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Biomedical subjects

M C Kew

Publications and source records attributed to M C Kew.

At least 91 records · Page 5Linked to original sources
PubMed1988

Resectability rate of hepatocellular carcinoma in rural southern Africans.

The purpose of this analysis was to ascertain the resectability rate of symptomatic hepatocellular carcinoma in rural southern African black males. All 224 such patients proven to have hepatocellular carcinoma in a single hospital were included in the study. Of 205 patients undergoing a complete diagnostic work-up, 134 [65.3 per cent) were judged on clinical criteria to be inoperable, 23 (11.2 per cent) had pulmonary or osseous metastases, and 38 (18.5 per cent) proved on hepatic imaging and 5 (2.4 per cent) on hepatic arteriography to have an irresectable tumour. Thus, only five (2.4 per cent) of these patients proceeded to laparotomy. Another 7 patients who did not have an arteriogram, 9 with surgical emergencies, and 2 mistakenly believed to have an amoebic hepatic abscess also underwent laparotomy. Only 2 patients (0.9 per cent of 223) proved to have a resectable tumour. The extremely low resectability rate reinforces the urgent need for a surveillance programme to detect early tumours in high-risk members of this population.

Adult↗
PubMed1988

High serum levels of secretory component in hepatocellular carcinoma.

PURPOSE: Elevated levels of secretory IgA (S-IgA) have been detected in serum samples from patients with liver diseases and neoplasia with liver metastasis. We undertook the current study in order to determine the concentrations of different forms of free secretory component (SC) in sera from patients with hepatocellular carcinoma. MATERIALS AND METHODS: The concentrations of SC, S-IgA, and secretory IgM (S-IgM) were quantified in the sera of 100 patients with hepatocellular carcinoma, and in 77 matched healthy control subjects by using an enzyme-linked immunosorbent assay. RESULTS: Free SC serum levels exceeded the upper limits of control values in 82 percent of patients with hepatocellular carcinoma, S-IgA levels in 88 percent of them, and S-IgM levels in 32 percent. Free SC levels were positively correlated with S-IgA and S-IgM levels. They were weakly correlated with gamma-glutamyl transpeptidase activity, but not with alpha-fetoprotein, beta 2-microglobulin, albumin, or IgA serum concentrations, nor with alkaline phosphatase activity. CONCLUSION: The data clearly demonstrate the elevation of serum free SC concentrations as a novel biologic alteration in hepatocellular carcinoma since free SC levels appear to be correlated neither with tumor markers (alpha-fetoprotein, beta 2-microglobulin) nor with biliary obstruction.

Adult↗
PubMed1988

Effect of age on the etiologic role of the hepatitis B virus in hepatocellular carcinoma in blacks.

Hepatocellular carcinoma often affects blacks at an early age. The purpose of this study was to ascertain if the association between chronic hepatitis B virus infection and hepatocellular carcinoma is the same in young and older black patients. Serum markers of hepatitis B infection were measured by radioimmunoassay in 391 blacks with hepatocellular carcinoma, 173 of whom were less than or equal to 30 yr old and 218 of whom were greater than or equal to 50 yr old. Only 2 of the young patients showed no markers of current or past hepatitis B infection compared with 31 (14.3%) of the older patients (p less than 0.001). Hepatitis B surface antigen was present in 81.5% of the young patients and of these 34.5% were e antigen-positive. The corresponding figures in the older patients were 29.8% and 10.9% (p less than 0.001 in each instance). It is concluded that whereas the association between hepatocellular carcinoma and hepatitis B infection is almost universal in young blacks, a subgroup of older blacks shows no evidence of ever having been infected with this virus.

Adolescent↗
PubMed1988

Interrupted replication of hepatitis B virus in liver tissue of HBsAg carriers with hepatocellular carcinoma.

To search for events underlying reduction of peripheral viremia and integration of hepatitis B virus (HBV) DNA into the liver cell genome in long-term virus carriers with hepatocellular carcinoma, paired samples of liver and tumor tissue were analyzed by molecular hybridization and immunological methods. Most tumor tissues contained integrated viral DNA; in none was extrachromosomal HBV DNA detected. Integrated HBV DNS was also found in peritumor liver tissue in the majority of patients. However, liver of patients either with or without peripheral viremia also contained free HBV DNA and replicative intermediates. In three nonviremic patients with replicative HBV DNA in liver, viral core antigen expression was markedly reduced or absent, whereas viral envelope protein (surface antigen) expression was normal. In one case, replicative intermediates in liver were sensitive to DNase I digestion, indicating that viral DNA was not encapsidated in normal viral core particles. These results suggest that decreased or defective core antigen production can lead to reduced viremia associated with blocked virus assembly/secretion and accumulation of unencapsidated HBV DNA replicative intermediates in the liver cell. Accumulation of such HBV DNA molecular forms in the liver may lead to an increased propensity for HBV DNA to integrate into the host genome, which has been found with high frequency in hepatic neoplasms from patients infected with hepatitis B virus.

Carcinoma, Hepatocellular↗
PubMed1988

Cytokeratin expression in hepatocellular carcinoma: an immunohistochemical study.

Normal human hepatocytes express cytokeratins no. 8 and 18, whereas bile duct cells contain the same cytokeratins and, in addition, cytokeratins no. 7 and 19. This cytokeratin pattern is believed to be preserved during neoplastic transformation. Thirty-four cases of hepatocellular carcinoma (11 well differentiated, 16 moderately differentiated, 7 poorly differentiated) were studied on frozen sections using monoclonal antisera directed against individual cytokeratins no. 7, 8, 18, and 19 in an immunoperoxidase procedure. In 17 of 34 cases, tumor cells showed only reactivity with monoclonals anticytokeratin no. 8 and 18. However, 17 of 34 cases showed an aberrant pattern in that a variable number of tumor cells were stained with anticytokeratins no. 7 and/or 19 in addition to no. 8 and 18. Only three of 11 well-differentiated cases displayed an unexpected cytokeratin pattern, whereas an aberrant pattern was present in all seven of seven poorly differentiated cases. These results are in conflict with previously published data obtained by two-dimensional gel electrophoresis and immunohistochemistry. They indicate that the cytokeratin pattern might not always be preserved during neoplastic transformation. The implication of this finding for the differential diagnosis of metastatic gastrointestinal carcinomas is discussed.

Adolescent↗
PubMed1988

HLA expression in human hepatocellular carcinoma.

This study examines the expression of MHC class I and II antigens and their related invariant chains in 70 cases of human hepatocellular carcinoma (HCC), using monoclonal (Mabs) and polyclonal antibodies. In comparison with normal hepatocytes, the majority (94.3%) of HCCs show enhancement or acquisition of HLA-A, B, C in either a cytoplasmic or membranous distribution, with staining being uniformly distributed throughout the specimen. HLA-A, B, C was accompanied by beta 2-microglobulin expression in all but two cases. Although 44.9% of specimens showed HLA-DR expression, positively staining tumour cells were often sparse and heterogeneously distributed. By contrast, the invariant (I) chain, present in 47.1% of cases, was frequently intensively stained and extensive in distribution. HLA-DR staining was usually cytoplasmic although two cases showed faint membranous enhancement. In addition to HLA-DR and I-chain, two cases also showed HLA-DQ staining. Display of MHC antigens was not related to tumour differentiation or size of the lesion (resected vs. advanced tumours). It is possible that the acquisition of class I antigens by the majority of HCCs may influence tumour behaviour.

Carcinoma, Hepatocellular↗
PubMed1988

Epidemiology of hepatitis B virus infection in South African Chinese.

The authors determined the age-specific prevalence of hepatitis B virus markers in 1,408 Chinese who resided in South Africa in 1983-1985. The small South African Chinese community consists of original Chinese settlers, almost all of whom migrated from the hepatitis B virus endemic mainland China province of Guangdong, and their South African-born descendants. The Chinese live among the white South African community, which has a very low hepatitis B virus carrier rate. The overall hepatitis B virus carrier rate was 5.3%, and the carrier rate was highest in age group 30-39 years (11.9%) and significantly lower in children aged 1-9 and 10-19 years (2.4% and 2.0%, respectively). Overall infection rates increased progressively with increasing age, starting at about 10% in the children aged 1-19 years and reaching 50% in adults aged 60-69 years. Among carrier children, 89% had carrier mothers, and all of the latter were also hepatitis e antigen (HBeAg)-positive. The prevalence of hepatitis B virus carriers in South African Chinese women of child-bearing age was 6.1%, and 41.9% of these carriers were HBeAg-positive. The age-specific prevalence of hepatitis B virus markers among South African Chinese is appreciably lower than that of Chinese in southeastern China, who have carrier rates of 15-20% with a peak in childhood. The prevalence of hepatitis B virus infection appears to be decreasing in South African Chinese, probably because improved hygienic and socioeconomic circumstances, in comparison with those in Guangdong, have resulted in less horizontal transmission of the virus. A diminishing pool of carriers is maintained by perinatal maternal-infant infection.

Adolescent↗
PubMed1988

Transferrin receptor expression in human hepatocellular carcinoma: an immunohistochemical study of 34 cases.

Using a panel of five monoclonal anti-transferrin receptor antibodies, we investigated the transferrin receptor expression in 34 human hepatocellular carcinomas of Belgian (n = 6), Italian (n = 7) and South African (n = 21) origin. For comparison the tumours were also stained with the monoclonal antibody BK 19.9, recognizing an antigen biochemically similar to the transferrin receptor, and with a monoclonal antibody against the epidermal growth factor receptor. Hepatocellular carcinomas express large amounts of transferrin receptors as demonstrated by the intense transferrin receptor immunostaining in 33/34 cases. Differences in staining pattern between and within the tumours were not related to the degree of tumour differentiation, nor to the origin or race of the patient. In 15 cases which included non-tumoural tissue, the tumour was more intensely stained than the surrounding liver parenchyma. The BK 19.9 immunoreactivity was generally weaker and mainly involved stromal cells, except in three cases where an intense staining of the tumour cells was seen. The epidermal growth factor receptor staining was also weaker and only in four cases was the immunoreactivity of the tumour stronger than the surrounding parenchyma. Demonstration of the transferrin receptor may be useful for the detection of malignant foci in liver biopsies. This may be of particular interest in the histological investigation of minute hepatocellular carcinomas.

Biopsy↗
PubMed1988

Hepatitis B virus infection and hepatocellular carcinoma: correlation between IgM antibody to hepatitis B core antigen, hepatitis B e antigen, and hepatitis B DNA.

Sera from 102 black patients with primary hepatocellular carcinoma (PHC) and hepatitis B surface antigenemia were tested for immunoglobulin M antibody against hepatitis B core (IgM anti-HBc), hepatitis B e antigen (HBeAg), and hepatitis B viral (HBV) DNA. Their prevalences were compared to those of a control group of 124 age and sex matched black HBV carriers without tumor. IgM anti-HBc was present in 68.6%, HBeAg in 32.3%, and HBV-DNA in 26.7% of the patients. In the control population, IgM anti-HBc was present in 45%, HBeAg was detected in 3.2%, and HBV-DNA in 25.8%. We conclude that IgM anti-HBc is present appreciably more often than either HBeAg or HBV-DNA in patients with PHC. HBeAg or IgM anti-HBc in serum of HBsAg positive carriers may predict an added risk of PHC development in South African blacks.

Adolescent↗
PubMed1988

The use of radionuclide venography in the differential diagnosis of inferior vena caval obstruction.

In using radionuclide imaging of the inferior vena cava (RIVC) to investigate the prevalence of membranous obstruction of the inferior vena cava (IVC) in patients with hepatocellular carcinoma, it was necessary first to determine if this technique would distinguish membranous obstruction of the IVC both from other causes of IVC obstruction likely to be encountered in these patients and from the picture obtained with severe ascites. RIVC readily distinguished an obstructed from a normally patent IVC. However, membranous obstruction of the IVC could not in most instances be differentiated from extrinsic compression of the IVC by an enlarged tumourous liver, occlusion of the lumen of the IVC by tumour, or the effect of severe ascites. In a proportion of the patients with membranous obstruction of the IVC, flow of the radionuclide through large superficial collateral vessels was seen, enabling this diagnosis to be made with confidence. Thus, if RIVC shows the IVC to be obstructed or if severe ascites is present, contrast venography will usually be necessary to determine the nature of the obstructing lesion.

Ascites↗
PubMed1988

Inferior vena caval and right atrial thrombosis complicating an amebic hepatic abscess.

We describe a 50-yr-old black laborer who presented with right lower chest pain, weight loss, and pedal edema. Ultrasonography and computed tomograms showed a large abscess cavity in the right lobe of the liver which extended very close to the inferior vena cava. The lumen of the adjacent inferior vena cava was partially occluded by thrombus, which could be traced up into the cavity of the right atrium. The hepatic veins were normally patent. Sterile blood-stained pus was aspirated from the abscess. Antibodies against Entamoeba histolytica were present in high titer in the patient's serum. Although propagation of hepatocellular carcinoma into the inferior vena cava and even up into the right atrium is well recognized, inferior vena caval thrombosis extending up into the right atrium has not hitherto been reported as a complication of amebic hepatic abscess.

Heart Atria↗
PubMed1987

Prevalence of chronic hepatitis B virus infection in pregnant black women living in Soweto.

Urban black children have an appreciably lower hepatitis B virus (HBV) carrier rate than rural Black children. The purpose of this study was to determine the carrier rate in the preceding generation of urban-born Blacks, in order to establish how rapidly the reduction in carrier rate following urbanization has occurred. HBV markers were measured by radioimmunoassay in the serum of 616 urban-born and 618 rural-born pregnant Black women living in Soweto. HBV carriage was significantly less frequent in the urban-born (1.3%) than in the rural-born women (4.0%; P less than 0.05). Total HBV exposure was also less common in the urban-born women (35.2% compared with 44.7%; P less than 0.001). HBV carrier rates were the same in women whose mothers were urban-born (1.31%) and those with rural-born mothers (1.68%). Only three rural-born and no urban-born women had replicative HBV infection. These findings suggest that the decrease in the HBV carrier rate with urbanization is abrupt, occurring in the first generation born in the urban environment.

Adult↗
PubMed1987

Depressed natural cytotoxicity but normal natural killer cytotoxic factor (NKCF) production by mononuclear cells derived from patients with hepatocellular carcinoma.

This study investigated the relation between the production of natural killer cytotoxic factors (NKCF) and the phenomenon of natural killing (NK) activity against target K562 cells. Two different models of defective NK cell activity were employed. In the first instance, cytotoxic activity of mononuclear cells (MN) derived from patients with hepatocellular carcinoma was compared to the ability of these cells to produce NKCF. Although direct cytotoxicity was considerably impaired in these patients, the ability of their MN to produce NKCF when stimulated with K562 cells was found to be normal. In the second model, MN treated with the lysosomotropic drug monensin showed considerably reduced direct cytotoxic activity, although they were capable of producing normal amounts of NKCF when activated by K562 cells. These results therefore indicate that there is no correlation between NK activity and corresponding NKCF release, and suggest that NKCF production and activity is independent of direct NK cytotoxic activity.

Adult↗
PubMed1987

Expression of the hepatitis B virus genome in chronic hepatitis B carriers and patients with hepatocellular carcinoma.

We examined the methylation status of CCGG sites in hepatitis B virus (HBV) DNA to determine whether methylation could be responsible for the selective expression of the HBV surface gene in chronic hepatitis B infection and hepatocellular carcinoma. Infected liver tissue from patients with low levels of viral replication was analyzed for HBV DNA copy number per haploid cell genome. Total cellular DNA, with sufficient HBV DNA, was digested with the restriction endonucleases Msp I and Hpa II, to determine whether the HBV DNA was methylated, or HindIII, to determine whether the HBV DNA was integrated or episomal. The cleavage fragments were analyzed by Southern blotting and hybridization to 32P-labeled HBV DNA. In replicative chronic hepatitis B, hypomethylation of the HBV genome correlated with HBV expression in both virions and infected tissue. In carriers with nonreplicative infection, it was difficult to ascertain the role of methylation as copy number was low. HBV DNA copy number was also low in 17 out of 29 of the tumor tissues tested and as many as 14 out of 16 of the adjacent non-neoplastic tissues tested. Integrated sequences were hypermethylated in the PLC/PRF/5 cell line and in six of the tumor tissues suggesting that methylation plays a role in HBV gene repression. However, since DNA from five other tumors was hypomethylated, the belief that methylation per se is an absolute determinant of HBV core gene repression does not hold for human hepatocellular carcinoma tissue. Additional factors, such as gene rearrangements, therefore, must influence HBV expression in hepatocellular carcinoma.

Base Sequence↗
PubMed1986

Serum erythropoietin concentrations in patients with hepatocellular carcinoma.

Erythrocytosis (polycythemia) is a well-described paraneoplastic phenomenon in patients with hepatocellular carcinoma, but its pathogenesis remains uncertain. Using a radioimmunoassay, we have measured serum erythropoietin concentrations in 65 southern African blacks with this tumor and 61 matched controls. Four patients had an increased hemoglobin concentration and packed cell volume, and the remainder had normal values. Twenty-three percent of the patients with hepatocellular carcinoma (15/65) were found to have raised serum erythropoietin concentrations, the values ranging up to 344 mu/ml. Only one of these patients had an increased hemoglobin concentration and packed cell volume. This apparent anomaly could be explained if the erythrocytosis that would normally result from high serum erythropoietin values had been counteracted by the inhibition of erythropoiesis which occurs in advanced malignant disease. Alternatively, the erythropoietin produced by the tumor might not always be biologically active. Three patients had increased hemoglobin values and packed cell volumes in the presence of normal serum erythropoietin concentrations. One of these patients was hypoxic as a result of multiple pulmonary metastases, and the others may also have been. There was no correlation between serum erythropoietin and alpha-fetoprotein concentrations in individual patients.

Adolescent↗