hypertension.1* It is commoner than angiosarcoma.2 Although fibrosis was found in tumour-free portions of the liver tissue from VCM workers dying of angiosarcoma,* transition of hepatic fibrosis to angiosarcoma, although postulated,* has not been observed. The two patients described here were originally included in a series of seven VCM workers with por tal hypertension.1 They were followed for five and 10 years respectively from the time of diagnosis of portal hypertension to death from angiosarcoma. During this period they were not further exposed to VCM. Their case histories indicate that hepatic fibrosis in a VCM worker may be a precursor of future malignant change and life-long follow-up is necessary. We know of only one other similar patient who died seven years after a portacaval shunt from an angiosarcoma.* Non-cirrhotic fibrosis can also occur in the Wc thank Dr D M D Evans and Professor Peter Scheuer for their help in interpreting the biopsy material. References 1 Creech JL. Jutioaun MN. Angiosarcoma uf the liver in ike met* factors at polyvinyl chloride./OM 1974;t6:lM. 1 South PM. Crowley IR, Willem DMJ. Portal hypertension in vinyl chloride monomer worker*. Lancet IV76;ii:6U2-4. * Popper H. Malloni SclikoCT U. Vinyl vhiuride-induced hepatic ledum in him and rodents. A aimpimaiM. Liver tUMI;l:7-2U. 4 Tamberro CH. Ifee hepatic rub in onmupimli and iu carty detection ihe vinyl chluride awikl. Yale J Biot Med IV7H;SI:67*H0. * Popper il. 'Humus LB. IcHc* NC\ Falk H. Sciikirf IJ. Dcvclnpmew uf hepwk inpuamuma in man induced by vinyl chloride. thorutmn awl arsenic. Am J Pathol I V7N;92:34W-6M. 4 MakkL.OdmoreF.CraediJL.crnf. Clinical and morphotopcnl paiterm uf hepatic angiosarcoma in vinyl chloride workers. Cancer IV76;17:l4V-63. ' Ouermann-Gulkar S. Haknurk O, Segerbuck O, at aL Alkyla tion of ONA and protein in mice esposed to vinyl chloride. Bittchem Blophyt Ret Common I 77;76:259-66. * ScfaaJfner F, Popper H. Sdikuff IJ. Initial features of vinyl chloride (VC) hepatic injury. Gainmmerufugy 1976;7X:A35. 4 Kent G, Gay S, Inouye T, Balm R. Minick OT. Popper H. Vita min A containing lipocytes and formation of type III collagen in liver injury. Prvc Sail Acad JU USA IV76;73:37l<k-22. BIcadH LM. Smith PM, Laurie BW, Stephen MR, Evans WD. Portal hypertension in vinyl chloride monomer workers. A hemodynamic study. GattroefUerohgy 1971;79:206-11. " Wiliams DMJ. Smith PM, Taylor KJ W. Crowley IR, Dw BW. Monitoring Uver dbordeti in vinyl chloride mooomer workers using grayscale uitraaonopaphy.Br/ M Med I976;3J:1527.