studies

438A AASLD ABSTRACTS HEPATOLOGY, October, 2015
The following authors have nothing to disclose: Atsuo Takigawa, Ryotaro Sakamori,
Tomohide Tatsumi, Takayuki Yakushijin, Tadashi Kegasawa, Yuki Makino,
Seiichi Tawara, Yoshinobu Saito, Yoshiki Onishi, Satoshi Tanaka, Kunimaro
Furuta, Minoru Shigekawa, Naoki Hiramatsu
Disclosures:
The following authors have nothing to disclose: Li Huang, Kunsong Zhang, Wei
Chen, Mengjun Hou, Yuyan Han, Fanyin Meng, Sharon DeMorrow, Xiaoyu Yin,
Jiaming Lai, Bingyan Tan, Lijian Liang
454
Dysregulated peripheral and local endocannabinoid
system promote tumor pathogenesis in biliary tract cancers
Li Huang 1 , Kunsong Zhang 1 , Wei Chen 1 , Mengjun Hou 2 , Yuyan
Han 3 , Fanyin Meng 4 , Sharon DeMorrow 5 , Xiaoyu Yin 1 , Jiaming
Lai 1 , Bingyan Tan 2 , Lijian Liang 1 ; 1 Department of Pancreatobiliary
Surgery, The First Affiliated Hospital, Sun Yat-sen University,
Guangzhou, China; 2 Department of Nutrition, School of Public
Health, Sun Yat-Sen University, Guangzhou, China; 3 Department
of Medicine, Baylor and Scott & White Digestive Disease Research
Center, Texas A&M HSC College of Medicine and Scott & White
Hospital, Temple, TX; 4 Department of Medicine; Department of
Research, Scott & White Digestive Disease Research Center; Texas
A&M Health Science Center College of Medicine; Central Texas
Veterans Health Care System, Temple, TX; 5 Department of Internal
Medicine, Texas A&M Health Science Center College of Medicine;
Baylor Scott & White Health Digestive Disease Research Center;
Central Texas Veterans Health Care System, Temple, TX
Background: The endocannabinoid system (ECS) is dysregulated
in various liver diseases. Biliary tract cancers (BTCs)
encompass gallbladder carcinoma, intrahepatic, perihilar and
distal cholangiocarcinoma. Previously we have shown that the
two major endocannabinoids (ECs), anandamide (AEA) and
2-arachidonoyl glycerol (2-AG) exert opposing effects on proliferation
of BTCs cell lines. However, regulation and clinical
significance of ECS in BTCs remain inconclusive. Method: Levels
of AEA and 2-AG in preoperative peripheral plasma and
bile in 22 BTCs patients and 8 patients with benign biliary
diseases, and paired resection samples in 15 BTCs patients
were quantitated by gas chromatography/electron ionization
(EI)-mass spectrometry (GC/MS). Expression and activity of
the enzymes involved in ECs biosynthesis (phospholipase D
for AEA and diacylglycerol lipases (DAGLs, including DAGLα
and DAGLβ) for 2-AG) and ECs degradation (fatty acid amide
hydrolase-1 (FAAH-1) for AEA and monoaclyglycerol lipase
(MAGL) for 2-AG) were also analyzed. Levels of ECs were correlated
with patients’ clinicopathologic features. Results: Level
of AEA was lower in plasma and bile (median [interquartile
range]: 1.804 pmol/mL [0.502 to 5.004 pmol/mL] vs 10.150
pmol/mL [2.684 to 17.491 pmol/mL]) in BTCs than in benign
biliary diseases, though the former didn’t reach significance.
AEA was significantly lower in BTCs cancer nest than in adjacent
normal tissue (22.01 fmol/mg [16.55 to 53.61 fmol/mg]
vs 58.68 fmol/mg [25.36 to 68.97 fmol/mg]). Level of 2-AG
was upregulated in plasma (180.0 pmol/mL [140.7 to 283.8
pmol/mL] vs 42.3 pmol/mL [25.6 to 148.9 pmol/mL]) and
bile in BTCs, though the latter didn’t reach significance. 2-AG
was significantly higher in BTCs cancer nest than in adjacent
normal tissue (1.967 pmol/mg [1.439 to 5.433 pmol/mg] vs
1.101 pmol/mg [0.358 to 1.473 pmol/mg]). Upregulated
expressions and activities of DAGLs, FAAH-1 and MAGL were
demonstrated in BTCs. Lower cancer nest level of AEA, higher
plasma and cancer nest level of 2-AG were correlated with
more advanced tumor stage in BTCs. Conclusion: ECS is dysregulated
in BTCs and it may foster a tumor promoting microenvironment.
Modulation of ECS could be regards as a promising
therapeutic strategy for BTCs.
455
Prospective cohort study for evaluating clinical effects
and safety of intra-arterial infusion therapy of Cisplatin
suspension in lipiodol combined with 5-fluorouracil and
sorafenib for advanced hepatocellular carcinoma with
macroscopic vascular invasion, without extra-hepatic
spread
Niizeki Takashi, Masahito Nakano, Takuji Torimura; Gastroenterology,
Kurume University, school of medicine, Kurume, Japan
Purpose Sorafenib is the standard first line treatment for patients
with BCLC stage C hepatocellular carcinoma (HCC). However
sorafenib monotherapy confers less than three months of
actual survival benefit in both Western and Asian populations.
Hepatic arterial infusion chemotherapy (HAIC) is recognized
as a useful therapeutic option for advanced HCC in Japan, and
response to HAIC is known as an important prognostic factor.
While sorafenib has been proven to improve the prognosis in
HCC patients with macroscopic vascular invasion (MVI), it is
still unknown which is better, Sorafenib or HAIC. The aim of
this multicenter none- randomized prospective cohort study was
to investigate the efficacy and safety of HAIC compared with
Sorafenib in patients with advanced HCC with MVI, without
extra-hepatic spread (EHS) and Child-Pugh class A disease.
Method: This study was conducted from April 2009 to March
2014, total 64 HCC patients were registered. 44 were treated
with HAIC, 20 were treated with Sorafenib. HAIC regimen
comprised a combination of 50 mg fine powder formulation of
Cisplatin in 5-10 ml lipiodol and contimuous infusion of 5-fluorouracil
(1,500 mg/5 days). The primary efficacy endpoint
was progression-free survival (PFS), while the secondary endpoints
were Median survival time (MST), tumor response rate,
and safety. PFS and MST were estimated by Kaplan- Meier
method. Therapeutic effect was evaluated according to RECIST.
Results: There were no statistica differences in clinical factors
between two groups. PFS in HAIC and Sorafenib was 9.3
months and 4.1 months respectively. (P = 0.002, 95% CI,
0.221- 0.713) CR or PR rate in HAIC and Sorafenib was 71%
and 10%.(P 0.001, 95% CI, 4.32- 106.09) MST in HAIC and
Sorafenib was 30.0 months and 13.0 months respectively. (P
= 0.016, 95% CI, 0.219- 0.854) Severe adverse events were
observed in 5 patients. In Sorafenib group, 2 had hepatic
failure, in HAIC group, 2 had hepatic failure, 1 had pseudo
aneurysm. In HAIC group, treatment- related mortality was not
observed. By multivariate analysis, independent predictor of
survival were therapeutic effect (CR or PR, P= 0.009, 95% CI,
0.220- 0.752), Child- Pugh score (score 5, P= 0.022, 95%
CI, 0.191- 0.752), grade of portal vein invasion (trunk, P=
0.002, 95% CI, 0.118- 0.614), and independent predictor of
therapeutic effect was therapeutic regimen (HAIC, P 0.0001).
Conclusion: In HAIC group, PFS was 9.3 months, MST was
30.0 months and response rate was 74%, and these results
were superior to Sorafenib. In conclusion, this regimen should
be the first choice for patients with advanced HCC with MVI,
without EHS and Child Pugh A disease.
Disclosures:
The following authors have nothing to disclose: Niizeki Takashi, Masahito
Nakano, Takuji Torimura