[A case of hypervascular hyperplastic nodules mimicking hepatocellular carcinoma in alcoholic liver cirrhosis].

Benign hypervascular hyperplastic nodules (HHN) in liver cirrhosis are very rare. It is important to distinguish between regenerative nodules (hyperplastic nodules) and tumorous nodules (dysplastic or neoplastic nodules) in hepatocellular nodular lesions. The differential diagnosis between HHN and hepatocellular carcinoma on the basis of radiologic imaging is often difficult, and is clinically important when determining the therapeutic plan. Therefore, histological confirmation by needle biopsy sampling of the liver is necessary for a correct diagnosis of HHN. We report herein a case of benign HHN mimicking hepatocellular carcinoma in a 32-year-old male alcoholic liver cirrhosis patient without viral hepatitis infection.

Effect of biliary stenting combined with ursodeoxycholic acid and terpene treatment on retained common bile duct stones in elderly patients: a multicenter study.

OBJECTIVES: For frail, elderly patients with large impacted common bile duct (CBD) stones, long-term treatment with biliary stenting provides palliation. Biliary stenting with choleretic agents such as ursodeoxycholic acid (UDCA) and terpene preparations may promote CBD stone size reduction. We studied the effectiveness of biliary stenting combined with UDCA and a terpene preparation as a medical treatment for difficult-to-remove CBD stones in patients older than 65 years in this multicenter, prospective study. METHODS: A total of 28 elderly patients with CBD stones refractory to conventional endoscopic removal, including mechanical lithotripsy, underwent endoscopic placement of a straight 10-F plastic biliary stent. Each patient was administered 600 mg of UDCA and 300 mg of a terpene preparation daily for a mean of 6 months. After 6 months of medication following the initial endoscopic retrograde cholangiopancreatography (ERCP), a second ERCP was performed and endoscopic stone removal was again attempted. Differences in stone size and CBD diameter before and after biliary stenting and medication were compared. The complete stone removal rate after treatment was obtained. RESULTS: The mean size (transverse x longitudinal diameter) of the CBD stones was initially 21.6 x 29.5 mm, and it decreased significantly to 12.2 x 20.1 mm at the second ERCP (P<0.01). The mean CBD diameter measured initially at the cystic duct insertion level was 23.2 mm, and it decreased significantly to 19.5 mm at the second ERCP (P<0.01). After biliary stenting with medication, endoscopic stone removal was successful in 26 of 28 patients (92.8%), with a mean of 1.7 subsequent ERCP sessions. CONCLUSIONS: Endoscopic biliary stenting with a period of combined UDCA and terpene preparation administration seems to be a safe and effective method for retained CBD stones in elderly patients. A prospective study with randomization and a control group is required to confirm these results.

Serum enzyme half life can be a useful factor for follow-up management of biliary pancreatitis.

BACKGROUND AND OBJECTIVE: The purpose of this study was to show that the half lives of serum amylase and lipase activities could be useful factors for follow-up management of biliary pancreatitis. METHODS: Ten patients with initial biliary pancreatitis (IBP) and six with post-endoscopic pancreatitis (PEP) were selected from those who had undergone endoscopic surgery. Serum amylase and lipase activities were examined and the relaxation patterns were investigated continuously after the endoscopic removal of the pancreatico-biliary obstruction causing this disease. RESULTS: Pancreatitis in the subjects was confirmed as a biliary type since the serum bilirubin activities decreased exponentially after removal of the obstruction. The average half lives of serum amylase and lipase were both larger in the IBP, while the average peak values were higher in the PEP. CONCLUSIONS: Half life can be a useful factor for follow-up management of this disease.

[Hepatocellular carcinoma with lymphoid stroma: report of two cases].

We report two cases of hepatocellular carcinoma with prominent lymphocytic infiltration, which has been described as a subtype of hepatocellular carcinoma with good prognosis. One case showed lymphoid follicles and dense lymphocytic infiltrates within the tumor and its periphery, and the other case showed marked lymphocytic infiltration in the cancerous tissue. Piecemeal necrosis of cancer cells and atypical reactive changes were evident. The two cases were seronegative for hepatitis B surface antigen, antibody to hepatitis C virus, and Epstein-Barr virus DNA. One of the cases showed Clonorchis infestation. The prognostic significance of lymphocytic stroma in hepatocellular carcinoma requires further investigation.

[Change of HBV DNA level as a predictor of HBeAg loss after lamivudine treatment].

BACKGROUND AND AIMS: Lamivudine is an effective, safe therapeutic agent for the treatment of chronic hepatitis B. The aim of this study was to investigate whether early suppression of the viral load predicts HBeAg loss within 1 year during lamivudine therapy. METHODS: This prospective study encompassed 74 patients (mean age: 37.1 years, male/female: 51/23) who were positive HBeAg, their AST or ALT levels were > or =2 times the upper limit of normal and their HBV DNA was > or =10(5) copies/mL. The patients received lamivudine 100 mg for 12 months with monitoring their HBV DNA, AST, ALT, HBeAg and anti-HBe, and all these tests were performed at pretreatment and 1, 3, 6, 9 and 12 months after treatment. The serum HBV DNA was measured by HBV branched DNA assay. RESULTS: HBeAg loss was observed in 12 patients (16.2%), and 9 patients achieved anti-HBe seroconversion during up to 1 year of lamivudine therapy. The mean time to HBeAg loss was 5.6 months (range: 1-12 months). The posttreatment HBV DNA (<2,000 copies/mL) after 3 month (P=0.008) and 6 month (P=0.012)) were significant predictors of HBeAg loss after 1 year of lamivudine treatment on univariate analysis. Pretreatment HBV DNA, AST/ALT, gender, age and liver cirrhosis had no impact on HBeAg loss. The six-month posttreatment HBV DNA level <2,000 copies/mL was a significant predictor of HBeAg loss on multivariate analysis (P=0.008, odds ratio=0.108). CONCLUSION: We suggest that an HBV DNA level <2,000 copies/mL at 6 month after lamivudine therapy is the most important predictor of HBeAg loss during up to 1 year of lamivudine therapy.

Molecular and biochemical characterization of hemoglobinase, a cysteine proteinase, in Paragonimus westermani.

The mammalian trematode Paragonimus westermani is a typical digenetic parasite, which can cause paragonimiasis in humans. Host tissues and blood cells are important sources of nutrients for development, growth and reproduction of P. westermani. In this study, a cDNA clone encoding a 47 kDa hemoglobinase of P. westermani was characterized by sequencing analysis, and its localization was investigated immunohistochemically. The phylogenetic tree prepared based on the hemoglobinase gene showed high homology with hemoglobinases of Fasciola hepatica and Schistosoma spp. Moreover, recombinant P. westermani hemoglobinase degradaded human hemoglobin at acidic pH (from 3.0 to 5.5) and its activity was almost completely inhibited by E-64, a cysteine proteinase inhibitor. Immunohistochemical studies showed that P. westermani hemoglobinase was localized in the epithelium of the adult worm intestine implying that the protein has a specific function. These observations suggest that hemoglobinase may act as a digestive enzyme for acquisition of nutrients from host hemoglobin. Further investigations may provide insights into hemoglobin catabolism in P. westermani.

Amelioration of pancreatic fibrosis in mice with defective TGF-beta signaling.

OBJECTIVES: Pancreatic fibrosis is a characteristic feature of chronic pancreatic injury, which is a result of the imbalance between synthesis and degradation of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta) plays a central role in biosynthesis and turnover of the ECM. In this study, we evaluated the role of TGF-beta signaling in pancreatic fibrosis induced by repetitive acute pancreatic injuries with mice of dominant-negative mutant of TGF-beta receptor II selectively in pancreas. METHODS: TGF-beta signaling was inactivated by overexpressing a dominant-negative mutant form of TGF-beta type II receptor (pS2-dnR II) only in the pancreas under control of pS2/TFF1 promoter. Pancreatic fibrosis was induced by repeated intraperitoneal injections of 40 microg/kg cerulein for 5 or 10 weeks. RESULTS: Repeated administration of cerulein induced significant pancreatic fibrosis, but of which fibrosis was remarkably attenuated in pS2-dnR II mice compared with wild-type littermates (P < 0.01). The ameliorated fibrosis was due to the reduction of synthesis of ECM proteins such as collagen type I, fibronectin, and ICAM-1. DNA binding activity of transcriptional factors including nuclear factor (NF)-kappaB and AP-1, responsible for the induction of immediate early genes of inflammatory responses, were significantly decreased in pS2-dnR II mice. While TGF-beta1 treatment in isolated pancreatic stellate cells (PSCs) stimulated the expression of alpha-SMA and fibronectin, PSCs transfected with TGF-beta dnRII showed attenuation of the ECM components. CONCLUSION: Conditional loss of TGF-beta signaling selectively in the pancreas led to a failure in fibrogenic responses of repeated injections of cerulein, signifying that the modulation of TGF-beta signaling could be the therapeutic target for the prevention of chronic fibrosing pancreatitis.