studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 411A
Disclosures:
Lewis R. Roberts - Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals,
BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences, Five
Prime Therapeutics
The following authors have nothing to disclose: Jonggi Choi, Hassan M. Ghoz,
Thoetchai Peeraphatdit, Esha Baichoo, Benyam D. Addissie, William S. Harmsen,
Terry M. Therneau, Janet E. Olson, Roongruedee Chaiteerakij
398
The autophagy marker LC3 is significantly associated
with overall survival in human hepatocellular carcinoma
underwent resection
Chih-Wen Lin 1,3 , Jhy-Shrian Huang 1 , Chia-Yen Dai 2,3 , Jee-Fu
Huang 2,3 , Wan-Long Chuang 2,3 , Ming-Lung Yu 2,3 ; 1 Division of
Gastroenterology and Hepatology, Department of Medicine, E-DA
Hospital/ I-SHOU University, Kaohsiung, Taiwan; 2 Hepatobiliary
Division, Department of Internal Medicine, Kaohsiung Medical
University Hospital, Kaohsiung Medical University,, Kaohsiung,
Taiwan; 3 Graduate Institute of Medicine, College of Medicine,
Kaohsiung Medical University, Kaohsiung, Taiwan
BACKGROUND: Hepatocellular carcinoma (HCC) is one of
the most common malignancies, with an increasing incidence
and is the third leading cause of cancer-related mortality in
the world. Most HCC patients are diagnosed at an advanced
stage and have very poor prognosis and low survival. Despite
the improvements of therapeutic modalities in HCC, the rate of
5-years tumor-related death has remained as high as at 30-50
%. Therefore, identification of prognostic factors to develop
newer targeted therapy is urgently needed to improve HCC
patient survival. Autophagy is a process through which longlived
proteins and damaged organelles are conveyed to the
lysosome for removal by degradation and recycling. Some
studies have shown that autophagy plays a key role in the
progression and development of cancer. But, the role of autophagy
in the prognosis and metastasis of human HCC is not
well unknown. AIMS: The study aims to explore the expression
of markers of autophagy genes using immunohistochemistry
(IHC) in human HCC tissues. We also investigate the autophagy
markers associated with clinicopathological characteristics
and prognosis. METHODS: We retrospectively analyzed
200 patients diagnosed with HCC by histology after surgical
resection at the Chunghua Christian Hospital, Chunghua, and
Kaohsiung Medical University Hospital, Kaohsiung, Taiwan,
from 2009 to 2014. The demographic data, recurrence, and
survival were collected until December 2014. The expression
of autophagy-related markers (LC3 and p62) were analyzed
by IHC staining using HCC tumor tissues and non-tumor tissues.
RESULTS: Two hundreds HCC patients were collected.
The average age is 62.8 years old and the rate of male is
74%. The rate of HBV, HCV, HBV+HCV, and Non-HBVHCV is
48%, 28%, 4%, and 20%, respectively. Median survival was
26.3 months (range 3-42 months). The positive rate of LC3 was
significantly higher in HCC tumor tissues than non-tumor tissues
(85.5 vs. 50.0%, P < 0.001). In HCC, The overall survival was
significantly correlated with cirrhosis background, TMN stage,
BCLC stage, Child-Pugh class, and LC3 tumor part staining in
univariate Cox regression analysis. Furthermore, the overall
survival was significantly correlated with cirrhosis background
(P = 0.01), TMN stage, BCLC stage (P = 0.49), and LC3 tumor
part staining (P = 0.015) in multivariate Cox regression analysis.
The strong positive of LC3 staining is significantly associated
with increasing the 3-year survival rates by Kaplan-Meier
survival analysis (P=0.046). CONCLUSIONS: Our results show
that the expression of autophagy marker, LC3, might be a
strong prognostic factor of overall survival in HCC patients
underwent liver resection.
Disclosures:
Wan-Long Chuang - Advisory Committees or Review Panels: Gilead, Abbvie;
Speaking and Teaching: BMS, Roche, MSD
The following authors have nothing to disclose: Chih-Wen Lin, Jhy-Shrian Huang,
Chia-Yen Dai, Jee-Fu Huang, Ming-Lung Yu
399
Conversion therapy with hepatic arterial infusion
chemotherapy and hepatic resection prolongs overall
survival of patients with advanced hepatocellular carcinoma
involving vascular invasion
Hiroaki Nagamatsu 1,2 , Takuji Torimura 2 ; 1 Department of Gastroenterology
and Hepatology, Yame general hospital, Yame, Japan;
2 Division of Gastroenterology, Kurume University School of Medicine,
Kurume, Japan
[Objectives] Sorafenib is recognized as a standard treatment
for advanced unresectable hepatocellular carcinoma (HCC)
with vascular invasion worldwide. However, the therapeutic
efficacy is marginal. We retrospectively evaluated the therapeutic
effectiveness of conversion therapy with hepatic arterial
infusion chemotherapy (HAIC) . [Subjects] From January 2004
to December 2014, among 270 patients who received HAIC
with cisplatin (CDDP) and 5-fluorouracil (5-FU) at our institution
and affiliated Kurume university hospital, 189 patients with
unresectable HCC involving vascular invasion without extrahepatic
metastasis were enrolled in the study (mean age, 68.9
years; Child-Pugh class A/B/C, 114/66/9 cases; portal vein
tumor thrombosis in 2nd branch/1st branch/trunk, 80/66/43
cases ). [Methods] All 189 patients received HAIC via the
reservoir system. After chemolipiodolization, the patients were
treated with CDDP 50 mg followed by 5-FU 1,250 mg via a
balloon pump for 5 days (NFP therapy 1) ). For patients who
achieved partial response (PR) after NFP and in whom conversion
therapy was feasible, hepatectomy (Hr), trancecatheter
arterial chemoembolization (TACE), or radiotherapy (RT) was
performed to achieve cancer-free outcome. Tumor response
by NFP was evaluated with m-RECIST. Cumulative overall survival
(OS) after NFP was estimated using Kaplan-Meier survival
curves, and multivariate analysis was performed to identify
prognostic factors affecting OS using Cox proportional hazards
models. For factors with significant difference in the multivariate
analysis, OS was compared using log-rank test. [Results] 136
patients (72%) responded to NFP therapy (CR, 17; PR,119).
41 patients who showed PR received conversion therapy,(
NFP +Hr, 18 patients; NFP +TACE, 18 patients, NFP +RT, 5
patients). 58 patients (31%) achieved cancer-free outcome.
Median OS (MST) after HAIC in all patients was 18 months.
Significant factors for OS included cancer-free outcome (hazard
ratio, 0.184; P=0.001) and addition of Hr (hazard ratio,
0.105; P=0.003). MST in patients who responded was 29
months, and in patients who achieved cancer-free outcome, it
was extended to 57 months.Three - and five-year survival rates
were 78% and 21% in patients treated with NFP only, 87%
and 71% in NFP+Hr, 47% and 16% in NFP+TACE, and 67%
and 33% in NFP+RT patients (P=0.028), respectively. [Conclusions]
NFP therapy demonstrated favorable tumor response in
patients with advanced hepatocellular carcinoma with vascular
invasion. Addition of conversion therapy, specifically, Hr, targeting
cancer-free outcome made possible long-term survival.
Disclosures:
The following authors have nothing to disclose: Hiroaki Nagamatsu, Takuji Torimura