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Long term survival for unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization (TACE) combined with alpha interferon in liver cirrhosis patients
Papers read by title I C04/09 ]
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LONG TERM SURVIVAL FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) COMBINED WITH ALPHA INTERFERON IN LIVER CIRRHOSIS PATIENTS ?. Soemarno I. N. Akbar2. S. Noer 2, ?. Soewandi 3 qnternal Medicine Department Sint Carolus Hospital, Indonesia. 2Department of Internal Medicine University of Indonesia, Indonesia. 3Radiologic Department of Gatot Subroto Army Hospital, Indonesia. 4 Aims : TACE is an veay useful approeda to the palliative llrCatolcmof unresectable HCC in fiver cirrhotic patients. Alpha intctferun has andinplamation,antiprolifcxative,and anticalreinog¢~icaction. In this study we compaxed the TACE alone to TACE combination with alpha intcrfca'onfor r o l e HCC. M a l ~ i ~ and Methods : From Septcmb¢~ 1992 through S~tcmb~ 1998, 155 patients with HCC were seen by investigators. Only thirty-runt of these paticxJts actually received TACE, consist of 32 males and 2 fcmal¢~, age range fi'om 35 yem's, mean age 51 years. The diag~msis was based on a combinMionof clinically findings, US, CT Scan, fme needle biopsy, Inboratory findings included AFP, sc~onmrker, size of the HCC., single or nmltiple lesions, kc,~un, hcludcd andoscxxpi¢findings of oesophagcal vaxices, Child-Pugh class A : 7 patients; Child-B: 12 patkats, and Child C: 15 pmkats. The ¢ h e m o ~ agent used was mitomycin C 20 nag mixed with Lipiodol and arterial embolization was ac,hieved using Gelfcem. TACE was pea'formedsevea'altimes eveary4 weeks until AFP become nearly normal, 34 patients randomized divided into 2 groups. Group A: 17 patients pel'formedTACE alone. Group B: 17 patients performed TACE combination with alpha interferon 6 mlU there times a week Re~dt : Grunp A : 3 patients Child A sin-rivalrate wes 36 months, 5 pafiems Child B survival rate was 24 months, 9 patients Child C survival rate was 12 momha, Group B: 4 patients Child A alive until now, stwvival rate was more than 60 months of 5 years survival rate was 28% 7 patients Child B survival rate was 36 months 6 patients Child C survival rate was 16 patients. Coaclusion : These data suggest that TACE oombimtiun with alpha interfeaon6 mlU thr~ times a week significamly prolong the survival rate (i)<0.005) compared to TACE alone only for Child-Pugh A. For ChildPugh B and C of the two groups TACE alone and TACE combination with alpha interfezondid not significantlydifference.
PATTERNS OF CONTRAST ENHANCEMENT BY DOUBLE PHASED HERICAL CT AND HISTOLOGICAL FEATURES IN HEPATOCELLULAR CARCINOMAS Y. Suyama, H. Kimura, S. Fujimoto Department of Gastroenterology, Kyoto First Redcross Hospital Kyoto, Japan. In this study, we investigated the patterns of contrast enhancement in hepatocellular carcinoma (HCC) by Double Phased Hedcal CT compared with its histological findings in 42 tumors of 30 cases. Tumor size were 8 mm to 32 mm in diameter (27 tumors were less than 20mm, 14 tumors were less than 30mm in diameter). Bolous contrast material were injected
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EARLY DOWN-REGULATION OF CYTOCHROME P 450 3A AND 2El IN THE REGENERATING RAT LIVER IS NOT RELATED TO THE LOSS OF LIVER MASS E Starkel 1, S. Laurent 1, L. Lambotte2, Y. Horsmans l 1Laboratories of Gastroenterology, Universit6 Catholique de Louvain, Brussels, Belgium. 2Experimental Surgery, Brussels, Belgium. Conflicting data have been reported concerning the modification of cytochrome P450s (CYP) expression in the regenerating liver. Partial ligation of branches o f the portal vein (PBL) which produces regeneration and atrophy allows to study the relative specificity of the early events in the regenerating liver and their relationship to the loss o f liver mass. In PBL model and in sham, the expression and the metabolic activities of CYP3A and 2 E l , and inducible nitric oxide synthase protein (iNOS) were studied by Western Blot and HPLC. The CYP activities were transiently and simultaneously down-regulated in the both lobes during the first two to five hours after PBL. This was already significant 0.5 hours after PBL (p<0.05 for CYP3A and p<0.01 for CYP2E1). No modification was observed at the protein level. In contrast, iNOS protein analysis showed a strong increase in both lobes (p<0.05 and p<0.001, respectively). Similar results were observed after sham. The reduction of these CYP activities in both lobes after PBL and sham suggest that mechanisms other than the regenerating process itself or the reduction of the liver mass might account for such downregulation during the early phase o f liver regeneration. The modulation o f iNOS should be further investigated.
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intravenously on Hedcal CT, and histological specemines were taken by US guided biopsy method, using 21 G Majima needles. Four nodules of five enhanced stlongly at first phase (arterial phase), revealed moderately differentiated HCC. Six nodules of twelve which enhansed heterogeneously were moderately differenciated HCC. Eleven nodules of twelve enhanced softly and homogeneously were well differentiated HCC. Thirteen nodules showed negative enhancement, and twenty of them were well differentiated HCC. At second phase (portal phase), twenty nine tumors were detected as low density area, nineteen of them were well differentiated and nine of them were moderately differentiated HCC. Nine tumors were shown as heterogeneous low density or as iso-density area, seven of them were well differentiated HCC. Four tumors revealed ring enhancement at second phase, and two of them were moderately differentiated HCC. In conclusion, evaluation of the pattern of contrast enhancement in HCC by Double Phased Herical CT is useful to diagnose the tumor histological grade non-invasively.
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p53, c-Ha-rasAND IL-lp AFTER SURGICAL PROCEDURES NOT INDUCING HEPATOCYTES PROLIFERATION S. Laurent 1, C. De Saeger 1, E Lause 2, A. Saliez3, D. Maiter2, L. Lambotte 3, Y. Horsmans 1 ILab. of Gastroenterology, Brussels, Belgium. 2Lab. of Diabetology, Brussels, Belgium. 3Lab. of Experimental Surgery, UCL, Brussels, Belgium.
Induction of NF-KB, STAT3, IL-6 and early protooncogenes after Partial Hepatectomy (PH) and Portal Branch Ligation (PBL) also occurs after Portacaval Shunt (PCS) and Sham (Hepatology 1999; 30, 255A). The early events are thus produced by surgical stress and can be followed by very different outcome. We investigated after PCS and Sham the presence at 24 hours o f signals associated with proliferation (p53 and c-Ha-ras) after PH and PBL or with atrophy (IL-113) after PBL. p53 and c-Ha-ras mRNA were measured by Northern Blot and IL-1 [3 m R N A by R T - P C R . p53 was downregulated in PCS (p<0.001) and after Sham (p<0.05) whereas it was unchanged after PH and PBL. c-Ha-ras decreased only in PCS (p<0.001) but increased after PH or PBL in proliferating lobes. IL-113 was up-regulated after PCS (p<0.01) but also after Sham (p<0.05) and in atrophying lobes after PBL. It remained at control values in proliferating lobes after PH or PBL. p53 and c-Ha-ras expression were not found in situations leading to atrophy or statu quo. Whereas, an IL-II3 increase was observed in atrophying situations and after sham suggesting that IL- 1 [3 may play a role in interrupting a process initiated by the surgical stress.
C04/11
]
LONG TERM SURVIVAL FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) COMBINED WITH ALPHA INTERFERON IN LIVER CIRRHOSIS PATIENTS ?. Soemarno I. N. Akbar2. S. Noer 2, ?. Soewandi 3 qnternal Medicine Department Sint Carolus Hospital, Indonesia. 2Department of Internal Medicine University of Indonesia, Indonesia. 3Radiologic Department of Gatot Subroto Army Hospital, Indonesia. 4 Aims : TACE is an veay useful approeda to the palliative llrCatolcmof unresectable HCC in fiver cirrhotic patients. Alpha intctferun has andinplamation,antiprolifcxative,and anticalreinog¢~icaction. In this study we compaxed the TACE alone to TACE combination with alpha intcrfca'onfor r o l e HCC. M a l ~ i ~ and Methods : From Septcmb¢~ 1992 through S~tcmb~ 1998, 155 patients with HCC were seen by investigators. Only thirty-runt of these paticxJts actually received TACE, consist of 32 males and 2 fcmal¢~, age range fi'om 35 yem's, mean age 51 years. The diag~msis was based on a combinMionof clinically findings, US, CT Scan, fme needle biopsy, Inboratory findings included AFP, sc~onmrker, size of the HCC., single or nmltiple lesions, kc,~un, hcludcd andoscxxpi¢findings of oesophagcal vaxices, Child-Pugh class A : 7 patients; Child-B: 12 patkats, and Child C: 15 pmkats. The ¢ h e m o ~ agent used was mitomycin C 20 nag mixed with Lipiodol and arterial embolization was ac,hieved using Gelfcem. TACE was pea'formedsevea'altimes eveary4 weeks until AFP become nearly normal, 34 patients randomized divided into 2 groups. Group A: 17 patients pel'formedTACE alone. Group B: 17 patients performed TACE combination with alpha interferon 6 mlU there times a week Re~dt : Grunp A : 3 patients Child A sin-rivalrate wes 36 months, 5 pafiems Child B survival rate was 24 months, 9 patients Child C survival rate was 12 momha, Group B: 4 patients Child A alive until now, stwvival rate was more than 60 months of 5 years survival rate was 28% 7 patients Child B survival rate was 36 months 6 patients Child C survival rate was 16 patients. Coaclusion : These data suggest that TACE oombimtiun with alpha interfeaon6 mlU thr~ times a week significamly prolong the survival rate (i)<0.005) compared to TACE alone only for Child-Pugh A. For ChildPugh B and C of the two groups TACE alone and TACE combination with alpha interfezondid not significantlydifference.
PATTERNS OF CONTRAST ENHANCEMENT BY DOUBLE PHASED HERICAL CT AND HISTOLOGICAL FEATURES IN HEPATOCELLULAR CARCINOMAS Y. Suyama, H. Kimura, S. Fujimoto Department of Gastroenterology, Kyoto First Redcross Hospital Kyoto, Japan. In this study, we investigated the patterns of contrast enhancement in hepatocellular carcinoma (HCC) by Double Phased Hedcal CT compared with its histological findings in 42 tumors of 30 cases. Tumor size were 8 mm to 32 mm in diameter (27 tumors were less than 20mm, 14 tumors were less than 30mm in diameter). Bolous contrast material were injected
I c04/10
I
[
EARLY DOWN-REGULATION OF CYTOCHROME P 450 3A AND 2El IN THE REGENERATING RAT LIVER IS NOT RELATED TO THE LOSS OF LIVER MASS E Starkel 1, S. Laurent 1, L. Lambotte2, Y. Horsmans l 1Laboratories of Gastroenterology, Universit6 Catholique de Louvain, Brussels, Belgium. 2Experimental Surgery, Brussels, Belgium. Conflicting data have been reported concerning the modification of cytochrome P450s (CYP) expression in the regenerating liver. Partial ligation of branches o f the portal vein (PBL) which produces regeneration and atrophy allows to study the relative specificity of the early events in the regenerating liver and their relationship to the loss o f liver mass. In PBL model and in sham, the expression and the metabolic activities of CYP3A and 2 E l , and inducible nitric oxide synthase protein (iNOS) were studied by Western Blot and HPLC. The CYP activities were transiently and simultaneously down-regulated in the both lobes during the first two to five hours after PBL. This was already significant 0.5 hours after PBL (p<0.05 for CYP3A and p<0.01 for CYP2E1). No modification was observed at the protein level. In contrast, iNOS protein analysis showed a strong increase in both lobes (p<0.05 and p<0.001, respectively). Similar results were observed after sham. The reduction of these CYP activities in both lobes after PBL and sham suggest that mechanisms other than the regenerating process itself or the reduction of the liver mass might account for such downregulation during the early phase o f liver regeneration. The modulation o f iNOS should be further investigated.
166
intravenously on Hedcal CT, and histological specemines were taken by US guided biopsy method, using 21 G Majima needles. Four nodules of five enhanced stlongly at first phase (arterial phase), revealed moderately differentiated HCC. Six nodules of twelve which enhansed heterogeneously were moderately differenciated HCC. Eleven nodules of twelve enhanced softly and homogeneously were well differentiated HCC. Thirteen nodules showed negative enhancement, and twenty of them were well differentiated HCC. At second phase (portal phase), twenty nine tumors were detected as low density area, nineteen of them were well differentiated and nine of them were moderately differentiated HCC. Nine tumors were shown as heterogeneous low density or as iso-density area, seven of them were well differentiated HCC. Four tumors revealed ring enhancement at second phase, and two of them were moderately differentiated HCC. In conclusion, evaluation of the pattern of contrast enhancement in HCC by Double Phased Herical CT is useful to diagnose the tumor histological grade non-invasively.
C04/12
I
p53, c-Ha-rasAND IL-lp AFTER SURGICAL PROCEDURES NOT INDUCING HEPATOCYTES PROLIFERATION S. Laurent 1, C. De Saeger 1, E Lause 2, A. Saliez3, D. Maiter2, L. Lambotte 3, Y. Horsmans 1 ILab. of Gastroenterology, Brussels, Belgium. 2Lab. of Diabetology, Brussels, Belgium. 3Lab. of Experimental Surgery, UCL, Brussels, Belgium.
Induction of NF-KB, STAT3, IL-6 and early protooncogenes after Partial Hepatectomy (PH) and Portal Branch Ligation (PBL) also occurs after Portacaval Shunt (PCS) and Sham (Hepatology 1999; 30, 255A). The early events are thus produced by surgical stress and can be followed by very different outcome. We investigated after PCS and Sham the presence at 24 hours o f signals associated with proliferation (p53 and c-Ha-ras) after PH and PBL or with atrophy (IL-113) after PBL. p53 and c-Ha-ras mRNA were measured by Northern Blot and IL-1 [3 m R N A by R T - P C R . p53 was downregulated in PCS (p<0.001) and after Sham (p<0.05) whereas it was unchanged after PH and PBL. c-Ha-ras decreased only in PCS (p<0.001) but increased after PH or PBL in proliferating lobes. IL-113 was up-regulated after PCS (p<0.01) but also after Sham (p<0.05) and in atrophying lobes after PBL. It remained at control values in proliferating lobes after PH or PBL. p53 and c-Ha-ras expression were not found in situations leading to atrophy or statu quo. Whereas, an IL-II3 increase was observed in atrophying situations and after sham suggesting that IL- 1 [3 may play a role in interrupting a process initiated by the surgical stress.