Page 313 - ebook HCC

EASL
GENEVA, SWITZERLANDA, SWITZERLAND
PROGRAMME AND ABSTRACTSAND ABSTRACTS
310 PROGRAMME GENEV EASL HCC SUMMITHCC SUMMIT 311
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FEBRUAR
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
Poster Board Number C75 Poster Board Number C76
HEPATOCELLULAR CARCINOMA AND MULTIMODALITY TREATMENT OF
QUERCETIN: A CURIOUS RELATIONSHIP HEPATOCELLULAR CARCINOMA IN A SINGLE
TERTIARY REFERRAL CENTRE
Ana F. Brito , Marina Ribeiro , Ana M. Abrantes , Ana C. Gonçalves ,
1 2
2
1 2
1
Ana B. Sarmento-Ribeiro, Francisco Castro Sousa , Angelo Sangiovanni , Michela Triolo , Matteo Angelo Manini , Massimo Lavarone
1 3
1
1
1
José G. Tralhão 1 2 3 , Maria F. Botelho 1 2 1 , Sara Vavassori , Cristina Della Corte , Laura Virginia Forzenigo , Antonio Nicolini ,
1
2
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1 Biophysics Unit, Faculty of Medicine, University of Coimbra, Giorgio Rossi , Massimo Colombo 1
3
2 Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), 1 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
3 Surgical Department, Surgery A, HUC, Coimbra, Portugal Policlinico , Division of Radiology, Division of Surgery and Liver Transplant, Fondazione
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2
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Corresponding author’s e-mail: anabrito816@gmail.com
Corresponding author’s e-mail: massimo.colombo@unimi.it
Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy.
Glucose transporter-1 (GLUT1) expression is increased in HCC and promotes tumorigenesis. Aims: Multimodality treatment of hepatocellular carcinoma (HCC) is a common clinical
Flavonoids, including quercetin, have shown potential as GLUT1 function inhibition and they practice. Comorbidities, liver and no-liver related conditions, led to an incomplete
adherence to the AASLD guidelines for the treatment of HCC. The impact of this behavior
can be useful as therapeutic weapons against this highly aggressive kind of tumor. is not fully investigated. The aim is to define the clinical impact of multimodality treatment
of HCC in cirrhotic patients attending a single tertiary referral centre.
Aims: The aim of this study is to evaluate the potential anticancer effect of quercetin on
two HCC cell lines which differ on p53 expression, evaluate its effect on F-FDG uptake Methodology: 292 consecutive cirrhotic patients with a de-novo diagnosis of HCC, 218
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and in GLUT-1 expression. (75%) males, mean age 66 (31-87), 230 (79%) Child-Pugh A, 145 (50%) BCLC A0-3, 54
(18%) A4, 49 (17%) B and 45 (15%) C, were observed between 2007 and 2011. HCC
Methodology: Two different HCC cell lines (HepG2 (wp53) and HuH7 (mp53)) were used. treatments were decided by a multidisciplinary team of experts on intention-to-treat
In order to assess the effect of quercetin in these cell lines, the cells were incubated in the according to the AASLD guidelines. Restaging was performed every 1-3 months by CT/
presence of different concentrations of this compound for different periods of time, and after MRI after treatment. Patient and tumor characteristics and blood tests were considered as
cell proliferation was evaluated by the MTT test in order to calculate half maximal inhibitory predictors of survival and tested by univariate and multivariate Cox proportional hazards
concentration (IC ). The type of cell death was assessed by flow cytometry using the model (STATA 10.0 Statistical Package).
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double staining with annexin-V and propidium iodide. Bax, Bcl2 and GLUT1 expression Results: During a mean trial time of 36 months 78 (27%) patients died and 25 (9%) were
was also assessed by flow cytometry. For uptake studies, F-FDG was incubated in a lost. Overall 1, 3 and 5 yr survival was 91%, 68% and 53 % respectively (99%, 81% and
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CLINICAL POSTER ABSTRACTS centrifuged and radioactivity of pellets and supernatants was measured with a well-type ablation, 53 (18%) chemoembolization, 27 (9%) sorafenib, 22 (8%) best supportive care CLINICAL POSTER ABSTRACTS
cell suspension in cells pre-incubated with quercetin and control cells. At different times,
68% for BCLC A, 94%, 62%, 35% for BCLC B, 52%, 12% and 0% for BCLC C). First line
samples were collected to eppendorf tubes for uptake calculation. Eppendorfs were then
treatment was: 31 (11%) liver transplantation (OLT), 43 (15%) resection, 116 (40%) local
(BSC). Adherence to AASLD guidelines was in 220 (75%) patients. 43 (15%) received
gamma counter.
a treatment recommended by AASLD for a more advanced stage, 29 (10%) for a less
advanced stage. Complete response was achieved in 137 (47%) after first line treatment
Results: Quercetin inhibits cell proliferation in HepG2 and HuH7 cell lines in a time-
(including 31 OLT), in 19 (6%) after second line, in 5 (2%) after third line. HCC recurred
dependent manner. Quercetin does not inhibit GLUT1 expression, however this compound
is able to decrease the F-FDG uptake in both cell lines. Flow cytometry results have
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95% CI 1.39-2.24, p <0.000), BCLC (HR 1.83, 95% CI 1.29-2.61, p=0.001), AFP > 100ng/
shown that quercetin has a cytotoxic effect only at high concentrations of this compound.
mL, (HR 2.53, 95% CI 1.48.4-32, p=0.001), encephalopathy (HR 2.29, 95% CI 1.21-4.37,
When cell death occurs, is mainly by apoptosis and this is accompanied by a Bax activation. after OLT in 6 (19%). Independent predictors of survival were: treatment choice (HR 1.76
p =0.01), ascites (HR 1.78, 95% CI 1.08-2.95, p=0.024).
Conclusion: This study showed that quercetin has a considerable anti-proliferative effect Conclusion: In the clinical practice of a tertiary referral centre, adherence to AASLD
in HepG2 and Huh7 cell lines. This compound probably modifies the function but not the guidelines for HCC treatment was in two third of the patients and a complete response in
expression of GLUT1, since it inhibits F-FDG (a glucose analogue that is transported more than half of the cases. The multidisciplinary decision of treatment choice is one of the
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into the cell by GLUT1 and GLUT3) uptake. In this context quercetin may represent a new strongest predictors of HCC survival.
therapeutic option in HCC.