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Twenty-eight cases with non-resectable hepatocellular carcinoma were examined. Chemoembolization using degradable starch microspheres (DSM) was performed in 19 cases. DSM, 40-45 micron in diameter, which are degraded by serum amylase, temporarily obstruct arterial blood flow at capillary bed. Adriamycin mixed with DSM was injected into patients through the proper hepatic artery. Hyperthermia (8 MHz radiofrequency) combined with chemoembolization was performed in 9 cases. In all cases treated by hyperthermia combined with chemoembolization, the intratumoral temperature was measured by a thermocouple thermometer during heating alone and heating after injection of DSM. The therapeutic effect was evaluated by the change in tumor size measured by angiography or computed tomography. The efficacy of hyperthermia combined with chemoembolization was compared with that of chemoembolization alone. Intratumoral temperature was 1.0 degree C higher by heating after injection of DSM than by heating alone. Partial response (tumor regression of over 50%) was observed in 8 of 19 cases (42%) with chemoembolization alone. Partial response was observed in 6 of 9 cases (67%) with hyperthermia combined with chemoembolization. One-year survival rate was 58% in chemoembolization alone, against 83% in hyperthermia combined with chemoembolization. Our results suggest that hyperthermia combined with chemoembolization using DSM is effective in the treatment of hepatocellular carcinoma.

cDNA clones having a nucleotide sequence encoding a human monocyte chemotactic and activating factor (MCAF) were isolated and sequenced. The amino acid sequence deduced from the nucleotide sequence reveals the primary structure of the MCAF precursor to be composed of a putative signal peptide sequence of 23 amino acid residues and a mature MCAF sequence of 76 amino acid residues. The amino acid sequence of MCAF showed 25-55% homology with other members of an inducible cytokine family, including macrophage inflammatory protein and some putative polypeptide mediators known as JE, LD78, RANTES and TCA-3. This suggests that MCAF is a member of family of factors involved in immune and inflammatory responses.

A 45-year-old man with right hypochondralgia and marked leukocytosis was found to have Borrmann type II carcinoma of the sigmoid colon and its metastasis to the liver. The peripheral leukocyte count gradually increased up to 150 X 10(3)/mm3 according to the tumor enlargement. The patient died of hepatic insufficiency, and autopsy revealed carcinoid of the colon and its metastasis to the liver. Leukemoid reaction has been reported in various kinds of malignancies. However, the present case seems to be of particular interest because of the rare association with carcinoid and marked leukocytosis of more than 100 X 10(3)/mm3 without any evidence of infection.

The induction of a novel Ca2+-dependent protease in rat liver treated with various liver promoters, as well as its increase in preneoplastic lesions during liver carcinogenesis, was demonstrated. Six groups of male Fischer 344 rats (150 g body weight) were fed separately diets containing one of the following promoters: 0.05% phenobarbital (PB), 0.05% dichlorodiphenyltrichloroethane (DDT), 0.25% ethyl-alpha-chlorophenoxyisobutyrate (CPIB), 0.5% butylated hydroxytoluene (BHT), 10 ppm 17-alpha-ethynylestradiol (EE), and 0.05% of the non-promoter diphenylhydantoin (DH). After feeding the indicated diets for 1 week, rats were killed and protease activity in the microsomal fraction of liver tissue was determined using N-benzoyl-L-tyrosine ethyl ester as substrate. The activity of protease increased 3- to 5-fold after treatment with the promoters and compared with normal liver; the non-promoter (DH) induced a slight increase in activity. Hyperplastic nodules were induced according to the method of Solt and Farber. The activity of protease was significantly high in these preneoplastic lesions compared with the surrounding liver tissue. Biochemical characterization of this protease revealed the following properties: high Ca2+ dependency, different molecular weight and optimum pH from previously reported proteases, and preferential distribution in the SER fraction. These results suggest that a novel type of protease is induced specifically in the liver by promoters of liver carcinogenesis. The possible importance of this protease in the carcinogenic process is discussed.

The activity of a novel Ca2+-dependent protease in preneoplastic and neoplastic tissues of male Fisher 344 rat liver was examined during experimental liver carcinogenesis. This protease activity is significantly high in hyperplastic nodules and hepatocellular carcinomas which were induced by the method of Solt and Farber. Taken together with our previous report on the promoter-specific induction of this protease, the results suggest the possible importance of this protease in the promotion stage of liver carcinogenesis.

Transcatheter chemoembolization using Degradable Starch Microspheres (DSM) was performed in 22 patients with metastatic liver cancer. DSM, 45 micron in diameter, which are degraded by serum amylase, temporarily obstruct arterial blood flow at the arteriolar capillary bed. Mitomycin C mixed with DSM was injected into the proper hepatic artery. The therapeutic effect of this chemoembolization was evaluated by the change in tumor size measured by angiography or computed tomography. Tumor regression of over 50% was observed in 15 of 22 cases (68%). Elevated serum CEA levels (greater than 10 ng/ml) decreased in 13 of 18 cases (72%). The overall one-year survival rate was 55%. The one-year survival rate was 83% in 8 patients with H2 type liver metastasis. Although half of the patients had transient pain within 2 hours, no major side effects such as bone marrow suppression or hepatotoxicity were observed. Our results suggest that chemoembolization using DSM is effective in the treatment of metastatic liver cancer.