Tsuyoshi Ichikawa

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus

Aim:  Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV‐related hepatocellular carcinoma (HCC).

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma

BACKGROUND A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. METHODS Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. RESULTS Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. CONCLUSIONS Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

Immunohistologic Attempt to Find Carcinogenesis from Hepatic Progenitor Cell in Hepatocellular Carcinoma

Aim: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. Methods: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. Results: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. Conclusion: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

Surgical treatment for hepatocellular carcinoma detected after successful interferon therapy.

PurposeInterferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC.MethodsRisk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response).ResultsAccording to a univariate analysis, large tumor (>2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (<5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery.ConclusionAn anatomic resection with an appropriate surgical margin (≥5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.

Prognostic effects of causative virus in hepatocellular carcinoma according to the Japan integrated staging (JIS) score.

BackgroundThe Japan integrated staging (JIS) score is recognized to be useful in managing hepatocellular carcinoma (HCC). We evaluated the effects of the causative virus in patients stratified by this system.MethodsWe compared clinicopathologic features, cumulative and tumor-free survival rates, and causes of death between 301 hepatitis C virus-positive patients (HCV group) and 60 hepatitis B virus-positive patients (HBV group).ResultsAmong patients with low JIS scores (0 or 1), the proportions of patients with high aspartate and alanine aminotranferase activities, moderate-to-severe active hepatitis, and with cirrhosis were significantly higher in the HCV than in the HBV group. Among patients with high JIS scores (2 to 4), the proportion with moderate-to-severe active hepatitis was also significantly higher in the HCV group. In patients with low JIS scores, those in the HCV group had significantly lower tumor-free and cumulative survival rates than those in the HBV group. Although no patient in the HBV group died of causes other than liver disease (HCC or hepatic failure), some patients in the HCV group died of causes other than liver disease. The proportion of patients who died because of HCC recurrence tended to be higher among patients with high JIS scores than among patients with a low JIS score.ConclusionsThe effects of viral status on survival outcomes are greatest in patients with JIS scores of 0 or 1.

Adenomyoma of the common hepatic duct mimicking bile duct cancer: report of a case.

We report an unusual case of adenomyoma of the common hepatic duct mimicking bile duct cancer. A 50-year-old woman was referred to our hospital for the investigation of general fatigue. Laboratory data showed abnormal liver test results and computed tomography showed a mass lesion in the hepatic hilum and dilatation of the intrahepatic bile ducts. These findings led to a preoperative diagnosis of hilar bile duct carcinoma, and we performed a left lobectomy with resection of the extrahepatic bile duct. Macroscopically, an elevated lesion was found in the common hepatic duct, which was confirmed histologically to be an adenomyoma. Bile duct strictures are rarely caused by benign tumors of the biliary tract, such as adenomyoma. Surgical resection of the bile duct should be considered for all bile duct strictures because it is often difficult to differentiate malignant from benign lesions in this location preoperatively, and malignant cells may be present in the lesion.

Hepatobiliary and pancreatic : Cholangiocarcinoma in a double bile duct

What biliary disorders predispose to cancer of the bile duct (cholangiocarcinoma)? In Asia, one predisposing factor is chronic infestation of the biliary tree with the liver fluke, Opisthorchis viverrini. Other established predisposing factors include sclerosing cholangitis, choledochal cysts and previous treatment with Thorotrast. Other associations are less clear but bile duct cancer has been reported in biliary atresia, von Meyenburg complexes and gallstones in intrahepatic ducts. The patient described below had bile duct cancer in a duplicated bile duct. This created significant difficulties with the interpretation of cholangiograms. The patient was a 62-year-old Japanese woman who presented with obstructive jaundice. Her plasma bilirubin was 9.5 mg/dL (162 mmol/L). She had normal serum concentrations of carcinoembryonic antigen (1.1 ng/mL; N 0–6.5) but elevated levels of carbohydrate antigen 19–9 (606 U/mL; N 0–37) and Span-1 (191 U/mL; N 0–30). Cholangiograms are shown in Figures 1 and 2. In Figure 1, injection of contrast through a nasobiliary tube has outlined the left bile duct. The duct is mildly dilated and there is a filling-defect at the lower end. In addition, a branch of the left duct was abnormal and was subsequently shown to be a bridging duct between the left and right bile ducts. In Figure 2, contrast has outlined both the left and right bile ducts. The right bile duct is largely replaced by tumor. Only a small amount of contrast has passed into dilated intrahepatic ducts. Cytological evaluation of duct fluid revealed adenocarcinoma. At operation, the patient was treated with a right hepatic lobectomy, resection of the right bile duct and bridging duct and resection of perihepatic lymph nodes. The operative specimen revealed a tumor largely arising from the right bile duct and expanding into the liver and into a bridging hepatic duct. The cystic duct entered into the right bile duct. Histological examination revealed a poorly differentiated cholangiocarcinoma. The patient is alive and well 4 years after surgery. This appears to be the first report of a cholangiocarcinoma arising in a double bile duct.

Hepatocellular carcinoma (HCC) recurring 10 years after clearance of hepatitis B surface antigen and 20 years after resection of hepatitis B virus-related HCC

A 62-year-old man had been followed up for chronic hepatitis B (HB) since 1973. Hepatocellular carcinoma (HCC) was detected in 1985, at the age of 42 years. Serum HB surface antigen and anti-HB envelope antibody were positive at that time. A right hepatic lobectomy was performed. In 1995, serum HB surface antigen had cleared spontaneously and liver function had normalized. In March 2005, at the age of 62 years, a 1.5-cm diameter hepatic mass was detected in the left lateral segment. At that time, he was seropositive only for anti-HB core antibody. A diagnosis of recurrent HCC was made, and partial hepatectomy was performed. Covalently closed circular HBV DNA was detected in both cancerous and noncancerous tissues by nested polymerase chain reaction (PCR). Cassette-ligationmediated PCR showed that HBV DNA was integrated into the telomerase reverse transcriptase gene located on chromosome 5p15.