Kensuke Nuruki

Interleukin 8 in Human Hepatocellular Carcinoma Correlates With Cancer Cell Invasion of Vessels But Not With Tumor Angiogenesis

BackgroundAngiogenic factor seems necessary for the development of hepatocellular carcinoma (HCC), which is a hypervascular malignancy. This study examined the expression of interleukin (IL)-8, a potent angiogenic factor, in HCC samples.MethodsWe measured IL−8 expression by using reverse transcriptase-polymerase chain reaction in clinical HCC tissues from 45 patients who underwent surgical resection. We then assessed correlations between IL−8 expression and microvessel growth or clinicopathologic factors. We also elucidated the in vitro effect of IL−8 on HepG2 development by using fluorometric assays of proliferation, chemotaxis, and invasion.ResultsThe expression of IL−8 did not significantly correlate with the microvessel count in HCC tissues, but the incidence of microscopic vessel invasion was significantly higher in IL−8–positive than in IL−8–negative tissues. Thus, more IL−8 was expressed in HCCs at pathologic stage III/IV than in those at stage I/II. Assays in vitro showed that IL−8 stimulates HepG2 chemotactic and invasive activities rather than cell proliferation.ConclusionsThe expression of IL−8 in human HCC has more relevance to metastatic potential, such as vessel invasion, than to angiogenesis or cell proliferation.

Response of patients with cirrhosis who have undergone partial hepatectomy to treatment aimed at achieving supranormal oxygen delivery and consumption

BACKGROUND This study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index > than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170 ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and to assess the relationship between those parameters and outcome. METHODS Thirty-four consecutive patients underwent elective hepatectomy for hepatocellular carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values in 16 patients (group S) who maintained supranormal values were compared with those in 18 patients (group N) treated to maintain normal hemodynamic values. Patients in group S received volume expansion and then, if necessary, dobutamine (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and oxygen comsumption simultaneously during the first 12 hours. RESULTS The hemodynamic targets were reached by 56% of patients in group S during the first 12 hours and 31% during the next 12 hours. Postoperative blood lactate levels at 12 and 24 hours were lower in group S than in group N, and total bilirubin concentrations, hepatic venous oxygen saturation, and arterial ketone body ratio, useful markers of postoperative liver function, also showed more favorable changes in group S than in group N. Postoperative morbidity and mortality rates were not significantly different in the two groups, but the incidence of hyperbilirubinemia and liver failure was much lower in group S than in group N. CONCLUSIONS These results suggest that fluid therapy aimed at achieving a supranormal pattern by 12 hours after hepatectomy improved the systemic oxygen demand-supply dynamics and hepatic hemodynamics, decreasing the incidence of postoperative hyperbilirubinemia and liver failure in patients with liver cirrhosis.

The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer.

Although impaired expression of E-cadherin (E-cad) is frequently observed in tumors with aggressive histopathologic characteristics, the correlation between α-catenin (α-cat) expression and the clinicopathologic features of early gastric cancer have not been fully examined. In this study, we evaluated the expression of E-cad and α-cat by early gastric carcinomas, and examined the relationships between this expression and various clinicopathologic characteristics. A total of 69 specimens obtained from surgery were studied by immunohistochemistry. Reduced expression of E-cad and α-cat were found in 53.6% and 65.2% of the tumors, respectively, and a significant correlation was observed between the decreased expression of E-cad or α-cat and tumor histology, the quantity of stroma, and the infiltration pattern of the tumor. The reduced expression of α-cat correlated more strongly with these features than E-cadherin expression. Furthermore, α-cat expression was also related to the lymph node metastasis of tumors. The expression of E-cad or α-cat in the primary tumor was consistent with the expression of tumor cells that invaded the lymphatic vessels, but discordant with staining in the metastasized lymph nodes. In some cases, as the tumor invaded deeper, the expression of E-cad or α-cat changed from preserved to reduced. Our observations suggest that the reduced expression of E-cad or α-cat may be involved in the initial steps leading to the invasion and metastasis of early gastric cancer.

Serum hepatocyte growth factor (HGF) levels predict the outcomes in hepatectomized patients with postoperative hyperbilirubinemia

Abstract The purpose of this report is to evaluate the usefulness of serum hepatocyte growth factor (HGF) levels as a prognostic factor in hepatectomized patients with early postoperative hyperbilirubinemia (HB). The serum HGF levels of 14 patients with early postoperative HB (serum total bilirubin level above 5 mg/dl lasting at least 3 days), were measured perioperatively (prior to and 6 h, 1, 2, 3, 4, 7 and 14 days following surgery) and the relationship between changes in serum HGF levels and postoperative outcome was analyzed. The 14 patients were divided into two groups; 6 patients (Group A) ameliorated by conservative therapies within 7 days after surgery, and 8 patients (Group B) with prolonged HB more than 2 weeks after surgery. Five patients (83%) in Group A showed relatively low maximum serum HGF levels ( 2.0 ng/ml). Six of the 7 patients in Group B developed hepatic failure and died. These results suggest that, in patients with HB or those in whom it is expected to occur soon after hepatectomy, the measurements of serum HGF levels would be beneficial for determining therapy and predicting postoperative outcomes.

Abnormal expression of β- and γ-catenins in early gastric cancer

BackgroundE-cadherin and α-catenin are closely correlated with the clinicopathology of advanced gastric cancer, but little is known about the functions and mechanisms of β- and γ-catenins. In this study, we evaluated the expression of β- and γ-catenins in early gastric cancer.MethodsSixty-nine specimens, obtained by surgery from patients with early gastric cancer, were studied by immunohistochemistry, using monoclonal anti-β- and anti-γ-catenin antibodies.ResultsReduced expression of β- and γ-catenins was found in 28% and 39% of early gastric cancer specimens, respectively. The reduction in the expression of β-catenin was related to patient age and tumor size, while the reduction in γ-catenin expression was related to the histologic type and infiltration pattern of the tumor. A significant correlation was observed between the expression of β-catenin and that of γ-catenin. Tumors in which simultaneous staining showed heterogenous expression of β- and γ-catenins had a higher rate of lymph node metastasis.ConclusionsChanges in the quantity of β- or γ-catenin act as factors that take part in some process that indirectly affects cell-to-cell adhesion and detachment. Combined examination of β- and γ-catenins may be helpful in predicting the outcome for patients with early gastric cancer.

Prognosis and Quality of Life after Hepatectomy in Patients with Hepatocellular Carcinoma.

背景肝病変にもとづく肝細胞癌手術203例の遠隔期の病態とQOLについての検討を行い, 以下の結論を得た.(1) 肝細胞癌切除例のQOLは, 術後1年を過ぎるとおおむね良好であるが, 初回手術時・再発時のInformed consentは重要である.(2) 再発症例は, 無再発期間が1年以内あるいは再発治療中の場合にとくにQOLが低下する.(3) Normal-CPH症例の比較的良好な予後・QOLに対し, CAH症例は早期からの易再発性と, 再発・肝炎治療による社会的, 精神的機能の低下が問題である. また, LC症例も易再発性であるが, 約50%は多中心性発生であり, さらに, 術後高度合併症発生例で重篤な長期PS低下がみられる. 以上のことから, 長期予後・QOLを考慮したHCCの外科的治療戦略として, Normal-CPH症例は根治性を重視した肝切除, CAH症例は無再発期間を延長するための効果的な肝障害増悪防止・再発予防治療, さらに, LC症例は初回・再発時の治療法選択がとくに重要と考えられた.