Naondo Sohara

Hepatocellular carcinoma with portal vein tumor thrombosis: clinical characteristics, prognosis, and patient survival analysis.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a poor prognosis. New therapeutic modalities, such as continuous hepatic arterial infusion chemotherapy (CHAIC), have recently been reported to be promising strategies. The aim of this study was to evaluate the clinical characteristics, prognosis, and survival of patients with PVTT according to treatment regimen. One hundred ninety-three patients with HCC complicated with PVTT at the time of diagnosis were included in this study. All patients were newly diagnosed to have HCC and were observed from January 1992 to December 2003. CHAIC was performed using an implanted drug delivery system with low-dose cisplatin and 5-fluorouracil. Clinical characteristics, prognosis, and patient survival were analyzed by the Kaplan-Meier method and Coxs proportional hazards model. The mean age of the patients complicated with PVTT was 64.3±10.3 years (range, 20–88 years). The survival of the 193 patients with PVTT was 37.5%, 24.0%, 18.9%, and 8.3% at 1, 2, 3, and 5 years, respectively. According to treatment, the survival of patients who underwent surgical treatment was the best, followed by CHAIC, transcatheter arterial infusion/embolization, and supportive care. The 3-year survivals for each treatment regimen were 53.0%, 19.3%, 15.0%, and 4.0%, respectively. Although the survival of patients who received surgical treatment was best, such patients were restricted. There was no difference in survival between treated and untreated patients demonstrating Child-Pugh grade C. In Child B patients, treatment for HCC significantly increased survival (P<0.01). Coxs proportional hazards model revealed the Child-Pugh classification to be an independent prognostic factor for patients with HCC and PVTT (P<0.01). We conclude that the prognosis of HCC with PVTT was quite poor. The treatment did not improve the survival of Child C patients. As a result, the prevention, early diagnosis, and development of new treatment strategies are required.

Primary liver cancers with nonalcoholic steatohepatitis.

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.

The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis

Background: Non-alcoholic fatty liver disease is a common liver injury, but the pathophysiological mechanisms leading to the development of non-alcoholic steatohepatitis (NASH) remain unclear. The pathological roles of the nuclear receptor constitutive androstane receptor (CAR), a key regulator of drug-metabolising enzymes, in the development of NASH were investigated. Methods and results: CAR+/+ and CAR−/− mice were given a methionine and choline-deficient (MCD) diet to establish a dietary model of NASH. Increases in serum alanine aminotransferase (ALT) and in infiltration of inflammatory cells were dominant in CAR+/+ mice at 8 weeks. There was no significant difference in the lipid concentration of the liver—namely, the first hit between CAR+/+ and CAR−/− mice. The index of lipid peroxidation increased in liver of the CAR+/+ mice, as demonstrated by 8-iso-prostaglandin F2α (F2-isoprostanes). Western blotting analysis showed that nuclear translocation of CAR occurred in CAR+/+ mice fed the MCD diet. As a result, the CAR activation caused the lipid peroxidation—namely, the second hit. The expressions of cytochrome P450 (CYP)2B10, 2C29, 3A11 all increased considerably in the CAR+/+ mice. Furthermore, α smooth muscle actin immunohistochemistry and Sirius red staining showed an increase in the degree of fibrosis in CAR+/+ mice fed the MCD diet at 16 weeks. The mRNA expressions of collagen α1(1) and the tissue inhibitor of metalloproteinase-1 were found to be elevated in CAR+/+ mice. Conclusion: CAR caused the worsening of the hepatic injury and fibrosis in the dietary model of NASH. Our results suggest that the CAR nuclear receptor may thus play a critical role in the pathogenesis of NASH.

Endoscopic treatment of rectal carcinoid tumors.

BACKGROUND: Various methods have been reported for the endoscopic treatment of rectal carcinoid tumors. The present study was designed to identify the optimal treatment strategy for an endoscopic resection. METHODS: Forty rectal carcinoid tumors of 38 patients were treated endoscopically. The indication criteria, complete resection rate, selection of treatment, local recurrence, distant metastases, and complications were analyzed. All tumors were estimated to measure 1 cm or less in diameter, without muscular invasion, atypical features, and lymph node metastases to the pararectal region. RESULTS: Complete resection of the lesions was obtained in 75.0% (30/40). The complete resection rates were 20.0% (1/5) by conventional polypectomy, 84.6% (22/26) by a two-channel endoscopic mucosal resection, and 77.8% (7/9) by endoscopic submucosal dissection. The 10 cases that did not show a clear submucosal layer after initial endoscopic treatment received additional endoscopic microwave coagulation therapy. There were no local or distant recurrences in the followed-up periods (median, 6.4 years). No difference was observed in the complete resection rate between two-channel endoscopic mucosal resection and endoscopic submucosal dissection. CONCLUSIONS: Small carcinoid tumors measuring less than 1 cm in diameter can therefore be managed endoscopically with no recurrence or spread. The selection of endoscopic treatment should be made after taking such factors as cost-effectiveness, expertise, and experience into careful consideration.

Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection

Background:  Despite the progression of therapeutic approaches, a high frequency of recurrence is what determines the long‐term prognosis of patients with hepatocellular carcinoma (HCC). In this study, the chemopreventive effects of vitamin K2 on the recurrence and survival of patients with HCC after curative therapy were evaluated.

Long-term outcome of interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.

Abstract: Background: Autoimmune thyroid disorders are among the well‐known adverse effects of interferon‐α (IFN‐α) therapy in patients with chronic hepatitis C. However, there are few reports regarding the long‐term outcome of this complication. We aimed to evaluate the natural history of IFN‐α‐induced autoimmune thyroid disorders with long‐term follow‐up.

STRICTURE AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCERS AND ADENOMAS

Background and Aim:  Stricture is a complication that may occur after endoscopic submucosal dissection (ESD) of gastric neoplasms. The goal of the present study was to investigate the incidence, risk factors and management of gastric stricture after ESD.

Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis

Patients with chronic hepatitis C virus (HCV) infection often develop liver cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection. Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at random into two groups. Forty-four patients were treated with alpha-tocopherol (Vit E group) while the other 39 were followed as controls. The clinical background (gender, age, and laboratory data) was similar in the two groups. Serum levels of alpha-tocopherol, albumin, alanine aminotransferase (ALT), and total cholesterol and platelet count were measured serially over a period of five years. The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment. Platelet count, serum albumin, ALT, and total cholesterol were not different between the two groups during the five-year period. Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls, albeit statistically insignificant. The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV. Although the administration of alpha-tocopherol normalized the level one month later, it could neither improve liver function, suppress hepatocarcinogenesis, nor improve cumulative survival. Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant.

Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels

Abstract: Background: Adiponectin is a hormone secreted by adipocytes and has anti‐diabetic and anti‐atherogenic properties. Hypoadiponectinemia is associated with insulin‐resistant diabetes and liver dysfunction. The aim of this study was to determine plasma adiponectin and insulin levels in patients with liver cirrhosis.

Primary Sjogren's syndrome complicated by bilateral pleural effusion

Abstract:  Sjogrens syndrome can cause many organic changes, but is rarely accompanied by pleuritis. We report a 65‐year‐old patient with primary Sjogrens syndrome who developed bilateral pleuritis with moderately large effusions. He was diagnosed as having Sjogrens syndrome, based on xerophthalmia, xerostomia, positive results for anti‐Sjogrens syndrome (anti‐SS‐A/SS‐B) antibodies, the Schirmer test and biopsy findings in the minor salivary glands. The pleural fluid was lymphocyte rich and contained high levels of anti‐SS‐A/SS‐B antibodies. There was no evidence of infection, malignancy or other collagen diseases which cause pleuritis. We conclude that this case adds to the eight previously published reports of primary Sjogrens syndrome complicated by pleural effusion.