Eiichiro Yumoto

Serum gamma-interferon-inducing factor (IL-18) and IL-10 levels in patients with acute hepatitis and fulminant hepatic failure.

Background and Aims: The aim was to determine the role of T‐helper (Th)1/Th2 cytokine responses in the clinical outcome of patients with acute liver injury.

Preoperative estimation of remnant hepatic function using fusion images obtained by 99mTc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography

Assessment of hepatic functional reserve is important in hepatic resection. The aim of this study was to evaluate the role of hepatic asialoglycoprotein receptor (ASGP‐R) analysis in the preoperative estimation of remnant liver function in liver surgery.

Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution

SummaryAfter 12 days of culture, VX2 carcinoma cells were inoculated into the liver of 16 rabbits; 14 days later,131I-labeled iodized oil ([131I]-Lp) suspended in lipiodol was injected into the hepatic artery. Selective accumulation of the contrast material in the tumor for an extended time was evident on X-rays and hepatic scintiphotographs. The antitumor effect was remarkable. [131I]-Lp agents warrant further examination for their clinical usefulness. Internal radiation therapy by transcatheter hepatic arterial injection of [131I]-Lp (group A) was evaluated in 9 patients with hepatocellular carcinoma (HCC, tumor stage III or IV) associated with liver cirrhosis (LC) and compared with combination therapy of Lp-TAE (group B) in 18 patients with HCC (tumor stage III or IV) associated with LC. In group A, serum AFP levels dropped rapidly in eight of the nine patients who had an elevated intial level of more than 500 ng/ml. The average reduction in tumor size was 50% in eight cases as determined by computed tomography. Histological examination of one resected liver specimen at 3 months after the third injection of [131I]-Lp revealed microscopic features highly suggestive of a radiation effect in the [131I]-Lp-containing area. The 1-year survival value for patients with HCC was estimated at 49.0% using the Kaplan-Meier method. The survival of patients treated with internal radiation therapy tended to be better than that of those treated with Lp-TAE (P=0.119).

Estimation of remnant liver function before hepatectomy by means of technetium-99m-diethylenetriamine-pentaacetic acid galactosyl human albumin

To improve the results of hepatectomy in cirrhotic patients, the likely reserve function of the liver was evaluated before surgery. Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m-diethylene triamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is a newly developed analog ligand to ASPG-R. The probable functional reserve of the remnant liver after hepatectomy was estimated preoperatively as the hepatic binding protein (HBP) concentration specific for ASGP-R on the hepatocellular membrane of the remnant liver. This estimate was based on the effective liver volume rate, obtained by the uptake of99mTc-GSA. In all, 3 normal volunteers, 3 patients with chronic hepatitis (CH), 9 patients with liver cirrhosis (LC), 2 patients with hepatic cystadenoma, 3 patients with hepatocellular carcinoma (HCC) associated with CH, and 21 HCC patients with LC were studied. The mean value ±SD obtained for HBP in normal volunteers (three cases) and in patients with mild (four cases), moderate (two cases), and severe liver damage (five cases) were 0.74±0.03 μM, 0.43±0.042 μM, 0.31±0.05 μM, and 0.20±0.05 μM, respectively. Most of the cases in which the preoperative HBP of the remnant liver was above 0.22 μM had a good postoperative course irrespective of the type of hepatectomy. On the other hand, in subjects with a remnant liver HBP of between 0.22 and 0.11 μM, postoperative severe liver dysfunction occurred in about 50% of cases. In all cases with a remnant liver HBP below 0.1 μM, the prognosis was very poor, indicating that hepatectomy should be avoided. The HBP concentration detected by the99mTc-GSA study is a very sensitive indicator of changes in the hepatic functional reserve, and the HBP value for the functional reserve of the remnant liver is extremely useful for estimating the liver function before and after hepatectomy.

Cellular distribution of telomerase reverse transcriptase in human hepatocellular carcinoma

Background and Aim:  Telomerase is the enzyme that synthesizes telomeric DNA, and the activation of telomerase is closely related to cellular immortality. Telomerase activity has been reported in many human cancer tissues and is regulated by the expression of human telomerase reverse transcriptase (hTERT). The aim of the present study was to identify hTERT‐expressing cells in human liver tissues and evaluate the feasibility of the hTERT promoter for gene therapy of hepatocellular carcinoma (HCC).

Elevated levels of tissue inhibitor of metalloproteinases (TIMPS) in human hepatocellular carcinomas

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in Japan. Invasion and metastasis of HCC are frequently observed during the development of HCCs, and are regulated by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). We have previously reported the strong expression of TIMP-1 and TIMP-2, and cellular localization of the transcripts in HCCs [1]. But the mechanisms of invasion and metastasis of HCCs, and particularly the role of TIMPs are still unclear. The purpose of this study was to examine the tissue concentration of the TIMP-1 and to study the potential involvement of TIMP-1 in the development of HCCs.