Yoshisato Tanimoto

Treatment strategy for early hepatocellular carcinomas: Comparison of radiofrequency ablation with or without transcatheter arterial chemoembolization and surgical resection

The preferred choice between surgical treatment and radiofrequency ablation (RFA) for the treatment of small resectable hepatocelluar carcinoma (HCC) has become a subject for debate.

Rho inhibitor prevents ischemia–reperfusion injury in rat steatotic liver

BACKGROUND & AIMS Hepatic stellate cells are thought to play a role in modulating intrahepatic vascular resistance based on their capacity to contract via Rho signaling. We investigated the effect of a Rho-kinase inhibitor on ischemia-reperfusion injury in the steatotic liver. METHODS Steatotic livers, induced by a choline-deficient diet in rats, were subjected to ischemia-reperfusion injury. Hepatic stellate cells isolated from steatotic livers were analyzed for contractility and Rho signaling activity. The portal pressure of the perfused rat liver and the survival rate after ischemia-reperfusion were also investigated. RESULTS Hepatic stellate cells from steatotic livers showed increased contractility and upregulation of Rho-kinase 2 compared with those from normal livers. Furthermore, endothelin-1 significantly enhanced the contractility and phosphorylation level of myosin light chain and cofilin in hepatic stellate cells isolated from steatotic livers. A specific Rho-kinase inhibitor, fasudil, significantly suppressed the contractility and decreased the phosphorylation levels of myosin light chain and cofilin. Serum levels of endothelin-1 were markedly increased after IR in rats with steatotic livers, whereas fasudil significantly decreased endothelin-1 serum levels. Rats with steatotic livers showed a significant increase in portal perfusion pressure after ischemia-reperfusion and a significant decrease in survival rate; fasudil treatment significantly reduced these effects. CONCLUSIONS Activation of Rho/Rho-kinase signaling in hepatic stellate cells isolated from steatotic livers is associated with an increased susceptibility to ischemia-reperfusion injury. A Rho-kinase inhibitor attenuated the activation of hepatic stellate cells isolated from steatotic livers and improved ischemia-reperfusion injury in steatotic rats.

Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria.

BackgroundThe appropriate treatment strategy for advanced hepatocellular carcinoma (HCC) that does not meet the Milan criteria (MC) is unclear. The aim of this study was to determine the significance of surgical treatment for such patients.Study designFrom January 1990 to December 2007, 151 patients with HCC exceeding MC who underwent curative surgical treatment were enrolled. Survival and recurrence data and clinicopathological factors were examined. Prognostic factors were analyzed to identify those that contributed to improved surgical outcomes retrospectively.ResultsAfter the initial hepatectomy, the overall 3-, 5-, and 10-year survival rates were 73%, 55%, and 33%, respectively, for the 151 patients in this study; the corresponding disease-free survival rates were 36%, 30%, and 17%, respectively. A platelet count under 105/mm3, multiple tumors, and liver cirrhosis of noncancerous tissue were adverse survival and disease-free survival factors by univariate analysis. Platelet count was an independent prognostic factor by multivariate analysis. The 3-, 5-, and 10-year overall survival rates of HCC exceeding MC in patients whose platelet count was 105/mm3 or greater reached 76%, 65%, and 44%, respectively, and were comparable with those that met MC (86%, 68%, and 37%, respectively).ConclusionsHepatectomy for patients with advanced HCC exceeding MC improves survival, especially for patients with a sufficiently high platelet count, although recurrence rates after initial hepatectomy are high.

Comparative study of the Japan Integrated Stage (JIS) and modified JIS score as a predictor of survival after hepatectomy for hepatocellular carcinoma

BackgroundThe purpose of the study was to compare the abilities of the JIS and modified JIS (m-JIS) scores to predict survival after hepatectomy for hepatocellular carcinoma (HCC).MethodsData for patients who underwent hepatectomy for HCC at Hiroshima University Hospital between 1986 and 2006 were included. The overall survival and disease-free survival were calculated by the Kaplan-Meier method, and differences between groups were tested by the log-rank test. The statistics of the Akaike information criterion (AIC) were used to show the more appropriate model.ResultsA total of 626 patients were included (male/female, 468/158; mean age, 63.4 ± 9.6 years; Child-Pugh class A/B, 524/102; liver damage grade A/B/C, 356/261/9). Mean survival and disease-free survival were 8.04±0.39 and 4.69 ± 0.32 years, respectively. There was a significant difference in the overall survival rate between JIS scores 1 and 2, and 2 and 3 (P < 0.05), but not between scores 0 and 1, or 3 and 4 (P > 0.05). Except between m-JIS scores 0 and 1, there was excellent discriminatory ability in overall survival rate between other consecutive groups. Concerning disease-free survival, a significant difference was found only between JIS scores 1 and 2. However, the disease-free survival rate could be well differentiated between m-JIS scores 1 and 2, and 3 and 4. The m-JIS score had a higher discriminatory ability, indicated by a linear trend analysis, and a higher homogeneity likelihood ratio, and lower AIC statistics, than the original JIS score in predicting both overall and disease-free survival.ConclusionsThe modified-JIS scoring system using liver damage grade is better than the original JIS scoring system in predicting survival after hepatectomy for HCC in Japan.

Suppression of hepatocellular carcinoma recurrence after rat liver transplantation by FTY720, a sphingosine-1-phosphate analog.

Background. Although the outcome of liver transplant patients with hepatocellular carcinoma (HCC) has improved with the introduction of strict criteria, tumor recurrence still remains a significant problem. Sphingosine-1-phosphate (S1P) is a phospholipid mediator that can induce diverse cellular responses, such as proliferation, migration, adhesion, and cell-rounding, in cancer cells. We investigated whether FTY720, a S1P analog, suppresses tumor recurrence after experimental liver transplantation in a rat HCC model. Methods. HCC-bearing rats were subjected to orthotropic liver transplantation. HCC cells were analyzed for cell migration, proliferation, and S1P receptors. Results. FTY720 induced the down-regulation of the S1P-1 receptor of HCC cells and suppressed both cancer cell migration and proliferation. FTY720 also suppressed mitogen-activated protein kinase phosphorylation. The suppression of tumor recurrence after liver transplantation and a significant prolongation of survival were observed in the FTY720-treated rats, in comparison with FTY720-untreated rats. Conclusion. FTY720 suppresses the invasiveness and proliferation of HCC through a down-regulating S1P-1 receptor to suppress the recurrence of HCC after liver transplantation; FTY720 may be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.

Using recipient's middle hepatic vein for drainage of the right paramedian sector in right liver graft.

Background. Congestion in the right paramedian sector of a right liver graft without a middle hepatic vein (MHV) may lead to graft dysfunction. To solve this problem, we have developed a technique for reconstructing the MHV tributaries of the right liver grafts by using the preserved recipient’s native MHV trunk. Methods. Between 2005 and 2007, among 34 right liver graft liver transplant patients with significant MHV tributaries (>5 mm in diameter), 21 patients underwent right liver graft living-donor liver transplantation: draining MHV tributaries with recipient’s native MHV trunk. We evaluated the patency of the reconstructed MHV tributaries, graft regeneration, and graft survival. Results. The 3-month patency rates of the reconstructed V8 and V5 were 92% and 76%, respectively. The 1-year survival rate and the regeneration index of the right paramedian sector 6 months after transplantation were higher in patients with reconstructed MHV tributaries than that for patients without reconstructed MHV tributaries. Conclusion. The use of the recipient’s MHV trunk for the reconstruction of the MHV tributaries of the right liver grafts is considered to be a valuable and a feasible strategy in right liver graft living-donor liver transplantation.

A huge metastatic liver tumor from leiomyosarcoma of the inferior vena cava: report of a case

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumor, and only a few cases of the resection of IVC leiomyosarcomas with synchronous liver metastases have been reported. This report describes a female patient who initially presented with a solitary, huge liver tumor and a retroperitoneal tumor. Following our preoperative diagnosis of primary liver cancer with a retroperitoneal lymph node metastasis, the patient underwent combined resection of both tumors. The surgical findings revealed that the retroperitoneal tumor originated from the IVC wall. The pathological and immunohistochemical findings revealed that both tumors were leiomyosarcomas. Although the liver tumor was much larger than the IVC tumor, we considered that the metastatic liver tumor arose from the IVC leiomyosarcoma. This was an instructive case because the metastatic liver tumor from the IVC leiomyosarcoma was so large as to be mistaken for a primary liver tumor.

Hepatic venous outflow obstruction after right lateral sector living-donor liver transplantation, treated by insertion of an expandable metallic stent

Hepatic venous outflow obstruction is a relatively uncommon but important and devastating complication occurring after liver transplantation. Recently, right lateral sector liver grafts have sometimes been used in living-donor liver transplantation (LDLT), but, to our knowledge, early hepatic venous outflow obstruction has never been reported in right lateral sector LDLT. A 58-year-old woman was diagnosed with liver cirrhosis and hepatocellular carcinoma and underwent right lateral sector LDLT. Postoperatively, she developed liver dysfunction. Doppler ultrasound examination revealed flat waveforms and low-flow velocity in the right hepatic vein (RHV). A computed tomography (CT) scan revealed a ventrally distorted RHV due to hypertrophy of the liver graft. Hepatic venous obstruction was suspected and a hepatic venogram was performed. The venogram revealed stenosis of the RHV due to the distortion of the vein. We performed percutaneous transfemoral balloon dilatation, but this was not effective. We then inserted an expandable metallic stent (EMS) into the RHV. After the EMS placement, the condition of the patient improved. Venogram and CT data suggested that the obstruction of the RHV developed because of distortion of the RHV to the ventral side during liver regeneration.