Oral (pre-recorded)
OL02 Liver: Primary Tumours 
Selection of Presentations from Abstract Submissions

OL02-01 Risk Factors, Patterns and Long-Term Prognosis of Early and Late Recurrence in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma
Tian Yang, China

M.-D. Wang1, C. Li1, L. Liang1, H. Xing1, Y. Lau Wan2, T.M. Pawlik3, F. Shen1, T. Yang1
1Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, China, 2Faculty of Medicine, Chinese University of Hong Kong, China, 3Department of Surgery, Ohio State University, Wexner Medical Center, United States

Background: Survival after liver resection of hepatocellular carcinoma (HCC) remains poor due to a high incidence of recurrence. We sought to investigate risk factors, patterns, and long-term prognosis among patients with early and late recurrence after liver resection for hepatitis B virus (HBV)-associated HCC.
Methods: Data of consecutive patients undergoing curative resection for HBV-associated HCC were analyzed. According to the time to recurrence after surgery, recurrence was divided into early (≤ 2 years) and late recurrence (> 2 years). Characteristics, patterns of initial recurrence and post-recurrence survival (PRS) were compared between patients with early and late recurrence. Risk factors of early and late recurrence, and predictors of PRS were identified by univariable and multivariable Cox-regression analyses.
Results: Among 894 patients, 322 (36.0%) and 282 (31.5%) developed early and late recurrence, respectively. On multivariable analyses preoperative HBV-DNA>104 copies/ml was associated with both early and late recurrence, while postoperative no/irregular antiviral therapy was associated with late recurrence. Compared with patients with late recurrence, patients with early recurrence had a lower proportion of intrahepatic only recurrence (72.0% vs. 91.1%, P< 0.001), as well as a lower chance of receiving potentially-curative treatments for recurrence (33.9% vs. 50.7%, P< 0.001) and a worse median PRS (19.1 vs. 37.5 months, P< 0.001). Multivariable analysis demonstrated that early recurrence was independently associated with worse PRS (HR 1.361, P=0.006).
Conclusions: Risk factors associated with early recurrence and late recurrence were different. Early recurrence was associated with worse post-recurrence survival among patients with recurrence.
OL02-02 Effect of Performance Status on Short-term and Long-Term Outcomes After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study
Tian Yang, China

H. Wu1, H. Xing1, L. Liang1, B. Huang1, Y. Lau Wan2, Y.-H. Zhou3, T.M. Pawlik4, F. Shen1, T. Yang5
1Eastern Hepatobiliary Surgery Hospital, China, 2Chinese University of Hong Kong, China, 3Pu’er People’s Hospital, China, 4Ohio State University, Wexner Medical Center, United States, 5Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, China

Background: The Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. However, in real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.
Methods: Using a multi-institutional database, 1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified. After categorizing patients into PS-0 (n=836) versus PS-1 (n=695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.
Results: Overall perioperative mortality and major morbidity among patients with PS-0 (n=836) and PS-1 (n=695) were similar (1.4% vs. 1.6%, P=0.525 and 9.7% vs. 10.2%, P=0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P< 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111-1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034-1.358, P = 0.007).
Conclusions: Patients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.
[Figure. Comparison of overall survival (A) and recurrence-free survival (B) curves between patient]
OL02-03 Prognostic Impact of ATM expression in Asian Patients with NonBnonC-Hepatocellular Carcinoma
Yuki Hirose, Japan

Y. Hirose, J. Sakata, K. Yuza, K. Takizawa, K. Miura, T. Katada, K. Toge, T. Kobayashi, T. Wakai
Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Japan

Background: The aim of this study was to clarify the prognostic value of expression of Ataxia telangiectasia mutated (ATM) in hepatocellular carcinoma (HCC).
Methods: The Cancer Genome Atlas (TCGA) database was used to examine ATM mRNA expression in HCC (n = 371). In addition, immunohistochemical phospho-ATM (pATM) expression in HCC was assessed for 22 Japanese patients with NAFLD-related HCC who underwent hepatectomy.
Results: TCGA data showed that patients with nonBnonC-HCC (n = 199) had significantly worse overall survival (OS) than those with Hepatitis B and/or Hepatitis C (HB/HC)-related HCC (n = 172) (p < 0.001). In Asian nonBnonC-HCC cohort in TCGA (n = 52), patients with ATM high expression had significantly worse OS than those with ATM low expression (p = 0.046). Whereas in non-Asian nonBnonC-HCC (n = 147), Asian HB/HC-HCC (n = 106), or non-Asian HB/HC-HCC (n = 66) cohort in TCGA, there were no significant differences in OS between patients with ATM high expression and those with ATM low expression. Immunohistochemical examination in Japanese patients with NAFLD-related HCC revealed that patients with pATM high expression had significantly worse OS than those with pATM low expression (p = 0.007). Furthermore, multivariate analysis in OS showed that pATM expression was an independent prognostic factor (HR, 4.311, p = 0.026).
Conclusions: ATM high expression in HCC might be an adverse prognostic factor for Asian patients with nonBnonC-HCC.
OL02-04 Combined Hepatectomy and Microwave Ablation for Multifocal Hepatocellular Carcinoma: Long-Term Outcomes and Prognostic Factors
Tomoki Ryu, Japan

T. Ryu, Y. Takami, Y. Wada, S. Sasaki, H. Imamura, H. Ureshino, H. Saitsu
Department of Hepato-Biliary-Pancreatic Surgery, Kyushu Medical Center, Japan

Background: It remains to be clarified whether combined hepatectomy and microwave ablation for multifocal hepatocellular carcinoma (HCC) is feasible. This aim of this study was to examine the perioperative and oncological outcomes after combined hepatectomy and microwave ablation for multifocal HCC.
Methods: This retrospective study included 81 patients who underwent combined hepatectomy and microwave ablation for multifocal HCC in our institute between July 1994 and December 2017. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis.
Results: The 81 patients included 57 men and 24 women, with a median age of 67 years. Fifty-four patients (67%) were infected to Hepatitis C virus, and 71 patients (88 %) had Child-Pugh class A liver function. The median maximum tumor size was 32 mm and the median number of tumors was three. Median follow-up time was 45.6 months for the entire cohort. OS rates were 1-year: 96%,
3-year: 72%, 5-year: 54%, and 10-year: 35%; RFS rates were 1-year: 77%, 3-year: 37%, 5-year: 22%, and 10-year: 12%. The major complication rate (Clavien-Dindo classification IIIa or above) after surgery was 10%, with one patient of in-hospital mortality. Multivariate analysis showed that des-γ-carboxy prothrombin level > 100 mAU/mL was an independent risk factor for OS, and maximum tumor size > 5 cm was an independent risk factor for RFS.
Conclusions: Our results indicate that combined hepatectomy and microwave ablation is safe and feasible for selected patients with multifocal HCC.
OL02-05 The Utility of Immune-Nutritional Index as Prognostic Indicator for Intrahepatic Cholangiocarcinoma: A Multi-Center Analysis of 385 Resected Cases
Tomokazu Fuji, Japan

T. Fuji1, Y. Umeda2, T. Kojima1, T. Niguma1, Y. Endo3, M. Oishi4, T. Ota5, T. Yagi2, T. Fujiwara2, Okayama Study Group of Hepatobiliary and Pancreatic Surgery
1Department of Surgery, Okayama Saiseikai General Hospital, Japan, 2Department of Gastroenterological Surgery, Okayama University, Japan, 3Department of Surgery, Himeji Japanese Red Cross Hospital, Japan, 4Department of Surgery, Tottori Municipal Hospital, Japan, 5Department of Surgery, National Hospital Organization Okayama Medical Center, Japan

Introduction: The prognosis of Intrahepatic cholangiocarcinoma (IHC) after resection has been poor because of high rate of recurrence. Preoperative immune-nutritional index has been reported as useful prognostic assessment in various malignancies.
Purpose: The aim of this study was to evaluate the prognostic value of immune-nutritional index in patients with ICC after curative resection.
Materials and methods: Overall survival (OS) of 385 cases of ICC between 2000 and 2016 were analyzed, according to various immune-nutritional indexes containing Glasgow Prognostic score (GPS), Controlling Nutrition Status (CONUT), Prognostic nutritional index (PNI), Neutrophil/Lymphocyte ratio (NLR), and Lymphocyte/Monocyte ratio (LMR).
Results: The 2-, 5-, and 10- years OS were 66.2%, 40.6%, and 22.7%, respectively. Every immune-nutritional index could be identified as a significant prognostic factor: GPS (1/2 vs 0, Hazard ratio [HR]= 2.2, p< 0.0001), CONUT (≥2 vs 0/1, HR=1.4, p=0.011), PNI (< 40 vs ≥40, HR=1.5, p=0.0044), NLR (≥2.6 vs 2.6>, HR=1.4, p=0.0099), and LMR (3.7> vs ≥ 3.7, HR=1.5, p=0.0079). In multivariate analysis, CONUT could be an independent reliable predictor which had no relation to background tumor profiles such as tumor size, multiple lesion, CA19-9 level, and lymph-node metastasis. Thus, patients with high CONUT (≥2) showed poorer prognosis than patients with low CONUT 0/1 (Median survival 33 vs 51 months, p=0.01).
Conclusions: The prognosis of ICC after surgery would rely on preoperative immuno-nutritional status. Immuno-nutritional, especially CONUT, could be utilized as prognostic indicator for preoperative assessment of ICC.
OL02-08 Repeat Hepatectomy Versus Radiofrequency Ablation in the Management of Recurrent Hepatocellular Carcinoma: An Average Treatment Effect Analysis
Yu Chuan Tan, Singapore

D. Chua1, Y. Koh1, Y.C. Tan2, N. Syn2, J.Y. Ho2, B. Goh1, S.Y. Lee1, J.Y. Teo1, C.Y. Chan1
1Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore, 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Introduction: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with high rates of recurrence post-resection. Various treatments are available for managing recurrent HCC following initial curative resection. This is a retrospective study which aims to determine the average treatment effect of liver re-resection over radiofrequency ablation (RFA) in patients with recurrent HCC following initial curative resection.
Methods: From 2000 to 2016, a total of 219 patients who met the study criteria were included. This group was selected from a cohort of 1063 patients who had recurrent HCC following initial resection during the study period.
Results: The median overall survival (OS) for RFA and repeat hepatectomy (RH) was 56.6 months (IQR, 29.6 - Not Reached) and 85.5 months (IQR, 31.0 - Not Reached) (p = 0.6006) respectively while the median time to recurrence was 16.2 months (IQR, 7.8 - 78.0) and 26.1 months (IQR, 9.1 - 126.5) (p = 0.0269) respectively. After propensity score matching, the median OS for RFA and RH was 53.3 months (IQR, 27.5 - Not Reached) and 85.5 months (IQR, 33.5 - Not Reached) (p = 0.8474) respectively while the median time to recurrence months was 11.1 (IQR, 5.0 - 33.2) and 28.0 months (IQR, 9.1 - Not Reached) (p = 0.0225) respectively.
Conclusion: Repeat hepatectomy is preferred in the management of recurrent HCC following initial resection.
OL02-09 The Use of Statin Is Associated With Better Disease-Free Survival In Patients with Hepatitis B-Related Hepatocellular Carcinoma after Curative Treatment
Charing Chong, Hong Kong

C. Chong1, G. Wong2, P. Ip1, T. Yip2, J. Wong1, K. Lee1, K. Ng1, P. Lai1
1Department of Surgery, The Chinese University of Hong Kong, Hong Kong, 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

Background and aims: The association of use of statins and risk of hepatocellular carcinoma (HCC) hepatitis B-infected (HBV) patients has been reported. This study aimed to examine the effect of statin on survival after curative treatment for HCC in HBV population.
Methods: We conducted a hospital-based population study of HBV-related HCC patients by using the Hospital Authority database. We use propensity score (PS) weighting to minimise baseline confounders and “indication bias”. The weighted Cox regression analyses was performed for the overall and disease-free survival.
Results: A total of 4337 patients with HBV-related HCC received curative treatment during study period. After PS weighting of baseline covariates, the 1-year, 3-year and 5-year overall survival of statin users and non-statin users were 93.1% vs 90.5%, 77.9% vs 74.8% and 69.0% vs 63.4% respectively (p=0.946). The 1-year, 3-year and 5-year disease-free survival of statin users and non-statin users were 71.6% vs 62.9%, 52.9% vs 43.0% and 47.7% vs 34.3% respectively (p=0.005). In subgroup analysis, concurrent use of statin and antiviral therapy was associated with a better disease-free survival (p=0.022) compared to antiviral therapy alone.
Conclusion: Statin use is associated with better disease-free survival in patients with HBV-related HCC after curative treatment. Additive HCC chemopreventive effect was seen with the concomitant use of antiviral and statin. Further prospective studies are warranted to investigate the potential use of statin in antiviral therapy users.
OL02-11 Repeated Surgical Resection of Recurrent Tumor after Initial Hepatectomy for Intrahepatic Cholangiocarcinoma
Junichi Arita, Japan

J. Arita, A. Ichida, Y. Kawaguchi, T. Ishizawa, N. Akamatsu, J. Kaneko, K. Hasegawa
Hepato-Biliary and Pancreatic Surgery Division, University of Tokyo, Japan

Background: Treating strategy for recurrent tumor after initial hepatic resection of intrahepatic cholangiocarcinoma (ICC) is yet controversial.
Methods: Patients undergoing surgical resection for initial tumor of ICC between 1995 and 2016 were identified and recurrence was researched. A retrospective analysis was performed to assess the oncological benefit of resection of recurrent tumors.
Results: A total of 133 patients underwent initial radical resections for ICC. The 3- and 5-year overall survival rates in the 133 patients after initial surgery were 68% and 48%, respectively. The median and range of tumor size was 4.5 (1.2-12) cm. Hilar invasion was seen in 44 of 133 patients. Lymph node metastasis was histologically diagnosed in 29 patients. Tumor recurrence was diagnosed in 94 of 133 patients; 18 patients of them underwent repeated resection of the recurrent tumor. The resected recurrent tumor sites were liver in 13 patients, lung in 4 patients, and bile duct in 1 patient. The median OS after diagnosis of tumor recurrence was 34.8 months in re-resection group and 19.6 months in non-re-resection group (P = 0.04). The 3- and 5-year overall survival rates were 48% and 21% in re-resection group, and 13% and 5% and non-re-resection group. The median disease-free survival after re-resection of recurrent tumors (n = 18) was 11.2 months and 1-year disease-free survival was 36%.
Conclusion: Re-resection of recurrent tumor may be useful for selected patients. Effective adjuvant chemotherapy would be needed because disease-free survival after re-resection was unsatisfactory.
OL02-13 Regional Lymphadenectomy in Hepatoma Resection: Insight into Prognosis
John Bergquist, United States

J. Bergquist, A. Li, M. Dua, B. Visser
HPB Surgery, Stanford University, United States

Background: Developing chemotherapeutics for hepatocellular carcinoma (HCC) suggest adjuvant therapy trials are coming. Selection criteria for these trials are undetermined, but prior experience with intrahepatic cholangiocarcinoma suggests that surgical determination of lymph node is important.
Methods: Patients with HCC who underwent liver resection (LR) were identified from Surveillance Epidemiology and End Results (SEER-18) database (2003-2015). Cohort-based clinicopathologic comparisons were made based on completion of regional lymphadenectomy. Propensity-score matching reduced bias. Unadjusted and adjusted analysis of overall (OS) and disease-specific survival (DSS) were performed.
Results: Among 5395 patients, 835 (15.4%) underwent regional lymphadenectomy. Patients undergoing lymphadenectomy had larger tumors (7.0vs4.8cm) and higher t-stage (30.9 vs. 17.6% T3+,p< 0.001). Node positivity rate was 12.0%. Median OS (50 months), and DSS (28vs.29 months) were similar between cohorts, but node-positive patients had decreased OS (20 months) and DSS (16 months,p< 0.01). Matched patients undergoing lymphadenectomy had equivalent unadjusted OS (46vs.43 months,p=0.869) and DSS (27vs.29 months, p=0.306) to non-lymphadenectomy patients. The prognostic impact of node positive disease persisted after matching (OS 24 months, DSS 19 months, p< 0.01). Adjusted overall mortality hazard was independently elevated in patients with N1 disease (1.71 unmatched, 1.56 matched,p< 0.01). Disease-specific mortality hazard was independently elevated at 1.40,p< 0.01 before matching, 1.25,p=0.09 after matching).
Conclusion: Regional lymphadenectomy is seldom performed in patients undergoing surgery for HCC, but it provides useful prognostic information which persists when adjusted for T-stage. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional lymphadenectomy to facilitate optimal multidisciplinary management.
[Survival comparison in HCC patients undergoing lymphadenectomy]
OL02-14 Should We Resect or Transplant Hepatocellular Carcinoma beyond UCSF Criteria?
Tiffany CL Wong, Hong Kong

T.C. Wong1, J. Dai1, J. Fung2, B. She1, K. Ma1, A. Chan1, T. Cheung1, C. Lo1
1Surgery, The University of Hong Kong, Hong Kong, 2Medicine, The University of Hong Kong, Hong Kong

Introduction: Limited data is available on long-term outcomes after surgical treatment for advanced hepatocellular carcinoma(HCC). The aim of this study was to evaluate the perioperative and long-term outcomes after resection vs. living donor liver transplant(LDLT) for HCC beyond UCSF criteria.
Methods: This was a single-center retrospective study from 2000-2018.Data was collected from a prospective maintained dataset. All HCC patients who had tumor stage beyond UCSF criteria were include. Propensity score matching(PSM) at 1:2 was used to adjust for age, tumor number and size between the 2 groups.
Results: During study period, 55 and 721 patients underwent LDLT and resection for HCC beyond UCSF. Table 1 showed the patient demographic and tumor stage before/after PSM. There was no difference in hospital mortality(1.8% in LDLT, 0% in resection,p=0.810) but LDLT patients had a higher risk of perioperative complication(38.5 vs. 17%,p=0.048). Despite matching of age, tumor number and size, LDLT patients had better overall and recurrence free survivals.(Figure 1) at 1-, 3- and 5-year(OS: 96.4 vs.80.2%, 79.8 vs.46.4% and 68.7 vs.35.6%) and(RFS: 96.4 vs.37.6%, 78 vs.22.6%, 65.2 vs.19.5%).
Conclusion: LDLT offered better OS and RFS for HCC beyond UCSF criteria, and should be offered as a treatment option for advanced HCC.
[Figure and table]
OL02-15 ALPPS versus PVE in Hepatitis-related Hepatocellular Carcinoma- Comparison of Oncological Outcomes
Ka Wing Ma, China

K.W. Ma, A.C.Y. Chan, T.T. Cheung, W.H. She, W.C. Dai, C.M. Lo
The University of Hong Kong, China

Introduction: ALPPS has been popularised for future liver remnant (FLR) augmentation in liver metastasis or noncirrhotic liver tumors in recent years. Data on the oncological outcomes of ALPPS in chronic hepatitis or cirrhosis related HCC remained limited.
Methods: Consecutive patients received hepatectomy after future liver remnant (FLR) modulation by either ALPPS or PVE were recruited. Inclusion criteria were hepatitis B or C carrier, pathologically confirmed HCC and successful flow modulation. Data for clinicopathological details and oncological outcome were reviewed for ALPPS and compared with portal vein embolization (PVE).
Results: From 2002 to 2019, 126 patients with HCC underwent FLR modulation (54 ALPPS and 72 PVE) followed by hepatectomy. Hepatitis B surface antigenicity was positive in 112 patients. ALPPS induced absolute FLR volume increment by 47.1%, or FLR estimated total liver volume by 11.7% in 6 days. No difference in morbidity (19.6% vs 31.4%, P=0.2) and mortality (5.6% vs 5.8%, P =1.000) with PVE was observed. Five-year overall survival for ALPPS and PVE was 52.8% and 61.8% (P =0.663). The overall HCC recurrence rate was 50% and there was no significant difference between two groups (48.1% vs 51.4%, P=0.86). Presence of vascular invasion (P=0.038 OR 1.6 95%CI 1.03-2.74) and post-operative complication (P=0.008 OR 1.95 95%CI 1.19-3.2) were the two independent factors associated with post-hepatectomy HCC recurrence.
Conclusion: No significant difference in HCC recurrence between two FLR modulation approach was demonstrated. ALPPS conferred a comparable efficacy and oncological outcomes in comparison to PVE
OL02-16 Molecular Validation of the 8th Edition AJCC Cancer Staging System in Patients with Resected Pancreatic Cancer: Proposal of Integrative Translational Staging System
Sung Hwan Lee, Korea, Republic of

S.H. Lee1, S. Lee2, J.-S. Lee3
1Department of Surgery, CHA Univesity/Bundang CHA Medical Center, Korea, Republic of, 2Department of Medical Oncology, MD Anderson Cancer Center, United States, 3Department of Systems Biology, MD Anderson Cancer Center, United States

Introduction: Even though the 8th edition AJCC cancer staging system for pancreatic cancer has validated with major clinicopathologic factors in multiple clinical cohorts, there is still an unmet need for integrative consideration using multi-omics data to stratify the patients with pancreatic cancer elaborately.
Methods: We performed a comprehensive analysis and profiling using genomic, transcriptomic, and proteomic data from TCGA-PAAD and other translational cohorts (4 cohorts, n=340). Molecular features and major subtypes were analyzed mutually with clinical and pathologic factors, especially the 8th AJCC staging system.
Results: Aggressive molecular subtypes, basal-like and squamous subtype, were significantly associated with a higher nodal stage, but tumor size didn't show a clear association with molecular features. The activated stroma of pancreatic cancer microenvironment was significantly correlated with poor differentiation and large tumor size. The mutational pattern of KRAS and several transcriptomic pathways such as eptihelial-mesenchymal transition and DNA repair were differently presented in each clinical stage from the 8th AJCC TNM staging system. The optimal algorithm was identified to show significantly higher performance for the prediction for cancer relapse and cancer-specific survival in discovery and validation cohorts. The in silico prediction for molecular target agents and immunotherapy were performed for final clusters from optimal stratification system revealed from the integrative analysis.
Conclusions: Our comprehensive multi-omics analysis reveals clear needs for the combination of clinical staging and molecular profiling and provides crucial evidence for precision strategy in patients with resectable pancreatic cancer.
OL02-18 Consensus Molecular Subtypes Reflecting Distinct Clinical Phenotypes of Hepatocellular Carcinoma: Deciphering Resectable Hepatocellular Carcinoma
Sung Hwan Lee, Korea, Republic of

S.H. Lee1, S. Lee2, Y.S. Chun3, J.-S. Lee4
1Department of Surgery, CHA Bundang Medical Center, CHA University, Korea, Republic of, 2Department of Medical Oncology, MD Anderson Cancer Center, United States, 3Department of Surgical Oncology, MD Anderson Cancer Center, United States, 4Department of Systems Biology, MD Anderson Cancer Center, United States

Purpose: Hepatocellular carcinoma (HCC) is a heterogeneous disease with therapeutic resistance even in the early stage. Current genomic subtyping systems reflect the heterogeneity of HCC, but its clinical use is hampered by discrepancies among different studies.
Method: By integrating 15 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes using transcriptomic data from 8 HCC cohorts with 1754 patients (Discovery set; n=1006, Validation set; n=748).
Result: We demonstrated five consensus subtypes of HCC showing distinct molecular and clinical features regarding STM, CIN, IMH, BCM, and DLP subtypes. Briefly, STM (STeM) is characterized by high stem cell features, vascular invasion, and sensitivity to sorafenib. CIN (Chromosome INstable) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity predicting possible responders for immunotherapies. BCM (Beta-Catenin with Male high predominance) is characterized by prominent beta-catenin activation, low miRNA expression, and hypomethylation. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. Lastly, we developed and validated a robust predictor of integrated consensus subtype with subtype-specific serum biomarkers using integrative genomic and statistical analysis.
Conclusion: Consensus subtypes of HCC from the comprehensive genomic analysis showed distinct biological and clinical phenotypes, including different dependency for oncogenic pathways and discriminated therapeutic efficacy. Based on clinical relevance of consensus subtypes for current available therapeutic options in terms of molecular target therapies and immunotherapies, our findings may provide the foundation for rationalized biomarker-based clinical trials for resectable HCC.
OL02-19 Role of Robotic Liver Resection in Patients with HCC and Clinically Significant Portal Hypertension
Paolo Magistri, Italy

P. Magistri, G. Assirati, C. Guidetti, V. Serra, R. Ballarin, G.P. Guerrini, S. Di Sandro, F. Di Benedetto
University of Modena and Reggio Emilia, Italy

Introduction: Clinically significant portal hypertension (CSPH) increases the risks of complications after surgery, although a minimally invasive approach seems to improve outcomes. The aim of this work is to evaluate peri-operative and long-term outcomes in patients with and without CSPH who underwent robotic liver resection (RLR) for HCC.
Methods: This is a single center, retrospective study on prospectively collected data, including all consecutive patients treated for HCC with RLR from June 2014 to November 2019. Patients were divided in two groups, with and without CSPH.
Results: 76 patients were enrolled, 48 without CSPH and 28 with CSPH. No statistically significant differences were found in terms of complexity of liver resections (p=0,17), operative time (p=0,20), estimated blood loss (p=0,41), conversion to laparotomy (p=0,27) and intra-operative need of packed red blood cells (p=0,50). No differences were found analyzing length of hospital stay (p=0,42), length of intensive care unit stay (p=0,87), post-operative complications (p=0,73), and readmission rate at both 30-days (p=0,70) and 90-days (p=0,78). No cases of unresolved liver decompensation were registered.
Conclusions: Our study shows that robotic approach reduces the gap in terms of post-operative outcomes between CSPH and no-CSPH patients. RLR is safe in patients with preserved liver function or with a mild impairment (Child-Pugh A-B8) and CSPH. BCLC criteria should be implemented with a better defined role of minimally invasive liver surgery, to offer more radical treatments in this subgroup of patients.
OL02-21 Blockade of CXCR4 in Hepatocellular Carcinoma Cell Lines Inhibit Angiogenesis in Vivo Using Xenograft Mice
Ming-Chin Yu, Taiwan, Republic of China

C.-N. Tsai1, M.-C. Yu2,3, C.-W. Lee4, Chang-Gung Medical Foundation
1Institute of Clinical Medical Sciences, Chang-Gung University, Taiwan, Republic of China, 2Surgery, Chang-Gung Memorial Hospital, Taiwan, Republic of China, 3Surgery, New Taipei Municipal TuCHeng Hospital, Taiwan, Republic of China, 4Surgery, Chang-Gung, Taiwan, Republic of China

Introduction: Previously we identified SOX4 modulates the CXCL12 promoter in HCC cells, and CXCR4 in endothelial cells was regulated for tumor neovascularization in turn. This mechanism of angiogenesis via chemotaxis should be validated in animal study.
Methods: Hep 3B cells (BCRC 60434) were inoculated in Male BALB/c nude mice and the tumor size was observed twice week. at a cell density of 2×106 in xenograft mice for 8-10 weeks and monitored for tumor growth with AMD3100 treatment or DMSO as vehicle control. The growth of tumors was compared via the SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the control and treated groups.
Results: In vitro study showed the tube formation and migration could be inhibited with AMD3100. PET images, representative via18F-FDG PET/CT, was shown in tumor activity images in whole-body coronal views. The MTV and TLG of the treated group showed significantly decreased values compared to those of the control group (MTV and TLG of control vs. treated, P< 0.05). Reticulin and CD34 staining, but not SOX4 in tumor sections derived from Hep3B cells treated with AMD3100 had significant decrease in angiogenesis.
Conclusion: These data showed that the CXCL12/CXCR4 axis was crucial for SOX4-mediated angiogenesis in vivo, which was blocked via its receptor antagonist, AMD3100.
OL02-22 Preoperative Inflammatory Markers as Prognostic Predictors after Hepatocellular Carcinoma Resection: Data from a Western Tertiary Referral Center
Jaime Arthur Pirola Kruger, Brazil

J.P. Maciel, F.F. Coelho, A.J.F. Cassenote, V.B. Jeismann, G.M. Fonseca, J.A.P. Kruger, P. Herman
Liver Surgery Unit, University of Sao Paulo - Hospital das Clinicas, Brazil

Background: Recently, systemic inflammatory markers have been validated as preoperative risk factors for patients with hepatocellular carcinoma (HCC) in several eastern series. Our aim was to evaluate prognostic significance of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and prognostic nutritional index (PNI) after HCC curative resection.
From a prospective database, consecutive adult patients undergoing HCC resection were included from 2000 to 2018. Exclusion criteria were:extra-hepatic disease, R1/R2 resection, perioperative death, and other preoperative locoregional treatments.Prognostic index were calculated until 7 days before surgery. Optimal cut-offs for NLR, PLR, MLR and PNI were determined by plotting the Receiver Operator Curves (ROC) using the Youden index to determine the best cut-off. Overall survival (OS) and disease free survival (DFS) curves were calculated using the Kaplan-Meier method and compared with log-rank test.
162 patients with a mean age of 62±11 years were included. Based on the ROC curve, the optimal cut-offs for OS were NLR (1.715), PLR (115.05), MLR (1.750), and PNI (39.0). The optimal cut-offs for DFS were NLR (2.475), PLR (100.25), MLR (2.680), and PNI (48.2). High preoperative NLR (>1.715) was associated with poor OS (P=0.018, Figure 1A). PLR, MLR and PNI were not predictors for OS. High NLR (>2.475, P=0.047, Figure 1B) and PLR (>100.25, P=0.028) were significantly associated with poor DFS.
High preoperative NLR was a negative prognostic factor for OS and DFS, and high PLR was adversely associated with DFS following curative resection in HCC patients.
[Figure 1: Kaplan-Meier survival curves comparing overall survival (A) and disease free survival (B)]
OL02-23 Incidence of Cholangiocarcinoma in Patients with History of Colorectal Cancer. Multicenter Experience
Federico Mocchegiani, Italy

F. Mocchegiani1, G. Conte1, D. Nicolini2, A.M. De Rosa3, F. Giuliante3, M. Vivarelli1
1Clinica di Chirurgia Epatobiliare, Pancreatica e dei Trapianti, Dipartimento di Medicina Sperimentale e Clinica, Università Politecnica delle Marche, Italy, 2Medicina Sperimentale e Clinica, Università Politecnica delle Marche, Italy, 3Unità Operativa Complessa Epatobiliare, Università Cattolica del Sacro Cuore, Italy

Introduction: Cholangiocarcinoma (CCA) represents one the most common primary malignancy of the liver. Cirrhosis, HCV infection, Cholestatic diseases represent well known predisposing factors. Late diagnosis of CAA is associated with a poor prognosis. History of colorectal cancer (CRC) is supposed to be a risk factor.
Method: Data were retrospectively collected from two different HPB surgical centers in Italy (Ancona, Roma-Gemelli) to identify all patients with CCA and CRC between January 2000 to December 2018. All the data from patient history, surgical and oncological treatments were examinated. Histopatological examination of both CCA and CRC characteristics were analised. Genetics characteristics of both tumours were collected.
Results: A total of 26 patients developed biopsy-proven CCA after CRC. The median time between CRC and CCA diagnosis was 111,7 months. All the CRC were successfully treated with surgery and 5 patients underwent adjuvant chemotherapy. Median age at the CCA diagnosis was 66,8 years. 23 (88,4%) patients underwent R0 surgical treament. 3 patients underwent palliative treatments. After a median followup of 73,4 months, 5 years survival was 61,5%.
Conclusions: To our knowledge, this is the largest series of patients with CCA and CRC. Treatment can allow a significant 5 year survival. It is also mandatory a follow up for CAA in CRC patients.
OL02-24 Prediction of Futility in Ruptured Hepatocellular Carcinoma
Tiffany CL Wong, Hong Kong

T. Wong1, J. Dai1, J. Fung2, A. Chan1, T.-T. Cheung1, C. Lo1
1Surgery, The University of Hong Kong, Hong Kong, 2Medicine, The University of Hong Kong, Hong Kong

Introduction: Prognosis of ruptured hepatocellular carcinoma(HCC) was often poor despite aggressive treatment.This study aimed to identify factors that predict futility in ruptured HCC.
Method: A retrospective analysis of all ruptured HCC patients from 2003-2016 was performed.Significant predictors for hospital mortality was analyzed using Cox regression and predictive performance was assessed using receiver operating characteristics(ROC) curve. The scoring system was subsequently validated in a prospective observational study from 2017-2019.
Results: The training set consisted of 315 ruptured HCC patients with overall hospital mortality=137/315(43.5%).Transarterial embolization was the mainstay of treatment(145/315,46%) and 51(16.2%)received surgical treatment.
Comparison of baseline characteristics between patients with/without hospital mortality was listed in table 1. In multivariate analysis, MELD>14[HR 7.322(4.128-12.988), bilobar HCC[HR 2.555(1.383-4.719),p=0.003], known history of HCC[HR 3.129(1.771-5.529),p< 0.001] and complicated by variceal bleeding[HR 53.414(5.919-481.999),p< 0.001]were significant predictors for hospital mortality. With such scoring system, the ROC curve of training set was in Figure 1(AUC=0.834,p< 0.001).
It was validated prospectively from 2017-2019 with 70 patients.Hospital mortality was similar(27/70,38.6%). The median age was 62(32-89) year old and most had hepatitis B related HCC (52/70,74.3%).Rupture was the first clinical presentation in 20(28.6%)patients. The median MELD was 13.33(6-29) and 15(36.6%) presented with shock. The median size of HCC was 12.3(6-29) and most patients had multifocal disease.The area under curve was 0.823(0.719-0.926),p< 0.001 in validation cohort.(Figure 1) When the score was >5, patients had 100% hospital mortality.
Conclusions: The scoring system(>5) accurately predicted hospital mortality after ruptured HCC.It could be used to guide treatment intervention and resuscitation in this population.
[table and figure]