[Frequency of gastroesophageal reflux disease (GERD) as a complication in patients with chronic liver diseases: estimation of frequency scale for the system of GERD].

Recently, a questionnaire, Frequency Scale for the System of GERD (FSSG), has been estimated to be clinically useful for the initial diagnosis of gastroesophageal reflux disease (GERD). We investigated the frequency of GERD as a complication in patients with chronic liver diseases by using the questionnaire, FSSG. As a result, it may be considered that, as a complication of chronic liver disease, GERD exists in about 20% of patients and mainly belongs to a dyskinetic type.

[Estimation of indication for living donor liver transplantation in patients with HCV and/or HBV infection].

We evaluated 78 patients with chronic viral hepatitis for liver transplantation. 51 patients met our original criteria for liver transplantation, and 35 patients of them suffered from hepatocellular carcinoma (HCC). Patients with HCC were significantly older and showed higher prothrombin activity than those without HCC. Eighteen of 35 patients with HCC did not meet the Milan criteria, and they showed lower levels of total bilirubin, Child-Pugh score, and MELD score than those who met the criteria. Theses results indicate that acceptability for transplantation should be evaluated soon after the patients have become candidates for liver transplantation. In Japan, decompensated liver cirrhosis is a necessary condition for the application of public health insurance against liver transplantarion and, in cases with HCC, it is necessary to meet the Milan criteria. Application to liver transplantation should also be considered based on HCC stage such as the UNOS scoring system.

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure.

AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure. METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

[Tailored-dose chemotherapy using gemcitabine for advanced pancreatic cancer].

Eighteen patients with metastatic or post-surgery recurrent pancreatic cancer were given weekly gemcitabine therapy. Almost all of these patients were aged or had other complications. We determined the individualized maximum repeatable dose (iMRD)as follows. We started at 500 mg/m(2) gemcitabine and repeated the treatment with an increase or a decrease of 100mg/m(2) each week, if the hematological toxicity was 0 or more than grade 1. If toxicity was grade 1, the same dose was given. And the third-week dose was an iMRD. Dose intensity was 286 mg/m(2)/week. The median survival time was 262 days. Of these 18 patients, 2 (11.1%), 11(61.1%) and 5 (27.8%) patients showed partial response, stable disease, and progressive disease, respectively. The therapeutic effects of iMRD equaled those of standard administration of gemcitabine.

[A case of pancreatic ductal adenocarcinoma with rapid progress in a young man].

A 17-year-old man was admitted to hospital because of epigastric pain. Various imaging studies showed a solid tumor (4cm in diameter) in the tail of the pancreas, multiple hypovascular tumors in liver. Serum levels of DUPAN2, SPAN1 and NSE were elevated slightly. Biopsy of hepatic tumor demonstrated that tumor cells had eosinophilic cytoplasm generally and unevenly distributed polymorphic nucleus. These data suggested that this tumor is poorly differentiated pancreatic carcinoma originated from the epithelium. Therefore, we administered 5-fluorouracil and cisplatin, combined with gemcitabine. The clinical status improved temporarily by the treatment, however, worsened rapidly. He died 81days after the treatment. Final diagnosis of autopsy was pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma in the young patients is rare, and we reported this case in addition to consideration on literature.

Serum albumin is present at higher levels in alcoholic liver cirrhosis as compared to HCV-related cirrhosis.

Residual hepatic functional reserve in cirrhotic patients is generally evaluated by a multivariate scoring system (Child-Pugh classification), which includes serum albumin levels as a variable. However, several patients show discrepancies between serum albumin levels and the progression of liver fibrosis, especially those with alcoholic cirrhosis. To assess whether hepatic capacity of protein synthesis varies with the etiology of cirrhosis, serum albumin and cholinesterase levels, and prothrombin time were compared between alcoholic cirrhosis and hepatitis C virus (HCV)-related cirrhosis. To minimize the influence of malnutrition and extrahepatic platelet destruction, patients with hepatocellular carcinoma, uncontrolled diabetes, appetite loss and/or splenal longitudinal size >15 cm were excluded. The patients with compensated liver cirrhosis were divided into three groups as follows: alcohol(+)/HCV(+) (alcohol + HCV group; n=31), alcohol(-)/HCV(+) (HCV group; n=31) and alcohol(+)/HCV(-) (alcohol group; n=27). These groups were adjusted with respect to age, gender, body mass index and platelet count. Serum albumin levels in the alcohol group were significantly higher than those in the HCV group, with a difference of approximately 0.5 g/dl in every class of platelet count. The correlation of the alcohol + HCV group was intermediate between the alcohol and HCV groups. On the other hand, the correlations between serum cholinesterase levels and platelet counts were similar among the three groups. The prothrombin time was also comparable among the groups. Accordingly, serum albumin levels were higher in patients with alcoholic cirrhosis and alcohol consumption should be carefully considered when evaluating hepatic functional reserve.

Investigation of hyperuricemia during pegylated-interferon-alpha2b plus ribavirin combination therapy in patients with chronic hepatitis C.

OBJECTIVE: Hyperuricemia has been reported as being an adverse effect of pegylated-interferon-alpha2b (Peg-IFNalpha2b) and ribavirin combination therapy for chronic hepatitis C and hyperuricemic changes occur in some patients during the therapy. However, detailed investigation of the elevation of uric acid has not been carried out previously. The incidence and mechanism of hyperuricemia were investigated in this study. METHODS: The data of 50 patients with chronic hepatitis C who had been treated with Peg-IFNalpha2b and ribavirin combination therapy or pegylated-interferon-alpha2a monotherapy for more than 24 weeks were analyzed. The effects of these treatments were evaluated clinically by the serum uric acid level and its urinary excretion rates. RESULTS: In patients with pegylated-interferon-alpha2a monotherapy, no significant elevation was shown either in serum uric acid concentrations or excretion rates. On the other hand, serum uric acid concentrations were significantly elevated during the combination therapy, reaching > or =7.0 mg/L in men and > or =6.5 mg/L in women in 15% of patients. The urinary uric acid excretion rate was also elevated significantly. CONCLUSION: Peg-IFNalpha2b plus ribavirin combination therapy induced an elevation of uric acid concentration, although the elevated levels were still within normal limit in many cases. It may be that ribavirin plays a leading role in its elevation and other factors may also be involved.

Decreased portal flow volume increases the area of necrosis caused by radio frequency ablation in pigs.

BACKGROUND/AIMS: Although radio frequency ablation (RFA) has been widely accepted as an effective treatment for hepatocellular carcinoma (HCC), severe complications are not uncommon. Major complications seem to occur as a result of over-ablation beyond the intended area. As most patients with HCC have underlying cirrhosis, we speculated that decreased portal flow might cause the necrosis associated with RFA. To confirm this hypothesis, we examined the area of necrosis resulting from RFA under varying conditions of portal flow in a porcine model. METHODS: RFA was performed using ultrasonographic guidance in anesthetized pigs. During the RFA procedure, portal flow was regulated by a balloon catheter, which was set in a portal trunk. The necrosis area was measured after sacrifice and was compared with the hyperechoic area that appeared during ablation. In another session, RFA was performed close to the hepatic vein and endothelial damage was examined. RESULTS: The necrosis area caused by RFA was significantly larger when the portal flow volume was decreased by 50% or more. The hyperechoic lesion was always larger than the area of pathological necrosis regardless of portal flow volume. Under conditions of decreased portal flow, the vessel endothelium near the ablated area was more readily damaged. CONCLUSION: Decreased portal flow volume resulted in enlargement of the area of necrosis caused by RFA. Our results indicate that over-ablation could easily occur in patients with advanced cirrhosis, and that this could lead to major complications. Ultrasonographic guidance may be helpful for avoiding over-ablation.

Early phase II study of uracil-tegafur plus doxorubicin in patients with unresectable advanced biliary tract cancer.

BACKGROUND: Standard chemotherapy for advanced biliary tract cancer has not been established. The purpose of this study was to evaluate the efficacy and toxicity of a combination chemotherapy of uracil-tegafur (UFT) and doxorubicin in patients with unresectable advanced biliary tract cancer. METHODS: Patients with histologically or cytologically confirmed, measurable biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of Vater cancer, which was not amenable to surgery, were eligible for the study. Patients received oral UFT 300 mg/m(2) per day divided into two doses on Days 1-14 and intravenous doxorubicin 30 mg/m(2) on Day 1. This cycle was repeated every 21 days. Additional courses of this regimen were given until a maximum of 15 courses, disease progression or the appearance of unacceptable toxicity. RESULTS: Twenty-four patients from five institutions were enrolled between March 2004 and November 2004. Of the 24 patients, three had partial responses for an objective response rate of 12.5% (95% confidence interval, 2.7-32.4%), 13 patients had stable disease, 7 had progressive disease and the final patient was not evaluated. Grade 3 toxicity was observed in 5 of the 24 patients (20.8%), and these toxicities included anorexia, fatigue, anemia and neutropenia. None had grade 4 toxicity. The median progression-free and overall survival time was 2.5 and 7.6 months, respectively. CONCLUSIONS: Combination chemotherapy of UFT and doxorubicin was well tolerated and showed preliminary moderate activity against advanced biliary tract cancer. Further investigation in a late phase II study involving a large number of patients is recommended.