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Stent placement into the portal vein for hepatocellular carcinomas invading the main portal vein
AASLDA1263
April 1998 L0267 INFLUENCE OF CERULETIDE GALLBLADDER CONSTRICTION ON INTENSIVE CARE PATIENTS WITH HYPERBILIRUBINEMIA. K. Ishii, M. Shinohara, T. Sora, S. Hata, H. Nagai, W. Yamamuro, T. Hatori, Y. Sumino. 2rid Dept. of Internal Medicine, Toho University School of Medicine, Tokyo, Japan. Prophylaxis of acute acaiculous cholecystitis in intensive care patients using ceruletid (CD) was described by Hasse (Digestion,56:389-394,1995). We have encountered a number of cases of hyperbilirubinemia of unknown origin in intensive care patients without liver disease. The aim of this study is to investigate the effects of CD on these patients. PATIENTS AND METHODS: Eight patients (7 males and 1 female with an average age of 55.4 ± 13 years) who had not experienced any of Hasse's exclusion criteria - cholecystectomy or other operation at the extrahepatic biliary system, cholecystitis, shock, severe cardiovascular disease, common bile duct stones, acute pancreatitis, bowel obstruction, severe renal insufficiency (creatinine > 2.0 mg/dl), pregnancy, diabetes mellitus, gallbladder volume < 12 cm3 before administration of study drug - were the subjects of this study. They were treated with 40 - 60 lag/day of CD by intramuscular injection for 4 - 7 (5.5 ± 1.6) days, when their serum bilirubin levels were elevated (2.6 - 23.9, mean 12.9 ± 9.2 mg/dl). Serum levels of total bilirubin (T-Bil), direct bilirubin (D-Bil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and ~t glutamyltranspeptidase 0' GTP), as well as the base excess (BE) of arterial blood were determined before and after administration of CD. RESULTS: Serum levels of T-Bil, D-Bil and ALP were changed significantly (p<0.05 by Freedman tes0 after CD administration. However, other serum parameters remained unchanged.
Before
2 days
4 days 7 days (after administrationof CD) T-Bil* (mg/dl) 12.9 + 9.2 13.9 ± 11.3 12.1 -" 9.5 8.9 ± 7.1 D-BiI* (mg/dl) 8.6-.6.3 9.1-.7.9 8.5-.6.8 6.0-.4.9 ALT (IU/L) 71-.32 72-.48 82-.70 91-.111 , AST (IU/L) 37 -. 25 47 ± 30 64 ± 46 39 -. 38 ALP* (IU/L) 313 -. 163 410 -. 245 450 -. 243 495 -. 271 i "t GTP (IU/L) 40 -. 34 38 -. 29 45 ± 35 52 ± 27 HCO3- (mM) 0.6 ± 4.6 0.0 -" 5.6 -1.1 -" 4.8 0.0 -. 5.5 *: significant difference. Data are expressed as mean ± SD. CONCLUSIONS: Our results suggest that gallbladder constriction by CD injection improves cases of hyperbilirubinemia of unknown origin in intensive care patients. • L0268 HUMAN HERPESVIRUS 6 FROM PATIENTS WITH NANBNC FULMINANT HEPATITIS IN JAPAN. K. Ishikawa, K. Hasegawa, S. Noguchi, A. Iizuka, T. Shizuma, N. Torii, T. Naritomi, E. Hashimoto, K. Yamauchi, Y. Kato, N. Sakayori, M. Kobayashi and N. Hayashi. Inst. of Gastroenterology and First Dept. of Pathology, Tokyo Women's Medical College, Tokyo, Japan.
In more than half of fulrninant hepatitis, no etiological agent could not be identified in Japan. These cases, non-A, non-B, non-C (NANBNC) fulminant hepatitis (FH), have usually shown a poor response to intensive medical care and high mortality rate. Therefore, to identify the causative agent of NANBNC FH is an urgent issue. Previously, it has been reported that several members of herpesviridae family, HSV, CMV, EBV and HHV-6, were associated with fatal hepatic failure. In the present study, we proposed to clarify the association of herpesviridae with the pathogenesis of NANBNC FH. Six patients with fulminant hepatitis without any serum viral markers and the possibilities of autoimmune, drug-induced, alcoholic and metabolic liver diseases. DNA and RNA were extracted from liver tissue and sera and served as a template of PCR amplification. Primers were designed in the highly conserved region of each virus, HBV, HCV, HGV, CMV, HSV, EBV and HHV-6. Among these viruses, HHV-6 was detected in the liver tissue from all of the patients with NANBNC FH. Two patients had also EBV and CMV in t h e liver. Since HHV-6 and EBV were not amplified in sera, the possibilities of contamination of viral sequence through blood transfusion might be excluded. Furthermore, in one patient with living hepatocytes in the specimen taken at liver transplantation, giant cell hepatitis was observed. Thus, our results strongly suggested the association of HHV-6 with NANBNC FH in Japan. HHV-6 has been shown to infect into lymphocytes and establish long-lasting latent infection. Consequently, we analyzed the localization of HHV-6 genome in the liver specimen by in sitn hybridization. Digoxigenin labeled HHV-6 probe was hybridized with liver specimen after denature of DNA and viral sequence was detected by non-isotopic method using alkariphosphatase conjugated antibody. As a result, HHV-6 sequence was detected in numerous hepatocytes and localized mainly in the nuclei. The present results indicated that HHV-6 might infect into hepatocyte and correlate with the pathngenesis in large proportion of NANBNC FH patients in Japan.
• L0269 VOLTAGED-DEPENDENT CALCIUM CHANNELS IN STELLATE CELLS ARE UPREGULATED BY ETHANOL. T.Itatsu, H.Oide, M.Hirose, A.Miyazaki, S.Watanabe, N.Sato, M.Tateyama*, R.Ochi*. Dept. of Gastroenterology, Dept. of Physiology*,. Juntendo University Sch. Med. Tokyo, Japan.
Stellate (Ito) cells have been reported to play important roles in the regulation of hepatic microcirculation. We have already reported the existence of calcium channels in stellate cells as well as muscle cells(Hepatology, 1994; 20: 1009). Ethanol was known to increase portal vein pressure, resulted in liver injury. In this process, stellate cells contraction through calcium channels are supposed to cause disturbance of the hepatic microcirculation. However, the relationship between ethanol and calcium channel in stellate cells is unknown. AIM: To investigate the detailed mechanism of the role of steUate cell contraction on ethanol-induced liver injury, the effect of ethanol on the expressin of calcium channels in stellate cells was assessed using the whole-cell patch clamp technique with the special attention to cellular transformation. METHODS: Stellate cells were isolated from Wistar female rats by collagenase digestion and Nycodenz centrifugation, and were seeded on cover glass and cultured in DMEM with 10% FCS for up to 14 days with or without ethanol (100 mM). Ethanol was replenished daily. Both control cells and ethanol-treated ceils were studied using whole-cell patch clamp on day 5, 7, 10 and 14. The transformation of stellate cells was assessed by the staining of ix-smooth muscle action (or SMA). RESULTS: In controls, calcium channels did not appeare in early stage of culture. Calcium channels were detected in 21% on day 10 and in 63% on day 14. In ethanol-treated ceils, calcium channels were detected in 38% on day 7, in 92% on day 10, and 100% in day 14 (p<0.05). Ethanol induced earlier expression of calcium channels than control ceils. In controls, ct-SMA was detected after 10 days of culture, while it was detected after 5 days of culture in ethanol-treated ceils. CONCLUSIONS: Voltage dependent-calcium channels in steUate cells were upregulated by the treatment with ethanol and this upregulation was associated with the induction of transformation of stellate cells. Therefore, the stellate ceils activated and transformed by ethanol have stronger capacity for contraction and might play an important role in alcoholic liver damage via disturbed of hepatic microcirculation. • L0270 STENT PLACEMENT INTO THE PORTAL VEIN FOR HEPATOCELLULAR CARCINOMAS INVADING THE MAIN PORTAL VEIN. T Ito, K Shiraki, K Sugimoto, H Wagayama, K Murata, A Shimizu, K Takase, T Nakano, K Yamakado*. First Department of Internal Medicine, *Department of Radiology, Mie University School of Medicine, Tsu, MIE, Japan. Hepatocellular carcinoma(HCC) frequently invades the portal vein, and once invades the main portal vein, the prognosis is disappointingly poor. So, we tried to open the main portal vein of patients with HCC invading the main portal vein using stent placement and evaluate the clinical efficiency of this method. Materials and Methods: Forty-two patients were studied. Eighteen patients underwent stent placement in the portal vein (stenting group), and the remaining 24 patients were treated without stenting (non-stenting group). Stents (wall-stent ;15pts, Z-stent ; lpts, covered Z-stent; 2pts) were transhepatically placed into the portal veins to compress tumor thrombi using ultrasonographical guide, followed by portography to confirm the open of the portal vein. Anticoagulation therapy (warfarin) was performed to prevent thrombosis in 11 pts. Results: Stents were successfully implaced in all patients. Occlusion (n=6) or stenosis (n--12) of the main portal vein was immediately eliminated. A covered-stent could not open the portal vein completely. After stent placement, gastro-esophageal varices, melena and ascites improved promptly. Portal vein pressure decreased from 26.1+/- 8.4 mmHg to 23.1 +/- 7.0 mmHg (p<0.001). A-P shunt disappeared in 2 pts with covered-stent. There was no major complication except one patient who showed hemobilia, and needed coil embolization of hepatic artery. Twelve patients uneventfully underwent transcatheter arterial chemoembolization (TACE) after stent placement. Blood flow through the stents was maintained during survival periods in 13 of 18 patients. Nine patients (37.5%) died of gastro-inestinal bleeding or a rupture of HCC within 3 months in the non-stenting group. In contrast, early death (within 3 months) due to bleeding or a rupture of HCC was significantly prevented except one patient (7.7%: p<0.02) in the stenting group, because of a relief of portal hypertension and subsequent TACE. A cumulative survival rate was significantly higher in the stenting group than in the non-stenting group; 61.2% vs 21.0% at 6 months and 15.3% vs 12.5% at 1 and 2~years, respectively (p<0.02). ConcluSions: Stent placement into the portal vein may be a great weapon to improve prognosis of patients with HCC invading portal vein.
April 1998 L0267 INFLUENCE OF CERULETIDE GALLBLADDER CONSTRICTION ON INTENSIVE CARE PATIENTS WITH HYPERBILIRUBINEMIA. K. Ishii, M. Shinohara, T. Sora, S. Hata, H. Nagai, W. Yamamuro, T. Hatori, Y. Sumino. 2rid Dept. of Internal Medicine, Toho University School of Medicine, Tokyo, Japan. Prophylaxis of acute acaiculous cholecystitis in intensive care patients using ceruletid (CD) was described by Hasse (Digestion,56:389-394,1995). We have encountered a number of cases of hyperbilirubinemia of unknown origin in intensive care patients without liver disease. The aim of this study is to investigate the effects of CD on these patients. PATIENTS AND METHODS: Eight patients (7 males and 1 female with an average age of 55.4 ± 13 years) who had not experienced any of Hasse's exclusion criteria - cholecystectomy or other operation at the extrahepatic biliary system, cholecystitis, shock, severe cardiovascular disease, common bile duct stones, acute pancreatitis, bowel obstruction, severe renal insufficiency (creatinine > 2.0 mg/dl), pregnancy, diabetes mellitus, gallbladder volume < 12 cm3 before administration of study drug - were the subjects of this study. They were treated with 40 - 60 lag/day of CD by intramuscular injection for 4 - 7 (5.5 ± 1.6) days, when their serum bilirubin levels were elevated (2.6 - 23.9, mean 12.9 ± 9.2 mg/dl). Serum levels of total bilirubin (T-Bil), direct bilirubin (D-Bil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and ~t glutamyltranspeptidase 0' GTP), as well as the base excess (BE) of arterial blood were determined before and after administration of CD. RESULTS: Serum levels of T-Bil, D-Bil and ALP were changed significantly (p<0.05 by Freedman tes0 after CD administration. However, other serum parameters remained unchanged.
Before
2 days
4 days 7 days (after administrationof CD) T-Bil* (mg/dl) 12.9 + 9.2 13.9 ± 11.3 12.1 -" 9.5 8.9 ± 7.1 D-BiI* (mg/dl) 8.6-.6.3 9.1-.7.9 8.5-.6.8 6.0-.4.9 ALT (IU/L) 71-.32 72-.48 82-.70 91-.111 , AST (IU/L) 37 -. 25 47 ± 30 64 ± 46 39 -. 38 ALP* (IU/L) 313 -. 163 410 -. 245 450 -. 243 495 -. 271 i "t GTP (IU/L) 40 -. 34 38 -. 29 45 ± 35 52 ± 27 HCO3- (mM) 0.6 ± 4.6 0.0 -" 5.6 -1.1 -" 4.8 0.0 -. 5.5 *: significant difference. Data are expressed as mean ± SD. CONCLUSIONS: Our results suggest that gallbladder constriction by CD injection improves cases of hyperbilirubinemia of unknown origin in intensive care patients. • L0268 HUMAN HERPESVIRUS 6 FROM PATIENTS WITH NANBNC FULMINANT HEPATITIS IN JAPAN. K. Ishikawa, K. Hasegawa, S. Noguchi, A. Iizuka, T. Shizuma, N. Torii, T. Naritomi, E. Hashimoto, K. Yamauchi, Y. Kato, N. Sakayori, M. Kobayashi and N. Hayashi. Inst. of Gastroenterology and First Dept. of Pathology, Tokyo Women's Medical College, Tokyo, Japan.
In more than half of fulrninant hepatitis, no etiological agent could not be identified in Japan. These cases, non-A, non-B, non-C (NANBNC) fulminant hepatitis (FH), have usually shown a poor response to intensive medical care and high mortality rate. Therefore, to identify the causative agent of NANBNC FH is an urgent issue. Previously, it has been reported that several members of herpesviridae family, HSV, CMV, EBV and HHV-6, were associated with fatal hepatic failure. In the present study, we proposed to clarify the association of herpesviridae with the pathogenesis of NANBNC FH. Six patients with fulminant hepatitis without any serum viral markers and the possibilities of autoimmune, drug-induced, alcoholic and metabolic liver diseases. DNA and RNA were extracted from liver tissue and sera and served as a template of PCR amplification. Primers were designed in the highly conserved region of each virus, HBV, HCV, HGV, CMV, HSV, EBV and HHV-6. Among these viruses, HHV-6 was detected in the liver tissue from all of the patients with NANBNC FH. Two patients had also EBV and CMV in t h e liver. Since HHV-6 and EBV were not amplified in sera, the possibilities of contamination of viral sequence through blood transfusion might be excluded. Furthermore, in one patient with living hepatocytes in the specimen taken at liver transplantation, giant cell hepatitis was observed. Thus, our results strongly suggested the association of HHV-6 with NANBNC FH in Japan. HHV-6 has been shown to infect into lymphocytes and establish long-lasting latent infection. Consequently, we analyzed the localization of HHV-6 genome in the liver specimen by in sitn hybridization. Digoxigenin labeled HHV-6 probe was hybridized with liver specimen after denature of DNA and viral sequence was detected by non-isotopic method using alkariphosphatase conjugated antibody. As a result, HHV-6 sequence was detected in numerous hepatocytes and localized mainly in the nuclei. The present results indicated that HHV-6 might infect into hepatocyte and correlate with the pathngenesis in large proportion of NANBNC FH patients in Japan.
• L0269 VOLTAGED-DEPENDENT CALCIUM CHANNELS IN STELLATE CELLS ARE UPREGULATED BY ETHANOL. T.Itatsu, H.Oide, M.Hirose, A.Miyazaki, S.Watanabe, N.Sato, M.Tateyama*, R.Ochi*. Dept. of Gastroenterology, Dept. of Physiology*,. Juntendo University Sch. Med. Tokyo, Japan.
Stellate (Ito) cells have been reported to play important roles in the regulation of hepatic microcirculation. We have already reported the existence of calcium channels in stellate cells as well as muscle cells(Hepatology, 1994; 20: 1009). Ethanol was known to increase portal vein pressure, resulted in liver injury. In this process, stellate cells contraction through calcium channels are supposed to cause disturbance of the hepatic microcirculation. However, the relationship between ethanol and calcium channel in stellate cells is unknown. AIM: To investigate the detailed mechanism of the role of steUate cell contraction on ethanol-induced liver injury, the effect of ethanol on the expressin of calcium channels in stellate cells was assessed using the whole-cell patch clamp technique with the special attention to cellular transformation. METHODS: Stellate cells were isolated from Wistar female rats by collagenase digestion and Nycodenz centrifugation, and were seeded on cover glass and cultured in DMEM with 10% FCS for up to 14 days with or without ethanol (100 mM). Ethanol was replenished daily. Both control cells and ethanol-treated ceils were studied using whole-cell patch clamp on day 5, 7, 10 and 14. The transformation of stellate cells was assessed by the staining of ix-smooth muscle action (or SMA). RESULTS: In controls, calcium channels did not appeare in early stage of culture. Calcium channels were detected in 21% on day 10 and in 63% on day 14. In ethanol-treated ceils, calcium channels were detected in 38% on day 7, in 92% on day 10, and 100% in day 14 (p<0.05). Ethanol induced earlier expression of calcium channels than control ceils. In controls, ct-SMA was detected after 10 days of culture, while it was detected after 5 days of culture in ethanol-treated ceils. CONCLUSIONS: Voltage dependent-calcium channels in steUate cells were upregulated by the treatment with ethanol and this upregulation was associated with the induction of transformation of stellate cells. Therefore, the stellate ceils activated and transformed by ethanol have stronger capacity for contraction and might play an important role in alcoholic liver damage via disturbed of hepatic microcirculation. • L0270 STENT PLACEMENT INTO THE PORTAL VEIN FOR HEPATOCELLULAR CARCINOMAS INVADING THE MAIN PORTAL VEIN. T Ito, K Shiraki, K Sugimoto, H Wagayama, K Murata, A Shimizu, K Takase, T Nakano, K Yamakado*. First Department of Internal Medicine, *Department of Radiology, Mie University School of Medicine, Tsu, MIE, Japan. Hepatocellular carcinoma(HCC) frequently invades the portal vein, and once invades the main portal vein, the prognosis is disappointingly poor. So, we tried to open the main portal vein of patients with HCC invading the main portal vein using stent placement and evaluate the clinical efficiency of this method. Materials and Methods: Forty-two patients were studied. Eighteen patients underwent stent placement in the portal vein (stenting group), and the remaining 24 patients were treated without stenting (non-stenting group). Stents (wall-stent ;15pts, Z-stent ; lpts, covered Z-stent; 2pts) were transhepatically placed into the portal veins to compress tumor thrombi using ultrasonographical guide, followed by portography to confirm the open of the portal vein. Anticoagulation therapy (warfarin) was performed to prevent thrombosis in 11 pts. Results: Stents were successfully implaced in all patients. Occlusion (n=6) or stenosis (n--12) of the main portal vein was immediately eliminated. A covered-stent could not open the portal vein completely. After stent placement, gastro-esophageal varices, melena and ascites improved promptly. Portal vein pressure decreased from 26.1+/- 8.4 mmHg to 23.1 +/- 7.0 mmHg (p<0.001). A-P shunt disappeared in 2 pts with covered-stent. There was no major complication except one patient who showed hemobilia, and needed coil embolization of hepatic artery. Twelve patients uneventfully underwent transcatheter arterial chemoembolization (TACE) after stent placement. Blood flow through the stents was maintained during survival periods in 13 of 18 patients. Nine patients (37.5%) died of gastro-inestinal bleeding or a rupture of HCC within 3 months in the non-stenting group. In contrast, early death (within 3 months) due to bleeding or a rupture of HCC was significantly prevented except one patient (7.7%: p<0.02) in the stenting group, because of a relief of portal hypertension and subsequent TACE. A cumulative survival rate was significantly higher in the stenting group than in the non-stenting group; 61.2% vs 21.0% at 6 months and 15.3% vs 12.5% at 1 and 2~years, respectively (p<0.02). ConcluSions: Stent placement into the portal vein may be a great weapon to improve prognosis of patients with HCC invading portal vein.