- Email: [email protected]
788 INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA (HCC): TO TACE OR NOT TO TACE?
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Poster Session − Saturday, April 25
786 DEVELOPMENT AND VALIDATION OF THE NAPOLI PROGNOSTIC INDEX (NAPI): A NEW RISK SCORE FOR PREDICTING DEATH IN CIRRHOTIC PATIENTS WITH TREATABLE HEPATOCELLULAR CARCINOMA (HCC) G.G. Di Costanzo1 , P. Pagliano2 , M. De Luca1 , L. Addario1 , C. Pacella3 , M.T. Tartaglione1 , F. Lampasi1 , A. Galeota Lanza1 , A. Ascione1 . 1 Liver Unit, Cardarelli Hospital, 2 I Divisione, Cotugno Hospital, Naples, 3 Radiology Unit, Regina Apostolorum Hospital, Roma, Italy E-mail: [email protected] Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and cancer progression affect survival by complex interactions. Aim of our study was to construct a prognostic index called NAPI tailored for cirrhotic patients with treatable HCC. Methods: We prospectively evaluated 282 patients with Child–Pugh 7 cirrhosis and HCC within Milan criteria seen at our Liver Unit (training cohort). Survival was estimated by the Kaplan–Meier method, and differences between groups assessed by the log-rank test. Potential risk factors for death were identified by Cox proportional-hazards analysis and, to develop a practical prognostic score, we assigned these factors weighted points proportional to the b-regression coefficient values. The system was validated in 171 consecutive patients selected from the database of another hospital (validation cohort) and was compared with the CLIP and BCLC systems. Results: During a median follow-up of 34 months, 163 patients in the training cohort died. Four independent prognostic factors were identified: no HCC treatment or incomplete treatment effect (4 points), 3.3 g/dL (3 points), MELDalbumin >11 (2 points), and abnormal serum alkaline phosphatase (2 points). Risk score for each patient was calculated and the population divided in three groups: low-risk (0 points), intermediaterisk (2−5 points), and high-risk (6−11 points). In the training cohort, the median survival for these groups was 108, 42, and 25 months respectively. In the validation cohort, the corresponding median survival was 77, 45, and 24 months. Considering the 5-year mortality risk, the C-statistic was 0.786 in the training cohort and 0.716 in the validation cohort. The corresponding C-statistics for the BCLC and the CLIP staging systems were 0.679 and 0.736 in the training cohort, and 0.476 and 0.517 in the validation cohort respectively. Conclusions: A new risk score for predicting death in cirrhotic patients with treatable HCC was developed and validated in an independent cohort. This score performed better than the two score systems more diffusely used in clinical practice. NAPI score may be an useful tool in clinical practice to optimize the therapeutic strategy.
patients with solid malignancies with liver metastases and normal hepatic function. The primary objective was to assess the pharmacokinetics (PK) of brivanib, the active moiety of the prodrug brivanib alaninate. The secondary objective was to assess safety and tolerability. Patients received a single dose of brivanib 400 mg on Day 1. Continuous daily dosing began on Day 15 based on Day 1 exposure. Single-dose PK results on Day 1 were used to determine the starting dose for patients with moderate or severe HI and HCC. PK profiles were collected on Day 1 (full) and Day 28 (sparse). Results: Data from 6 patients with HCC and mild HI (Child Pugh A score 5 in 1 patient and score 6 in 5 patients), and 6 patients with solid malignancies with liver metastases and normal hepatic function are presented. The PK parameters of brivanib were similar in both groups. No patients required a reduced starting dose on Day 15 due to high exposure on Day 1. Single-dose PK results supported the use of a 400-mg starting dose in the moderate HI group and 200 mg in the severe HI group. Brivanib was well tolerated in both patient groups, with only grade 1/2 adverse events. Conclusions: The PK profile of brivanib in patients with HCC and mild HI is similar to that observed in patients with solid malignancies with liver metastases and normal hepatic function. Brivanib demonstrates encouraging tolerability in both patient groups. Enrollment is ongoing in HCC patients with moderate and severe HI. PK parameters
Cmax, ng/mL, geometric mean (CV %) AUCinf, ng/mL, geometric mean (CV %) AUCtau geometric mean (CV %) Tmax, hours median (min, max) T1/2 mean (SD)
Day Day Day Day Day Day Day Day Day Day
1 28 1 28 1 28 1 28 1 28
HCC patients with mild hepatic impairment (Child–Pugh A) (n = 6*)
Patients with solid malignancies and liver metastases, and normal hepatic function (n = 6)
1,928 (34) – 26,852 (45) – 18,471 (41) 30,318 (78) 3 (1, 6) – 14.5 (1.6) –
1,984 (45) – 24,450 (34) – 18,693 (40) 26,541 (43) 3 (0.5, 6) – 12.3 (4.5) –
*N = 5 on Day 28.
788 INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA (HCC): TO TACE OR NOT TO TACE?
A. El-Khoueiry1 , H.J. Lenz1 , J. Posey2 , T. Wood2 , B. Fischer3 , V. Sankar3 , S. Shariq3 , G. Kollia3 , E. Masson3 , I. Walters3 . 1 USC Norris Comprehensive Cancer Center, Los Angeles, CA, 2 University of Alabama at Birmingham, Birmingham, AL, 3 Bristol-Myers Squibb R & D, Princeton, NJ, USA E-mail: [email protected]
F. Farinati1 , A. Giacomin1 , P. Tartaro1 , V. Vanin1 , A. Sergio1 , P. Burra1 , U. Cillo2 , M.A. Di Nolfo3 , P. Del Poggio4 , L. Benvegn`u5 , M. Zoli6 , F. Borzio7 , E.G. Giannini8 , E. Caturelli9 , F. Trevisani6 . 1 Department of Surgical and Gastroenterological Sciences, 2 Department of General Surgery and Organ Transplantation, University of Padua, Padua, 3 Division of Medicine, Bolognini Hospital, Seriate, 4 Division of Medicine, TreviglioCaravaggio Hospital, Treviglio, 5 Department of Clinical and Sperimental Medicine, University of Padua, Padua, 6 Department of Clinical Medicine, University of Bologna, Bologna, 7 Department of Medicine, Gastroenterology Unit, Fatebenefratelli Hospital, Milan, 8 Department of Internal Medicine, University of Genoa, Genoa, 9 Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy E-mail: [email protected]
Background: Brivanib alaninate is an orally available dual inhibitor of vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR) under development as a treatment for hepatocellular carcinoma (HCC). Patients with HCC frequently have underlying liver cirrhosis and hepatic impairment (HI). HI in HCC patients may lead to increased exposure to brivanib, the parent compound of brivanib alaninate, compared with patients with normal hepatic function and solid malignancies with liver metastases. Methods: This was a Phase I, open-label, multidose study in patients with HCC and varying levels of HI (mild, moderate, or severe) and in
Background and Aims: The BCLC staging system, recently endorsed by AASLD, is presently the most used for HCC. An important share of HCC is detected in intermediate stage where the guidelines indicate transcatheter arterial chemoembolization (TACE). We aimed at determining: 1) how many patients are diagnosed in Intermediate stage according to BCLC staging system in Italy and any variation over time of the percentage; 2) their global survival and its trend over time; 3) whether the various treatments have a different impact on survival; 4) how many patients are treated in accordance with AASLD guidelines; 5) which are the independent predictors of survival.
787 EFFECTS OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS OF BRIVANIB IN A PHASE I, OPEN-LABEL, MULTIDOSE STUDY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND OTHER SOLID TUMORS
03b: LIVER TUMORS − b) CLINICAL (EPIDEMIOLOGY, DIAGNOSIS, MANAGEMENT) Methods: We selected the 581 patients with Intermediate HCC from 2042 cases recruited by the Italian Liver Cancer (ITA.LI.CA) group between 1986 and 2006. They were analysed with respect to age, gender, etiology, size and number of lesions, Child–Pugh class and type of treatment. Survival was estimated with the Kaplan–Meier (log rank) and independent predictors with Cox multivariate analysis. Results: Patients with Intermediate stage HCC represented 29% of the overall series. Median survival was 21 month and survival at 1, 3 and 5 years was 68%, 31% and 16% respectively, with significant differences according to Child–Pugh class, AFP, size and number of nodes. Median survival was 15 months in 1986–1996 and 24 months in 1997–2006 (p < 0.001), with significant differences according to the same variables. Overall 38% of patients were treated with TACE, following AASLD guidelines (35% in 1997–2006 subgroup). Survival curves showed that TACE performed better than BSC, but worse than PEI and RFTA. The independent predictors of survival by Cox were treatment, Child–Pugh class, etiology, age, number and size of the lesions. Conclusions: In our experience, in Intermediate stage, where TACE is the treatment suggested, compliance to AASLD guidelines is weak and the choice probably varies depending on the experience of the center and the patients’ conditions. Our data confirmed that TACE guarantees a survival better than BSC, but worse than percutaneous treatments: accordingly, a percutaneous treatment option should be accurately excluded before adopting TACE for Intermediate HCC, since it might be to prefer.
789 LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: THE NEEDLE IN THE HAYSTACK F. Farinati1 , A. Giacomin1 , V. Vanin1 , A. Sergio1 , P. Burra1 , U. Cillo2 , M.A. Di Nolfo3 , P. Del Poggio4 , L. Benvegn`u5 , M. Zoli6 , F. Borzio7 , E.G. Giannini8 , E. Caturelli9 , F. Trevisani6 . 1 Department of Surgical and Gastroenterological Sciences, 2 Department of General Surgery and Organ Transplantation, University of Padua, Padua, 3 Division of Medicine, Bolognini Hospital, Seriate, 4 Division of Medicine, Treviglio-Caravaggio Hospital, Treviglio, 5 Department of Clinical and Sperimental Medicine, University of Padua, Padua, 6 Department of Clinical Medicine, University of Bologna, Bologna, 7 Department of Medicine, Gastroenterology Unit, Fatebenefratelli Hospital, Milan, 8 Department of Internal Medicine, University of Genoa, Genoa, 9 Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy E-mail: [email protected] Background and Aims: Hepatocellular carcinoma (HCC), the world sixth most common neoplasm and the third most common cause of cancer-related death, is a routine indication to liver transplantation (LT), but selection criteria are still under debate. This study was aimed at ascertaining: 1. percentage and characteristics of patients with HCC transplanted in Italy; 2. number of patients eligible for LT according to the AASLD criteria; 3. figure of patients transplanted despite the lack of an indication and 4. impact on survival of observance to the available guidelines. Methods: From 2042 cases prospectively recruited by the Italian Liver Cancer (ITA.LI.CA.) group (1987–2006), we selected the 50 HCC patients who underwent LT and the 228 eligible for LT according to AASLD guidelines. Survival was estimated with the Kaplan–Meier (log rank) method and the independent predictors with Cox multivariate analysis. Results: Median survival of transplanted patients (2.5% of the series) was 133 months (C.I. 104–163), with significant differences according to the number of lesions. Two thirds were transplanted according to Milan criteria and survived significantly longer than the outliers. No difference in the survival of patients transplanted according (48%) or against to the AASLD guidelines was detected. AFP and number of lesions were identified as independent predictors of survival. Patients eligible to LT according to AASLD guidelines were 228 (11% of the series). In this group, best results in terms of survival were achieved by LT in comparison with other treatments. Treatment, tumour size, AFP and Child–Pugh class were the independent predictors of survival.
S289
Conclusions: Patients undergoing LT represent a tiny minority of the overall cases of HCC detected in Italy and the number of those transplanted according to the AASLD guidelines is even lower (1%). LT represents the best therapeutic option for selected patients, but it remains a strategy for few cases, both because of the strict criteria and because of the limited availability of organs. Finally, in contrast with the Milan criteria, the AASLD therapeutic algorithm is not crucial, as most of the patients transplanted do not fulfil these indications and, whether or not they do, has no impact on survival. 790 INTRAHEPATIC CHOLANGIOCARCINOMA IN CIRRHOTIC LIVER; ROLE OF DELAYED PHASES A. Forner1 , J. Rimola2 , C. Ayuso2 , R. Vilana2 , M. Reig1 , C. Rodriguez de Lope1 , J.M. Llovet1,3 , J. Bruix1 . 1 BCLC Group. Liver Unit, Hospital Clinic. IDIBAPS. CIBEREHD. University of Barcelona, 2 BCLC Group. Radiology Department, IDIBAPS, CIBEREHD. University of Barcelona, Barcelona, Spain; 3 Mount Sinai Liver Cancer Program, Division of Liver Disease, Mount Sinai School of Medicine, New York, NY, USA E-mail: [email protected] Background: The implementation of screening by ultrasonography in cirrhotic patients has allowed the detection of small malignant nodules, most of them being hepatocellular carcinomas (HCC). However, intrahepatic cholangiocarcinomas (ICC) could also emerge in cirrhotic livers and it is key to establish properly distinguish both entities. Aim: To describe the imaging features at Magnetic Resonance (MR) of ICC in the cirrhotic patient with analysis of the dynamic vascular pattern of contrast enhancement and rule out a potential overlap with the specific pattern of HCC. Patients and Methods: We retrospectively reviewed the dynamic MR findings of 25 cirrhotic patients with 31 histological confirmed ICC nodules diagnosed between September 2001 and November 2008. All studies were done following an established protocol for liver tumors. Signal intensity on T1-weighted and T2-weighted images without contrast and characteristics of enhancement after extracellular endovenous contrast administration on arterial, portal and delayed phase were registered. An enhancement pattern was defined in basis of characteristics of the lesions in each of these MR phases. Analysis was done according to nodule size. Results: The median size was 2.5 cm (range: 1.3−8.7 cm). Nine nodules were <2 cm, 11 between 2 and 3 cm and 11 nodules larger than 3 cm. The most frequent appearance was hypointense in T1 (n = 25; 80.6%) and hyperintense in T2 (n = 22; 71%). Capsular retraction and intralesional scar were present in 7 and 6 cases, respectively. All lesions displayed contrast uptake during the arterial phase, that in most cases was peripheral (26 cases; 83.9%). Two of the ICC <2 cm displayed homogeneous arterial enhancement indistinguishable from HCC. In 14 cases (45.2%) the contrast uptake remained stable over time and in 17 cases (54.8%) the lesions showed a progressive enhancement. None of the ICC had contrast washout in the venous/delayed phases. Conclusion: ICC in cirrhosis exhibit a persistent contrast uptake on dynamic MR. Arterial uptake is usually peripheral, but small nodules may present a homogeneous uptake. Hence, arterial contrast uptake does not allow proper distinction between ICC and HCC and recognition of washout is the sole parameter that may avoid the need to request a diagnostic biopsy. 791 INTERLEUKIN-6, GENDER AND RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH END-STAGE LIVER DISEASE E. Fumolo1 , E. Fornasiere1 , D. Bitetto1 , E. Fontanini1 , A. Cussigh1 , W. Bragagnini1 , E. Falleti1 , C. Fabris1 , R. Minisini2 , P. Toniutto1 , M. Pirisi2 . 1 University of Udine, Udine, 2 University of Novara, Novara, Italy E-mail: [email protected] Background and Aim: Recent animal studies suggest that estrogens might protect from hepatocellular carcinoma (HCC) by suppressing a proinflammatory cytokine, interleukin-6 (IL-6), whose production by Kupffer
Poster Session − Saturday, April 25
786 DEVELOPMENT AND VALIDATION OF THE NAPOLI PROGNOSTIC INDEX (NAPI): A NEW RISK SCORE FOR PREDICTING DEATH IN CIRRHOTIC PATIENTS WITH TREATABLE HEPATOCELLULAR CARCINOMA (HCC) G.G. Di Costanzo1 , P. Pagliano2 , M. De Luca1 , L. Addario1 , C. Pacella3 , M.T. Tartaglione1 , F. Lampasi1 , A. Galeota Lanza1 , A. Ascione1 . 1 Liver Unit, Cardarelli Hospital, 2 I Divisione, Cotugno Hospital, Naples, 3 Radiology Unit, Regina Apostolorum Hospital, Roma, Italy E-mail: [email protected] Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and cancer progression affect survival by complex interactions. Aim of our study was to construct a prognostic index called NAPI tailored for cirrhotic patients with treatable HCC. Methods: We prospectively evaluated 282 patients with Child–Pugh 7 cirrhosis and HCC within Milan criteria seen at our Liver Unit (training cohort). Survival was estimated by the Kaplan–Meier method, and differences between groups assessed by the log-rank test. Potential risk factors for death were identified by Cox proportional-hazards analysis and, to develop a practical prognostic score, we assigned these factors weighted points proportional to the b-regression coefficient values. The system was validated in 171 consecutive patients selected from the database of another hospital (validation cohort) and was compared with the CLIP and BCLC systems. Results: During a median follow-up of 34 months, 163 patients in the training cohort died. Four independent prognostic factors were identified: no HCC treatment or incomplete treatment effect (4 points), 3.3 g/dL (3 points), MELDalbumin >11 (2 points), and abnormal serum alkaline phosphatase (2 points). Risk score for each patient was calculated and the population divided in three groups: low-risk (0 points), intermediaterisk (2−5 points), and high-risk (6−11 points). In the training cohort, the median survival for these groups was 108, 42, and 25 months respectively. In the validation cohort, the corresponding median survival was 77, 45, and 24 months. Considering the 5-year mortality risk, the C-statistic was 0.786 in the training cohort and 0.716 in the validation cohort. The corresponding C-statistics for the BCLC and the CLIP staging systems were 0.679 and 0.736 in the training cohort, and 0.476 and 0.517 in the validation cohort respectively. Conclusions: A new risk score for predicting death in cirrhotic patients with treatable HCC was developed and validated in an independent cohort. This score performed better than the two score systems more diffusely used in clinical practice. NAPI score may be an useful tool in clinical practice to optimize the therapeutic strategy.
patients with solid malignancies with liver metastases and normal hepatic function. The primary objective was to assess the pharmacokinetics (PK) of brivanib, the active moiety of the prodrug brivanib alaninate. The secondary objective was to assess safety and tolerability. Patients received a single dose of brivanib 400 mg on Day 1. Continuous daily dosing began on Day 15 based on Day 1 exposure. Single-dose PK results on Day 1 were used to determine the starting dose for patients with moderate or severe HI and HCC. PK profiles were collected on Day 1 (full) and Day 28 (sparse). Results: Data from 6 patients with HCC and mild HI (Child Pugh A score 5 in 1 patient and score 6 in 5 patients), and 6 patients with solid malignancies with liver metastases and normal hepatic function are presented. The PK parameters of brivanib were similar in both groups. No patients required a reduced starting dose on Day 15 due to high exposure on Day 1. Single-dose PK results supported the use of a 400-mg starting dose in the moderate HI group and 200 mg in the severe HI group. Brivanib was well tolerated in both patient groups, with only grade 1/2 adverse events. Conclusions: The PK profile of brivanib in patients with HCC and mild HI is similar to that observed in patients with solid malignancies with liver metastases and normal hepatic function. Brivanib demonstrates encouraging tolerability in both patient groups. Enrollment is ongoing in HCC patients with moderate and severe HI. PK parameters
Cmax, ng/mL, geometric mean (CV %) AUCinf, ng/mL, geometric mean (CV %) AUCtau geometric mean (CV %) Tmax, hours median (min, max) T1/2 mean (SD)
Day Day Day Day Day Day Day Day Day Day
1 28 1 28 1 28 1 28 1 28
HCC patients with mild hepatic impairment (Child–Pugh A) (n = 6*)
Patients with solid malignancies and liver metastases, and normal hepatic function (n = 6)
1,928 (34) – 26,852 (45) – 18,471 (41) 30,318 (78) 3 (1, 6) – 14.5 (1.6) –
1,984 (45) – 24,450 (34) – 18,693 (40) 26,541 (43) 3 (0.5, 6) – 12.3 (4.5) –
*N = 5 on Day 28.
788 INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA (HCC): TO TACE OR NOT TO TACE?
A. El-Khoueiry1 , H.J. Lenz1 , J. Posey2 , T. Wood2 , B. Fischer3 , V. Sankar3 , S. Shariq3 , G. Kollia3 , E. Masson3 , I. Walters3 . 1 USC Norris Comprehensive Cancer Center, Los Angeles, CA, 2 University of Alabama at Birmingham, Birmingham, AL, 3 Bristol-Myers Squibb R & D, Princeton, NJ, USA E-mail: [email protected]
F. Farinati1 , A. Giacomin1 , P. Tartaro1 , V. Vanin1 , A. Sergio1 , P. Burra1 , U. Cillo2 , M.A. Di Nolfo3 , P. Del Poggio4 , L. Benvegn`u5 , M. Zoli6 , F. Borzio7 , E.G. Giannini8 , E. Caturelli9 , F. Trevisani6 . 1 Department of Surgical and Gastroenterological Sciences, 2 Department of General Surgery and Organ Transplantation, University of Padua, Padua, 3 Division of Medicine, Bolognini Hospital, Seriate, 4 Division of Medicine, TreviglioCaravaggio Hospital, Treviglio, 5 Department of Clinical and Sperimental Medicine, University of Padua, Padua, 6 Department of Clinical Medicine, University of Bologna, Bologna, 7 Department of Medicine, Gastroenterology Unit, Fatebenefratelli Hospital, Milan, 8 Department of Internal Medicine, University of Genoa, Genoa, 9 Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy E-mail: [email protected]
Background: Brivanib alaninate is an orally available dual inhibitor of vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR) under development as a treatment for hepatocellular carcinoma (HCC). Patients with HCC frequently have underlying liver cirrhosis and hepatic impairment (HI). HI in HCC patients may lead to increased exposure to brivanib, the parent compound of brivanib alaninate, compared with patients with normal hepatic function and solid malignancies with liver metastases. Methods: This was a Phase I, open-label, multidose study in patients with HCC and varying levels of HI (mild, moderate, or severe) and in
Background and Aims: The BCLC staging system, recently endorsed by AASLD, is presently the most used for HCC. An important share of HCC is detected in intermediate stage where the guidelines indicate transcatheter arterial chemoembolization (TACE). We aimed at determining: 1) how many patients are diagnosed in Intermediate stage according to BCLC staging system in Italy and any variation over time of the percentage; 2) their global survival and its trend over time; 3) whether the various treatments have a different impact on survival; 4) how many patients are treated in accordance with AASLD guidelines; 5) which are the independent predictors of survival.
787 EFFECTS OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS OF BRIVANIB IN A PHASE I, OPEN-LABEL, MULTIDOSE STUDY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND OTHER SOLID TUMORS
03b: LIVER TUMORS − b) CLINICAL (EPIDEMIOLOGY, DIAGNOSIS, MANAGEMENT) Methods: We selected the 581 patients with Intermediate HCC from 2042 cases recruited by the Italian Liver Cancer (ITA.LI.CA) group between 1986 and 2006. They were analysed with respect to age, gender, etiology, size and number of lesions, Child–Pugh class and type of treatment. Survival was estimated with the Kaplan–Meier (log rank) and independent predictors with Cox multivariate analysis. Results: Patients with Intermediate stage HCC represented 29% of the overall series. Median survival was 21 month and survival at 1, 3 and 5 years was 68%, 31% and 16% respectively, with significant differences according to Child–Pugh class, AFP, size and number of nodes. Median survival was 15 months in 1986–1996 and 24 months in 1997–2006 (p < 0.001), with significant differences according to the same variables. Overall 38% of patients were treated with TACE, following AASLD guidelines (35% in 1997–2006 subgroup). Survival curves showed that TACE performed better than BSC, but worse than PEI and RFTA. The independent predictors of survival by Cox were treatment, Child–Pugh class, etiology, age, number and size of the lesions. Conclusions: In our experience, in Intermediate stage, where TACE is the treatment suggested, compliance to AASLD guidelines is weak and the choice probably varies depending on the experience of the center and the patients’ conditions. Our data confirmed that TACE guarantees a survival better than BSC, but worse than percutaneous treatments: accordingly, a percutaneous treatment option should be accurately excluded before adopting TACE for Intermediate HCC, since it might be to prefer.
789 LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: THE NEEDLE IN THE HAYSTACK F. Farinati1 , A. Giacomin1 , V. Vanin1 , A. Sergio1 , P. Burra1 , U. Cillo2 , M.A. Di Nolfo3 , P. Del Poggio4 , L. Benvegn`u5 , M. Zoli6 , F. Borzio7 , E.G. Giannini8 , E. Caturelli9 , F. Trevisani6 . 1 Department of Surgical and Gastroenterological Sciences, 2 Department of General Surgery and Organ Transplantation, University of Padua, Padua, 3 Division of Medicine, Bolognini Hospital, Seriate, 4 Division of Medicine, Treviglio-Caravaggio Hospital, Treviglio, 5 Department of Clinical and Sperimental Medicine, University of Padua, Padua, 6 Department of Clinical Medicine, University of Bologna, Bologna, 7 Department of Medicine, Gastroenterology Unit, Fatebenefratelli Hospital, Milan, 8 Department of Internal Medicine, University of Genoa, Genoa, 9 Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy E-mail: [email protected] Background and Aims: Hepatocellular carcinoma (HCC), the world sixth most common neoplasm and the third most common cause of cancer-related death, is a routine indication to liver transplantation (LT), but selection criteria are still under debate. This study was aimed at ascertaining: 1. percentage and characteristics of patients with HCC transplanted in Italy; 2. number of patients eligible for LT according to the AASLD criteria; 3. figure of patients transplanted despite the lack of an indication and 4. impact on survival of observance to the available guidelines. Methods: From 2042 cases prospectively recruited by the Italian Liver Cancer (ITA.LI.CA.) group (1987–2006), we selected the 50 HCC patients who underwent LT and the 228 eligible for LT according to AASLD guidelines. Survival was estimated with the Kaplan–Meier (log rank) method and the independent predictors with Cox multivariate analysis. Results: Median survival of transplanted patients (2.5% of the series) was 133 months (C.I. 104–163), with significant differences according to the number of lesions. Two thirds were transplanted according to Milan criteria and survived significantly longer than the outliers. No difference in the survival of patients transplanted according (48%) or against to the AASLD guidelines was detected. AFP and number of lesions were identified as independent predictors of survival. Patients eligible to LT according to AASLD guidelines were 228 (11% of the series). In this group, best results in terms of survival were achieved by LT in comparison with other treatments. Treatment, tumour size, AFP and Child–Pugh class were the independent predictors of survival.
S289
Conclusions: Patients undergoing LT represent a tiny minority of the overall cases of HCC detected in Italy and the number of those transplanted according to the AASLD guidelines is even lower (1%). LT represents the best therapeutic option for selected patients, but it remains a strategy for few cases, both because of the strict criteria and because of the limited availability of organs. Finally, in contrast with the Milan criteria, the AASLD therapeutic algorithm is not crucial, as most of the patients transplanted do not fulfil these indications and, whether or not they do, has no impact on survival. 790 INTRAHEPATIC CHOLANGIOCARCINOMA IN CIRRHOTIC LIVER; ROLE OF DELAYED PHASES A. Forner1 , J. Rimola2 , C. Ayuso2 , R. Vilana2 , M. Reig1 , C. Rodriguez de Lope1 , J.M. Llovet1,3 , J. Bruix1 . 1 BCLC Group. Liver Unit, Hospital Clinic. IDIBAPS. CIBEREHD. University of Barcelona, 2 BCLC Group. Radiology Department, IDIBAPS, CIBEREHD. University of Barcelona, Barcelona, Spain; 3 Mount Sinai Liver Cancer Program, Division of Liver Disease, Mount Sinai School of Medicine, New York, NY, USA E-mail: [email protected] Background: The implementation of screening by ultrasonography in cirrhotic patients has allowed the detection of small malignant nodules, most of them being hepatocellular carcinomas (HCC). However, intrahepatic cholangiocarcinomas (ICC) could also emerge in cirrhotic livers and it is key to establish properly distinguish both entities. Aim: To describe the imaging features at Magnetic Resonance (MR) of ICC in the cirrhotic patient with analysis of the dynamic vascular pattern of contrast enhancement and rule out a potential overlap with the specific pattern of HCC. Patients and Methods: We retrospectively reviewed the dynamic MR findings of 25 cirrhotic patients with 31 histological confirmed ICC nodules diagnosed between September 2001 and November 2008. All studies were done following an established protocol for liver tumors. Signal intensity on T1-weighted and T2-weighted images without contrast and characteristics of enhancement after extracellular endovenous contrast administration on arterial, portal and delayed phase were registered. An enhancement pattern was defined in basis of characteristics of the lesions in each of these MR phases. Analysis was done according to nodule size. Results: The median size was 2.5 cm (range: 1.3−8.7 cm). Nine nodules were <2 cm, 11 between 2 and 3 cm and 11 nodules larger than 3 cm. The most frequent appearance was hypointense in T1 (n = 25; 80.6%) and hyperintense in T2 (n = 22; 71%). Capsular retraction and intralesional scar were present in 7 and 6 cases, respectively. All lesions displayed contrast uptake during the arterial phase, that in most cases was peripheral (26 cases; 83.9%). Two of the ICC <2 cm displayed homogeneous arterial enhancement indistinguishable from HCC. In 14 cases (45.2%) the contrast uptake remained stable over time and in 17 cases (54.8%) the lesions showed a progressive enhancement. None of the ICC had contrast washout in the venous/delayed phases. Conclusion: ICC in cirrhosis exhibit a persistent contrast uptake on dynamic MR. Arterial uptake is usually peripheral, but small nodules may present a homogeneous uptake. Hence, arterial contrast uptake does not allow proper distinction between ICC and HCC and recognition of washout is the sole parameter that may avoid the need to request a diagnostic biopsy. 791 INTERLEUKIN-6, GENDER AND RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH END-STAGE LIVER DISEASE E. Fumolo1 , E. Fornasiere1 , D. Bitetto1 , E. Fontanini1 , A. Cussigh1 , W. Bragagnini1 , E. Falleti1 , C. Fabris1 , R. Minisini2 , P. Toniutto1 , M. Pirisi2 . 1 University of Udine, Udine, 2 University of Novara, Novara, Italy E-mail: [email protected] Background and Aim: Recent animal studies suggest that estrogens might protect from hepatocellular carcinoma (HCC) by suppressing a proinflammatory cytokine, interleukin-6 (IL-6), whose production by Kupffer