Hepatocellular carcinoma in rural southern African blacks.
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Biomedical subjects
Publications and source records attributed to E W Geddes.
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Liver cell dysplasia was noted on histological examination of nontumorous liver from 24 of 50 (48%) black southern African males with hepatocellular carcinoma (HCC). Macronodular cirrhosis was present in 40 (80%). There was no statistically significant difference between the frequency of dysplasia in 50% of 40 cirrhotic and 40% of 10 noncirrhotic livers, or in 52.6% of 38 hepatitis B antigen (HBAg) positive and 33.3% of 12 HBAg negative HCC patients. HBAg positivity was present in 80% of 40 cirrhotic and in 60% of 10 noncirrhotic HCC patients. This lack of significant correlation between liver cell dysplasia, and both cirrhosis and HBAg positivity in HCC patients in contrast to findings in Uganda and the United States, suggests a different pathogenetic mechanism for dysplasia in southern Africa. Liver cell dysplasia in man appears to be analogous to preneoplastic experimentally-induced hyperplastic foci or areas.
Formalin-fixed paraffin-embedded autopsy tissue of liver and tumor from 50 male black mineworkers with hepatocellular carcinoma were examined by orcein stain for the presence of cytoplasmic hepatitis B surface antigen. The results were correlated with the serum hepatitis B antigen (HBAg). In 72% serum HBAg was positive. Orcein staining of nontumor liver cell cytoplasm was present in 18 (36%). Sixteen (89%) of these orcein-positive cases were serum HBAg positive. The two false negative serum HBAg results were obtained by immunodiffusion, immunoelectrophoresis and complement fixation. Serum HBAg, measured by radio-immunoassay and hemagglutination, was positive in 14 orcein-negative cases. Six other negative orcein results appeared to be due to sampling error. Orcein staining was noted in tumor cells of three serum HBAg positive patients. Provided the limitations of the technique are realized, orcein staining of liver tissue from hepatocellular carcinoma patients may prove useful for retrospective screening surveys to assess the prevalence of HBAg positivity in these patients.
Certain characteristics of 328 Mozambican male Shangaans with primary hepatocellular cancer (PHC) have been compared with those of 163 Shangaan men with hepatomegaly from causes other than PHC and with those of 122 Black Southern African men with the same tumour but who belonged to tribes other than the Shangaan. Shangaans with PHC were significantly younger than non-Shangaans with the tumour (mean age 33,4 cf. 40,0 years; Pless than 0,001). They also had a significantly higher positivity rate of alpha-fetoprotein by immunodiffusion (71,4%) than the non-Shangaans (16%), although in other respects the tumours appeared to be similar. Cirrhosis of the non-tumorous part of the liver was present at necropsy in 62% of the Shangaans and in 66% of the non-Shangaans. The hepatitis B (surface) antigen (HBsAg) was detected in the serum of 60% of the Shangaans with PHC compared with only 9% of the controls. The antigen was present in 53,4% of the non-Shangaans with PHC (the difference between this fifure and that in the Shangaans was not significant). HBsAg was detected in the serum of 64% of the Shangaans with PHC and cirrhosis, but also in 74% of those with the tumour without associated cirrhosis. The possible role of the hepatitis B verus in the aetiology of PHC is considered in the light both of these findings and of the possibility that the frequency with which the tumour is associated with cirrhosis may be decreasing in Shangaans. Some of the dietary habits of the Shangaans with PHC were compared with those of the controls. Virtually all the patients with PHC, but also almost all the controls, ate groundnuts in large quantities from an early age, as well as cashew nuts in smaller amounts. Cycad pips, mopani leaves and pods, mopani worms and locusts were not eaten by significantly more of the Shangaans with PHC than the controls. The limitations of this type of dietary analysis are discussed.
A continuously growing cell line has been established from autopsy material taken from a primary liver carcinoma, a cancer which has a high incidence in Southern Africa. The cell line was initiated from multifocal areas of outgrowth in the primary culture, and adaptation to in vitro conditions was completed after 18 months. The cells resemble hepatocytes in culture, have a doubling time of 35-40 hours and a plating efficiency of 40-50%. No virus particles have been found in the cells by ultrastructural examination. The isozyme pattern and the karyology of the cells are human. The chromosome pattern is heteroploid (mean number 56) and there are marker chromosomes.
The value of plain chest radiography in the diagnosis of primary hepatocellular cancer (PHC) was assessed in 449 patients. An elevated right hemidiaphragm and pulmonary metastases were present in 11% and strongly suggest a diagnosis of PHC. In all, the right hemidiaphragm was raised in 30% of patients. Pulmonary metastases were present on admission in 19% of patients and appeared later in a further 6%. Secondary deposits were found in the lungs at necropsy in 52% of patients, compared with only 24% in whom there was radiological evidence of metastases during life. In 36% of patients chest radiographs were normal on admission.
Hepatitis-B surface antigen (HBsAg) was found in the serum of 58 of 158 (36-4%) southern African Bantu patients with primary hepatocellular cancer by counter immunoelectrophoresis and in 94 (59-5%) by radioimmunoassay (RIA). The prevalence of this antigen in the general Bantu population using these methods was 7% and 9% respectively. Antibody against HBsAg was detected in 11-6% of the patients by passive haemagglutination (PH) and 13-4% by RIA, and in 33-4% (by PH) of a control population. Antibody sub-types were predominantly "adw" (69-2%) with a lesser frequency of "ayw" (23%), while 7-8% were indeterminate. The corresponding figures in the controls were 80-4, 8-4 and 11-2%. HBsAg was more common in younger patients. No relationship could be demonstrated between hepatitis-B antigenaemia and the presence of alpha-foetoprotein in high concentration, although there were far fewer patients in the alpha-foetoprotein-negative group.
The pattern of cancer in African gold miners over the 8-year period 1964-71, comprising 2,926,461 man-years of employment was studied. Of the 1344 cancers found, primary liver cancer accounted for 52-8%, oesophageal cancer 12-1%, cancer of the respiratory system 5-4% and cancer of the bladder 4-8%. Analysis of the spatial distribution of these four cancers, both on subcontinental and local scale, showed distinct gradients of occurrence between areas of significantly higher and lower incidence than expected. In the case of primary liver cancer in Mozambique and oesophageal cancer in the Transkei, the spatial distribution reflects closely that found in the general resident population of each territory. The crude incidence rate of primary liver cancer in gold miners from Mozambique dropped sharply over the period of the survey.
Serum IgG, IgM and IgA levels were measured by the single radial diffusion method in 107 South African Negro patients with primary hepatocellular cancer (PHC) and 112 healthy Negro blood donors. The mean serum IgG ANd IgM concentrations were significantly higher (P less than 0-001) in the PHC patients. In those patients in whom PHC was associated with cirrhosis, the serum IgG level was greater (P less than 0-02) than in those without cirrhosis. However, the mean serum IgG concentration in the non-cirrhotic cancer patients was still significantly higher than the control value (P less than 0-001). Thus, while cirrhosis may contribute to the raised IgG levels in PHC, other factors must also be involved. There was no difference in the serum immunoglobulin concentrations in PHC patients with and without hepatitis-B antigenaemia.
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