Arthur A. Dunk

Controlled Trial of Propranolol for the Prevention of Recurrent Variceal Hemorrhage in Patients with Cirrhosis

We conducted a prospective randomized trial of propranolol for the prevention of recurrent variceal bleeding in 48 patients with cirrhosis of the liver. During a follow-up period of up to 21 months, 12 of 26 patients in the propranolol group and 11 of 22 in the control group had rebleeding from esophageal varices. There was no significant difference in rebleeding between the two groups. This contrasts with a previous report of the efficacy of propranolol in preventing recurrent gastrointestinal bleeding in alcoholic cirrhosis. The difference in results may be due to the inclusion in our study of patients with other causes of cirrhosis and more severe liver disease. Propranolol may not be indicated for the prophylaxis of variceal rebleeding in such patients, and we advocate that its use be limited at present to controlled clinical trials.

Natural killer cell activity in hepatocellular carcinoma: in vitro and in vivo responses to interferon

We have measured natural killer (NK) cell activity in patients with hepatocellular carcinoma (HCC) and have examined the effects of in vitro and in vivo administration of alpha-interferon (IFN) on NK cell activity. The NK cell cytotoxicity of HCC patients was significantly lower than that of patients with cirrhosis or healthy controls. Reduced NK cell cytotoxicity in HCC did not correlate significantly with either the serum alpha-foetoprotein concentration or the patient WHO performance grade. NK cell cytotoxicity in all groups could be increased by prior incubation of effector cells with IFN, but this was significant only in HCC patients, in whom 10 IU/ml of IFN increased NK cell cytotoxicity from 37 +/- 10% to 53 +/- 8% (effector to target ratio, 50:1, mean +/- SEM; p less than 0.05). Further increases in IFN concentration failed to increase NK cell activity further. NK cell cytotoxicity was measured immediately before and 24 h after 2.5 x 10(6) IU/m2 of IFN was given subcutaneously to four HCC patients. NK cell cytotoxicity rose from 27 +/- 9% to 61 +/- 5% (effector to target ratio, 50:1, mean +/- SEM; p = 0.05).

In vitro and in vivo tumour localisation with a monoclonal antibody directed against a membrane antigen on the human hepatocellular carcinoma cell line PLC/PRF/5

A monoclonal antibody, designated K-PLC1, has been produced to a tumour-associated antigen on the cell membrane of the PLC/PRF/5 cell line. Using an indirect immunofluorescence technique this antibody produced membrane staining of three hepatocellular carcinoma (HCC) cell lines and it has positively stained 10 of 11 human HCC biopsy specimens. In vitro, 125I-labelled K-PLC1 binds specifically to PLC/PRF/5 cells, as shown by competitive inhibition experiments. Tumours derived from the PLC/PRF/5 cell line were grown in nude mice and groups of tumour-bearing animals were injected with either [125I]K-PLC1 or [125I]mouse IgG, and then killed at 1, 4 or 7 days post injection. Bound radioactivity was counted in a variety of solid organs. Tumour:liver ratios for K-PLC1 were greater than those for mouse IgG at each time point, the differences being greatest on day 4 (ratio K-PLC1 4.4 +/- 0.93, ratio mouse IgG 1.53 +/- 0.60, mean +/- SD, P less than 0.05). The amount of [125I]K-PLC1 bound was greater in the tumour than in any other solid organ, the differences again being maximal on day four. Blood pool radioactivity however remained high throughout the study period. We conclude that anti-HCC monoclonal antibodies may be of value as immunodiagnostic and immunotherapeutic agents in human HCC.

Review: the treatment of hepatocellular carcinoma

Surgical resection offers the only realistic hope of cure in hepatocellular carcinoma (HCC) but is usually not possible, either because the tumour is widespread throughout the liver at diagnosis, or because liver function is adversely affected by concomitant cirrhosis. The results of operation in early asymptomatic disease are, however, encouraging and efforts should be made to screen regularly the cirrhotic population at risk of HCC development.

Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas

Human lymphoblastoid interferon, in an initial dose of 2.5 MU m−2 weekly i.m., was given with mitozantrone 12 mg m−2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long‐term survivors in those not given interferon; more side‐effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.

Human hepatocellular carcinoma tumor xenografts

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivostudies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.

Hepatocellular Carcinoma: Clinical and Prognostic Features in British Residents

Hepatocellular carcinoma (HCC) is a disease with a pronounced geographic variation in incidence, and, though rare in Western Europe, is, on a global scale, one of the commonest malignancies affecting Man (1, 2). The clinical features in high incidence areas are well described (3-5). Hepatocellular carcinoma, as seen in Britain, seems to be diagnosed late in its natural history and most patients die within a few weeks of diagnosis. We have therefore analysed the clinical features of 50 consecutive British patients with histologically proven HCC to determine whether some common presenting clinical features may suggest HCC development, and whether some simple clinical and laboratory parameters may be of prognostic importance. Most patients were male (M:F, 2.8:1) and median age was 58 years (range 16-77 years), 12 patients (23%) being less than 40 years at diagnosis. Forty-one patients (82%) were white Caucasians born in Britain, and the remaining nine patients (18%) were from the immigrant population. Only 54 per cent of patients were known to