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Liver dysplasia in transplanted patients due HCV related cirrhosis with or without hepatocellular carcinoma (HCC): study of liver explants
Hepatocellulur
carcinoma,
liver
regenerution,
179
apoptosis
LIVER DYSFxAsIA lN TRANSPLANTED PATIENTS DUE HCV RELATED CIRRHOSIS WlTH OR WlTHOUT HEF’ATOCELLULARCARCINOMA (HCC): STUDY OF LIVER ExptAEFIs.
‘Pathology Depertment. Univexaitary General Hospital ‘yiregorio Ma&6n”: CiDr. Esquerdo n”46.28007-Madrid. Spain.
PROSPECTIVE CONTROLLED TRIAL OF TAMOXIFEN VERSUS TAMOXIFEN ASSOCIATED TO BETA-INTERFERON IN THE TREATMENT OF ADVANCED HEPATOCELLULAR CARCINOMA. GP Lorenzelli, GL Rapaccini, G Sica*, G Pignataro, A Cedrone, D Valle. M Sanalitro, M Pompili, G Gasbarrini. Cattedra di Medicina Interna II, *Istituto di Istologia Umana, Universith Cattolica, Roma, Italy.
INTRODUCTION: The role of liver eel1 dysplasia aa a jmxeoplastic lesion is still debated. AIM To am&e dearee and liver dwolasia nrevalenee in HCV related &rboais liver e@a~~~remo&d during o&e& Ii& transplant (OLT). PATIENTS AND METHODS It had been shnlied 61 liver exvlanta removed tium HCV cirrhotic patients wito undawent OLT at Univexsitay&.neralHospital ‘yhegorio Marafkk” (M&i& Spain). It WBsdew liver dysplasia according to previous stabliahed criteria (1). It ~88 cxmaidered -, moderate or mild dysFlasiaasgrade3,~2orgradel,~~ly.(l) RESULTS: Solitary HCC related to cirrhosis was fouad in 14 patients (22.9%). All of them (1UO%)had concomitant multifocal dvs~laaia (86.6% Grade 3 and 13.4% Cbnde 2j. In 47, liver explants witbout HCC, I& cell hysplasie wua d&cted in 27 cases (44.2%) (7(25,9%) Grade 3,6(22.2%) Grade2 and 14(51.9%) t3mde 1). Mean age of patients with HCC was higher(han tboae with dysplasie &me, end patients without HCC nor dysplasia (57.1,54.1 and47.5 years, rwpectively (pe0.M). CONCLUSIONS: 1. Moderate or severe multifocal dysplasia was d&x&d in all patients with solitary HCC. 2. It’s possible that cirmsisdyaplasia-HCC evolution had a temporal sequence. 3. OLT seems to be tbe best themp&ic option in patients with solitary HCC, because new metacrhonic tumeurs develqnnent could be avoided. (1)Cohen C, Berson S. Cancer 1986,57: 1535-1538
Sexual hormones are implicated in the control of neoplastic proliferation in hepatic disease through the binding to steroid receptors. Therefore the antiestrogen tamosifen (TAM) is used in the treatment of patients with advanced hepatocellular carcinoma (HCC). Clinical and experimental studies show that interferon-beta (IFN-Beta) caused a significant enhancement of estrogen receptors (ER) and progesteron receptors (PR) TAM is in neoplastic cells of breast and endometrium. Therefore associated to IFN-Beta in the treatment of advanced breast cancer. A randomized trial of TAM versus TAM associated to IFN- Beta was performed in patients with advanced HCC. Seventeen (17) patients were randomly allocated in two groups. GROUP I included 9 patients who were treated with TAM (10 mg tid) and Group II 8 patients treated with TAM (10 mg tid) associated to low dose of Beta-IFN (9 MU/week for two weeks and 3 MU/week for 6 months). The two groups were homogeneous and did not show significant difference as regard sex, age, Child-Pugh class, etiology of cirrhosis, tumor mass and AFP. Median survival was 32.33 f 33.55 weeks in group I and 34 k 22.58 weeks in group II. There were no significant differences between the two groups (Mann-Whitney-U Test, p=O.531). Our results do not support a significant beneficial effect of Beta-IFN added to TAM in increasing survival in patients with advanced HCC. These findings need to be confirmed in a largerseriesandafter a longer follow up period.
[ co4/020
ASSESSMENT OF ALPHA-FETOPROTEIN VARIANTS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND LIVER METASTATIC TUMORS V. KuP~ov~‘. L. Tureckq2. M. SzBntov2’. E. UhlikovB’ 3rd Dept. of Medicine’, Inst. Med. Chemistrv. Biochemistrv and Clinical Biochet&try2, Med. School ‘of Comenius University, Bratislava, Slovakia
.’ A Concanavalin A reactive (R Con A) and Concanavalin A non reactive (NR Con A) alpha-fetoprotein (AFP) variants were measured in patients with primary hepatocellular carcinoma (HCC), liver metastases (MTS), liver cirrhosis (Ci) with histological confirmation and in mean values of AFP in the control group (C). The patients with Ci, MTS and HCC were significantly higher than in C. In patients with high activity of liver cirrhosis, we have found significantly higher serum AFP levels than in patients in the inactive period. The highest AFP concentrations were found in the patients with HCC, mean values in this group were significantly higher than in the patients with MTS and Ci. The mean values of the NR Con A fraction of AFP of the examined groups did not differ significantly. This indicates that estimation of NR Con A AFP variants in patients with liver diseases does not provide useful information in addition to that provided by the values of total serum AFP. The different rise in the concentration of AFP in the serum of patients with HCC and MIS can be useful in differential diagnosis of the liver tumor type. Long-term observation of AFP serum concentrations can be used to advantage in patients with Ci for early diagnosis of HCC developing in a cirrhotic tissue. The higher levels of AFP determined in the serum of cirrhotic patients presumably reflect regeneration of the liver parenchyma in these pathological processes.
ed Embriologia
1
ALPHA-FETOPROTEIN PREDICT THE NCE AND MORTALITY OF HCC PATIENTS ATED BY LIVER TRANSPLANT?. ’ er Unit, Hcqital Vail d’HeW. U.A.B. Barcelona. Spain. pha-fetoprotein (AFP) is an hepatocellular carcinoma (HCC) 6;: ker and high levels has been correlated with recurrence and Wival after surgery. Mm: To know if pretransplant AFP levels are a predictive factor of hunoral xcumxxe and mortality iu HCC cirrhotic patients treated by liver transplant (LTx). htimts and methods:Pxbansplant AFP levels were evaluated in 56 patitzts with HCC and cirrhosis. Patients were followed at three monthly intervals with ultrasonography controls. Patientsweredividediutwogroups, group1 (n=45, AFPe60 &ml) and group II (n= 11, AFP> 60 ng/ml). In both groups ulative overall survivals and tumor-free survivals were culated by Kaplan-Meier method. ultsz’l-bzmedian follow-up was 2040 days. HCC mce F as observed in 7 patients (12.5%); 3/45 (6.6%) in group I @ 4/l 1 (36,4%) in group II (p=O.O3). Eighteen patients died; o/45 (22.2%) in group I anl 8111 (73%) ill group II = 0.004). Oae, 2 and 3 year overall actuarial survival rates t re 90%,75% and 71% in group I (AFpc60) and 6496, 45% and 34% in group II (AFP> 60) (p=O.oOS). Tumor-factuarial survival ratea were 88%, 75% and 71% in group I (AFPe60) and 54%, 45% and 23% ingroup II (AFP>60). Conclusions: High pretraasplant AFP levels is a predictive factor of tumoral s and mortality after LTx.
carcinoma,
liver
regenerution,
179
apoptosis
LIVER DYSFxAsIA lN TRANSPLANTED PATIENTS DUE HCV RELATED CIRRHOSIS WlTH OR WlTHOUT HEF’ATOCELLULARCARCINOMA (HCC): STUDY OF LIVER ExptAEFIs.
‘Pathology Depertment. Univexaitary General Hospital ‘yiregorio Ma&6n”: CiDr. Esquerdo n”46.28007-Madrid. Spain.
PROSPECTIVE CONTROLLED TRIAL OF TAMOXIFEN VERSUS TAMOXIFEN ASSOCIATED TO BETA-INTERFERON IN THE TREATMENT OF ADVANCED HEPATOCELLULAR CARCINOMA. GP Lorenzelli, GL Rapaccini, G Sica*, G Pignataro, A Cedrone, D Valle. M Sanalitro, M Pompili, G Gasbarrini. Cattedra di Medicina Interna II, *Istituto di Istologia Umana, Universith Cattolica, Roma, Italy.
INTRODUCTION: The role of liver eel1 dysplasia aa a jmxeoplastic lesion is still debated. AIM To am&e dearee and liver dwolasia nrevalenee in HCV related &rboais liver e@a~~~remo&d during o&e& Ii& transplant (OLT). PATIENTS AND METHODS It had been shnlied 61 liver exvlanta removed tium HCV cirrhotic patients wito undawent OLT at Univexsitay&.neralHospital ‘yhegorio Marafkk” (M&i& Spain). It WBsdew liver dysplasia according to previous stabliahed criteria (1). It ~88 cxmaidered -, moderate or mild dysFlasiaasgrade3,~2orgradel,~~ly.(l) RESULTS: Solitary HCC related to cirrhosis was fouad in 14 patients (22.9%). All of them (1UO%)had concomitant multifocal dvs~laaia (86.6% Grade 3 and 13.4% Cbnde 2j. In 47, liver explants witbout HCC, I& cell hysplasie wua d&cted in 27 cases (44.2%) (7(25,9%) Grade 3,6(22.2%) Grade2 and 14(51.9%) t3mde 1). Mean age of patients with HCC was higher(han tboae with dysplasie &me, end patients without HCC nor dysplasia (57.1,54.1 and47.5 years, rwpectively (pe0.M). CONCLUSIONS: 1. Moderate or severe multifocal dysplasia was d&x&d in all patients with solitary HCC. 2. It’s possible that cirmsisdyaplasia-HCC evolution had a temporal sequence. 3. OLT seems to be tbe best themp&ic option in patients with solitary HCC, because new metacrhonic tumeurs develqnnent could be avoided. (1)Cohen C, Berson S. Cancer 1986,57: 1535-1538
Sexual hormones are implicated in the control of neoplastic proliferation in hepatic disease through the binding to steroid receptors. Therefore the antiestrogen tamosifen (TAM) is used in the treatment of patients with advanced hepatocellular carcinoma (HCC). Clinical and experimental studies show that interferon-beta (IFN-Beta) caused a significant enhancement of estrogen receptors (ER) and progesteron receptors (PR) TAM is in neoplastic cells of breast and endometrium. Therefore associated to IFN-Beta in the treatment of advanced breast cancer. A randomized trial of TAM versus TAM associated to IFN- Beta was performed in patients with advanced HCC. Seventeen (17) patients were randomly allocated in two groups. GROUP I included 9 patients who were treated with TAM (10 mg tid) and Group II 8 patients treated with TAM (10 mg tid) associated to low dose of Beta-IFN (9 MU/week for two weeks and 3 MU/week for 6 months). The two groups were homogeneous and did not show significant difference as regard sex, age, Child-Pugh class, etiology of cirrhosis, tumor mass and AFP. Median survival was 32.33 f 33.55 weeks in group I and 34 k 22.58 weeks in group II. There were no significant differences between the two groups (Mann-Whitney-U Test, p=O.531). Our results do not support a significant beneficial effect of Beta-IFN added to TAM in increasing survival in patients with advanced HCC. These findings need to be confirmed in a largerseriesandafter a longer follow up period.
[ co4/020
ASSESSMENT OF ALPHA-FETOPROTEIN VARIANTS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND LIVER METASTATIC TUMORS V. KuP~ov~‘. L. Tureckq2. M. SzBntov2’. E. UhlikovB’ 3rd Dept. of Medicine’, Inst. Med. Chemistrv. Biochemistrv and Clinical Biochet&try2, Med. School ‘of Comenius University, Bratislava, Slovakia
.’ A Concanavalin A reactive (R Con A) and Concanavalin A non reactive (NR Con A) alpha-fetoprotein (AFP) variants were measured in patients with primary hepatocellular carcinoma (HCC), liver metastases (MTS), liver cirrhosis (Ci) with histological confirmation and in mean values of AFP in the control group (C). The patients with Ci, MTS and HCC were significantly higher than in C. In patients with high activity of liver cirrhosis, we have found significantly higher serum AFP levels than in patients in the inactive period. The highest AFP concentrations were found in the patients with HCC, mean values in this group were significantly higher than in the patients with MTS and Ci. The mean values of the NR Con A fraction of AFP of the examined groups did not differ significantly. This indicates that estimation of NR Con A AFP variants in patients with liver diseases does not provide useful information in addition to that provided by the values of total serum AFP. The different rise in the concentration of AFP in the serum of patients with HCC and MIS can be useful in differential diagnosis of the liver tumor type. Long-term observation of AFP serum concentrations can be used to advantage in patients with Ci for early diagnosis of HCC developing in a cirrhotic tissue. The higher levels of AFP determined in the serum of cirrhotic patients presumably reflect regeneration of the liver parenchyma in these pathological processes.
ed Embriologia
1
ALPHA-FETOPROTEIN PREDICT THE NCE AND MORTALITY OF HCC PATIENTS ATED BY LIVER TRANSPLANT?. ’ er Unit, Hcqital Vail d’HeW. U.A.B. Barcelona. Spain. pha-fetoprotein (AFP) is an hepatocellular carcinoma (HCC) 6;: ker and high levels has been correlated with recurrence and Wival after surgery. Mm: To know if pretransplant AFP levels are a predictive factor of hunoral xcumxxe and mortality iu HCC cirrhotic patients treated by liver transplant (LTx). htimts and methods:Pxbansplant AFP levels were evaluated in 56 patitzts with HCC and cirrhosis. Patients were followed at three monthly intervals with ultrasonography controls. Patientsweredividediutwogroups, group1 (n=45, AFPe60 &ml) and group II (n= 11, AFP> 60 ng/ml). In both groups ulative overall survivals and tumor-free survivals were culated by Kaplan-Meier method. ultsz’l-bzmedian follow-up was 2040 days. HCC mce F as observed in 7 patients (12.5%); 3/45 (6.6%) in group I @ 4/l 1 (36,4%) in group II (p=O.O3). Eighteen patients died; o/45 (22.2%) in group I anl 8111 (73%) ill group II = 0.004). Oae, 2 and 3 year overall actuarial survival rates t re 90%,75% and 71% in group I (AFpc60) and 6496, 45% and 34% in group II (AFP> 60) (p=O.oOS). Tumor-factuarial survival ratea were 88%, 75% and 71% in group I (AFPe60) and 54%, 45% and 23% ingroup II (AFP>60). Conclusions: High pretraasplant AFP levels is a predictive factor of tumoral s and mortality after LTx.