Hepatocellular carcinoma (a 28-year necropsy review).

Although primary liver carcinoma is one of the most common forms of malignancy in most parts of Africa and the Far East, recent reports indicate that the incidence of primary liver cancer has been increasing in Western countries. Our retrospective study is in agreement with this suggestion. From 28,311 autopsies performed at the Department of Pathology in Hradec Kralove from 1951 to 1978, 91 primary liver carcinomas were found. The increase was apparent in the period 1971 to 1978: 0.53% compared to 0.22% in the period 1951 to 1970. Of the 91 cases, 68 were in association with cirrhosis. In 6 of 17 liver samples, aflatoxin B1 was proved. Some authors suggest that the increase of liver cancer is related to the increase of cirrhosis. Other authors note a striking association of tumors with HBAg. The increase of cirrhosis has not been confirmed in our study. We assume that the carcinogenic mechanism is more complex and that the determinating factor might be an interaction of HB infection and some of the environmental carcinogenic factors, e.g., aflatoxin.

[Myoblastic myoma of the tendon of long flexor of the thumb]. / Myoblastický myom slachy dlouhého flexoru palce ruky.

The case history of a female patient with flexion contracture of the thumb, having been caused by a tumour originated in the tendon of musculus flexor pollicis longus and histologically classified as a myoblastic myoma is presented. After a complete resection of the tumour and substitution of the originated defect of the tendon the function of the right hand became possible to a full extent and no signs of a relapse may be seen four years after the operation.

Immunoassay procedures to detect exposure to aflatoxin B1 and benzo(a)pyrene in animals and man at the DNA level.

Immunological methods were used to examine human liver for the presence of aflatoxin-DNA adducts and human lung for benzo(a)pyrene diol-epoxide DNA (BPDE-DNA) adducts. Eight liver samples obtained from Czechoslovakian patients with primary hepatocellular carcinoma were studied, seven of which had detectable anti-aflatoxin inhibitory material. Values ranged between 0.63 and 3.51 picomoles aflatoxin per mg DNA. In a separate, independent study performed in another laboratory the one sample with no aflatoxin bound to DNA also had no free aflatoxin present in the liver. In the case of the human lung DNA samples, 12 samples were examined, the samples having been removed during thoracic surgery, and five had detectable anti-BPDE-DNA antibody activity. The positive samples were all from smokers and had inhibitory values ranging from 4 to 12 femtomoles per mg DNA. Samples were prepared by immunoconcentration prior to analysis. These preliminary results support the view that immunological methods can be used to examine human tissue DNA for carcinogen adducts.

Aflatoxin, viral hepatitis and primary liver cancer.

Thirty-eight cases of primary liver cancer (PLC) from the Department of Pathology, Charles University, Hradec Kralové were investigated. The viral hepatitis HBsAg antigen was found in the sera of 8 of the 38 patients. Radioimmunoassay demonstrated aflatoxin in 27 of 34 cases. Fluorescence microscopy revealed a fluorescence characteristic of aflatoxin and its fluorescent metabolites in the peritumoral tissue and the tumor for all of the cases studied. This study emphasizes the increasing incidence of PLC over the last 15 years. In addition, this type of cancer now appears to develop in a different manner: reduction in the number of cases with cirrhosis, progressive rise in the number of women affected, and occurrence of PLC in children and adolescents. These observations tend to indicate that aflatoxin might play a significant role in the genesis of PLC.

Pulmonary interstitial fibrosis with evidence of aflatoxin B1 in lung tissue.

Three cases of pulmonary interstitial fibrosis, two in agricultural workers and one in a textile worker, are reported. In lung samples of all three patients the presence of aflatoxin B1 was demonstrated by radioimmunoassay (RIA). A possible occupational risk of aflatoxin exposure via the respiratory tract is suggested.

The time course of biochemical and histological changes following carbon tetrachloride-induced liver damage in rats of both sexes.

A detailed analysis is presented of the time changes in the development of liver damage 6, 12, 24, 48 and 72 hours after i.p. administration of carbon tetrachloride [CCl4] in a dose of 0.75 ml, i.e. 1 200 mg/kg body weight to rats of both sexes. The severity of liver damage was assessed from the histological and biochemical changes of AST, ALT, alkaline phosphatase and GMT serum activity. From our experiments it follows that in male rats the level of transaminases increases earlier than in female rats, as early as 6 h after the administration of CCl4, reaching a maximum 12 h later. These changes prevail for a longer time period, the level of transaminases remaining increased even 72 h after CCl4 administration. In female rats the biochemical changes occur later reaching the maximum elevation of AST and ALT 24 h after CCl4 administration. The values slowly return to normal after 48 h, and after 72 h the levels of transaminases are identical with the control group. The above given biochemical results are in good agreement with the histological findings demonstrating a higher regenerative activity in female rats. This finding was also proved by specific liver DNA activity assay.

Aflatoxin and Reye's syndrome.

This study indicates the association of a mycotoxin (aflatoxin B1) with Reye's syndrome. The presence of aflatoxin B1 in livers from 4 girls and 1 boy aged from 3 to 11 months was detected using two different techniques: a) direct chemical titration of aflatoxin B1 in liver extracts; and b) fluorescence microscopy of unstained liver sections. Our results suggest the existence of acute intoxication by aflatoxin in these children.

Characterization of aflatoxin BI (AFB) in human liver cancer.

The occurrence of aflatoxin BI in human liver cancers was evidenced by thin layer chromatography followed by spectrophotometry of the chloroformic extract of tissue samples. Microscopic slides obtained from the same samples were also examined by direct fluorescence microscopy. In five cases, the chemical identification of aflatoxin BI was associated with the demonstration of a strong blue fluorescence of the tumor cells. In seven other samples, a slight blue fluorescence similar to that of AFB was observed, but the toxin was not detected by the chemical assay. In two cases, negative results were registered by both methods. The occurrence of AFB-macromolecules complexes not extractible by organic solvents and differences in the sensitivities of the two methods may explain the observed discrepancies.

Influence of antithymocytic serum on the regenerating activity of the liver after partial hepatectomy in mice.

In experiments on mice the effect of rabbit-anti-mouse antithymocytic serum on the growth of the liver and on the onset of proliferating activity of the liver after partial hepatectomy was studied to elucidate the question of assumed participation of the lymphoid system in the proliferation of hepatic tissue. Administration of three doses of antithymocytic serum (0.1 ml/10 g) by the i.p. route in 24 hour intervals led to a marked increase of the weight of the spleen and increase of DNA synthesis in liver of non-operated mice. Administration of serum 24 hours before partial hepatectomy (PHE) concomitantly with PHE and 24 hours after PHE did not influence substantially the rate of DNA synthesis in the regenerating liver 34 and 48 hours after PHE and did not influence the mitotic index of hepatocytes. In the livers of mice to whom antithymocytic serum was administered proliferation of cells of the lymphocyte series and phagocyte activation occurred. These cells were located in the hepatic sinuses and periportal areas. Antithymocytic serum--contrary to chemical immunosuppressive substances--does not exert an inhibitory action on regeneration of hepatic tissue; alone does not even cause inhibition of the lymphoid system which could exert a negative effect on regeneration of the liver.

Congenital dyserytropoietic anaemia, type II (HEMPAS) in three siblings.

These siblings of a Czech family aged 21, 19 and 6 years, respectively, with congenital dyserythropoietic anemia, type II, (HEMPAS) are reported. In two elder siblings ferrokinetic studies revealed a rapid plasma 59Fe clearance, markedly decreased erythrocyte incorporation and shortened 51Cr red-cell survival. Direct anti-globulin test was found positive in one of them. Further investigations revealed low values of blood plasma cholesterol, total lipids, beta-lipoproteins, beta-carotine and vitamin E and A as well as low values of the prothrombin complex. Liver biopsy demonstrated siderosis and disseminated intravascular coagulation in the liver in both patients. The possible reasons for these humoral aberrations are discussed.

Aflatoxin and encephalopathy with fatty degeneration of viscera (Reye).

In the past 5 years we have observed 27 children at the age from 3 days to 8 years who died on the encephalic syndrome with fatty degeneration of the viscera (Reye). According to the morphological changes in the liver and to the clinical course, we have divided our cases into 3 groups. In the first group there were 20 children who died within 2-10 days after the first symptoms of the disease appeared. In their liver diffuse fatty degeneration was found. In the second group there were 3 children who died within 1-2 months after the acute onset of the disease. In their liver fibrosis with bile duct proliferation and steatosis were found. In the third group there were 4 children who died within 2-4 months after the first symptoms. Their liver showed cirrhosis. The bacteriological and virological investigations in all cases were negative, but in the most of them direct contacts with viral infections were proved. In the liver specimens of the children in all 3 groups the presence of aflatoxin B1 chromatographically and spectrophotometrically was found. The source of the intoxication in 5 cases was aflatoxin contaminated milk food. Our observations of 2 - 3 - days old newborns with the morphological changes similar to that of Reye's syndrome seems to support our hypothesis about the possibility of the intrauterine intoxication. We suggest that aflatoxin represents an important factor in the etiology of this syndrome and a high risk for human health.