A1476 AASLD ABSTRACTS

6685

EVALUATION OF THE RELATIONSHIP BETWEEN HEPATICENCEPHALOPATHY AND PORTOSYSTEMIC SHUNT USINGNONINVASIVE THREE·DIMENSIONAL PORTOGRAPHY OB·TAINED BY MULTI·SLICE HELICAL COMPUTED TOMOGRA­PHY.Waka Ohishi, Akiko Matsumoto, Mikiya Kitamoto, Toshio Nakanishi,Hiroshi Aikata, Michio Imamura, Yoshiiku Kawakami, Koji Kamada,Hirotaka Kono, Goro Kajiyarna, Katsuhide Ito, 1st Dept of Internal Med,Univ Sch of Medicine, Hiroshima, Japan; Hiroshima Univ Sch of Med,Hiroshima, Japan; Dept of Radiology, Univ Sch of Medicine, Hiroshima,Japan.

Background/Aim: Hepatic encephalopathy is occurred by hepatic failureand/or portosystemic shunt. If the patient has large blood flow of theportosystemic shunt, even patient with good liver function occurs hepaticencephalopathy. In the present study, we evaluated the relationship be­tween hepatic encephalopathy and portosystemic shunt using three-dimen­sional portography obtained by multi-slice helical computedtomography(3D-CT portography). Patients and Methods: Seventy-two cir­rhotic patients (30 patients were classified as Child A, 37 as Band 5 as C)were included. A dynamic helical study was performed on a GE LightSpeed QXII system (GE Yokogawa Medical System) using a non-ioniccontrast agent administrated into an antecubital vein at 3-5 ml/sec for atotal volume of 100 ml. The slice data was retrospectively reconstructed at1.25 mm intervals and then we could acquire the 3D-CT portography assurface rendering image and maximum intensity projection image using theAdvantage Windows Workstation. Results:As major collateral vessels, leftgastric vein, gastrorenal shunt, and short gastric vein/posterior gastric veinwere well demonstrated by 3D-CT portography. The incidence of thesemajor collateral vessels was 11130 in Child A patients, 19/37 in Child Bpatients, and 3/5 in child C patients, which was increasing according toseverity of liver dysfunction. Moreover, collateral vessels presented by3D-CT portography tended to become large according to the severity ofliver dysfunction. Among ten patients who had past history of encepha­lopathy, gastrorenal shunt was revealed in 6, left gastric vein to azygos in2, left gastric vein to right renal vein in 1, and para-umbilical vein in I by3D-CT portography. Among 17 patients of Child A and B whose plasmaammonia level is over 80 /Lg/dl, 13 cases had large collateral vessels suchas left gastric vein to azygos and gastrorenal shunt. Conclusion:3D-CTportography proved to be the presence of collateral vessels in well com­pensated cirrhotic patients at high frequency more than our expected. Thesepatients might have the possibility of subclinical hepatic encephalopathy.

6686ANGIOGENESIS CORRELATES WITH DEVELOPMENT OFHEPATOCELLULAR CARCINOMA IN PATIENTS WITH HCV·ASSOCIATED LIVER CIRRHOSIS.Shigeru Ohmori, Katsuya Shiraki, Takahisa Sakai, Kazushi Sugimoto,Kojirou Takase, Takeshi Nakano, First Dept of Internal Medicine, MieUniv, Tsu, Japan.

Background: CD34 has been known as an antigen which has been ex­pressed on the vascular endothelial cells, and used as a marker of microvessels in various tissues including human liver. However, recently it hasbeen also shown that the endothelial progenitor cells are positive for CD34antigen and may differentiate into vessels. These evidence suggest thatCD34 positive cells may playa crucial role in angiogenesis of chronic liverdisease and hepatocellular carcinoma (HCC). Therefore, we investigate therelationship between the expression of CD34, vascular endothelial growthfactor (VEGF) and the development of HCC in patients with HCV­associated liver cirrhosis(LC). Method: Thirty four liver specimens wereobtained from patients with HCV-positive LC and pre-cirrhosis. Theyinclude the patients with the occurrence of HCC within 5 years after liverbiopsy (LC/HCC group, n= 16) and without HCC(LC group, n= 18). Thesespecimens were fixed in 10% buffered formalin, embedded in paraffin, and4 /Lm histological sections were prepared. They were immunostained withanti-CD34 monoclonal antibody (QBEnd lO;DACO NS, Copenhagen) at1:50 dilution and anti-VEGF antibody (Ab-3; Oncogene Science.union­dale, NY) at I :25 dilution. The standard avidin-biodin-peroxidase complextechnique was applied for color development and hematoxylin for coun­terstaining. VEGF score was classified 4 levels by the strength of irnmu­nostaining. CD34 positive cell was counted in three areas of liver paren­chyma under x200 fold magnification and average counts of these areaswere recorded as CD34 labeling index(L.I.). Results: In liver parenchyma,CD34 was stained with linear mainly on the sinusoid. CD34 positive cellswere strongly expressed of the patients with HCV-positive LC and earlyoccurrence of HCC. CD34 L.I. in LC/HCC group were significantly higher

GASTROENTEROLOGY Vol. 118, No.4

than that in LC group(16.1::'::8.6 vs. 10.5::'::4.4; p<0.05). The cumulativeoccurrence of HCC was significantly higher in patients with CD34L.I.> 12.0 than that with CD34 L.I.< 12.0 (p<0.05). VEGF was expressedmainly on the hepatocytes of HCV-positive LC, but VEGF expression wasnot significantly different between LC and LCIHCC groups (p=0.16).Conclusions: These results suggested that angiogenesis in patients withHCV-associated liver cirrhosis correlates with development of hepatocel­lular carcinoma,and various endothelial growth factors in addition toVEGF play an important role in angiogenesis.

6687INDUCTION OF APOPTOSIS BY MICROWAVE COAGULATIONTHERAPY IN RAT LIVER.Tsuyoshi Ohno, Seigo Kitano, Katsunori Kawano, Takanori Yoshida,Masanori Aramaki, Atsushi Sasaki, Koichiro Tahara, Yu Takeuchi, OitaMed Univ, Oita-gun, Japan.

Background: Microwave coagulation therapy (MCT), one of the localhyperthermia induced by direct insertion of an electrode which generates2450 MHz in the tumor, has been widely performed for the treatment bothprimary and metastatic liver cancer. In spite of the therapeutic efficacy, theprecise mechanism for expansion of cell death area following the treatmentremains unclear. Aim: The purpose of this study was to clarify the cellularmechanism of MCT, focusing on whether the ablation therapy inducedapoptosis in the liver tissue. Sequential examinations of caspase-3 activityand TUNEL staining of the liver were employed for the evaluation ofapoptosis. Methods: One bout of MCT was applied to the rat liver using amonopolar needle electrode under a setting of 30W for 30 sec as coagu­lation and 10 sec as dissociation. The rats were sacrificed immediately, 2,6, 12, 24, 72 and l68h after MCT. The discolored liver surface area wasmeasured for evaluation of expansion of cell death area. To assess thelocalization and the degree of DNA fragmentation, the TUNEL stainingwas carried out and the positive cells were counted. The caspase-3 activitywas measured in tissue homogenates extracted from MCT site for enzy­matic determination of apoptosis. Results: The caspase-3 activity showedten-fold increase from the value of Oh,having a peak at 2h after MCT. TheDNA fragmentation significantly increased at 6h, and decreased thereafter.The discolored liver surface area gradually increased during initial 12hafter MCT, sustained from l2h to 72h, and subsided thereafter. Conclu­sions: It was demonstrated that the apoptosis of hepatocytes was inducedaround the ablation area following MCT. This may explain the mechanismsfor the expansion of cell death area and suggest an additional cell deathpattern beside tissue necrosis subsequent to MCT.

6688HAVE DEVELOPMENT OF TREATMENT IMPROVED OUT·COME OF PATIENTS WITH BLEEDING GASTRIC VARICES?Kazuhiko Oho, Atsushi Toyonaga, Masafumi Kumamoto, Kenji Sakai,Yasunao Miyamato, Masahiro Sato, Tadashi Iwao, Michio Sata, KurumeUniv Hosp, Kurume, Japan.

Background: Bleeding from gastric varices is more massive and fatal.Tissue adhesive agents have been used for bleeding gastric varices withsuccessful hemostasis over 90%. Balloon-occluded retrograde transvenousobliteration (B-RTO) has been newly developed in the management ofgastric fundal varices. Aims: We performed a retrospective study to eval­uate effectiveness of the new treatment for bleeding gastric varices. Pa­tients and Methods: Between December 1982 and July 1998, 144 patientswith bleeding gastric varices treated at our hospital were retrospectivelyenrolled. The bleeding site was confirmed by endoscopic examination, andendoscopic treatment was performed at the same time to control thebleeding. Prior to 1989 we used 5%EO or absolute ethanol, whereas after1993 we began to use Histoacryl injection and B-RTO, especially in largegastric varices. Results: There were 107 males and 37 females, with a meanage of 56. The cause of portal hypertension was alcoholic cirrhosis in 21patients, posthepatitic cirrhosis in 114, primary biliary cirrhosis in three,and others in six. The mean Pugh-Child score was 9.1. Active bleeding(Spurting or oozing bleeding) was observed in 46 patients (32%), transientcease of bleeding (red or white plug, erosion, or ulcer) was observed in 98patients (68%). Bleeding was controlled in 86% (125/144) of all cases.Hemostasis rate was significantly lower in active bleeding than in cease ofbleeding (78% vs, 91%, P < 0.05). Hemostasis rate in cardiac varices was90% (63/70) and 84% (84/74) in fundal varices (N.S.). A comparison of thehemostasis rate before and after 1993 revealed that the successful rateincreased from 78% (59/76) to 96% (65/68) (p < 0.05). Reb1eedingoccurred in 29% before 1992 and in 16% after 1993. One-year survival ratewas significantly higher after 1993 than before 1992 (71% vs. 47%, P <0.05). Conclusion: Tissue adhesive agent and B-RTO have improvedoutcome of patients with bleeding gastric varices.