Takayuki Hamatsu

Bio: Takayuki Hamatsu is an academic researcher from Kyushu University. The author has contributed to research in topics: Hepatectomy & Hepatocellular carcinoma. The author has an hindex of 15, co-authored 40 publications receiving 1226 citations.

Bile Leakage After Hepatic Resection

Abstract: Because of recent advances in liver surgery, hepatic resections are being performed with increasing frequency, and the surgical death rate for such resections is decreasing. 1–7 Bile leakage, of course, is the primary complication occurring after liver surgery, and it can not only debase the quality of the postoperative course of patients, but also can lead to hospital death. Despite a significant decrease in the overall surgical complication rate in hepatic resections, the rate of bile leakage has not changed, with an incidence of 4.8% to 7.6% reported in recent large series. 2–8 The presence of bile, blood, and devitalized tissues in the dead space after hepatectomy may provide the ideal environment for bacterial growth and impair the normal host defense mechanisms. 9, 10 The combination of sudden reduction in the liver volume and development of an intraperitoneal septic complication after hepatectomy (IPSCH) frequently results in liver failure, leading to a grave prognosis. 11 The aims of this study were, therefore, to clarify the perioperative risk factors for postoperative bile leakage after hepatic resection, to evaluate the intraoperative bile leakage test as a preventive measure, and to propose a treatment strategy for postoperative bile leakage according to the outcome of these patients.

Clinical Significance of Histone Deacetylase 1 Expression in Patients with Hepatocellular Carcinoma

Abstract: Objective: Histone deacetylases (HDACs) play an important role in chromatin remodeling, gene repression and regulating cell cycle progression and differentiation. This study was des

Electroporation-mediated Interleukin-12 Gene Therapy for Hepatocellular Carcinoma in the Mice Model

Abstract: Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 ( IL-12 ) gene therapy for hepatocellular carcinoma (HCC) First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by sc implantation of MH134 cells to C3H mice This process made use of plasmid DNA that express the luciferase gene We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10 Second, we tried to treat sc HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 ( mIL-12 ) gene Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-γ and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3 + cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial

The role of macroscopic classification in nodular-type hepatocellular carcinoma.

Abstract: Background: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. Methods: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. Results: The α-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. Conclusions: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.

Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.

Abstract: Hypothesis Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. Design A prospective randomized trial. Setting A university hospital department of surgery. Patients Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. Main Outcome Measures Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. Results Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. Conclusions Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.

New and emerging HDAC inhibitors for cancer treatment.

Abstract: Epigenetic enzymes are often dysregulated in human tumors through mutation, altered expression, or inappropriate recruitment to certain loci. The identification of these enzymes and their partner proteins has driven the rapid development of small-molecule inhibitors that target the cancer epigenome. Herein, we discuss the influence of aberrantly regulated histone deacetylases (HDACs) in tumorigenesis. We examine HDAC inhibitors (HDACis) targeting class I, II, and IV HDACs that are currently under development for use as anticancer agents following the FDA approval of two HDACis, vorinostat and romidepsin.

Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings.

Abstract: Objective:To evaluate a new 2-step technique for obtaining adequate but short-term parenchymal hypertrophy in oncologic patients requiring extended right hepatic resection with limited functional reserve.Background:Patients presenting with primary or metastatic liver tumors often face the dilemma th

Portal vein embolization before right hepatectomy: prospective clinical trial.

Abstract: Objective To assess the impact of liver hypertrophy of the future liver remnant volume (FLR) induced by preoperative portal vein embolization (PVE) on the immediate postoperative complications after a standardized major liver resection.