Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.


Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.

Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.


A hydrolyzed whey peptide-based diet ameliorates hepatic ischemia-reperfusion injury in the rat nonalcoholic fatty liver.

The number of patients with nonalcoholic fatty liver disease (NAFLD) is increasing. Hepatic steatosis is a major risk factor for hepatic failure after ischemia-reperfusion (I/R) injury. Hydrolyzed whey peptide (HWP) is a functional liquid-type nutritional diet containing whey peptide, which has previously been shown to exert anti-inflammatory effects. In the present study, we examined the effects of HWP on the hepatic I/R injury in a rat NAFLD model. Rats fed a methionine/choline-deficient diet for 4 weeks were divided into two groups after 30 min of whole liver ischemia. In Group-M, HWP was given immediately after reperfusion and every 6 h thereafter. In Group-C, the vehicle was given in the same manner. The liver function tests and microscopic findings of the liver after reperfusion were compared between the two groups. The serum transaminase levels in Group-M were significantly lower than those in Group-C after reperfusion. The gene expression levels of IL-6 and inducible nitric oxide synthase (iNOS) were significantly lower in Group-M compared to Group-C. The TNF-α and uncoupling protein-2 (UCP-2) expression levels were also markedly lower in Group-M. The hepatic necrotic areas in Group-M were significantly smaller than those in Group-C. The administration of a HWP diet ameliorated the hepatic I/R injury in rats with NAFLD.


3.肝疾患 ウイルス性肝炎

3.肝疾患 ウイルス性肝炎


CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer.

It has been determined that the chemokine receptor CXC receptor 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), regulate several key processes in a wide variety of cancers. In this study, we investigate the possible role of SDF-1 (noncancerous liver tissue) and CXCR4 in liver metastases of colorectal cancer (CRC). Reverse transcription-polymerase chain reaction was performed to examine the expression of SDF-1 in noncancerous liver tissues of 16 CRC patients with liver metastasis and in normal liver tissues of six patients with benign liver disease. We also examined the expression of CXCR4 in cancerous tissues from primary and metastatic tumors. Using reverse transcription-polymerase chain reaction, CXCR4 expression in metastatic tumors tended to be higher than that in primary tumors (P = 0.16). High CXCR4 expression in a primary tumor was found to be related to an increased lymphatic invasion (P = 0.01), an advanced depth of tumor invasion (P = 0.07), and a decrease in the overall survival rate. The SDF-1 expression observed in noncancerous liver tissues of CRC with liver metastasis was significantly higher than that observed in normal liver tissues of benign liver disease (P < 0.05). In CRC with liver metastasis, CXCR4 expression demonstrated associations with local progression, liver metastasis, and poor overall survival.


Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases.

Recently, consensus on the optimal strategy for resectable synchronous colorectal liver metastases (LM) seems to have shifted toward simultaneous resection. However, there are still relatively few reports about simultaneous laparoscopic resection. The aim of this study is to evaluate the outcomes of patients who underwent simultaneous laparoscopic resection. We evaluated 14 patients who underwent simultaneous resection of primary colorectal cancer and LM in our hospital from 2004 to 2012. Patients were selected by matched pair analysis based on the number of LM (≤4) and tumor size (≤5 cm). We divided them into two groups: the simultaneous laparoscopic resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n = 7). Clinical and oncologic outcomes were compared between the groups. The Lap-S patients were significantly older than the Open-S patients. The mean operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the Open-S group (496 mL). There was no surgical mortality in either group. The incidence of postoperative complications in the Lap-S and Open-S groups was 12.3% and 33.0%, respectively. The mean postoperative hospital stay was significantly shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There was no significant difference in long-term survival between the two groups. Lap-S patients had equivalent long-term outcomes to Open-S patients. Therefore, given its technical feasibility and safety, Lap-S may be one of the most promising options in selected patients.


The role of Aurora B expression in non-tumor liver tissues of patients with hepatocellular carcinoma.

Aurora B is a serine-threonine kinase and chromosomal passenger protein involved in the control of chromosome assembly and segregation during mitosis. Aberrant expression of Aurora B has been reported in some tumors, including lung and hepatocellular carcinoma (HCC). We investigated the role of Aurora B expression in both HCC and matched adjacent non-tumor tissue. Sixty-three patients with HCC who underwent hepatic resection were enrolled in this study. Aurora B expression in tumor and non-tumor tissue was examined by use of quantitative reverse transcription-polymerase chain reaction. The patients were divided into high and low gene expression groups by median value, and clinicopathological data were compared between the two groups. Aurora B expression was significantly higher in tumor tissue than in non-cancerous tissue (P < 0.001). Disease-free survival was not significantly different between groups with high and low expression in the tumor tissues. For non-tumor tissues, disease-free survival of the low-expression group was significantly better than that of the high-expression group (P < 0.05). The gene expression level of Aurora B correlated with results from liver function tests, for example prothrombin time. Aurora B expression in non-cancerous tissues may be a prognostic factor for HCC.

International Journal of Clinical Oncology