Masahiro Hamanoue

A novel function of the receptor for advanced glycation end-products (RAGE) in association with tumorigenesis and tumor differentiation of HCC.

BackgroundThe expression of the receptor for advanced glycation end products (RAGE) has an impact on the mechanisms giving rise to characteristic features of various cancer cells. The purpose of this study was to elucidate the clinicopathological relevance of the level of RAGE expression in patients with hepatocellular carcinoma (HCC) and to explore the effect of RAGE expression on the characteristic features of HCC.MethodsThe expression of RAGE was assessed in paired cancer and noncancerous tissues with HCC, using reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. The quantitative RT-PCR data were analyzed in association with the clinicopathological factors of the patients with HCC. In in vitro experiments, the survival of RAGE-transfected Cos7 and mock-transfected Cos7 cells was compared under hypoxic conditions. In addition, after reducing RAGE levels in RAGE-transfected Cos7 cells by siRNA, similar experiments were performed.ResultsThe expression of RAGE mRNA was lower in normal liver than in hepatitis and highest in HCC. Furthermore, in HCC, it was high in well- and moderately differentiated tumors but declined as tumors dedifferentiated to poorly differentiated HCC. Furthermore, HCC lines resistant to hypoxia were found to have higher levels of RAGE expression, and RAGE transfectant also showed significantly prolonged survival under hypoxia.ConclusionsOur results suggest that HCC during the early stage of tumorigenesis with less blood supply may acquire resistance to stringent hypoxic milieu by hypoxia-induced RAGE expression.

Cholangiolocellular carcinoma of the liver : CT and MR findings

The authors report two cases of surgically proved cholangiolocellular carcinoma of the liver. Marked contrast enhancement was observed at the periphery of the tumor on CTs and MRIs obtained during the hepatic arterial and portal venous phases, with concentric filling on the delayed images. On T1-weighted and T2-weighted MRIs, the tumor was, respectively, hypointense and hyperintense, with a central hypointense area. Therefore, helical CT and MRI features of these cholangiolocellular carcinomas were thought to be similar to those of cholangiocarcinoma.

Exogenous hepatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs

Abstract Portal branch ligation (PBL) or embolization prior to extensive hepatectomy has been employed to increase the functional reserve of the remaining liver. This study investigated the effects of human recombinant hepatocyte growth factor (rh-HGF) on liver regeneration following PBL in dogs. Beagle dogs were subjected to PBL and were divided into two groups, a control group (n=11) without rh-HGF and a treated group (n=12) receiving postoperative rh-HGF at 250 ng/kg via the portal vein. Dogs were killed 72 h or 14 days following PBL. We studied the changes in serum HGF level, DNA synthesis of the liver, hepatocyte size, liver weight, and liver function tests. In the HGF group, the ratio of whole liver weight to body weight increased significantly, and both ligated and nonligated lobes showed marked increases in weight. The nonligated lobes in the HGF group showed significant increases in both DNA synthesis and hepatocyte size. Moreover, ligated lobes in the HGF group showed an increase in DNA synthesis without hypertrophy compared with the control group. Administration of rh-HGF did not significantly affect liver function tests. Ligation of the portal branch supplying the portion of liver to be resected, coupled with the administration of rh-HGF, is a useful strategy to increase hepatic reserve in advance of major hepatectomy.

Treatment for accidental occlusion of the hepatic artery after hepatic resection: Report of two cases

Two patients in whom accidental hepatic artery occlusion (HAO) occurred after hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for hepatocellular carcinoma with underlying liver cirrhosis developed HAO on postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy findings showed multiple necrosis in the remnant liver and an extraluminal hematoma of the hepatic artery, suggesting an injury caused by Pringle’s maneuver. The second case was a 53-year-old male who underwent Hx for cholangiocarcinoma without any underlying liver disease. He developed HAO on POD 6, and radiological studies indicated a pseudoaneurysma formation and severe stenosis of the hepatic artery. It was speculated that the cause of the HAO was intraluminal injury of the hepatic artery during an angiographic study conducted prior to Hx. Partial arterialization of the portal vein was performed, following which his liver function test results improved. In both cases, measuring the serum hepatocyte growth factor level and the hepatic vein oxygen saturation proved useful, not only for determining the degree of liver injury, but also for predicting the outcome after treatments for HAO. Furthermore, the partial arterialization of the portal vein for HAO after Hx may rescue the normal remnant liver.

Effects of exogenous prostaglandin E1 in hepatectomized patients

The efficacy of prostaglandin E1 (PGE1) in preventing hepatic failure after hepatectomy was investigated prospectively in eight PGE1-treated patients and in seven untreated controls. The patients in the PGE1-treated group received PGE1 (0.03 μg/kg per min) intravenously for 72 h beginning at the initiation of surgery. The cardiac index increased markedly and the systemic vascular resistance decreased markedly during PGE1 treatment, while no significant changes were observed in the control group. The platelet count in the PGE1-treated group decreased slightly, while that in the control group decreased significantly during the first 3 postoperative days. The percent change of alanine aminotranferase in the PGE1-treated group was less than that in the control group. These findings suggest that the administration of exogenous PGE1 following hepatectomy increases hepatic blood flow and suppresses platelet aggregation, and therefore may be cytoprotective to the remnant liver. Thus, PGE1 may be effective in preventing hepatic failure after hepatectomy.

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.

A correlation between arterial ketone body ratio and concentration of β-hydroxybutyrate as an indicator of hepatic functional reserve

We have investigated the correlation between the arterial blood ketone body ratio (AKBR) and β-hydroxybutyric acid (HBAC) in the course of a 75 g glucose tolerance test. The correlation was revealed to be represented by an equation of Y=A+BX [X=log(HBAC), Y=log(AKBR)] with high significance. This expression existed in both normal individuals and patients with liver, biliary tract or pancreas disease. The postoperative course was unsatisfactory because of liver dysfunction in cases whose value B was more than −0.6 in bisegmentectomy and more than −0.45 in uni- or subsegmentectomy. The coefficient B in the equation was suggested to contribute to the evaluation of hepatic functional reserve.

High Serum Alpha-Fetoprotein Concentration Associated with Pseudoinfarction of a Cirrhotic Liver: Report of a Case

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.

Hepatocellular carcinoma coexistent with adenomatous hyperplasia: Report of a case

We would like to draw attention to hepatic tumor-like lesions which frequently complicate the differential diagnosis of hepatocellular carcinoma (HCC), while considering their pathology and diagnosis by radiographic imaging. In particular, adenomatous hyperplasia is recognized as a precancerous lesion of HCC, and the relationship between adenomatous hyperplasia and the multicentric development of HCC is recognized. We observed a patient who demonstrated hyperplastic changes in both the liver cells and a well-differentiated HCC lesion adjacent to the adenomatous hyperplasia, suggesting a multicentric development of the HCC. The histopathological features of adenomatous hyperplasia are also described.

Postoperative Complication after Hepatic Resection by the Right Thoraco-abdominal Approach.

開胸開腹下の肝切除における術後合併症の発生状況と, 合併症発生に関与する因子についてretrospectiveに検討した. 対象は過去5年間の肝細胞癌肝切除114例中, 右葉系の切除を行った開腹例45例, 開胸腹例 (右開胸腹連続切開) 32例である. 両群の年齢, 臨床病期, 腫瘍径に差はなかったが, 切除部位は開胸腹群で上区が多かった (p<0.01). 術後合併症の発生率, 内容も両群間に差はなかった. 開胸腹群の術後合併症発生状況をA群 (合併症なしを含む;n=24), B群 (ビリルビン値10mg/dl以上またはDIC発生;n=8) とし, 比較すると, B群は, A群に比べ年齢が高く (p<0.01), 腫瘍が肝静脈根部と近接する症例が多く (p<0.01), 肝門部阻血未施行例が多かった (p<0.05). 開胸腹下肝切除においては, 高齢者や肝静脈根部腫瘍近接症例では術後重症合併症をきたしやすく, 術中肝静脈よりの出血コントロールが重要である.