Kojiro Takase

B-mode ultrasound with algorithm based on statistical analysis of signals: evaluation of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVE The purpose of this study was to evaluate the degree of liver fibrosis in patients with chronic hepatitis C by use of a method in which the homogeneity of the tissue texture of the liver on B-mode ultrasound images is analyzed on the basis of results of a statistical chi-square test of the echo amplitudes. The method includes an algorithm for removing small structures, such as cross sections of the thin vessels, in the background texture to minimize differences in analysis results between users. SUBJECTS AND METHODS Analysis was performed on images of 148 patients with histologically proven chronic hepatitis C without cirrhosis. The peak value of the C(m)(2) (modified chi-square distribution) histogram was calculated from B-mode ultrasound images, and the resulting value was compared with the histologic fibrosis grade. RESULTS The peak C(m)(2) histogram value for grade F3 fibrosis was higher than that for grades F0 and F1 (p < 0.0001) and F2 (p = 0.0003). The value for grade F2 was higher than that for grades F0 and F1 (p = 0.0027). The values gradually increased with an increase in liver fibrosis grade, although no difference was found between grades F0 and F1. CONCLUSION The grades of liver fibrosis in patients with chronic hepatitis C are well discriminated with the B-mode ultrasound-based analysis algorithm without discrimination between grades F0 and F1. Findings on conventional ultrasound images may reflect progression of liver fibrosis even in the absence of cirrhosis.

Clinical efficacy of portal vein stent placement in patients with hepatocellular carcinoma invading the main portal vein

BACKGROUND/AIMS Hepatocellular carcinoma frequently invades the portal veins, and when it invades the main portal vein, the patients prognosis is extremely poor. This study was undertaken to evaluate the clinical efficacy of stent placement into the portal vein in these patients. METHODS Twenty-one patients with hepatocellular carcinoma invading the main portal vein were studied. Stents were placed in the portal veins to compress tumor thrombi after percutaneous transhepatic portography. RESULTS Stents were successfully placed in the portal veins in all patients. Portal venous pressure significantly decreased from 25.3 +/- 7.4 mmHg to 22.4 +/- 6.6 mmHg (p < 0.0001) immediately after stent placement, leading to improvement in gastroesophageal varices, melena and ascites. Although a pseudoaneurysm of the hepatic artery related to portal vein puncture developed in one patient, there were no major complications in the other 20 patients. Blood flow through the stent was maintained during the survival period in 15 patients. The mean stent patency period was 12.4 months. Fifteen patients underwent transcatheter arterial chemoembolization without major complications after stent placement. The survival rate was 64.2% at 6 months and 29.2% at 1 and 2 years, respectively. The mean survival period was 13.7 months. CONCLUSION Stent placement into the portal vein is a relatively safe and feasible procedure. It improves portal hypertension, expands treatment options, and helps to prolong the survival period in patients with hepatocellular carcinoma invading the main portal vein.

Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next-generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species-level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma-in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile, Fusobacterium varium, Haemophilus parainfluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development.

LONG-TERM FOLLOW-UP ARTERIAL CHEMOEMBOLIZATION COMBINED WITH TRANSPORTAL ETHANOL INJECTION USED TO TREAT HEPATOCELLULAR CARCINOMA

PURPOSE This study was undertaken to evaluate the long-term efficacy of transcatheter hepatic arterial chemoembolization (TACE) combined with transportal ethanol injection (TPEI) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Twenty-six patients with unresectable HCC underwent TPEI 2-6 weeks after TACE. The size of the main tumor ranged from 2.0 to 9.0 cm (mean, 4.5 cm). Ethanol (10-65 mL) was injected via a percutaneous transhepatic approach into the portal vein, perfusing the segment to be treated. TACE was repeated after TPEI in 18 patients. RESULTS The combined therapy was technically successfully in all 26 cases; however, irreversible hepatic failure developed in two (8%) patients. Recurrent disease occurred either from the treated lesion (four patients) or apart from the treated liver segment (five patients) in nine of 21 patients (43%) followed up for a mean of 34 months. The survival rates were 87%, 72%, 72%, 63%, 51, and 51% at 1, 2, 3, 4, 5, and 6 years, respectively. Resected and autopsied specimens showed complete necrosis in seven of nine main lesions and severe parenchymal damage in the treated liver segment. CONCLUSION In selected patients, combined treatment with TACE and TPEI is safe and effective, decreasing recurrence rate in the treated segment, and resulting in a 51% 6-year survival.

Prognostic value of peritoneoscopic findings in cirrhosis of the liver

The prognostic value of peritoneoscopy was examined in 372 patients with liver cirrhosis according to the degree of development and size of regenerating nodules, the development of reddish markings, the development of small lymphatic vesicles, the presence or absence of patchy markings, the size of the right and left hepatic lobes, and the degree of splenomegaly. The cumulative survival rate was compared with these peritoneoscopic parameters. The usefulness of peritoneoscopic and histological findings in the prognosis of liver cirrhosis was evaluated using the proportional hazard model of Cox. Significant differences were observed in the cumulative survival rate with respect to the degree of development of regenerating nodules, the size of the right hepatic lobe, the formation of small lymphatic vesicles, and the degree of splenomegaly. Analysis using Coxs proportional hazard model indicated that peritoneoscopic findings are of greater clinical use than histological findings in determining the prognosis of liver cirrhosis.

Comparison of the effects of various vasodilators on the rat portal vein and mesenteric artery

The effects of various vasodilators on isolated helical strips of rat portal vein and mesenteric artery were examined. Dilazep, ibudilast, nifedipine, verapamil and papaverine relaxed the KCl- and norepinephrine-induced contractions of the portal vein to a greater extent than they relaxed those of mesenteric artery. Dibutyryl cyclic AMP and NKH477 did not show any significant difference in terms of the concentrations that produced 50% inhibition (IC50) of the KCl-induced contraction of the portal vein and mesenteric artery. The relaxant effects of nitroprusside and isosorbide dinitrate on the KCl- and norepinephrine-induced contractions of the portal vein were less potent than their effects on contractions of the mesenteric artery. The agents that inhibited the contractions of the portal vein more potently than those of the mesenteric artery were associated with parallel shifts to the right of the concentration-response curves for CaCl2 in both preparations. These results suggest that drugs with a Ca2+ channel blocking action may be preferable to those that cause a decrease in portal pressure for treatment of portal hypertension.

Binding rate constant of Tc-99m DTPA galactosyl human serum albumin measured by quantitative dynamic SPECT--clinical evaluation as a total and regional liver function test.

To evaluate the clinical utility of a new method with dynamic single photon emission computed tomography (SPECT) and scatter and attenuation compensation to estimate both total and regional liver function quantitatively. Five controls, 20 patients with chronic liver disease, and 2 patients with Budd-Chiari syndrome were studied. Dynamic liver SPECT data were acquired during 20 minutes after injection of Technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) with scatter and attenuation compensation. The binding rate constant of Tc-99m GSA, (Ku) was derived quantitatively from the Patlak plot based on kinetic models for GSA receptor binding. The mean Ku was obtained by dividing the Ku value (total Ku) by the liver volume. Both total and mean Ku were significantly lower in patients with chronic liver disease than in controls (302±112 vs. 523±78ml/min; p<0.001, 0.26±0.11 vs. 0.43±0.03 ml/min/cm3; p<0.001). In the patient group, both total and mean Ku were significantly correlated with the results of conventional liver function tests and the histological severity of chronic liver disease. In 2 patients with Budd-Chiari syndrome, the mean Ku was lower in the right lobe, where the hepatic veins were occluded, than in the left lobe, where draining veins were patent. In conclusion, this method is a reliable diagnostic technique for estimating total and regional liver function.

Hepatitis E virus subtype 3f strains isolated from Japanese hepatitis patients with no history of travel to endemic areas – The origin analyzed by molecular evolution

Hepatitis E virus subtype 3f (HEV-3f) strains are usually isolated in Europe and Thailand. Recently, HEV-3f strains were detected from six acute hepatitis E patients in Japan, none of whom had a history of travel to endemic areas. We inferred the origin and transmission route of the six HEV-3f strains. A time-scaled phylogenetic tree of the six strains with reference strains was constructed using a Bayesian statistical inference framework. The time-scaled tree indicated that the six strains independently derived from similar European strains between 2008 and 2014. The pattern suggested recent inflow of multiple HEV-3f strains from Europe to Japan. Japan imports a substantial amount of pork from European countries every year. The emergence of acute hepatitis cases caused by HEV-3f strains in Japan, in patients with no history of travel abroad, might be influenced by the increased opportunities to consume pork products imported from European countries.

FLOW CYTOMETRIC ANALYSIS OF IL-6 RECEPTORS ON PERIPHERAL LYMPHOCYTES IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS

Interleukin‐6 receptors (IL‐6R) and interleukin‐1 receptors (IL‐1R) on lymphocyte surfaces were analyzed, using flow cytometry and dye‐labeled IL‐6 and IL‐1β, to examine the clinical and immunological significance of these receptors. Incubation of peripheral blood mononuclear cells in the presence of mitogen resulted in a remarkable increase of lymphocytes expressing the IL‐6 and IL‐1β receptors on the cell surface. The increase in lymphocytes bearing these cytokine receptors may reflect an increase in stimulated lymphocytes. When peripheral blood from patients with primary biliary cirrhosis (PBC) was examined for these receptors, the percentage of IL‐6R positive cells was significantly higher in the patients than in healthy controls (P<0.01). The increase in IL‐6R positive cells was only significant for the T lymphocyte fraction (P<0.01). No significant change in IL‐1R was observed. There was a significant positive correlation between the percentage of IL‐6R positive T lymphocytes and the titer of antimitochondrial antibody in patients with PBC. These findings concerning IL‐6R may be noteworthy elucidating autoimmune etiological features of PBC. J. Clin. Lab. Anal. 12:83–87,1998.

Multiple Microhamartomas of the Biliary Tract System (Von Meyenburg Complexes) with Multiple Liver Cysts — Diagnostic Imaging and Laparoscopic Findings —

Abstract: We present two patients with multiple microhamartomas of the biliary tract (von Meyenburg complexes) with multiple liver cysts with special reference to their diagnostic imaging and laparoscopic findings. Case 1 was a 76‐year‐old male and case 2 was 51‐year‐old male, who was later found to have adenocarcinoma of the common bile duct as a complication. The characteristic findings of ultrasonography (US) were markedly heterogeneous and there was a severe hyperechoic pattern in the liver with small cystic lesions. Computed tomography (CT) demonstrated multiple low attenuation focal defects scattered throughout both lobes which showed no enhancement following the application of intravenous contrast medium.