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We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group).MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358).In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC.

The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer.Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors.By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV.Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.

Although curative surgical resection provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma, the presence of bile duct invasion decreases postoperative survival rates in patients with mass-forming intrahepatic cholangiocarcinoma. We carried out this study to determine a surgical strategy for patients with bile duct invasion of these tumors. Forty-one patients with mass-forming intrahepatic cholangiocarcinoma were classified as either having bile duct invasion (n= 26) or not having bile duct invasion (n= 15). Clinicopathologic findings, including postoperative outcomes, were compared between these two groups. Perineural invasion, lymphatic invasion, and a positive resection margin were more frequent in patients with ductal invasion. Patients with ductal invasion had lower survival rates than those without ductal invasion. Intraoperative frozen section examination of the bile duct stump to confirm a clear resection margin is required in patients with mass-forming tumors. Resection of the extrahepatic bile duct should be considered when tumor cells are identified at the surgical margin of the resected bile duct.

To clarify the variables related to survival after recurrence of resected hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), we studied 17 clinicopathological factors in 99 patients with recurrence of HCC associated with HCV infection after hepatic resection. The 1-, 3-, and 5-year survival rates after first resection in these patients were 91%, 81%, and 49%, while after recurrence they were 81%, 51%, and 29%, respectively. Multivariate analysis showed that the following six variables were independent prognostic factors after recurrence: platelet count, albumin level, bilirubin level, number of hepatic lesions, distant metastasis, and any treatment at recurrence. A correlation between second hepatic resection (SHR) and liver function tests was seen in regard to albumin and total bilirubin values at recurrence. Indeed, hepatic function and progression of intrahepatic tumors at recurrence were significant prognostic factors after recurrence of HCC associated with HCV infection, while any treatment at recurrence was also a significant prognostic factor. Therefore, in order to improve prognosis after recurrence, we should actively treat the recurrent hepatic lesions whenever possible.

We investigated morphological and functional changes after portal vein occlusion in rats. Portal branches for the median and left lateral lobes were ligated, after which the lobes were examined micromorphologically. After embolization of the same branches, regenerative capacity was evaluated in normal livers and in livers with CCl4-induced cirrhosis. Indocyanine green elimination, antithrombin III activity, and Kupffer cell density were also investigated. In another set of rats, the embolized lobes were resected 0, 2, 4, or 7 days after portal vein embolization (PVE), and endotoxin was injected intravenously 48h after each hepatectomy. In the ligated lobes, apoptotic hepatocytes were detected mainly around a widespread necrotic area on day 2, and among normal hepatocytes on day 7. In the nonembolized livers of control rats, increases were noted in liver weight, ornithine decarboxylase (ODC) activity, DNA synthesis, and mitosis of hepatocytes. In the cirrhotic livers, ODC activity was stimulated in a fashion similar to that seen in control liver, but DNA synthesis and weight change was delayed, although not significantly. On days 2, 4, 7, and 14 PVE, Kupffer cell density was about twice that seen in rats before PVE. Endotoxin-induced liver injury was slight if the rats had received PVE 4-7 days before the hepatectomy.

Hepatocellular carcinoma (HCC) is often associated with chronic liver disease, such as hepatitis or cirrhosis, and this association may limit the use of surgery as a therapy, and if surgery is pursued, may give rise to postoperative hepatic failure. We evaluated the outcome in patients with HCC given preoperative portal vein embolization (PVE) before they underwent major hepatectomy. After PVE, portal pressure increased significantly. Two weeks after PVE, both the volume of the non-embolized lobe and the 15-min indocyamine green retention rate (ICG R15) were significantly increased. The prognostic score, calculated on the basis of age, ICG R15, and the resection rate, was significantly decreased. The operative mortality rate was significantly lower in patients who underwent PVE before surgery than in patients who did not receive PVE. The cumulative survival rate of the PVE patients, even those with cirrhosis of the liver, was significantly higher. Prior PVE appears to allow more extensive major hepatectomy and to lessen the risk of this invasive surgery. However, patients in whom the portal pressure immediately after PVE was more than 30cm H2O and/or whose prognostic score exceeded 50 points developed postoperative hepatic failure. These features should be kept in mind when it is decided whether surgery is indicated. Nevertheless, preoperative PVE appears to be a beneficial procedure for patients undergoing major hepatectomy, particularly those with chronic liver disease.

Hilar bile duct carcinoma has a poor prognosis, but this has been improved in recent years by an aggressive surgical approach. We treated a 73-year-old woman who had obstructive jaundice due to bile duct carcinoma at the hepatic hilum. The jaundice decreased after percutaneous transhepatic biliary drainage. The tumor was resected with the left and caudate lobe of the liver and a part of portal vein. The right hepatic artery was located behind the common hepatic duct, and was suspected to be invaded by the tumor. We dissected the tumor from the arterial wall without carrying out combined resection of the hepatic artery. On the 6th postoperative day, the hepatic artery ruptured and the patient suffered hypovolemic shock. Resection of the hepatic artery and reconstruction were done, but the patient died 2 days later. Histological examination of the resected artery showed that the tumor had been curatively removed by dissection and that no tumor remained at the arterial wall. The rupture of the right hepatic artery was thought to have been caused by damage to the wall during the dissection procedure.

A case of cystadenocarcinoma of the liver is reported. The patient was a 73-year-old woman in whom a tumor was detected in the lateral segment of the liver during a health examination. Ultrasonograms and computed tomograms showed a multilocular cystic mass. Magnetic resonance imaging (MRI) showed a multilocular lowintensity mass, including a high-intensity portion and a portal branch compressed by the tumor. MRI with gadolinium showed an enhanced cyst wall. The cystic part of the tumor became smaller and the solid part became larger over a 1-month period, indicating that the tumor was malignant. Subsegmentectomy (S3) was performed and cystadenocarcinoma with cystadenoma was diagnosed by histopathological examination. Identification of changes in the appearance of a tumor should be helpful for the differential diagnosis of cystadenoma and cystadenocarcinoma.

CYFRA 21-1, a soluble fragment of cytokeratin 19, is increased in serum in some patients with hepatocellular carcinoma, but the clinical significance of this increase is still unknown.Serum concentrations of CYFRA 21-1 were measured in 240 patients with hepatocellular carcinoma prior to hepatic resection. The relationships between serum CYFRA 21-1 concentrations and clinicopathologic features were analyzed.The sensitivity of CYFRA 21-1 as a test for hepatocellular carcinoma was 18.8%. Serum CYFRA 21-1 was significantly higher in patients with portal vein tumor thrombus, and serum CYFRA 21-1 increased with the progression of portal vein tumor thrombus. Tumor size was related to serum CYFRA 21-1, but there were no significant correlations between serum CYFRA 21-1 concentrations and tumor differentiation or number of tumors. Although patients with stage IV tumor had significantly higher CYFRA 21-1 concentrations than those with stages I, II, and III, CYFRA 21-1 was not associated with postoperative prognosis.Although high concentrations of CYFRA 21-1 were often detected in patients with a tumor diameter greater than 5 cm or tumor thrombus in the major portal vein, CYFRA 21-1 is not a useful diagnostic tool for hepatocellular carcinoma because of its low sensitivity.

Although some gallbladder carcinomas are immunoreactive for c-Kit, the reasons for the c-Kit expression and its clinicopathologic implications are unknown.We investigated the prevalence of c-Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c-Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM-based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c-Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma.Cytoplasmic immunostaining for c-Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c-Kit positivity; however, there were no significant differences in the incidence of c-Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c-Kit-positive gallbladder carcinoma compared with c-Kit-negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19.Gallbladder carcinomas positive for c-Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.

Hepatocellular carcinoma with chondrosarcomatous variation is very rare. We report a case with the results of pathology examination, and review the literature. The patient, a 72-year-old may had a very large tumor in the liver revealed during follow-up for diabetes mellitus. The liver mass, which was 14 cm in diameter, was diagnosed as hepatocellular carcinoma by abdominal ultrasonography. Anterior segmentectomy and partial liver resection were performed. Histopathology examination revealed that the tumor consisted of two different components: the major one was hepatocellular carcinoma (HCC), which occupied most of the tumor; and a sarcomatous component, which occupied a smaller area, and included spindle-shaped cells with chondroscarcomatous variation. Intrahepatic metastases and tumor thrombi of HCC were also found in portal and hepatic veins. Investigations of the immunohistochemical localization of keratin (KRT), vimentin (VMT), and S-100 protein (S 100) were performed by the avidin-biotin complex method. Some of the spindle cells were immunohistochemically positive for both KRT and VMT, and the chondrosarcomatous cells were positive for S 100. These results strongly suggested that the sarcomatous lesion resulted from a sarcomatous change of HCC.