Wong, Ching Lung Lai, Dept of Medicine, Vniv of Hong Kong, Hong. Kong, P.R. China ... high doses thrice weekly (Lai CL et al, Hepatology 1993). However, the.
April 2000
septations on imaging studies. Open resection is a safe and effective treatment, and is associate with low recurrence rate. Malignant changes have not been encountered in our pts.
86 DELA YED LIVER REGENERATION, INCREASED INJURY AND MORTALITY IN HETEROZYOGOUS OR HOMOZYGOUS OB· MUTANT MICE. Aloke K. Mandai, Christine Chuckaree, Anna Mae Diehl, Johns Hopkins, Baltimore, MD. Background: Hepatic steatosis is thought to contribute to primary nonfunction (PNF)after orthotopic liver transplantation (OLT). Since ischemiareperfusion injury is inevitable during OLT, recovery requires hepatic regeneration. Thus, PNF may develop in fatty livers because regeneration is impaired. Aim: To determine if regeneration is inhibited in fatty livers. Methods: Regeneration after 70% partial hepatectomy (PH) in male C57BU 6 obese (ob/ob) mice with fatty livers was compared to age- and sex-matched lean, heterozygous (-lob) litter mates and wild-type (WT) C57BU6 mice. Both control groups had normal basal liver histology. Results: WT mice had < 10% mortality during the first 48h after PH. BrdV pulse-labeling demonstrated replicating hepatocytes at various times after PH: 2% BrdV( +) hepatocytes at 6 and l 2h, 8% at 24h, 33% at 36h, and 25% at 48h. Almost 60% of the initial liver weight was regained by 48h. In contrast, PH mortality was increased in lean, -lob mice (33% by 48h) and in obese, oblob mice (68% by 48h), ps .OOI. Liver regeneration was delayed in -lob mice (2:!:1% BrdV(+ )hepatocytes at 24h and 29:!:3% at 48h) and never occurred in oblob mice. Liver mass restoration also was decreased in -lob (l 4::!: 5%)and oblob (-2:!:6%) groups. FACS analysis of propidium iodide-stained liver nuclei not only confirmed the BrdV results but also demonstrated a basal shift in the cell cycle distribution of oblob hepatocytes. In oblob livers, 46:!:6% hepatocytes were in GO-GI and 52:!:6% in G2; however, in -lob livers, 71:!:6% hepatocytes were in GO-G I and 27:!:6% in G2 (psO.05 for both). After PH, in oblob fatty livers after PH, there were extensive areas of hemorrhage, dead hepatocytes, and inflammation. Heterozygous, -lob, mice developed severe microvesicular steatosis, with islands of dead hepatocytes (without much associated hemorrhage or inflammation) by 24-48h after PH. In WT mice after PH, mild microvesicular steatosis occurred at 6-12h, and minor focal liver injury rarely was noted at 24-48h. Conclusions: After PH, obese, oblob mice with fatty livers do not regenerate their livers and develop extensive liver injury with high mortality. Delayed regeneration and increased liver injury also occur post-PH in lean, -lob mice. Although these heterozygotes have non-fatty livers pre-PH, they develop severe steatosis post-PH. The inverse relationship between hepatic steatosis and regeneration supports the concept that inhibited regeneration contributes to PNF of fatty allografts after OLT.
87 ANAL YSIS OF PERFUSION KINETICS OF LIVER TUMORS USING LEVOVIST AND QUANTITATIVE COLOR DOPPLER UL· TRASOUND. Bita Boozari, Joerg Siegfried Bleck, Anja Piepenbrock, Michael Gebel, Babak Babapour, Mechtild Westhoff-Bleck, Michael Peter Manns, Med Hochschule Hannover, Hannover, Germany; Mcd Sch of Hannover, Hannover, Germany. Purpose: Since introduction of echocontrast agents into the fields of sonography dynamic investigations of blood flow circulation of liver tumors are possible. We developed a reproducible, dynamic color doppler quantification method in order to specify perfusion kinetics of liver tumors. Material and methods: A total of 50 tumors were included in this study, 7 haemangioma (HEM), 13 focal nodular hyperplasia (FNH), 18 hepatocellular carcinoma (HCC), 12 liver metastases of colorectal cancer (COM). After iv. injection of 2,5g 300mg/ml Levovist we documented the wash in/wash out kinetics of the tumors. 3 different plane sections of each tumor were saved every 15 seconds over a hole period of 5 minutes on videocassettes. These ultrasound images were digitized and parameterized with a color doppler quantification program. From the time dependent color pixel distribution of the velocity histogram, first order statistics and area under the curve s (AVC) were calculated. Results: time independent the relative number of FD-pixel can separates 3 Groups: FNH+ HCC > COM > HEM, (ANOVA p=O.OOOI, Duncan-Grouping). For time dependent velocity histogram data the highest maximum velocity value was presented by FNH s over 5 minutes: FNH>COM +HCC+HEM, p= O.ooOl. The AUC-calculation of the color pixels allows the detection of HEM s: FNH + HCC + COM> HEM, p=O .04. Time to peak of the AVC s for HEM s was tendentiously prolonged comparing to other groups, HEM 83sec> COM 63sec> HCC 49sec> FNH 46sec. Conclusion: Using this method we are able to distinguish FNH s from COM s and HEM s but not from HCC s, We believe in potential of this method characterizing liver tumors in future.
AASLDA915
88 A PILOT STUDY OF TRANSCATHETER ARTERIAL INTERFER· ON·EMBOLIZATION FOR HEPATOCELLULAR CARCINOMA. Man Fung Yuen, Clara Ooi, Wai Man Wong, On On Chan, Benjamin Cy Wong, Ching Lung Lai, Dept of Medicine, Vniv of Hong Kong, Hong Kong, P.R. China; Dept of Radiology, Univ of Hong Kong, Hong Kong, P.R. China. Background:lnterferon-alpha (lFN-a)is effective in 30% of patients with hepatocellular carcinoma (HCC) when given systemically using extremely high doses thrice weekly (La i CL et al, Hepatology 1993). However, the side effects were severe and the cost was high. Regional therapy through the transarterial route would concentrate the IFN-a on the tumor cells, reduce the systemic side effects and require only one dose of IFN-a every 2-3 months. We conduct a pilot study of transcatheter arterial interferonembolization (TAlE), using IFN-a2b and gelfoam, for the treatment of HCC to define the optimal dose and safety of IFN-a . Patients and methods: To date, a total of 13 patients with biopsy-proven HCC (M:F 11:2, median age 61 yrs) were recruited. Patients were randomized to receive IFN-a 2b 10 MVlm2 (3 patients), 30 MUlm 2 (8 patients) or 50 MVlm 2 (2 patients) intraarterially. Complete blood counts, liver function tests, prothrombin time and alpha-fetoprotein (AFP) were monitored. The treatment was given every 8 weeks. Side effects were closely monitored. Results: The median follow-up was 4 mths (range 1-12 mths). The mean diameter of HCC was 9.9 em (range 3.5-22 cm). A total of 29 sessions of TAlE were performed. For the 12 patients with baseline AFP > 20 nglml, all had a reduction of AFP after each session of TAlE . 311 2 (25%) patients had normalization of AFP. The median AFP levels dropped from 702 nglml to 365 nglml (p=0.07). 8 patients received 2 or more sessions of TAlE in whom the tumor response was assessed angiographically. 3/8 (37.5%) patients had 2'= 50% reduction in size of the index tumors. 4/8 (50%) patients had the static tumors and 1 (12.5%) patient had progressive tumor. In 3/8 (37.5%) patients the tumors became avascular angiographically and were assessed as totally necrotic. 5 patients died (median survival 6 months): 2 of uncontrolled HCC, 1 of brain metastasis, 1 of tumorlysis and 1 of ruptured HCC. The side effects included rigor usually lasting only I - 2 hrs, and fever (median 6 days; range 0 - 21 days). There was no deterioration of liver function tests and prothrombin time attributable to IFN-a. Conclusion: TAlE was effective in suppressing HCC. There was no liver decompensation. The main side effect was fever. More long-term studies are required to assess the efficacy. This study was supported by ScheringPlough Corporation
89 IMPORTANT ROLE FOR INTERLEUKIN 1 IN ENDOTOXIN-IN· DUCED RESPONSES IN CHOLESTATIC MICE. Miguel E. Sewnath, Tom Poll, Fiebo J. Kate, Huug Obertop, Sander 1. Deventer, Dirk 1. Gourna, Acad Med Ctr Amsterdam, Amsterdam, Netherlands. Septic complications after gastrointestinal procedures occur more frequently in patients with obstructive jaundice (OJ) than in non-jaundiced patients. This may be related to an increased susceptibility to endotoxin (LPS) and an increased inflammatory response to stress factors such as surgery. The cytokine interleukin- l (lL-I) plays an important role in infection and inflammation; IL-I exerts biological effects by an interaction with the type I IL-l receptor (IL- IR). To determine the role oflL-! in the inflammatory cascade induced by LPS during OJ, wild type (wt) C57BU6 mice were genetically altered by deleting the gene encoding for IL- IR, resulting in lL-IR deficient (IL- IR -1-) mice (IL-IR knock out mice). IL-IR-I- and wt mice received an i.p. injection of 100 /ig LPS at 2 weeks after bile duct ligation (bdl) or sham operation. After surgery mice were sacrificed at day 14 at t = 0 (before LPS challenge) and at t = 24 hours after LPS. Liver was harvested and collected in 0.4% formaldehyde for histology with routine HE staining. and heparin plasma was sampled for liver chemistry using a Hitachi auto-analyzer. All values are mean (::!: SEM). Statistics by Wilcoxon. During the 14 days after bdl, IL-IR-I- and wt mice showed similar weight loss (5.5 :!:: 0.7 /ig and 6.9 ::!: 1.3 /i g resp., NS), while none of the mice died. Sham operated mice did not show weight loss. Fourteen days after bdl. IL-1R-I- mice had more severe jaundice and liver injury than wt mice, as reflected by higher bilirubin (421:!: 48 liM vs. 371 ::!: 60 liM, NS), alkaline phosphatase (1088 :!: 133 UIL vs. 842 :!: 63 UIL, NS), ALAT (1165 :!: 302 VIL vs. 622 ::!: 213 VIL, NS) and ASAT levels (2273 ::!: 665 UIL vs. 697 ± 98 V IL, P
