Yoshinori Iwata

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma

OBJECTIVES:The present study was designed to assess the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) for predicting outcome in patients with hepatocellular carcinoma.METHODS:FDG-PET was performed in 48 patients with hepatocellular carcinoma. For quantitative evaluation, a region of interest (ROI) was placed over the area of maximum activity within the lesion. A background ROI was then placed over the nontumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-nontumor ratio of the SUV.RESULTS:The tumor-volume doubling time, as index of the growth rate of hepatocellular carcinoma, correlated significantly with SUV ratio but did not correlate with SUV. On the basis of the SUV ratio, the patients were divided into two groups of similar size: group A, SUV ratio of ≤1.5; and group B, SUV ratio >1.5. The cumulative survival rate was significantly lower in group B than in group A. On the basis of the SUV, the patients were divided into two groups of roughly equal size: group C, ≤SUV 2.6; and group D, >SUV 2.6. The cumulative survival rate was similar in these groups. On regression analysis with the Cox proportional hazards model, the SUV ratio and tumor number were significantly related to survival.CONCLUSIONS:These results suggest that FDG-PET is useful not only for the evaluation of the malignancy of hepatocellular carcinoma but also for the prediction of outcome in patients with hepatocellular carcinoma.

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma.FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV.The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the α-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

USE OF SHORT NEEDLE KNIFE FOR ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

Background:  The emergence of endoscopic submucosal dissection (ESD) has enabled en bloc resection of lesions, which were conventionally difficult. However, ESD has problems of technical difficulty and high incidence of complications. In order to improve the procedure of marking and submucosal dissection in the esophagus, we modified and adjusted the standard needle knife to a short needle knife having a tip portion with a projection length of 1.5 mm.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level and high-sensitivity C-reactive protein concentration in autoimmune hepatitis.

We aimed to examine the relationship between the Wisteria floribunda agglutinin positive Mac‐2‐binding protein (WFA+‐M2BP) level and high‐sensitivity C‐reactive protein (hCRP) concentration and liver histological findings for patients with autoimmune hepatitis (AIH).

Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K2

BackgroundVitamin K2 has been reported to suppress the growth of human hepatocellular carcinoma (HCC) in vitro and hepatocarcinogenesis in hepatitis C virus (HCV)-related cirrhosis in vivo. Hepatoma-derived growth factor (HDGF) is a unique nuclear targeting growth factor that is highly expressed in HCC cells and is a possible prognostic factor for patients with HCC. We investigated the regulation of HDGF expression by vitamin K2.MethodsThree HCC-derived cell lines, HepG2, HuH-7, and SK-Hep-1, were used. Cell number was determined with the MTT assay. The expression levels of HDGF mRNA and protein were measured by the real-time reverse transcriptase-polymerase chain reaction (PCR) method and ELISA and Western blot analysis, respectively. The HDGF promoter activity was measured by a dual luciferase-reporter assay.ResultsVitamin K2 suppressed the growth of the three HCC cell lines in a dose-dependent manner. Vitamin K2 significantly suppressed the expression of the HDGF protein and mRNA in three cell lines. By a luciferase assay, vitamin K2 significantly suppressed the promoter activity of the HDGF protein. Based on some luciferase-reporter plasmids containing truncated promoter regions, the possible responsive site of vitamin K2 seems to reside in the region −1 to −150 bp of the HDGF gene.ConclusionsThese findings suggested that regulation of the HDGF gene expression is one of the crucial mechanisms of vitamin K2-induced cell growth suppression for HCC.

Development of a new in situ hybridization method for the detection of global bacterial DNA to provide early evidence of a bacterial infection in spontaneous bacterial peritonitis

BACKGROUND & AIMS Despite the importance of identifying the causative pathogen(s), ascitic fluid cultures are occasionally negative in patients with spontaneous bacterial peritonitis (SBP). A novel strategy using the in situ hybridization (ISH) method was introduced to detect the bacterial genomic DNA phagocytized in the blood of patients with sepsis. In the present study, we developed a new ISH probe to detect global bacterial DNA (named as GB probe) and evaluated its utility for detecting the phagocytized bacterial DNA in SBP ascites. METHODS Hybridization of bacterial DNA with the GB probe was examined by dot-blot and ISH tests. In addition, the utility of the ISH method to detect the bacterial DNA in the leukocytes of SBP ascites was evaluated. RESULTS The GB probe hybridized with the genomic DNA of all 59 bacterial strains tested (59 species of 36 genus). Eleven of 51 patients with ascites (out of total 542 cirrhotic inpatients) were categorized as SBP. The ISH tests showed positive results in 10 of 11 SBP cases. However, the ISH tests all showed negative results in the 40 non-SBP ascitic samples. Therefore, the ISH tests yielded highly sensitive and specific results for detecting the phagocytized bacterial DNA in the leukocytes of SBP ascites. Moreover, all of the ISH test results were obtained within only one day. CONCLUSIONS Our newly established ISH method was found to provide both a rapid and sensitive detection of bacterial DNA in SBP ascites, thus suggesting its utility for providing early and direct evidence of bacterial infection in SBP ascites.

Cost‐effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast‐enhanced ultrasonography

Aim:  Sonazoid is a new contrast agent for ultrasonography (US). Contrast‐enhanced ultrasonography (CEUS) using Sonazoid enables Kupffer imaging, which improves the sensitivity of hepatocellular carcinoma (HCC) detection. However, there are no studies on the cost‐effectiveness of HCC surveillance using Sonazoid.

Impact of serum Wisteria floribunda agglutinin positive Mac‐2‐binding protein and serum interferon‐γ‐inducible protein‐10 in primary biliary cirrhosis

We aimed to examine the relationship between serum Wisteria floribunda agglutinin positive Mac‐2‐binding protein (WFA+‐M2BP) levels and serum interferon‐γ‐inducible protein‐10 (IP‐10) levels and liver histological findings for patients with primary biliary cirrhosis (PBC) compared with other laboratory fibrotic or inflammatory parameters.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level in non-alcoholic steatohepatitis

To examine the relationship between the Wisteria floribunda agglutinin positive Mac‐2‐binding protein (WFA+‐M2BP) level and histological findings for patients with non‐alcoholic steatohepatitis (NASH).

Gastric emptying in patients with chronic liver diseases

There have been a number of reports of gastric emptying in cirrhosis, all with unconfirmed results. Moreover, the mechanism for delayed emptying in cirrhotic patients is unclear. We evaluated gastric emptying in patients with chronic hepatitis and cirrhosis by means of gastric emptying scintigraphy.Methods: The subjects were 18 normal controls and 75 patients with chronic viral hepatitis (50 patients had chronic hepatitis and 25 patients had cirrhosis). Tc-99m diethyltriamine pentaacetic acid labeled solid meals were used to evaluate gastric emptying; the half-time (T 1/2) of which was calculated. Digestive symptom scores were determined at the time of gastric emptying tests.Results: Fourteen (28%) of 50 patients with chronic hepatitis and 16 (64%) of 25 patients with cirrhosis had delayed gastric emptying. T 1/2 in patients with cirrhosis was significantly higher than that in normal controls and patients with chronic hepatitis (p=0.0001 and 0.0003, respectively). The difference between T 1/2 in patients with chronic hepatitis and that in normal controls was not significant. On regression analysis, two indices—the serum albumin level and platelet count—were found to be significantly related to delayed gastric emptying.Conclusions: Gastric emptying was more delayed in cirrhotic patients than in those with chronic hepatitis and normal controls. Delayed gastric emptying may be related to liver function and portal hypertension.