Gen Tanabe

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.

Effective chemotherapy for small cell carcinoma of the esophagus

This article documents the use of chemotherapy in a case of small cell carcinoma of the esophagus with multiple liver and lymph node metastases. A multi‐drug regimen was used and included cisdichlorodiamine platinum (CDDP), VP‐16, vincristine (VCR), adriamycin (ADM), and cyclophosphamide (CPA). After chemotherapy, the esophageal tumor disappeared, and liver masses reduced in number and degenerated. Nine months later, however, the patient died of brain metastases. It was concluded that radiotherapy should be given to the brain for the prophylaxis of tumor relapse.

Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer.

AbstractBackground: Recent studies suggest that angiogenesis enhances tumor growth and metastasis. Lymph node metastasis influences the prognosis and selection of treatment modalities in cancers. In this study, the authors investigated the correlation between angiogenesis and clinicopathologic features to determine whether angiogenesis correlated with lymph node metastasis in early-stage gastric cancer. Methods: A total of 97 specimens from patients with early gastric cancer were studied by immunohistochemical methods using anti-Factor VIII-related antigen antibody. Results: Tumor size was significantly correlated with microvessel count, which increased as tumor size increased. Microvessel counts from tumors with lymphatic vessel invasion, lymph node metastasis, and submucosal invasion were significantly higher than those without. Furthermore, microvessel count was an independent factor that influenced lymph node metastasis (P=.0016) by multivariate logistic regression analysis. Conclusion: In the early stage of gastric carcinoma, angiogenesis is an independent factor that impacts on lymph node metastasis.

Cooccurrence of Reduced Expression of α-Catenin and Overexpression of p53 Is a Predictor of Lymph Node Metastasis in Early Gastric Cancer

Background and Objectives: Even though the pathological background contributes to lymph node metastasis, the biological characteristics of tumors have also gained wide attention. In this study, the expression of the cadherin-catenin complex and p53 was studied in early gastric cancer. Their correlation with lymph node metastasis and the predictability of lymph node metastases, by combining these factors, were also discussed. Methods: One hundred and one specimens obtained from surgery were studied by immunohistochemistry using monoclonal anti-E-cadherin, anti-α-catenin and anti-p53 antibodies. Results: Expression of E-cadherin and α-catenin was reduced in 50.5 and 64.4%, respectively. p53 protein staining was positive in 29.7%. There was a significant correlation between E-cadherin and α-catenin expression, but no correlation was found between p53 expression and E-cadherin or α-catenin expression. A reduction in α-catenin expression and p53 overexpression correlated to lymph node metastases, respectively. Multivariate analysis showed that cooccurrence of reduced expression of α-catenin and overexpression of p53 was an independent factor indicating lymph node metastases. Conclusion: A study of both α-catenin and p53 expression may be helpful to predict lymph node metastases in early gastric cancer.

p21 expression is a prognostic factor in patients with p53-negative gastric cancer

The expression of p21 and p53 proteins was analyzed by immunohistochemistry in 256 patients with advanced gastric cancer. The results showed that strong, weak and negative expression of p21 were detected in 22.2 (57/256), 68.0 (174/256) and 9.8% (25/256) of the patients, respectively. p53 expression was found in 28.9% (74/256). The expression of p21 was not associated with clinicopathological features. In p53 negative tumors, p21 expression was associated with the survival of patients who underwent curative operations (P = 0.007). The 5-year survival rates were 20.1, 36.6 and 59.8% in patients with p21-negative, -weakly positive and -strongly positive tumors, respectively. In contrast, in p53-positive tumors, prognosis did not differ in spite of p21 expression. Multivariate analysis showed that p21 expression was an independent factor in patients with p53-negative tumors. These results indicate that examination of p21 expression in p53 negative tumors will be useful for estimating the prognosis of patients with advanced gastric cancer.

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n=5), an 84% Hx group (n=5) and an 84% Hx+PSS group (n=5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immuno-histochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.

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.

Selectins induced by interleukin-1β on the human liver endothelial cells act as ligands for sialyl Lewis X-expressing human colon cancer cell metastasis

We have previously reported that colon cancer cells metastasized to the liver expressed an increased amount of sialyl Lewis X (SLeX) antigen compared to their corresponding primary lesions. It is now well known that SLeX antigen and sialyl Lewis A (SLeA) antigen are ligands for the selectins expressed on the endothelial cells. Therefore, it is assumed that SLeX-rich colon cancer cells could be easily adhered to the endothelial cells that express selectins. In this report we have tried to induce selectin expression on the human liver sinusoidal endothelial cells and have examined the adhesion of SLeX-high or -low expressing colon cancer cells to the interleukin-1beta (IL-1beta)-treated liver specimens using Stamper-Woodruff assay. These human colon cancer cells are termed KM12HX or KM12LX cells, respectively. A significantly increased number of KM12HX cells adhered to the IL-1beta-treated liver specimens compared to KM12LX cells. The adhesion of KM12HX cells was inhibited by the pretreatment of tumor cells with anti-SLeX antibody or by the pretreatment of liver specimens with anti-selectin antibodies. Selectin expression on the liver sinusoidal endothelial cells and endothelial cells of blood vessels after IL-1beta treatment was confirmed by immunohistochemically using anti-selectin monoclonal antibodies (MAbs). These findings strongly suggest that SLeX-expressing cancer cells could adhere to the sinusoidal endothelial cells via an SLeX-selectin interaction system and this could be a first step for colon cancer cells that metastasize to the liver. The mechanism by which these selectins can be induced in vivo is the next problem to be considered.

Ischemic liver cell damage and calcium accumulation in rats.

Regions of calcium accumulation were studied by 45Ca-autoradiography and microdensitometry during liver ischemia and reperfusion in rats. In autoradiographic studies 45Ca accumulated in all zones of the liver lobuli after 1-2 h of liver ischemia and 1, 3 and 6 h of reperfusion, but did not accumulate in non-ischemic liver lobes. Significant 45Ca accumulation occurred only with reperfusion after 1 or 2 h of liver ischemia. In the presence of reperfusion, 45Ca accumulation correlated with the length of ischemia. In histopathologic studies, liver necrosis was absent in lobuli after 1-h reperfusion. Some liver necrosis was observed in the group reperfused for 3 h and widespread liver necrosis appeared after 6-h reperfusion. Regions of 45Ca accumulation coincided with sites of microscopic liver cell damage and necrosis. These results suggested that calcium accumulation might be responsible for the liver cell damage induced by ischemia with reperfusion, that the intensity of calcium accumulation in 45Ca-autoradiograms indicates the degree of ischemia damage, and that the primary event leading to hepatocellular necrosis might be calcium accumulation and subsequent liver cell death.