Akinari Tabaru

Variable stiffness colonoscopes are associated with less pain during colonoscopy in unsedated patients

OBJECTIVES:Application of a new variable stiffness colonoscope (VSC) is expected to control loop formation and to lessen patient discomfort. The aim of this prospective study was to compare the efficacy of VSC with a conventional colonoscope (CC) in unsedated colonoscopy, based on the experience of examiners.METHODS:Four-hundred sixty-seven patients were randomly assigned to undergo colonoscopy with either VSC or CC by an endoscopist, including experienced and less-experienced examiners. The percentages of completed procedure and time to cecal intubation were recorded. Patients were asked to rate pain on a 5-point pain score.RESULTS:The percentages of completed procedure with VSC and CC were 98% and 95%, respectively, by less-experienced hands, and 99% and 98%, respectively, by experienced hands. Time for cecal intubation with VSC and CC was 15.7 and 18.5 min, respectively, by less-experienced hands, and 9.8 and 10.6 min, respectively, by experienced hands. A significantly lower mean pain score was noted in VSC patients compared with CC patients, irrespective of experience of the examiner. The percent of patients rating the procedure as moderately or severely painful was significantly lower with VSC than with CC, both in less-experienced (19% vs 40%; p < 0.01) and experienced hands (15% vs 26%; p < 0.05).CONCLUSIONS:Our results indicated that VSC allows favorable examination compared with CC regarding completeness, time to cecal intubation, and comfort of patients undergoing unsedated colonoscopy, irrespective of the examiners experience. These features suggest VSC as the preferred colonoscope for patients undergoing unsedated colonoscopy.

Safe and effective treatment of diabetes mellitus associated with chronic liver diseases with an alpha-glucosidase inhibitor, acarbose

Glucose intolerance and diabetes mellitus are both prevalent in patients with chronic liver diseases. We examined the efficacy and systemic safety of therapy with an alpha-glucosidase inhibitor, acarbose, in diabetes mellitus associated with chronic liver diseases. Twenty patients with chronic hepatitis or liver cirrhosis and overt diabetes mellitus received acarbose (taken orally) for 8 weeks. The initial dosage of acarbose was 50mg three times daily, taken before meals; this was increased to 100mg three times daily after 2 weeks. The mean fasting plasma glucose level was 173.7±18.6mg/dl (mean±SE) at entry, and was significantly decreased to 132.9±7.5mg/dl (P<0.05) after 8 weeks of acarbose treatment. The improved glycemic control was reflected by a significant decrease in glycosylated hemoglobin (HbA1c) from 7.2±0.3% at entry to 6.3±0.2% (P<0.05) after 8 weeks. Serum levels of both aspartate and alanine aminotransferases fluctuated during acarbose treatment, probably due to the natural course of chronic liver diseases, but the mean values had decreased after 8 weeks of treatment. Plasma ammonia levels increased, from 61.3±10.7μg/dl to 71.1±9.6μg/dl after 8 weeks of acarbose treatment but the increase was not significant. Clinically significant elevation of plasma ammonia concentration was seen in 2 cirrhotic patients (121 and 124μg/dl); this was asymptomatic and gradually returned to the normal range despite continuous acarbose treatment in one patient, and was reversed after the withdrawal of acarbose with the concomitant administration of lactulose in the other patient. No other blood tests results, including albumin, cholinesterase, and prothrombin time, or lipid profile and nutritional status, in terms of rapid turnover proteins, prealbumin, retinol binding protein, and transferrin, were altered throughout the study period. These results indicate that diabetes mellitus associated with chronic liver diseases may be safely and effectively treated with acarbose. However, clinicians must be aware of the possibility of hyperammonemia when they prescribe acarbose for patients with diabetes mellitus and advanced liver cirrhosis.

Plasma nitrite/nitrate concentrations as a tumor marker for hepatocellular carcinoma.

Since plasma concentrations of nitrite/nitrate, the stable end-products of nitric oxide, increase in patients with hepatocellular carcinoma (HCC) correlatively to tumor volume, we examined the ability of plasma nitrite/nitrate to discriminate between those patients with HCC and those without and compared the diagnostic performance of the parameter with that of serum alpha-fetoprotein (AFP) concentrations. Plasma nitrite/nitrate and serum AFP concentrations were measured using a Griess reaction and a solid phase enzyme immunoassay, respectively. Eighty-nine patients with chronic liver diseases (CLD) with (n=39) or without HCC (n=50) and 50 healthy control subjects participated in the study. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value and accuracy. The areas under ROC curves for nitrite/nitrate and AFP were calculated to be 0.758 and 0.812, respectively, which were not significantly different. There was no correlation between the concentrations of plasma nitrite/nitrate and serum AFP. The sensitivity, the specificity, and diagnostic efficiency were 79.5, 72.0, and 75.3%, respectively, for nitrite/nitrate, and 74.4, 76.0, and 75.3%, respectively, for AFP. Based on a partial ROC curve, the clinical utility of plasma nitrite/nitrate as a tumor marker approximated that of serum AFP, but exceeded in AFP-negative patients. Indeed, nitrite/nitrate was positive in 70% of AFP-negative HCC patients. The simultaneous determinations of serum AFP and plasma nitrite/nitrate concentrations gave significant improvement in detection of HCC in CLD patients compared with that of serum AFP alone.

Troglitazone prevents fatty changes of the liver in obese diabetic rats

Abstract Background and Aims: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator‐activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long‐term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long‐Evans Tokushima Fatty (OLETF) and control Long‐Evans Tokushima Otsuka (LETO) rats.

Effects of intravenous infusion of amino acids on cholecystokinin release and gallbladder contraction in humans

We investigated the effect of intravenous infusions of the therapeutically available amino acid solutions Moripron and Morihepamin (Roussel Morishita, Osaka, Japan) on gallbladder contraction and cholecystokinin (CCK) release in healthy male volunteers. Plasma CCK levels were measured by radioimmunoassay, using the antibody OAL-656, which is specific for the aminoterminus of CCK-8 and thus recognizes biologically active forms of all CCKs. The volume of the gallbladder was calculated by ultrasonographic measurements. Intravenous infusion of Moripron at the rate of 3.33 ml/min for 60 min, caused gallbladder contraction, with a peak response of 31.3±8.6% of the fasting volume at 45–60 min, and a significant increase in plasma CCK concentration, from 1.8±0.2 pmol/l to a peak of 9.9±1.5 pmol/l, at 30–45 min. The maximum gallbladder contraction and the peak CCK release during the Moripron infusion were not significantly different from findings after a test meal. There was a close relationship between the peak plasma CCK concentration and the maximal gallbladder contraction during the administration of Moripron, and this agent, even when infused at the rate of 1.67 ml/min, significantly increased plasma CCK levels and gallbladder contraction. Intravenous infusion of Morihepamin had no significant influence on gallbladder volume or plasma CCK levels. The discrepancy in responses appeared to be related to differences in composition between Moripron and Morihepamin, and not to the total dose of amino acid. Intravenous infusions of amino acids appear to have different effects on gallbladder contraction and plasma CCK secretion depending on the amino acids composition. Our findings suggest that an intravenous infusion of Moripron could be used for the prophylaxis of acute acalculous cholecystitis and sludge formation due to reduced biliary motility in patients on total parenteral nutrition.

Efficacy of Short-Term Interferon Therapy for Patients Infected with Hepatitis C Virus Genotype 2a

BACKGROUND AND AIMS:The efficacy of interferon (IFN)-based antiviral therapy for chronic hepatitis C (CHC) varies depending on predictive factors such as hepatitis C virus (HCV) genotype and viral load. For patients with good predictive factors, a low dose and short course of IFN-based therapy may be adequate. However, there is no evidence about the optimal duration of IFN-based therapy for these patients. The aim of this study was to clarify whether the duration of IFN therapy could be shortened to less than the conventional treatment period for patients with good predictive factors.METHODS:A total of 25 treatment-naive CHC patients with genotype 2a were randomized to receive either IFN monotherapy for 24 wks (group A: long-term IFN therapy, n = 13) or for 6 wks (group B: short-term IFN therapy, n = 12). Patients were monitored for HCV RNA and routine liver function tests during and following treatment, and data were examined according to intention-to-treat analysis.RESULTS:Eleven of 13 patients in group A and all patients in group B completed IFN therapy according to the original planned schedule. At the end of the treatment, viral clearance occurred in all patients. However, 4 patients in group A and 5 in group B relapsed within 6 months of follow-up. There was no significant difference of sustained response rate between group A (53.8%) and group B (58.3%). Among patients who had HCV viral load of <100 kIU/ml, the sustained response rate was 83.3% (5/6) in group A and 100% (5/5) in group B.CONCLUSIONS:In this study, our results suggest that the duration of IFN therapy can be shortened to less than 24 wks in patients with good predictive factors. Further studies, however, should examine the optimal regimen of IFN therapy based on the backgrounds of patients.

High-dose interferon-α therapy lowers the levels of serum fibrogenesis markers over 5 years in chronic hepatitis C

We examined the levels of serum N-terminal peptide of type III procollagen (P-III-NP) and the 7S domain of type IV collagen (IV-7S) as fibrogenesis markers in patients with chronic hepatitis C to clarify whether high-dose interferon-alpha (IFN-alpha) therapy has a suppressive effect on hepatic fibrogenesis for a long period (over 5 years) after the cessation of IFN therapy. Eighty patients with CHC were given 10 million units of IFN-alpha2b daily for 14 days followed by three times per week for a total of 24 weeks. Patients were divided into the following three groups according to the highest serum alanine aminotransferase levels during 1 year observation after the end of IFN therapy: complete responders (CR), partial responders (PR), and nonresponders (NR). We measured serum fibrogenesis markers before and at the end of IFN therapy, and again 1 year and more than 5 years after the end of IFN therapy. Liver biopsies were performed before IFN therapy in all patients and again over long-term observation in 10 patients (PR; 5 and NR; 5). Serum P-III-NP levels significantly decreased after IFN therapy in all three groups of patients, and further decreased in CR and PR over long-term observation. Serum IV-7S levels in CR significantly decreased after IFN therapy and further decreased over long-term observation. Serum IV-7S levels over long-term observation were significantly lower than those at the end of IFN therapy in CR and PR and significantly lower than the initial values in all three groups of patients. The progression of fibrosis was not significant over long-term observation in liver biopsy specimens of 10 patients. The results of the present study suggest that high-dose IFN-alpha therapy for 6 months suppresses the progression of hepatic fibrosis for more than 5 years not only in CR but also in PR.

Data mining reveals complex interactions of risk factors and clinical feature profiling associated with the staging of non-hepatitis B virus/non-hepatitis C virus-related hepatocellular carcinoma

Aim:  Non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma (NBNC‐HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC‐HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC using data mining techniques.

Biliary obstruction caused by intrabiliary transplantation from hepatocellular carcinoma

A rare autopsy case of hepatocellular carcinoma (HCC) presenting as extrahepatic bile duct obstruction is reported. A 54-year-old man who had been treated at another hospital for obstructive jaundice was referred to our hospital and admitted on March 1, 1998, because of progressive jaundice. On hospital day 94, he died of bleeding esophageal varices. At autopsy, a bile duct tumor, measuring 3.0 x 3.5 cm and adhering to the wall of the left hepatic duct, occluded the common hepatic duct at the hilus. A tumor measuring 2.0 x 2.0 cm was found in the parenchyma of the left liver lobe. The parenchymal tumor was not continuous with the extrahepatic bile duct tumor. Histologically, the bile duct tumor and the parenchymal tumor of the left lobe were diagnosed as HCC. The bile duct tumor was attached to the mucosa of the bile duct with a thin stalk. No invasive growth into the submucosa was observed. The tumor may have been an intrabiliary transplantation from the HCC in the left lobe via the bile duct.

Varioliform gastritis and duodenitis associated with protein-losing gastroenteropathy, treated with omeprazole

A 44-year-old female with varioliform gastritis and duodenitis had gastrointestinal protein loss revealed by111indium chloride scintigraphy. Treatment with omeprazole, a proton pump inhibitor, for 2 months, followed by famotidine, resulted in clinical improvement with resolution of the gastroduodenal lesions and protein loss. Colonization of the stomach withHelicobacter pylori was found before and after the treatment. The results in this patient suggest that omeprazole can be of value for the treatment of varioliform gastritis associated with protein-losing gastroenteropathy. The role ofHelicobacter pylori in the pathogenesis of this disease is unclear.