Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small-sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen-positive cases/hepatitis C virus antibody-positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA-II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small-sized HCCs.

The blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities. The portal blood supply was evaluated with computed tomography (CT) during arterial portography (CTAP); the arterial blood supply was evaluated with hepatic angiography, CT angiography, CT following intraarterial injection of iodized oil, or ultrasound following intraarterial injection of carbon dioxide microbubbles. A total of 84 surgically confirmed hepatocellular carcinomas (HCCs) (less than or equal to 3 cm) and 25 areas of adenomatous hyperplasia (AH) were included in the study. At CTAP, a portal blood supply was seen in 96% of cases of AH and only 6% of HCCs (chi 2, P less than .005). In contrast, an arterial supply greater than that of the surrounding liver was verified in 94% of the HCCs and only 4% of the cases of AH (chi 2, P less than .005). The blood supply of areas of AH with atypical hepatocytes and the blood supply of well-differentiated HCCs (Edmondson grade 1) tended to be intermediate between that of AH without atypia and that of HCC that was Edmondson and Steiner grade 2 or greater. Evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early-stage HCC.

The hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase (RdRP), which is the central catalytic enzyme of HCV replicase. We established a new method to purify soluble HCV NS5B in the glutathione S-transferase-fused form NS5Bt from Escherichia coli which lacks the C-terminal 21 amino acid residues encompassing a putative anchoring domain (anino acids 2990 -3010). The recombinant soluble protein exhibited RdRP activity in vitro which was dependent upon the template and primer, but it did not exhibit the terminal transferase activity that has been reported to be associated with the recombinant NS5B protein from insect cells. The RdRP activity of purified glutathione S-transferaseNS5Bt and thrombin-cleavaged non-fused NS5Bt shares most of the properties. Substitution mutations of NS5Bt at the GDD motif, which is highly conserved among viral RdRPs, and at the clustered basic residues (amino acids 2919 -2924 and 2693-2699) abolished the RdRP activity. The C-terminal region of NS5B, which is dispensable for the RdRP activity, dramatically affected the subcellular localization of NS5B retaining it in perinuclear sites in transiently overexpressed mammalian cells. These results may provide some clues to dissecting the molecular mechanism of the HCV replication and also act as a basis for developing new anti-viral drugs.

Background/Aims-The characteristics of pepsinogen screening for gastric cancer were investigated to establish a suitable cut oV point for identifying gastric cancer, using endoscopic diagnosis as the yardstick. Subjects/Methods-Serum pepsinogen concentrations were measured in 5113 subjects who were also screened for gastric cancer by endoscopy. The cut oV point for pepsinogen was determined using receiver operator characteristics curves. Results-The most suitable cut oV point was a pepsinogen I concentration of less than 70 ng/ml and a ratio of pepsinogen I to pepsinogen II of less than 3.0. Using this cut oV point, the sensitivity and specificity of pepsinogen screening for gastric cancer were 84.6% and 73.5% respectively. All cases of gastric cancer in patients with severe atrophic gastritis were detected. However, two of four cases of gastric cancer in patients with mild atrophic gastritis were overlooked. In subjects with mild atrophic gastritis, when gastric cancer arises within the fundic gland region, the size of the lesion determines whether it is possible to detect cancer by serum pepsinogen screening. Conclusion-Pepsinogen screening has many advantages, including its suitability for combination with other screening methods because it is simple and inexpensive. (Gut 1999;44:693-697)

Hepatitis C virus (HCV) NS5B is RNA-dependent RNA polymerase (RdRP), the essential catalytic enzyme for HCV replication. Recently, NS5A has been reported to be important for the establishment of HCV replication in vitro by the adaptive mutations, although its role in viral replication remains uncertain. Here we report that purified bacterial recombinant NS5A and NS5B directly interact with each other in vitro, detected by glutathione S-transferase (GST) pull-down assay. Furthermore, complex formation of these proteins transiently coexpressed in mammalian cells was detected by coprecipitation. Using terminally and internally truncated NS5A, two discontinuous regions of NS5A (amino acids 105-162 and 277-334) outside of the adaptive mutations were identified to be independently essential for the binding both in vivo and in vitro (Yamashita, T., Kaneko, S., Shirota, Y., Qin, W., Nomura, T., Kobayashi, K., and Mkyrakami, S. (1998) J. Biol. Chem. 273, 15479 -15486). We previously examined the effect of His-NS5A on RdRP activity of the soluble recombinant NS5Bt in vitro (see Yamashita et al. above). Wild NS5A weakly stimulated at first (when less than 0.1 molar ratio to NS5B) and then inhibited the NS5Bt RdRP activity in a dose-dependent manner. The internal deletion mutants defective in NS5B binding exhibited no inhibitory effect, indicating that the NS5B binding is necessary for the inhibition. Taken together, our results support the idea that NS5A modulates HCV replication as a component of replication complex.