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Abstracts of the 22
nd
National Congress of Digestive Diseases / Digestive and Liver Disease 48S2 (2016) e67–e231
e83
3-year survival (odds ratio: 0.57, 0.32-1,01, p=0.06). Meta-analysis of
plotted hazard ratios confirmed this trend (hazard ratio: 0.86, 0.71-
1.03, p=0.10). Pooled data of objective response showed no significant
difference between the two treatments (odds ratio: 1.21, 0.69-2.12,
p=0.51). Meta-regression analysis identified response criteria as
significant contributor to the high heterogeneity observed. No
statistically significant difference in adverse events was registered
(odds ratio:0.85, 0.60-1.20, p=0.36).
Conclusions:
Our results stand for a non-superiority of drug-
eluting beads chemoembolization with respect to conventional
chemoembolization in hepatocarcinoma patients.
OC.03.9
SPONTANEOUS BACTERIAL PERITONITIS (SBP) IS NOT
ASSOCIATED WITH HIGHER MORTALITY IF COMPARED
WITH OTHER INFECTIONS IN PATIENTS AWAITING LIVER
TRANSPLANTATION (LT)
Ferrarese A.*
1
, Zanetto A.
1
, Cillo U.
2
, Angeli P.
3
, Gringeri E.
2
, Zanus G.
2
,
Bortoluzzi I.
1
, Nadal E.
1
, Germani G.
1
, Russo F.P.
1
, Burra P.
1
1
Multivisceral Transplant Unit, Gastroenterology,, Padua University
Hospital,, Italy,
2
Hepatobiliary Surger and Liver Transplant Center,
Padua University Hospital,, Italy,
3
V Chair of Internal Medicine, Padua
University Hospital,, Italy
Background and aim:
Background: Infection represents the main
cause of decompensation or worsening of liver function in cirrhotic
patients; Spontaneous bacterial peritonitis (SBP) is considered a
life threatening cause of Systemic inflammation (SIRS) or sepsis,
especially amongst patients listed for LT. The present study aimed
to evaluate the prevalence of SBP amongst patients listed at Padua
LT Center from 2006 to 2014, and to compare the outcome between
the patients who did experience SBP to patients who experienced
non-SBP infections.
Material and methods:
All consecutive patient who had a first
episode of SBP in the waiting list (WL) were included. Re-LT, and
pediatrics were excluded. For each patient, MELD score before, at the
time of infection, and 30 days after SBP (MELD30) were calculated. A
control group of patients who experienced non-SBP infection while
on the WL was retrieved. All continuous variables are expressed as
mean±SD. Statistical analysis was performed using T-student test
and Fisher’s exact test. Data from intra-individual variables were
obtained using Wilcoxon signed rank test.
Results:
Forty two out of 940 (4.4%) patients (59% male; mean
age 57.2±7.3) developed SBP, 274±551 days after admission in
the WL. MELD score at infection was significantly higher than at
admission (17.8±5.89 vs 21.9±5.19; p 0.0001). For 33.3% SBP was
the cause of death and for those who survived, relapse of SBP was
not uncommon (11.9%). Patients who resolved infection presented
MELD30 significantly lower than during infection (p= .016), but
not different than MELD at admission (p=0.12). Control group
consisted of 78 patients who experienced non-SBP infections in the
WL, with similar MELD score at admission (19.1±5.5 vs 17.8±5.89;
p=0.12). Non-SBP infections produced a significant increase of
MELD (p=0.000024), and MELD30 significantly lower in those who
resolved infection (p=0.02). Mortality due to infection between two
groups was not significantly different (14/42 vs 22/78; p: .67).
Conclusions:
SBP is not an uncommon event in patients awaiting
LT, but its presence does not significantly worse the prognosis if
compared with other infections.
OC.04 Colon Cancer
OC.04.1
SMAD7 KNOCKDOWN IN COLON CANCER CELLS ACTIVATES
PROTEIN KINASE RNA-ASSOCIATED EIF2-ALPHA PATHWAY
THEREBY LEADING TO CELL DEATH
De Simone V.*, Bevivino G., Sedda S., Izzo R., Colantoni A.,
Ortenzi A., Del Brocco A., Fantini M.C., Pallone F., Monteleone G.
University Tor Vergata, Rome, Italy
Background and aim:
Background: Up-regulation of Smad7, an
inhibitor of TGF-
b
1, occurs in sporadic colorectal cancer (CRC).
Knockdown of Smad7 with a specific antisense oligonucleotide
(AS) leads to activation of eIF2
a
, an attenuator of protein synthesis,
and arrest of CRC cells in the S phase of the cell cycle with the
downstream effect of inducing cell death.
Aim:
To investigate the mechanisms by which Smad7 knockdown
activates eIF2
a
.
Material and methods:
Phosphorylation of eIF2
a
was evaluated
in CRC cell lines (i.e. HCT116 and DLD-1) either untreated or
treated with Smad7 sense (S) or AS by Western blotting (WB)
and immunofluorescence (IF). Expression of ATF4 and CHOP, two
downstream targets of eIF2
a
, were evaluated by IF and activation
of PKR, GCN2 and PERK, up-stream kinases that induce eIF2
a
phosphorylation, was assessed by WB. Wild type or PKR-deficient
CRC cells treated with Smad7 AS were monitored for eIF2
a
activation
and induction of death. Finally, we assessed whether enhanced
phosphorylation of eIF2
a
seen in cells treated with Smad7 AS was
also associated with reduced interaction between eIF2
a
and PP1, a
phosphatase that normally dephosphorylates eIF2
a
.
Results:
Smad7 knockdown increased ATF4 and CHOP expression
thus confirming previous data showing activation of eIF2
a
phosphorylation in CRC cells treated with Smad7 AS. Among
kinases that induce eIF2
a
phosphorylation, only PKR was activated
by Smad7 knockdown. Consistently, silencing of PKR reduced but
did not abolish Smad7 AS-induced eIF2
a
phosphorylation and cell
death, thus suggesting the existence of further mechanisms that
control eIF2
a
phosphorylation in Smad7-deficient cells. Indeed,
in CRC cells, Smad7 interacted with PP1 and Smad7 knockdown
reduced association of PP1 with eIF2
a
.
Conclusions:
Data show that Smad7 is involved in CRC cell survival
and suggest that Smad7 is a valid target for therapeutic intervention
in CRC.
OC.04.2
GENETIC DIVERSITY OF THE KIR/HLA SYSTEM AND OUTCOME
OF PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED
WITH CHEMOTHERAPY
De Re V.*, Caggiari L., De Zorzi M., Buonadonna A., De Paoli A.,
Belluco C., Fornasarig M., Maiero S., Orzes E., Cannizzaro R.
Centro di Riferimento Oncologico, Aviano, Italy
Background and aim:
To explore genes of the killer-cell
immunoglobulin-like receptor (KIR) and of the Human Leukocyte
Antigen (HLA) ligand and their relationship with the outcome of
metastatic colorectal cancer (mCRC) patients treated with first-line
5-fluorouracil, leucovorin, and irinotecan (FOLFIRI).
Material and methods:
A total of 224 mCRC patients were screened
for KIR/HLA typing and they were compared with 222 normal
control subjects. The determination of the KIR/HLA combinations
was based upon the gene content and variants. Genetic associations
with complete response (CR), time to progression (TTP) and overall
survival (OS) were evaluated by calculating odds and hazard