Tomohiro Kato

Prognostic Value of Energy Metabolism in Patients With Viral Liver Cirrhosis

The effect of energy malnutrition on survival in patients with non-alcoholic viral liver cirrhosis has not been well defined. We characterized energy metabolism at study entrance and prospectively analyzed its effect on subsequent survival in cirrhotics. One hundred nine consecutive patients with viral liver cirrhosis and 22 healthy control subjects participated in the study. By indirect calorimetry after overnight bedrest and fasting, resting energy expenditure (REE) was measured and non-protein respiratory quotient (npRQ) was calculated. Survival of cirrhotics were followed for up to 8 y. Survival rate was estimated with the Kaplan-Meier method. REE at entrance was significantly higher than the predicted basal metabolic rate (BMR) in cirrhotics (P < 0.001). NpRQ was significantly lower in cirrhotics than in controls (P < 0.001). Survival rate was significantly lower in patients with low npRQ ( < 0.85) than in patients with scores above 0.85 (P < 0.01) and was significantly higher in normal metabolic patients (0.9 < REE/BMR < 1.1) than in hypometabolic (REE/BMR < 0.9) or hypermetabolic (1.1 < REE/BMR) patients (P < 0.05). The proportional hazards model showed that npRQ (relative risk = 0.0003, 95% confidence interval = 0.0000-0.0970), REE/BMR (0.0199, 0.0007-0.5652), prothrombin time, and ammonia were independent significant factors determining survival. Thus evaluation of energy metabolism can be used to predict survival in patients with viral liver cirrhosis.

Green Tea Extracts for the Prevention of Metachronous Colorectal Adenomas: A Pilot Study

Background: Experimental studies indicate the chemopreventive properties of green tea extract (GTE) on colorectal cancer. Epidemiologically, green tea consumption of >10 cups daily reduced colorectal cancer risk in Japanese. Because colorectal adenomas are the precursors to most sporadic colorectal cancers, we conducted a randomized trial to determine the preventive effect of GTE supplements on metachronous colorectal adenomas by raising green tea consumption in the target population from an average of 6 cups (1.5 g GTE) daily to ≥10 cups equivalent (2.5 g GTE) by supplemental GTE tablets. Methods: We recruited 136 patients, removed their colorectal adenomas by endoscopic polypectomy, and 1 year later confirmed the clean colon (i.e., no polyp) at the second colonoscopy. The patients were then randomized into two groups while maintaining their lifestyle on green tea drinking: 71 patients supplemented with 1.5 g GTE per day for 12 months and 65 control patients without supplementation. Follow-up colonoscopy was conducted 12 months later in 125 patients (65 in the control group and 60 in the GTE group). Results: The incidence of metachronous adenomas at the end-point colonoscopy was 31% (20 of 65) in the control group and 15% (9 of 60) in the GTE group (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < 0.05). The size of relapsed adenomas was also smaller in the GTE group than in the control group (P < 0.001). No serious adverse events occurred in the GTE group. Conclusion: GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3020–5)

Metallic stents are more efficacious than plastic stents in unresectable malignant hilar biliary strictures: a randomized controlled trial

BackgroundEndoscopic biliary stenting is a well-established palliative treatment for unresectable malignant biliary strictures, for which plastic tube stents (PSs) and self-expandable metallic stents (SEMSs) are most commonly used. The efficacy of these stents has been extensively described in distal biliary strictures, but not in hilar biliary strictures. The present study aimed to compare the efficacy of PSs and SEMSs for unresectable malignant hilar biliary strictures.MethodsFrom June 2004 to November 2008, 60 patients were enrolled and prospectively randomized into the PS or SEMS group.ResultsThe 6-month patency rate was significantly higher in the SEMS group than in the PS group (81 vs. 20%; pxa0=xa00.0012). Kaplan–Meier analysis showed significantly longer patency in the SEMS group than in the PS group (pxa0=xa00.0002); the 50% patency period was 359xa0days in the SEMS group and 112xa0days in the PS group. There was no significant difference in the overall survival period between the PS and SEMS groups (pxa0=xa00.2834). The mean number of reinterventions for stent failures was significantly lower in the SEMS group (0.63xa0times/patient) than in the PS group (1.80xa0times/patient) (pxa0=xa00.0008). The overall total cost for the treatment was significantly lower in the SEMS group than in the PS group (pxa0=xa00.0222).ConclusionsSEMSs were associated with a longer patency than PSs in patients with unresectable hilar biliary stricture. SEMSs were also more advantageous in reducing the number of reintervention sessions and the overall treatment cost.

Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis.

Aims: patients with liver cirrhosis exhibit abnormal fuel metabolism, including increased fat and decreased glucose oxidation. Such altered energy metabolism is similar to that observed after starvation and could lead to malnutrition. We therefore studied whether nocturnal energy supplementation might improve the fuel metabolism in cirrhotic patients. Methods: 12 cirrhotic patients and 14 healthy controls participated in this study. Subjects in the two groups ate isonitrogenous (1.2 g/kg/day) and isocaloric (35 kcal/day) diets for 1 week before and during the study. On day 1 of the study, indirect calorimetry was carried out in the morning after an overnight fast. The next morning, the same measurement was performed after the patients took a liquid nutrient (Ensure Liquid(R), 250 kcal) at 23:00 on day 1. Respiratory quotient (RQ), resting energy expenditure (REE), and substrate oxidation rates of glucose (% CHO), fat (% FAT) and protein were estimated from measured VO(2), VCO(2) and urinary nitrogen. Results: Significant decreases in RQ, and % CHO and a significant increase in % FAT were observed at baseline in cirrhotic patients as compared with controls. After the nocturnal energy supplementation, RQ, % CHO and % FAT in cirrhotic patients were significantly recovered, ending at levels close to normal. Conclusions: These results suggest that nocturnal energy supplementation could be useful to correct abnormal fuel metabolism and to prevent malnutrition in cirrhosis.

Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson’s disease? An analysis using the 13C-acetate breath test

During the pre-symptomatic stage of Parkinson’s disease (PD), the idiopathic PD related abnormal synuclein immunostaining is confined to the medulla oblongata and olfactory bulb, according to Braak. In the study of the enteric nervous system of PD, it has reported that Lewy bodies were found in the Auerbach’s and Meissner’s plexuses. These lesions may cause dysfunction of the gastrointestinal tract (GI) as pre-clinical symptoms of PD. However, because l-dopa therapy itself may worsen the symptoms of the digestive tract function, it is needed to evaluate the gastrointestinal tract function in patients with early-stage, untreated (de novo) PD. In the present study, using the 13C-acetate breath test (13C-ABT), we investigated gastric emptying in 20 untreated, early-stage PD patients and 40 treated, advanced-stage PD patients, and 20 healthy volunteers. Gastric emptying was examined by the 13C-ABT [the half emptying time (HET), the peak time of the 13C% dose-excess curve (Tmax)]. The Tmax and HET of gastric emptying as assessed using the 13C-ABT was significantly delayed in untreated, early-stage PD patients as compared to the controls (Pxa0<xa00.001). The Tmax and HET of gastric emptying were not significantly delayed in untreated, early-stage PD patients as compared to treated, advanced-stage PD patients. The results demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients. Gastric emptying of untreated, early-stage PD is already delayed. Delayed gastric emptying may be one of markers of the pre-clinical stage of PD.

Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation

A 52-year-old woman was found to have a liver tumor during treatment for a liver abscess. The tumor was diagnosed as intrahepatic cholangiocarcinoma by closer examinations, including a percutaneous needle biopsy. Ten years previously, she had undergone excision of a choledochal cyst, with reconstruction by Roux-en-Y hepaticojejunostomy, as treatment for Todanis type Ia congenital biliary dilation, which had been confined only to the extrahepatic bile duct. The significant association between congenital biliary dilation and hepatobiliary malignancies is well known. Some patients have been reported to develop biliary cancer long after the excision of the entire extrahepatic bile duct and hepaticoenterostomy. However, in these patients, the development mostly took place in the remnant choledochal cyst, the anastomotic site, or in the dilated intrahepatic bile duct of Todanis type IV-A congenital biliary dilation. The development of intrahepatic cholangiocarcinoma after operation has not been reported previously in a patient with Todanis type I congenital biliary dilation. This case suggests that the entire biliary tree may have a high risk of field cancerization, even in extrahepatic congenital biliary dilation.

Clinical trial : rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection-a randomized controlled study

BackgroundEndoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8xa0weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4xa0weeks. We examined the efficacy of a combination therapy of PPI and rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing.MethodsPatients were randomly assigned to either the PPI and rebamipide therapy or the PPI alone. Sixty-two consecutive patients with gastric tumors gave informed consent for enrolling in the study. In all cases, the estimated size of the post-ESD ulcer was larger than 20xa0mm. Oral administration of the drug was started on the 2nd day post-ESD and continued to the 28th day.ResultsAll patients received the assigned pharmaceuticals and adhered well to the treatment regimen for 28xa0days. The endpoint ulcers reached S1 (scar stage) in 11/31 (36%) patients in the PPI-only group and in 21/31 (68%) in the combination group (Pxa0=xa00.010).ConclusionsThe combination of PPI plus rebamipide was more effective than the PPI alone for treating ulcers larger than 20xa0mm within 4xa0weeks after ESD.

Alpha-sulfanyl and alpha-selanyl propadienyl cations: regioselective generations and cycloadditions with thioamides and selemides controlled by MeNO2-H2O system.

Alpha-sulfanyl and alpha-selanyl propadienyl cations were easily generated by the catalytic system, scandium triflate-nitromethane-H(2)O in the presence of Bu(4)NHSO(4), to regioselectively afford the multifunctionalized thiazoles and selenazoles in high yields.

TNF-α and IL-6 signals from the bone marrow derived cells are necessary for normal murine liver regeneration

In the present study, we used bone marrow transplanted mice and revealed the role of bone marrow derived cells in liver regeneration after partial hepatectomy (PH). Irradiated wild type (WT) mice received a bone marrow transplant from either WT, TNF (tumor necrosis factor)-alpha knockout (KO), or interleukin (IL)-6 KO donors. Both TNF-alpha KO- and IL-6 KO-transplanted mice compared with WT-transplanted mice showed decreased hepatocyte DNA synthesis after PH. TNF-alpha KO-transplanted mice showed no nuclear factor kappa B (NF-kappaB) and signal transducer and activator of transcription (STAT) 3 binding after PH, while IL-6 KO-transplanted mice showed NF-kappaB, but not STAT3, binding. Lack of AP-1 or C/EBP binding or expression of c-jun or c-myc mRNA after PH was unrelated to the timing and amount of DNA replication. In conclusion, The TNF-alpha and IL-6 signals from the blood are necessary for liver regeneration and NF-kappaB and STAT3 binding are activated via TNF-alpha and IL-6 signal pathways.

Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice

Abstract: Aims/Background: Tumor necrosis factor‐α (TNF‐α) is known as a proinflammatory cytokine that has been implicated as a contributing factor in a number of disease processes. TNF‐α also influences liver repair following hepatotoxic damage, and regeneration following partial hepatectomy (PH). The aim of this study was to assess the mechanism by which TNF‐α influences liver cell apoptosis and regeneration following PH in TNF‐α‐deficient (TNF‐α−/−) mice.