PL02 Liver: Primary Tumours (ePoster) 
Selection of ePoster Presentations from Abstract Submissions
PL02-02 Aspartate Transaminase to Platelet Ratio Index (APRI) and Albumin-Bilirubin Grade (ALBI) Predict Postoperative Morbidity Following Hepatectomy for Hepatocellular Carcinoma: A Multicenter Cohort Study
Tian Yang, China

L.-Y. Sun1, L. Liang1, Y.-H. Zhou2, W.-M. Gu3, H. Wang4, T.-H. Chen5, Y. Lau Wan6, F. Shen1, T. Yang1
1Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, China, 2Department of Hepatobiliary Surgery, Pu’er People’s Hospital, China, 3First Department of General Surgery, The Fourth Hospital of Harbin, China, 4Department of General Surgery, Liuyang People’s Hospital, China, 5Department of General Surgery, Ziyang First People’s Hospital, China, 6Faculty of Medicine, Chinese University of Hong Kong, China

Background and aims: Postoperative morbidity following hepatectomy remains high, and understanding its risk factors is important to improve perioperative outcomes. We aimed to identify the role of two non-invasive markers - albumin-bilirubin (ALBI) and aspartate transaminase to platelet ratio index (APRI) - in predicting postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC).
Methods: A multicenter data of patients undergoing hepatectomy for HCC at 8 centers were retrospectively analyzed. These patients were divided into normal and high groups according to preoperative ALBI and APRI scores. ALBI and APRI's predictive accuracy of postoperative 30-day overall and major morbidity were evaluated by the area under the receiver operating characteristic curve (AUC) and compared with two conventional scores: Child-Pugh grade and model for end-stage liver disease (MELD).
Results: In 2,301 patients, 866 (37.6%) and 400 (17.4%) were in the high ALBI and APRI groups, respectively. There were significant differences of postoperative overall morbidity between the normal and high ALBI groups (26.2% vs. 40.1%, P < 0.001), as well as between the normal and high APRI groups (29.2% vs. 42.4%, P < 0.001). The AUCs of the ALBI and APRI scores for predicting overall morbidity are greater than those of Child-Pugh grade and MELD score. Multivariable analyses revealed that ALBI and APRI were independent predictors of overall morbidity in both preoperative and postoperative prediction models. Similar results existed in predicting postoperative major morbidity.
Conclusion: Preoperative ALBI and APRI could predict postoperative 30-day overall and major morbidity following hepatectomy for HCC before or after surgery.
[Figure. AUC for Major Morbidity.]
PL02-03 Systematic Review of the Role of High Intensity Focused Ultrasound (HIFU) in Treating Cancerous Lesions of the Hepatobiliary System
Arjan Sehmbi, United Kingdom

A. Sehmbi1, S. Froghi2, M. de Andrade3, N. Saffari3, B. Davidson2
1Anatomy, King's College School of Medicine, United Kingdom, 2HPB and Liver Transplantation, Royal Free Hospital, United Kingdom, 3Faculty of Engineering Sciences, University College London, United Kingdom

Introduction: High intensity focused ultrasound (HIFU) is an emerging minimally invasive, targeted treatment of malignancy. This review aims to explore the efficacy, safety and optimal technical parameters of HIFU to treat cancerous lesions of the hepatobiliary system.
Methods: A systematic search of the English literature was performed until December 2018, interrogating Pubmed, Embase and Cochrane Library databases. The following key-words were input in various combinations: 'HIFU', 'High intensity focussed ultrasound', 'Hepatobiliary', 'Liver', 'Cancer' and 'Carcinoma'. Two reviewers independently screened the abstracts and reviewed full texts of appropriate articles. Extracted content included: Application type, Exposure parameters, Patient demographics, and Treatment outcomes.
Results: Twenty-two articles reported on the clinical use of HIFU in 845 individuals to treat cancerous liver lesions. Nineteen series detailed the use of HIFU to treat hepatocellular carcinoma, whilst three covered other hepatobiliary cancers (cholangiocarcinoma, hepatoblastoma). Mean tumour size was 5.1cm. Across all studies HIFU resulted in complete tumour ablation in 51.68%. Data on technical parameters, and procedural structure was very heterogeneous. Eight studies described the use of HIFU alongside other modalities including TACE, RFA and PEI; 58.72% of which resulted in complete tumour ablation. Most common complications were skin burns(17.16%), local pain(5.56%) and fever(1.42%).
Conclusions: HIFU is a safe and well-tolerated treatment modality for cancerous lesions of the hepatobiliary system. Combining HIFU with other ablative therapies, particularly TACE, increases the efficacy without increasing complications. Future human clinical studies are required to determine the optimal treatment parameters, better define outcomes and explore the risks and benefits of combination therapies.
PL02-06 Right Hepatectomy Extended to Segment I with Prosthetic Replacement of the Inferior Vena Cava Due to Hepatocarcinoma Invasion
Natalia Pujol Cano, Spain

N. Pujol Cano1, F.X. Molina Romero1, J.M. Morón Canis1, F. Sena Ruiz2, E. Palma Zamora1, F.X. González Argenté1
1General Surgery, Hospital Universitario Son Espases, Spain, 2General Surgery, Hospital Comarcal de Inca, Spain

Introduction: Invasion of the inferior vena cava (IVCI) due to hepatocellular carcinoma (HCC) is considered an advanced stage and the proposed treatment is chemotherapy.However,recent studies support radical surgery so their results show longer survivals without major surgical complications.
Methods: Case - 62-year-old male with personal history of resection of a malignant melanoma and hepatitis B infection in the past.During the follow-up of the melanoma, a liver mass of 8cm is detected by abdominal ultrasound with normal tumor markers levels.Magnetic resonance verifies a 10cm hepatic mass in segments V, VI, VII and IVCI (Figure A). A liver biopsy reveals HCC.
Results: Right hepatectomy extended to segment I,exeresis of retrohepatic IVC and a 22mm Dacron prosthesis replacement was performed in 350minutes. (Figures B,C).
The patient was discharged after 15 days.Ascites was the only postoperative complication. Histopathology: HCC of 13cm and thrombosis of IVC with free margins (>1cm)(pT4).
The disease-free survival and the mean survival to this day were 10.7 and 21 months (Figure D).
Conclusions: There is no global consensus about the treatment of HCC with IVCI.The staging system of the Barcelona Clinic Liver Cancer (BCLC) recommends sorafenib with a survival time< 1year. In the last published series,mortality of patients with hepatic resection with concomitant IVC replacement is< 10% and most of the complications are managed by medical treatment.Some Japanese series observe a mean survival of 1.48 years, and a 1 and 3 year survival rates of 63.2% and 33.1%, respectively.
In conclusion, surgery with complex vascular resections due to IVCI by HCC can be a therapeutic option in hospitals with high volume of hepatobiliary surgeries.
PL02-08 Changes in the Peripheral Treg Cell Proportion and Immune Function in Hepatocellular Carcinoma Patients After Transarterial Chemoembolization with Gelatin Sponge Microparticles
Yuewei Zhang, China

Y. Zhang1,2
1Qinghua Changgen Hospital, Beijing, China, 2Affliated Hospital of Qinghua University, Beijing, China

Object: Observe the effect of gelatin sponge microparticles-transarterial chemoembolization (GSMs-TACE) on the immune function of patients with liver cancer by detecting the proportion of Treg cells in the peripheral blood.
Methods: 28 HCC patients treated with GSMs-TACE were enrolled. Functions of liver and kidney, blood test, alpha-fetoprotein (AFP) and upper abdominal CT plain were examined. Flow cytometry was used to determine the Treg cell proportion in peripheral blood.
Results: The efficacy of the GSMs-TACE was confirmed by imaging scan. The Treg cell proportion in the peripheral blood of patients with BCLC stage C was 11.61 ± 1.03%, higher than that of stage B patients (10.71 ± 1.52%; P< 0.05); The Treg cell proportion in the AFP positive HCC patients
(≥ 20 ng / ml) was 11.92 ± 0.80%, which was higher than that in the AFP negative patients (9 .77±0.99; P< 0.05). We also found that the larger the tumor diameter (≥ 8cm), the higher the Treg cell proportion in peripheral blood (P< 0.05). The Treg proportion of the patients without tumor encapsulation (11.77 ± 1.04) was higher than that of the patients with tumor encapsulation
(10.51 ± 1.32;P< 0.05). The Treg cell proportion at 10 days postoperatively was 8.85 ± 1.23%, which was significantly lower than that before the GSMs-TACE.
Conclusion: These results indicated that the peripheral Treg cell proportion in HCC patients was associated with tumor stage, AFP, tumor size and tumor encapsulation. GSMs-TACE could exert a positive regulatory effect on the anticancer immune function of HCC patients.
PL02-10 Staging Severity of Liver Cirrhosis Improves the Strategical Rationality of Surgical Treatment for Hepatocellular Carcinoma
Guang Yang, China

Z.-Y. Huang1, X.-P. Chen1, G. Yang2
1Tongji Hospital, Huazhong University of Science and Technology, China, 2huazhong University of Science and Technology, China

Hepatocellular carcinoma (HCC) commonly occurs in hepatitis-B or C related cirrhotic liver, and cirrhotic severity in term of pathological alternation varies greatly in different individuals even with a compensated liver function. Studies suggested that severe cirrhosis significantly decreased hepatic function reserve and increased tumor occurrence. Unfortunately, there is no staging consideration on cirrhotic severity in all HCC treatment guidelines . In the past decade, we focused on exploring surgical staging of cirrhotic severity and evaluating the long-term survivals of the patients with varied degrees of cirrhosis undergoing various surgical treatment modalities, and proposed a preliminary surgical staging algorithm for cirrhosis. It was found that the cirrhotic severity staging was helpful in selecting suitable surgical modalities ( transplant, hepatectomy or ablation) and determining the safe extent of hepatectomy ( anatomic or non-anatomic resection). For those with severe cirrhosis, liver transplant is the best choice of treatment for HCC who meets the transplant criteria, however, comparable survivals could also be achieved by hepatectomy in non- or mild-cirrhotic patients. There is a long-standing argument between anatomic and non-anatomic resection in term of effectiveness, if the severity of liver cirrhosis is staged, the argument could be easily settled. For those with serve cirrhosis, if hepatectomy has to be the choice, non-anatomic resection is a rational strategy. Anatomic resection is appropriate in the patients with non- or mild cirrhosis. Taking together, severity of cirrhosis is closely correlated with liver functional reserve and HCC occurrence, severity stages therefore determines the rationality of surgical strategy for HCC.
PL02-12 Clinical Study on Efficacy and Treg Cell Changes in Peripheral Blood of Massive Liver Cancer Treated with Gelfoam Microparticles (GSMs) TACE Combined with Surgical Resection
Yuewei Zhang, China

Y. Zhang1,2, C. Wang3,4
1Affliated Hospital of Qinghua University, China, 2Qinghua Changgen Hospital, China, 3Third Affiliated Hospital of Suzhou University, China, 4First People's Hospital of Changzhou, China

Objective: Observe the clinical efficacy and safety of using absorbable GSMs embolization agent to embolize massive liver cancer, and to observe the changes in the changes of Treg cells in peripheral blood.
Methods: During 2018-2019 GSMs-TACE combined with conventional resection of liver cancer treatment of 7 cases of massive liver cancer. GSMs particle of 150-350, mixed with 50 mg doxorubicin, 30 days later underwent conventional surgery. Flow cytometry is used to test the content of Treg cells in peripheral blood before , 10 days after GSMs-TACE and before conventional surgical.
Results: The average resection month after GSMs-TACE (14-48 days) was one month in 7 patients, and the volume of tumor necrosis after GSMs-TACE was more than 50%, among which 5 cases were more than 90%. After embolization, the tumor volume decreased by 20.2%, and the right hemihepatic resection was performed in 6 cases and the middle hepatic resection was performed in 1 case. There were no sever complications. The survival rates at 6 months and 12 months after resection were 100% (7/7) and 100% (5/5). The Treg cells in peripheral blood was 11.72 ±0.91%, 8.62 ±1.43%, and 10.34 ±1.12%, before, 10 days and 30 days after GSMs-TACE.
Conclusions: GSMs-TACE combined with surgical resection in the treatment of massive liver cancer has a good safety and clinical efficacy, GSMs-TACE has a positive regulatory effect on the body's immune function.GSMs-TACE 15 to 30 days after surgery is the best time for surgical resection.
PL02-16 Surgical Treatment of Patients with Hypoglycemia as Paraneoplastic Syndrome Associeted to Hepatocellular Carcinoma at the National Institute of Neoplastic Diseases in Lima-Peru
Ana Karla Uribe, Peru

A.K. Uribe, E. Ruiz Figueroa
National Institute of Neoplastic Diseases, Peru

Hypoglycemia associated to hepatocellular cancer is a rare entity. We analyzed the institutional data base of patients with hepatocellular carcinoma with surgical treatment and paraneoplastic hypoglycemia in the department of abdominal surgery of the National Institute of Neoplastic Diseases in Lima-Peru, from January 2001 to December 2018.
The patients' selection was related to hypoglycemia associated to hepatocellular carcinoma and surgical treatment. We collect their clinical (sex, age, glycemia value, severity of hypoglycemia, alpha-fetoprotein level, postoperative glycemia value) and surgical characteristics (tumor size, clinical stage, resection approach, adjuvant treatment, follow up and outcome),10 cases with paraneoplastic hypoglycemia associated to hepatocellular carcinoma in a period of 17 years, 60% were female, the median age was 32 years, 100% of cases present symptoms of hypoglycemia, 60% of them had severity grade 3 of hypoglycemia, 20% grade 2 and 20 % grade 1. The median value of alpha-fetoprotein was 126,382 IU / ml. Median tumor size was 18 cm, 60% in clinical stage IIIa, 10% IIIb, 10% IVa and 20% IVb. Adjuvant treatment in 50% and surgical management in 50%. The survival ranges of the first group was 6 to 27 months and the second one less than 6 months. In all the cases presented we saw normalization of glycemic values ​​at the first week after surgery.
Conclusions: Patients have a better glycemic control when performing total or partial
surgical exeresis of the tumor and the overall survive increase despite the poor prognosis that confers the association of hepatocellular cancer and paraneoplastic syndromes.
PL02-18 Primary Hepatic Neuroendocrine Tumor: A Case Report
José Manuel Ramia Ángel, Spain

R. Latorre Fragua1, A. Manuel Vazquez1, L. Diego García1, C. Ramiro Pérez1, D. Diaz Candelas1, M.D. Picardo Gomendio1, R. De La Plaza Llamas1, J.M. Ramia Ángel2,3
1General and Digestive Surgery, Hospital Universitario de Guadalajara, Spain, 2General and Digestive Surgery, Hospital General Universitario de Alicante, Spain, 3Universidad Miguel Hernández, Spain

Background: Liver is the most frequent site of neuroendocrine tumor metastasis but primary hepatic neuroendocrine tumors (PHNT) are rare, with fewer than 200 described in the literature.
The low number of recorded cases means that diagnosis, treatment and follow-up remain challenging and are not fully defined. We report a case of PHNT.
Case report: 76-year-old man who suffered acute pancreatitis during admission for trauma surgery, probably related to NSAIDs. CT is performed finding a 22x20mm focal lesion in hepatic segment III. The study was completed with MRI, confirming a nodular lesion of 2cm in segment III, slightly hyperintense in T2, hypointense in T1. Ultrasound-guided fine needle aspiration showed a well-differentiated neuroendocrine tumor.
Laboratory: Chromogranin A 331.9, without other analytical alterations. Gastroscopy, colonoscopy and thoracic CT were normal. Octreoscan showed a hepatic lesion with overexpression of somatostatin receptors without other pathological findings.
Treatment consisted on exploratory laparoscopy with intraoperative ultrasound, in which a single hepatic lesion is confirmed in segment III, and wedge resection of segment III was performed. Discharge after 48h (Clavien 0). Definitive histology showed a neuroendocrine tumor G2, 1.5cm, Ki67 3.47%. Currently under follow-up by endocrinology and surgery with no data on recurrence or primary lesions at 6 months.
Discussion: PHNT are rare but can occur, when a solitary and hypervascular tumor is detected in the liver, should be considered. Their diagnosis should be linked to the exclusion of primary lesions in other locations and sometimes this is only achieved with close monitoring of the patient postoperatively.
PL02-19 Generation of Patient-Specific Autologous Liver and Hepatocellular Carcinoma for Development of Cancer Therapies
David Al-Adra, United States

S. Sengupta1, F. Najmabadi2, K. Carlson2, J. Pavan2, J. Thomson1, D. Al-Adra3
1Morgridge Institute for Research, United States, 2University of Wisconsin, United States, 3Surgery, University of Wisconsin, United States

Introduction: The dire prognosis for patients with advanced Hepatocellular Carcinoma (HCC) is due to paucity of therapeutic options. For optimal patient care, it is critical to develop novel therapies tailored in a patient-specific fashion. This personalized approach requires preclinical models that faithfully recapitulate a patient's cancer and its microenvironment. For accurate evaluation of HCC therapies, we have developed conditions that allow us to grow HCC and non-cancerous hepatocytes in culture in a patient-specific fashion.
Hypothesis: Patient-derived proliferating normal hepatocytes and HCC cell lines will retain the genomic landscapes of the patient's liver and tumor, respectively.
Methods: Cancer and surrounding non-cancerous tissue from clinical HCC resections were collected. From these tissues, we isolated and expanded cancerous and non-cancerous cells. We developed culture methods to induce proliferation of primary human hepatocytes via generation of small hepatocyte proliferating cells (SHPCs). During cellular expansion, the SHPCs underwent gene expression profiling via RNA-sequencing at passages 0 and 3.
Results: We isolated cancerous (Fig.1A) and non-cancerous hepatocytes from HCC resection specimens and cultured these cells to grow HCC and SHPCs. After in vitro expansion, SHPCs maintained expression of hepatocyte specific genes after passaging (Fig.1B).
Conclusions: Expansion of human hepatocytes is an innovative technology to generate a proliferating hepatocyte population that maintains its gene expression profile over passages. Our goal is to humanize mouse livers with these non-cancerous hepatocytes followed by transplantation of tumor cells, from the same patient, to recreate HCC and tumor microenvironment to develop personalized therapies.
[Figure 1]
PL02-21 Diaphragmatic Hernia Developed after Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: Reports of Three Cases
Chol Kyoon Cho, Korea, Republic of

C.K. Cho, Y.H. Lee
Surgery, Chonnam National University Medical School, Korea, Republic of

Introduction: Radiofrequency ablation (RFA) has been widely accepted treatment for hepatocellular carcinoma (HCC) as primary choice for small HCC or alternative for unresectable cases. Because of the safety and effectiveness of procedure with a low mortality rate and a low major complication rate, the popularity of RFA has gradually increased. As one of rare complication of RFA, diaphragmatic hernia can occur after the procedure. There have been only ten case reports of diaphragmatic hernia developed after RFA for HCC in the literature.
Methods: We experienced and reviewed the three cases of diaphragmatic hernia following RFA for HCC.
Results: The patients presented abdominal pain and vomiting, and computed tomography and chest PA revealed diaphragmatic hernia showing colonic loops in the thoracic cavity. Duration from RFA to development of symptoms was 19 months, 23 months and 38 months, respectively. The location of HCC were hepatic dome, namely at the segment 7 in two cases and segment 4a in one case. One case were suspected diaphragmatic thermal injury at the time of RFA on post-RFA CT, however follow-up CT after 3 months shows no diaphragmatic injury or bowel herniation. For the treatment of diaphragmatic hernia, we performed emergency operation of diaphragmatic repair in two cases. However one case was tried to repair diaphragmatic defect, but the operative repair was not possible due to severe adhesion.
Conclusions: Patients who have undergone RFA for HCC adjacent to the diaphragm should be carefully followed up for possible development of diaphragmatic hernia.
PL02-22 The Role of Up-Regulation of miR-128 in the Pathogenesis of Hepatocellular Carcinoma
Chol Kyoon Cho, Korea, Republic of

C.K. Cho
Surgery, Chonnam National University Medical School, Gwangju, Korea, Republic of

Introduction: microRNAs(miRNAs) are endogenous non-coding 21-23 nucleotide RNAs that are involved in post-transcriptional regulation and they control various cellular processes, one of which is tumorigenesis. miRNAs has been suggested to be implicated in the pathogenesis of hepatocellular carcinoma(HCC).
Methods: To find yet-to-be-identified miRNAs associated with HCC tumorigenesis, we carried out miRNA microarray analysis with miRNAs extracted from normal and HCC liver tissues resected from the same patients. Of the miRNAs showing significantly different expression levels between normal and HCC liver tissues, we focused on miR-128. The difference in expression levels of miR-128 was verified by real-time PCR. In addition, the target gene of miR-128, axin1, was determined by bioinformatics study, luciferase assay and Western blotting.
Results: Four pairs of liver tissues were selected for RNA extraction. miRNA microarray and FDR calculation were performed and four genes were selected due to the previous report on their correlation with HCC. The results of luciferase assay and transfection of HepG2 cells indicated that miRNA-128 indeed binds to the 3' UTR of Axin1. In Western blotting study miR-128 indeed decreased Axin1 protein levels, demonstrating that Axin1 is indeed a target of miR-128 in HepG2 cells.
Conclusions: In this study we report that miR-128 is up-regualted in clinical HCC tissues and that miR-128 binds to 3' UTR of Axin1. The identification of miR-128 as oncomir and determination of its target gene Axin 1 will shed light on the pathogenesis of HCC.
PL02-24 The 99mTc-Mebrofenin Hepatobiliary Scintigraphy in Future Liver Remnant Function Examination in Pediatric Liver Surgery
Dmitry Akhaladze, Russian Federation

D. Akhaladze1, G. Rabaev2, Y. Likar2, D. Kachanov2, G. Tereshenko2, N. Merkulov2, N. Uskova2, N. Grachev2
1Pediatric Oncology and Surgery, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Russian Federation, 2Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Russian Federation

Introduction: 76% of children suffering from liver tumors require extensive liver resection. 25% of future liver remnant volume (FLR-V) is considered as an allowable in children. In cases of less
FLR-V the ALPPS is recommended as a procedure of choice. Existing cut-off value of future liver remnant function (FLR-F) evaluated by means of 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) for adults is 2.7%/min/m2. However there is no data considering the FLR-F in children.
The initial experience of FLR-F evaluation is described below followed by reassessment of the indications for two-staged hepatectomies in pediatric patients.
Methods: All children underwent the CT-volumetry and HBS before surgery. The hepatic resection volume was discussed on the basis of obtained values. All consecutive patients considered to major hepatectomy were retrospectively analyzed. Posthepatectomy liver failure (PHLF) was defined according to the International Study Group of Liver Surgery criteria.
Results: 32 patients (mean age 21 mo (2-199mo)) were submitted to major hepatectomy.
The median FLR-V came to 43.5% (16.5-67.8%). The median FLR-F remained 7.82%/min/m2
(1.8-25.98%/min/m2). 2 patients had insufficient FLR-V but appropriate FLR-F and PHLF did not develop. On the other hand PHLF grade B developed in 1 patient with FLR-V 43% but low FLR-F 1.8%/min/m2.
Conclusion: The FLR-F value is crucial before major hepatectomy even in cases with FLR-V less than 25%. The HBS seems to be an important tool estimating remnant liver function. No patients in presenting series required two-staged hepatectomy. The farther investigation is warranted to define new indications for two-staged hepatectomies in children.
PL02-25 Clinicopathologic Features and Outcomes of Primary Hepatic Angiosarcoma: One Single Center Experience
Xin Long, China

X. Long1, L. Zhang1, J. Zhao1, Q. Cheng1, P. Zhu1, Q. Chen2, Z. Huang1, X. Chen1
1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, 2Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

Introduction: Primary hepatic angiosarcoma is an extremely rare and aggressive malignancy.
At present, little is known about the disease. Clinicopathologic features and outcomes of hepatic angiosarcoma in our medical center were analyzed, aiming to accumulate the experience of management of hepatic angiosarcoma.
Method: The comprehensive data of nine patients with hepatic angiosarcoma confirmed by histopathological examination, from 2004 to 2019, was pooled and analyzed.
Results: The patients aged from 22 to 69 years (average 48.9 years), including three males and six females, whose performance status were 0~2. Four showed epigastralgia or abdominal distention, four were found liver mass accidently and one identified as hepatic angiosarcoma outside was admitted for regular postoperative check. Although AFP and CA19-9 were normal, combining with ultrasonagraphy, CT or MRI appearances, seven were initially diagnosed as HCC and one as liver cyst with bleeding. Seven underwent partial hepatectomy, one of which died of respiratory failure 49 days after the operation. One patient accepted needle biopsy of liver tumor because of intrahepatic and spleen metastasis. One received biopsy of bone metastasis in iliac crest. All the tumor cells expressed vimentin and CD31. Desmin, hepatocyte, and CKs including CK5/6/7/8/18/19/20 and PCK, were negative. The tumor recurred or progressed rapidly even with radical resection. Only one patient had the chance to received chemotherapy. Overall survival ranged from 49 to 1211 days (median survival 338 days).
Conclusions: Prognosis of primary hepatic angiosarcoma is very poor. Complete resection of the tumor and subsequent comprehensive treatment including chemotherapy might improve the survival.
PL02-26 Development of Nomogram Predicting 10-Year Survivors after Curative Hepatectomy for Hepatocellular Carcinoma
Kelvin K.C. Ng, Hong Kong

K.K.C. Ng, N.M.Y. Cheng, C.C.N. Chong, K.-F. Lee, J. Wong, P.B.S. Lai
Surgery, Chinese University of Hong Kong, Hong Kong

Background: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), clinical outcome and predictive factors of 10-year long-term survivors are rarely reported in the literature.
Aim of study: To analyze the clinico-pathological factors of 10-year long-term survivors following curative hepatectomy for HCC and to develop a predictive nomogram for 10-year survivors.
Methods: From 2004 to 2009, 325 patients with HCC underwent curative hepatectomy. There were 95 patients (29.2%) surviving 10 years or more (group 1), whereas 230 patients (70.8%) surviving < 10 years (group 2). Comparison of clinic-pathological data was made between two groups. Good prognostic factors identified by multivariate analysis were used to construct a nomogram predicting 10-year survivors. Internal validation using bootstrap sampling was also performed.
Results: Group 1 was younger, had more asymptomatic tumor, had more hepatitis B carriers, better functional status, better preoperative liver function, and higher albumin level, compared with group 2. Group 1 had smaller tumor, more solitary tumor, more tumor with microvascular invasion and rupture than Group 2. Independent good prognostic factors predicting 10-year survivor were young age, ASA status (≤ 2), high albumin, solitary tumor and no microvascular tumor invasion. A nomogram is constructed (Figure 1) with C-index of 0.801. Internal validation using bootstrap sampling reveals C-index of 0.792.
Conclusion: There are 29.2% patients with curative hepatectomy for HCC can survive up to or more than 10 years. Nomogram using age, ASA status, preoperative albumin, solitary tumor and microvascular tumor invasion can accurately predict 10-year survivor.
[Figure 1. Nomogram predicting 10-year survivor of HCC after curative hepatectomy]
PL02-29 Identification of ITIH4 as a Novel Biomarker for Hepatocellular Carcinoma with Nonalcoholic Fatty Liver Disease: From Pig Model to Human
Kohta Iguchi, Japan

K. Iguchi1,2, N. Nakamura2, E. Hatano2, M. Ikegawa3, H. Terajima1, S. Uemoto2
1Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Japan, 2Department of Surgery, Kyoto University, Japan, 3Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, Japan

Introduction: Noninvasive biomarkers are urgently needed for an optimal management of nonalcoholic fatty liver disease (NAFLD). Using a proteomics-based technology, we developed serum biomarkers from a pig model of hepatocellular carcinoma (HCC) associated with NAFLD and validated the clinical utility using human samples.
Methods: Microminipigs were fed a high-fat diet to induce NAFLD and a normal diet as the control. Diethylnitrosamine was intraperitoneally administered to induce HCC. Pathologists assessed biopsied liver samples every 12 weeks. Serum proteins were separated by two-dimensional gel electrophoresis, and proteins of interest were identified by MALDI-TOF MS/MS. Human serum samples were analyzed to validate the candidate protein using antibody-mediated characterization.
Results: In the NAFLD pigs, nonalcoholic steatohepatitis (NASH) was histologically confirmed at 36 weeks, and HCC developed at 60 weeks. Serum inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) was identified as the most characteristic protein in the NAFLD pigs. Elevated serum ITIH4 levels corresponding with NAFLD progression and HCC development were confirmed via immunoassay. Furthermore, immunohistochemistry showed that hepatic ITIH4 expression also increased in both cancer and non-cancer lesions as NAFLD progressed. Serum ITIH4 levels in NAFLD with HCC patients were significantly higher than those in NAFLD, NASH without HCC, and virus-related HCC patients. We also determined that NAFLD with HCC patients who had preoperatively higher serum ITIH4 levels exhibited poorer prognoses after hepatectomy.
Conclusions: We established a NAFLD-associated HCC pig model, and serum ITIH4 was identified as a novel biomarker reflecting NAFLD activity and the subsequent HCC development.
PL02-30 Role of Central Hypo-Enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma
Hiroki Teraoku, Japan

H. Teraoku, M. Shimada, Y. Morine, S. Imura, T. Ikemoto, Y. Saito, S. Yamada
Department of Surgery, Tokushima University, Japan

Introduction: The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to elucidate the role of central hypo-enhancement in the HAP in patients with mass-forming IHCC.
Methods: Forty patients who underwent initial hepatic resection for mass-forming IHCC were enrolled. The HAP was scanned 40 seconds after contrast agent injection. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). Hypoxia-inducible factor-1 (HIF-1) expression in the surgical specimen was evaluated by immunohistochemistry. The clinicopathological findings were compared among the groups.
Results: The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than Hyper group (p=0.03). OS was also significantly worse in the Rim+Hypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p=0.04). Furthermore, inclusion in the Rim+Hypo group was a prognostic factor for OS (hazard ratio=6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (25% in Hyper group and 72% in Rim+Hypo group).
Conclusions: Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.
PL02-31 Large Size Is Not a Contraindication to Laparoscopic Resection of Hepatocellular Adenoma
Bartholomew McKay, Australia

B. McKay, R. Bryant, D. Cavallucci, N. O'Rourke
Royal Brisbane Hospital, Australia

Introduction: Hepatocellular adenoma (HCA) is a neoplastic liver lesion with an increasing incidence and a strong association with oestrogen therapy. Laparoscopic resection has proven safe for small lesions whilst its use for large adenomas (≥10cm) requires further investigation.
Methods: All patients undergoing laparoscopic liver resection for HCA at the Royal Brisbane Hospital between January 2003 - April 2018 were analysed.
Results: 33 laparoscopic resections were performed in 32 female patients with a median age of 36 years (range 26 - 75). Nine (27%) laparoscopic resections were performed for large adenomas (≥10cm) and 17 laparoscopic resections were performed for adenomas of intermediate size
(5 - 9.9cm). No conversions to open were required in the large group whilst there was one case in the intermediate group. Haemorrhage, either intra-parenchymal or free intraperitoneal, was the indication for resection in 44% of the large group. Median operative time was 266 minutes in the large group reflecting that hemi-hepatectomy was performed in 55% of cases compared with none in the intermediate group (median operative time 143 minutes). No major complications
(Clavien-Dindo IIIb or greater) were seen in the large adenoma group and only one patient required transfusion. The median length of stay for large lesions was 5 days (range 4 - 9) which was comparable to the intermediate group (4 days, range 1 - 11).
Conclusions: Laparoscopic surgery has been demonstrated to be safe for the resection of HCA in this group of patients. Importantly, large size is not a barrier to laparoscopic resection.
PL02-32 Analysis of the Results of Complex Treatment of Patients with Hepatocellular Cancer
Mikhail Trandofilov, Russian Federation

M. Trandofilov1, E. Prazdnikov1, A. Sizova2, V. Svetashov1, O. Romanenko1
1A. Evdokimov Moscow State Medical and Dentistry University, Russian Federation, 2A. Evdokimov Moscow State University of Medicine and Dentistry under the Ministry of Healthcare of the Russian Federation, Russian Federation

To analyze the results of treatment of patients with primary liver cancer for the period from 2004 to 2019.
Materials and methods: The treatment results were analyzed 174 patients with primary liver cancer using liver resection, local destruction methods, transarterial chemoembolization, targeted therapy, and a combination of these methods.
Results: When performing liver resection, the median survival was 34 month. When performing local methods of destruction of a liver tumor, life expectancy increased from 23 before 31 months. The use of local destruction methods, transarterial chemoembolization made it possible to increase the resectability of patients.
Conclusion: The use of various methods of treatment of patients with primary liver cancer can increase the overall life expectancy of patients. The use of local destruction methods for tumor reccurences in previously operated patients and / or somatically burdened patients reduces the number of surgical and anesthetic complications, reduces the hospital stay of patients.
PL02-33 Primary Pseudocystic Hepatic Neuroendocrine Tumor: A Case Report and a Case for Changing Preoperative Evaluation
Tamara Floyd, United States

T. Floyd1, O. Saeed1, B. Herschman2, M. Jacobs1
1Surgery, Ascension Providence Hospital, United States, 2Pathology, Ascension Providence Hospital, United States

Introduction: Neuroendocrine tumors(NET) represent rare neoplasms with majority primary NETs being gastroenteropancreatic or bronchopulmonary origin. A hepatic NET is most likely a metastastic lesion. Cystic hepatic lesions are commonly either infectious, benign cystic lesions, or if malignant; a cystadenocarcinoma, hepatocellular carcinoma, or metastasis with cystic degeneration. Primary hepatic neuroendocrine tumors(PHNETs) and primary pseudocystic hepatic neuroendocrine neoplasms are exceedingly rare. Standard tumor markers, AFP and CEA, are almost invariably normal. Pre-operative neuroendocrine markers for solitary liver masses may prove beneficial.
Methods: We present a case of a 57-year old healthy female with a finding of a large multi-lobulated cystic right hepatic lesion, diagnosed histopathologically as a pseudocystic primary neuroendocrine tumor.
Case Presentation (Results): A 57-year old healthy female had a large hepatic cystic mass on ultrasound. An abdominal MRI showed a large, cystic, multi-lobulated, right hepatic lesion with internal septations. The mass grossly appeared to represent a biliary cystadenoma. Histopathologically, staining was positive for markers consistent with neuroendocrine origin, diagnostic of primary pseudocystic neuroendocrine tumor.
Discussion: NETs have a rare, but increasing incidence. When a hepatic neuroendocrine tumor is identified, the diagnosis usually represents metastasis. PHNET is extremely rare. PHNETs are difficult to diagnose pre-operatively. Tumor markers AFP, CEA, and Ca 19-9 are almost uniformly normal. As there has been a trend toward increasing incidence of NETs, this suggests an increasing trend in PHNET cases. Here, we present a case of pseudocystic PHNET diagnosed in a 57-year old female. Our case supports consideration for obtaining pre-operative CgA for all hepatic lesions.
PL02-34 The Using of Cryodestruction Methods in the Treatment of Primary Liver Cancer
Dmitry Ionkin, Russian Federation

D. Ionkin, A. Chzhao, Y. Stepanova
Oncology, A.V. Vishnevsky National Medical Research Center of Surgery, Russian Federation

Objective: to improve treatment outcomes, quality and life expectancy in patients with primary liver cancer.
Materials and methods: Since 2012, cryodestruction (CD) was performed in 14 patients with primary liver cancer, in 6 patients with hepatocellular cancer (HCR) and 8 patients with cholangiocellular cancer (CCR), 5 women and 8 men. The size of the lesions in the liver was 2-8 cm, the number of lesions was 1-8 (3±2). The exposure time was 3-5 min, the exposure temperature was -186С. CD in combination with RFA was performed in 5 patients, CD+liver resection-in 2 patients, a CD+RFA+liver resection - in 2 patients. All patients were subsequently given adjuvant chemotherapy.
Results: Severe life-threatening complications were observed in 2 (7.1%) operated patients: - 1 (7.1%) intra-abdominal bleeding, 1 - death due to progression of multiple organ failure during sepsis after application of CD in combination with liver resection and RFA. Survival in patients after the use of cryodestruction in combination with other methods of local destruction was 20.5±5 months, after cryodestruction - 12.56±3 months. (p < 0.05). Survival in patients after the use of cryodestruction in combination with other methods of local destruction with CCR was 9.2±4.5 months (p < 0.05), with cryodestruction - 7 + 2.5 months. (p < 0.05).
Conclusion: Cryodestruction in combination with other methods of local destruction in primary liver cancer in unresectable patients is an intervention that significantly improves the quality of life of cancer patients. When using adjuvant chemotherapy, there is also a slight improvement in survival rates.
PL02-35 Hepatic Angiomyolipoma (PECOMA): Comparison of Radiology and Morphological/ Immunogistochemical Datas
Yulia Stepanova, Russian Federation

Y. Stepanova, D. Ionkin, V. Shirokov, V. Vishnevsky, D. Kalinin
Oncology, A.V. Vishnevsky National Medical Research Center of Surgery, Russian Federation

According to modern concepts, angiomyolipoma refers to PEComas, a rapidly replenishing group of tumors from cells with light or granular eosinophilic cytoplasm expressing melanocytic markers, derivatives of a hypothetical perivascular epithelioid cell.
Objective: to compare radiology and morphological/immunohistochemical datas in patients with morphologically verified angiomyolipoma.
Materials and methods: At A.V. Vishnevsky NMRC of Surgery 9 patients with morphologically verified liver PEComas were treated (wemen were dominated (88.9%), average age 41.6±1.3 years) Preoperatively, the patients underwent ultrasound, MSCT, MRI. All patients were operated on.
Results: In the analysis of the lesions according to radiology, the following data were obtained. Structure: solid - 3; solid with minor areas of discharge - 3; solid with cysts - 1; solid with decay - 1; cystic - 1. Vascularization: hypervascular - 6; moderate vascularized - 2; weakly vascularized - 1.
The diagnoses made according to the preoperative examination (in one patient from one to two diagnoses were made): focal nodular hyperplasia; hepatocellular cancer; angiomyolipoma; mesenchymoma; cystadenoma; cystic lymphangioma; adenoma.
Morphological verification: angiomyolipoma - 4; malignant angiomyolipoma - 1; hepatocellular cancer - 4 (in all cases, after immunohistochemical examination, the diagnosis was changed to angiomyolipoma). In benign form, it was a mixed lipomatous type in 4 cases and myomatous in 4. Various image options correlate with the histological components of the tumor.
Conclusion: The presence of blood vessels and mature adipose tissue in the tumor structure according to radiology are the leading signs in the diagnosis of liver angiomyolipoma. Crucial for the diagnosis is immunohistochemical study.
PL02-36 Hepatic Cystadenocarcinoma Presenting as Ovarian New Growth: A Case Report
Stephen Matthew Santos, Philippines

S.M. Santos, D.A. de Castro, J. Betanio, W. Batucan
Surgery, Southern Philippines Medical Center, Philippines

Biliary cystadenoma and cystadenocarcinoma are rare hepatic neoplasms accounting less than 5% of all cystic liver diseases (Brittingham and Tuma 2019) with only less than 200 cases reported worldwide (Pillai et al., 2012). Cystadenocarcinoma accounts for only 0.41% of malignant hepatic epithelial tumors (M. Pitchaimuthu et al., 2015). It commonly arises from the intrahepatic ducts and rarely from extrahepatic areas as in our case. We present a case of a 65- year old female who consulted in a tertiary hospital for a 4-year history of gradual abdominal distension diagnosed as ovarian new growth but intraoperatively found as a hepatic mass measuring 34x30x20 cm involving the gallbladder. Intraoperative ultrasound revealed a multiloculated cystic mass with no intra hepatic infiltration while intraoperative cholangiogram did not show biliary communication and obstruction. The mass was completely excised from the liver and was confirmed on final biopsy as mucinous cystadenocarcinoma. The patient was discharged with no post-operative complications. Surgical resection remains to be the treatment of choice for hepatic lesions such as cystadenocarcinoma (Silva Neto et al., 2019). However, these lesions are often misdiagnosed preoperatively. Hence, in cases with intraoperative dilemma, an intraoperative ultrasound and a cholangiogram can aid in intraoperative planning and execution of safe surgery.
PL02-37 Hepatic Activation of FOXO3 Is Associated with Pentose Phosphate Pathway Activation as Well as mTORC2-Akt Signaling and Enhances Oxidative Damage-Associated Hepatocellular Carcinogenesis
Yoshiaki Sunami, Germany

M. Lu1,2, D. Hartmann1, R. Braren3, C. Mogler4, T. Wirth5, H. Friess1, J. Kleeff6, N. Hüser1, Y. Sunami6
1Department of Surgery, Klinikum rechts der Isar, Germany, 2Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, China, 3Institute for Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Germany, 4Institute of Pathology, Technical University of Munich, Germany, 5Institute of Physiological Chemistry, University of Ulm, Germany, 6Department of Visceral, Vascular and Endocrine Surgery, University Medical Center Halle, Germany

Introduction: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Mutations are commonly found in the signaling regulating the Akt pathway, leading to oncogenic cell proliferation and survival. Key transcription factors that are negatively regulated downstream of Akt signaling are members of the forkhead box O family (FOXO). FOXOs were initially considered as tumor suppressors by inducing cell cycle arrest and apoptosis. However, there is increasing evidence showing that FOXOs, especially FOXO3, can support tumorigenesis.
Method: To understand the roles of FOXO3 in liver tumorigenesis and hepatocarcinogenesis, we analyzed surgically resected HCC patient specimens and also established a doxycycline-regulated transgenic mouse model with hepatocyte-specific FOXO3 expression in a constitutively active form.
Results: We observed that FOXO3 protein is overexpressed and activated in livers of HCC patients. Hepatic activation of FOXO3 in mice induced extensive hepatic damage and elevated gene expression of several HCC-associated factors. Furthermore, FOXO3 expression enhanced hepatotoxicin-induced tumorigenesis. Mechanistically, FOXO3 activation caused oxidative stress and DNA damage and triggered positive feedback-loop for mTORC2-mediated Akt activation presumably in a cell-intrinsic manner. Interestingly, FOXO3 activated not only reactive oxygen species (ROS)-promoting pathways, but also ROS-eliminating systems, which can be associated with the activation of the pentose phosphate pathway.
Conclusions: FOXO3 is a master regulator of ROS. On one side, FOXO3 supports in protecting from ROS and may avoid cellular crisis but FOXO3 can also promote ROS signaling on the other side and support hepatocellular carcinogenesis.
PL02-38 Is Albumin-Bilirubin Grade an Effective Factor in Terms of Recurrence Following Resection in HCC Patients?
Pinar Tasar, Turkey

P. Tasar1, F.M. Hamad1, M. Sen1, D. Sigirli2, S. Kilicturgay1
1General Surgery, Bursa Uludag University, Turkey, 2Biostatistics, Bursa Uludag University, Turkey

Introduction: Recent studies have revealed the fact that albumin-bilirubin (ALBI) grade can be an independent prognostic factor in terms of liver failure, long-term survival and recurrence.
Material-Method: Patients who had undergone resection with pathologic diagnosis of HCC were examined retrospectively. Age, gender, etiologic factor, preoperative and postoperative 5th day ALBI grade, type of hepatic resection, length of hospital stay, tumor size, lymph node involvement and resection margin of tumor were examined. Recurrence and survival therefore in the long-term results were investigated. Patients who underwent non-HCC liver resection, those who died in early postoperative period, patients who went out of follow-up and patients who underwent R1-R2 resection were excluded from the study.
Results: Thirty-one patients were included in the study. The mean age was 65.52±10.87 years. The median tumor size was 5 cm (2-17). The median hospital stay was 4 (1-25) days. Kaplan-Meier mean recurrence time was 32.17 (standard error = 4.67) months. In the univariate analysis, surgical margin of < 1 mm was the only factor affecting recurrence (p = 0.001). Resection margin (p = 0.002) and lymph node involvement (p = 0.019) were found to be significant for overall survival. Preoperative ALBI grade was found to be significant in terms of recurrence (p = 0.026) (HR = 3.414 (95% confidence interval: 1.154-10.097)).
Conclusion: Preoperative ALBI grade is more significant compared to postoperative ALBI grade in postoperative recurrence. At the same time, surgical margin's being < 1 mm is the only negative prognostic factor in terms of recurrence and overall survival.
Gender (M / F)27 / 4
Tumor Size < 5 cm ≥ 5 cm14 / 17
Etiology HBV / HCV / Other15 /4 /12
Surgery Major resection / minor resection11/ 20
Preoperative ALBI grade Grade 1/Grade 2 /Grade 318/12 /1
Postoperative ALBI grade Grade 1/Grade 2 /Grade 32/ 21 / 7
Resection margin < 1 mm, ≥ 1- 5 mm, > 5- 10mm, > 10 mm8/ 15/ 5 /3
[Table 1: Characteristics of patients]
PL02-42 Increased Estimated Tumour Size to Total Liver Volume Ratio is Associated with Worse Survival in Resectable Hepatocellular Carcinoma
Miu Yee Chan, Hong Kong

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

Introduction: Tumour diameter is a known prognostic factor for hepatocellar carcinoma but does not fully reflect tumour burden. In this study we aim to explore the relationship between the estimated tumour volume to total liver volume ratio and overall survival.
Method: Patients who were diagnosed of hepatocellular carcinoma with computer tomography (CT) liver volumetry performed during the period of November 2009 to November 2019 were included. Patients underwent hepatic resection were included.
Estimated tumour volume (ETV) was defined as
2/3 x π x (largest tumour diameter/2)³
TLV was determined by CT volumetry. Statistical analysis with prospectively collected data was performed.
Results: 143 patients was included in the study. The median ETV was 220.9cm3 (0.9—4188.8cm3). The median TLV was 1379.2cm3 (541.6—136524.0) and ETV:TLV ranges 0.0007—7.7341. The hazard ratio was 1.138 for diameter of largest tumour (p< 0.001) and was 1.540 for ETV:TLV (p< 0.001). The optimal cut-off value of ETV:TLV was 0.065 by the ROC curve. Survival analysis showed that patients with ETV:TLV < 0.065 had significantly better 5-year overall survival than those with ETV:TLV >/=0.065 (84.7% vs 45.3%; p< 0.001). 5-year disease free survival was also better in patients with ETV:TLV < 0.065 (50.7% vs 20.5%; p< 0.001).
Conclusion: An increase in ETV:TLV to over 0.065 is associated with worse survival outcomes. This can be used as a prognostic tool in the management of HCC.
[Overall survival of patients with ETV:LTV <0.065 and >/=0.065]
PL02-43 Association between Portal Vein Thrombosis after Hepatectomy for Hepatocellular Carcinoma and Clinicopathological Factors
Hideyuki Takata, Japan

H. Takata1, A. Hirakata1, H. Makino1, T. Yokoyama1, N. Taniai2, M. Yoshioka3, Y. Kawano4, J. Ueda4, H. Yoshida3
1Nippon Medical School Tama Nagayama Hospital, Japan, 2Nippon Medical School Musashi Kosugi Hospital, Japan, 3Nippon Medical School, Japan, 4Nippon Medical School Chiba Hokusou Hospital, Japan

Introduction: The occurrence of portal vein thrombus (PVT) after hepatectomy is one of the important complications. Although the incidence of PVT after hepatectomy has been reported to be about 9%, the incidence limited to hepatectomy for hepatocellular carcinoma (HCC) has not been clarified. In this study, we investigated the incidence of PVT after hepatectomy for HCC and evaluated the association between PVT and clinicopathological factors.
Methods: Patients with HCC who underwent hepatectomy between 2014 and 2018 at in our institution were retrospectively reviewed. The presence of PVT was evaluated by contrast-enhanced CT routinely on postoperative day 7, and its clinicopathological correlations were evaluated. Furthermore, we evaluated whether activation of coagulation and fibrinolytic factors (PIC, total PAI1 and TAT) are related to portal vein thrombus formation.
Results: A total of 54 patients underwent hepatectomy. Postoperative PVT occurred in 10 patients (18.5%). No significant correlations were observed between PVT and any patient characteristics. However, PVT was associated with longer duration of Pringle's maneuver and major hepatectomy, though these associations were not significant (P>0.05). In the examination of coagulation and fibrinolytic factors, the rate of increase of TAT was significantly higher in patients with portal vein thrombosis (P< 0.05).
Conclusion: The present study suggests that PVT after hepatectomy for HCC may occur more frequently than hepatectomy for other diseases. In the PVT group, the rate of increase of TAT is high, and TAT may be a predictor of PVT after hepatectomy.
PL02-45 The Systemic Immune-inflammation Index Predicts Prognosis in Intrahepatic Cholangiocarcinoma: An International Multi-institutional Analysis
Diamantis Tsilimigras, United States

D. Tsilimigras1, A. Paredes1, A. Guglielmi2, L. Aldrighetti3, S. Maithel4, H. Marques5, F. Shen6, B.G. Koerkamp7, T. Pawlik8, International Intrahepatic Cholangiocarcinoma Study Group
1Ohio State University, Wexner Medical Center, United States, 2University of Verona, Italy, 3Ospedale San Raffaele, Italy, 4Emory University, United States, 5Curry Cabral Hospital, Portugal, 6Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, China, 7Erasmus University Medical Centre, Netherlands, 8Department of Surgery, The Ohio State University Wexner Medical Center, United States

Introduction: Inflammation has been associated with tumor progression and poor prognosis among patients with cancer. We sought to examine whether the systemic immune inflammation index (SII) was associated with prognosis among patients following resection of ICC.
Methods: Patients who underwent hepatectomy for ICC between 2000-2016 were identified using an international multi-institutional database. The impact of SII on overall (OS) was assessed. The performance of the final multivariable models that included clinicopathologic factors along with inflammatory markers (i.e. neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR] and SII [platelets*NLR]) was assessed using the Harrell's concordance index.
Results: Among 821 patients, median and 5-year OS were 44 months(95% CI: 36.4-51.6) and 29.9%, respectively. Median SII was 560 (IQR:379.2-901.8) and a total of 145 (17.7%) patients presented with an elevated preoperative SII(>1,050). Patients with high SII had worse OS compared with patients with low SII (median OS: 17.8 vs 47.1 months, p< 0.001, Figure 1a). Similarly, high NLR(>5) and high PLR(>190) predicted worse OS (both p< 0.05, Figure 1b,c). On multivariable analysis, an elevated SII independently predicted a worse OS (HR=1.40, 95%CI:1.01-1.96), whereas high NLR (HR=1.22, 95%CI:0.85-1.77) and high PLR (HR=1.08, 95%CI:0.78-1.49) were no longer associated with prognosis. Of note, the addition of SII to the multivariable model was associated with a c-index (0.694) that outperformed models that incorporated NLR (c-index:0.689) and PLR (c-index:0.690) alone.
Conclusion: SII independently predicted OS among patients with resectable ICC. SII may be a better predictor of outcomes compared with other markers of inflammatory response among patients with resectable ICC.
PL02-46 Development and Validation of a Novel Model to Predict Lymph Node Metastasis among Patients with Intrahepatic Cholangiocarcinoma
Diamantis Tsilimigras, United States

A. Moro1, D. Tsilimigras1, A. Guglielmi2, L. Aldrighetti3, S. Maithel4, H. Marques5, F. Shen6, B.G. Koerkamp7, T. Pawlik8, International Intrahepatic Cholangiocarcinoma Study Group
1The Ohio State University Wexner Medical Center, United States, 2University of Verona, Italy, 3Ospedale San Raffaele, Italy, 4Emory University, United States, 5Curry Cabral Hospital, Portugal, 6Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, China, 7Erasmus University Medical Centre, Netherlands, 8Department of Surgery, The Ohio State University Wexner Medical Center, United States

Introduction: The accuracy of preoperative imaging to assess the status of the nodal basin among patients with intrahepatic cholangiocarcinoma (ICC) remains relatively low. We sought to develop and validate a model to predict the likelihood of occult lymph node metastasis (LNM) among patients with resected ICC.
Methods: Patients who underwent hepatectomy for ICC between 1990-2016 were identified using a multi-institutional database. The cohort was randomly divided into a training- and validation-set. Clinicopathological data were assessed and a model to predict LNM was developed and validated. An online calculator was developed to estimate the risk of LNM.
Results: Among 843 patients who underwent resection of ICC, 198 (23.5%) individuals had at least one LNM identified on final pathology. Preoperative variables associated with LNM included sex (male: OR=2.91; 95%CI:1.65-5.15), LN status on preoperative imaging (suspicious: OR=8.93; 95%CI:4.56-17.5, metastatic: OR=8.83; 95%CI:3.77-20.7), morphologic sub-type (mass‐forming+intraductal growth vs periductal infiltrating, OR=7.45; 95%CI:3.31-16.78), preoperative CEA level (OR=1.40; 95%CI:1.09-1.80), low albumin level (OR=1.69; 95%CI 1.08-2.65), and number of nodules (OR=1.27; 95%CI:0.96-1.70). A model based on these preoperative factors had a sensitivity of 81% with a 69% specificity to predict LNM (Figure). The Harrell's concordance index (c-index) was 0.84 and 0.83 in the training and validation sets, respectively (
Conclusion: Preoperative estimation of LNM can be enhanced utilizing an online calculator that incorporated various clinical, morphologic, and tumor specific factors. Such a tool may guide surgeons in assessing patients for treatment with preoperative therapy, as well as lymphadenectomy at the time of surgical resection of ICC.
PL02-49 Characteristics of TP53 and CTNNB1 Mutation According to the Serum Tumor Markers in Hepatocellular Carcinoma
Keun Soo Ahn, Korea, Republic of

K.S. Ahn1,2, K.J. Kang2, Y.H. Kim2, T.-S. Kim2, S.J. Park3, L.R. Roberts4
1Surgery, Keimyung University Dongsan Medical Center, Korea, Republic of, 2Keimyung University Dong-San Hospital, Korea, Republic of, 3National Cancer Center, Korea, Republic of, 4Mayo Clinic, United States

Introduction: AFP, AFP-L3 DCP are useful biomarkers of hepatocellular carcinoma (HCC). However, association between molecular characteristics and serum biomarkers has not fully evaluated yet. We analyzed RNA expression and DNA mutation from TCGA-LIHC data in conjunction with clinical data.
Method: Genetic data were retrieved from data portal of TCGA. Among total sample of 371, we selected 91 samples which we could measure serum AFP, DCP and AFP-L3 using preoperatively obtained frozen stored serum. Integrative clinical and molecular analysis of those 91 patients focused on biomarker were performed, and validated with remaining TCGA-LIHC cohort of 280 patients.
Results: Patients were divided into 4 subgroups; patients with elevated AFP or AFP-L3 alone (AFP & L3), DCP alone (DCP), elevated all 3 biomarkers (All) and normal tumor marker (Normal) based on clinical and genetic characteristics. CTNNB1 mutation was related to low AFP and AFP-L3 level. It was frequently found in DCP and Normal group, but patients with CTNNB1 mutation in DCP group showed significant poor survival than those in Normal group. TP53 mutation was associated with elevated AFP and DCP and had different activating pathway according to biomarkers that dominant cell cycle arrest in AFP&L3 group, while RNA editing and DNA repair function in DCP group.
Conclusion: Serum AFP, AFP-L3 and DCP are helpful to predict mutation profile of HCC, especially TP53 and CTNNB1 mutations. These clinical oriented finding is useful to predict genetic profile of HCC and it may lead to more rational, targeted approach to treatment easily.
PL02-52 Hepatic Stem Cell-like Subtypes of Hepatocellular Carcinoma Revealed from the Integrative Multi-omics Analysis Using Developmental Hierarchies of the Liver
Sung Hwan Lee, Korea, Republic of

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

Background: Hepatocellular carcinoma (HCC) is lethal malignancy showing high relapse rates after curative resection in early-stage. Aggressive tumor biology in resectable HCC remains unclear.
Methods: Using human fetal liver signatures, multi-omics dataset from multiple clinical HCC cohorts were analyzed comprehensively to reveal molecular mechanisms for HCC stemness as well as potential biomarkers to enhance therapeutic efficacy for molecular targeted therapy or immunotherapy in stem cell-like HCC subtypes.
Results: The patients predicted to the hepatic stem cell (HS) subtype showed aggressive tumor features including large tumor size, high AFP, vascular invasion, and extrahepatic metastasis as well as worst prognosis with early recurrence even in early-stage. The oncogenic pathways in terms of cell cycle, epithelial-mesenchymal transition, and TGF-beta pathway were highly upregulated in the HS subtype. Higher mutations of TP53, RB1 with PTEN deletion were significantly identified in the HS subtype. We also identified subtype-specific tissue and serum biomarkers. Predicted responders for immunotherapy were significantly lower in stem cell-like subtypes due to higher accumulation of TAM and MDSC. The HS subtype showed potential higher response to multi-tyrosine kinase inhibitors, especially sorafenib and lenvatinib.
Conclusion: Stem cell-like HCC is not only associated with significantly higher relapse rate after curative resection but also with molecular biology for the aggressive subtype of HCC. We identified subtype-specific serum and tissue biomarkers for stem cell-like subtypes and precise therapeutic strategies for each subtype regarding immunotherapy and molecular-targeted treatment. Our findings may offer theoretical foundation of biomarker-based clinical trials for new therapeutic approaches to resectable early-stage HCC patients.
PL02-53 Robotic Liver Resection versus Percutaneous Ablation for Single HCC: Short- and Long-term Results
Paolo Magistri, Italy

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

Introduction: Single hepatocellular carcinoma may be approached with different therapeutic strategies. The aim of this study is to compare short and long-term outcomes of patients that underwent robotic liver resection (RLR) versus percutaneous ablation (PA) for single HCC up to 3 cm.
Methods: All consecutive patients presenting at our Institution, between January 2014 and October 2019, with a single HCC up to 3 cm, and treated by RLR or PA (radio frequency ablation [RFA] and microwave ablation [MWA]) were included in this retrospective study.
Results: A total of 60 patients were collected, 24 patients underwent RLR and 36 PA. No significant differences were found between the two groups regarding demographics, underlying liver disease, liver reserve and characteristics of HCC. The overall complication rate was 37.50% in RLR-group and 16.67% in PA-group (p=0.068). No early reinterventions were observed, and 30-day mortality was 0% in both groups. The incidence recurrence was 16.67% in RLR-group and 55.56% in PA-group (p=0.003), including residual disease and all-site recurrence., Disease free survival and overall survival at 3 years in RLR-group and PA-group were 75% vs 33.3 % (p=0.017) and 63.6% vs 40% (p=0.650), respectively.
Conclusions: According to our preliminary results, RLR provides a significantly higher disease-free survival, provides a more radical therapy, reduces the incidence of recurrence and shows similar peri-operative complication rates compared to PA procedures. Minimally invasive surgery, and in particular robotic approach, should be preferred over ablative treatments to treat single small HCC.
PL02-55 Biochemical Parameters and PIVKA-II in Patients with Hepatocellular Carcinoma on Waiting List for Liver Transplantation
Felipe Alconchel, Spain

F. Alconchel1,2, F. Villalba-López2,3, L. Sáez2,3, I. Sánchez-Lorencio2,3, B. Medievo2,3, T. Nicolás-López1,2, R. Robles1,2, F. Sánchez-Bueno1,2, P. Ramírez1,2
1Hepatobiliary Surgery and Liver Transplantation, Virgen de la Arrixaca University Hospital, Spain, 2Biomedical Research Institute of Murcia IMIB-Arrixaca, Spain, 3Clinical Analysis Laboratory, Virgen de la Arrixaca University Hospital, Spain

Liver transplantation (LT) is the treatment of choice in HCC but it has been seen that more than 10% of transplanted patients have recurrences within the first year after surgery. PIVKA-II, or prothrombin induced by the absence of vitamin K, is an abnormal prothrombin molecule that increases in HCC and numerous studies have shown that it could be a useful biomarker for HCC complementary to alpha-fetoprotein (AFP). Peripheral blood was obtained from 36 patients with HCC candidates for LT. PIVKA-II was determined by LUMIPULSE G1200 system. Biochemical parameters (GOT, GPT, GGT, LDH, PCR, bilirubin) were determined by enzymatic, colorimetric and immunoturbidimetric methods in Cobas C711. AFP levels were obtained by electrochemiluminescence (ECLIA) in Cobas e 601. Median levels of PIVKA-II were 87.5 (mAU/mL) (IR: 34.5-523.75). In the correlation analysis between biochemical parameters and PIVKA-II only LDH showed a statistically significant positive correlation with PIVKA-II levels (Rho= 0.367; p=0.046). Likewise, statistically significant differences in PIVKA-II levels were observed between patients with pathological and non-pathological LDH levels (U=50; p=0.044), so that patients with LDH levels ≤225 U/L had median PIVKA-II levels of 67 mAU/mL (RI: 30-154) while patients with LDH levels >225 U/L had 571 mAU/mL (RI: 138-6232). Therefore, the levels of pre-LT PIVKA-II could be a good predicting marker of the liver function after LT and it would reflect the status of liver inflammation and therefore an increase of these levels would mean a worse prognosis and would be very useful when selecting candidates for LT.
PL02-57 Single Surgeon Experience with Laparoscopic Liver Resection for Huge Hepatocellular Carcinoma: A Disease Risk Score-matched Cohort Study
Zoe Z.X Tan, Singapore

Z.Z.X. Tan1, T. Kabir1,2, N. Syn1,3, B.K.P. Goh1,4
1Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, 2Department of General Surgery, Sengkang General Hospital, Singapore, 3Yong Loo Lin School of Medicine, Singapore, 4Duke NUS Medical School, Singapore

Introduction: Liver resection is the mainstay of curative therapy for huge HCCs (≥10cm in diameter) in selected patients with preserved liver function and adequate remnant liver. We present here our early experience with laparoscopic liver resection (LLR) for huge HCCs.
Methods: We conducted a retrospective review of 210 consecutive patients who underwent LLR by a single surgeon, of which 87 were for HCC, and 8 patients had radiological diagnosis of huge HCC.
Results: Disease-risk score matching was used to compare 8 patients with huge HCC to 32 patients with non-huge HCC. After matching, both groups were well-balanced for baseline characteristics. The huge HCC patients had a higher mean Iwate difficulty score than the non-huge HCC patients (p=0.0039). Despite this, there were no significant differences in median operating time, estimated blood loss or proportion of patients requiring blood transfusion. More patients in the huge HCC group required inflow occlusion (p=0.0285), however the median Pringle duration was similar. Post-operatively, there were no significant differences in median LOS, overall complication and major morbidity rates between both groups. Median resection margins were also similar for both cohorts.
Conclusion: Our current study adds to the growing body of evidence in the literature that LLR when performed by skilled operators is feasible and safe even for giant HCCs in posterosuperior locations, in selected patients with preserved liver function.
PL02-59 Involvement of Liver Cirrhosis in Keratin 19-positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma
Takayuki Kawai, Japan

T. Kawai1,2, T. Ishii1, Y. Miyauchi1, S. Ogiso1, K. Fukumitsu1, S. Uemoto1
1Department of Surgery, Kyoto University, Japan, 2Department of Gastrointestinal Surgery, Medical Research Institute, Kitano Hospital, Japan

Introduction: Liver cirrhosis is known to be associated with the development and progression of hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC cancer stem cell (CSC) marker associated with epithelial-mesenchymal transition (EMT) through TGFb/Smad signaling. We also successfully created a 3D culture system preserving natural scaffolds of normal/fibrotic livers. Here, we investigated the relationship between liver cirrhosis and K19+ HCC-CSC.
Method: HCC cells were cultured in fibrotic and normal liver scaffolds generated from male Lewis rats, and examined the relationship between liver cirrhosis and K19+/K19- HCC cells by quantitative RT-PCR and immunohistochemistry. Additionally, K19 expression were evaluated by immunohistochemistry in 231 HCC patients who underwent liver resection or liver transplantation. The relationship between K19 expression level and liver cirrhosis was statistically analyzed.
Results: In HCC cells, K19+/K19- cells in fibrotic liver scaffolds progressed with an infiltrating pattern, in contrast to K19+/K19- cells in normal liver scaffolds progressing with a nodule-forming pattern. K19 immunohistochemistry revealed that the proportion of K19+ cells were significantly higher in fibrotic than in normal liver scaffolds (P< 0.05). Moreover, fibrotic liver scaffolds containing more K19+ cells showed significantly higher proliferation capacity and EMT-related gene expression than normal liver scaffolds (P< 0.05). In HCC patients, high and low K19 expression were detected in 9/231 and 16/231 patients, respectively. Liver cirrhosis was significantly correlated with K19 expression level (P< 0.05).
Conclusions: Liver cirrhosis might be involved in tumor growth and EMT through the maintenance of K19+ CSCs in HCC.
PL02-60 Transplant vs Resection for Intrahepatic Cholangiocarcinoma - Potential for Benefit with Transplant?
Abhishek Mathur, United States

A. Mathur, F. Tierney, P. Kurlansky, A. Griesemer, T. Kato, J. Emond
Columbia University, United States

Introduction: Complete tumor extirpation for intrahepatic cholangiocarcinoma (iCCA) was thought to be the only chance for long term survival. However, nearly 25-35% of patients have R1 resections. Moreover, majority recur and recurrences are initially isolated to the liver in 50% of patients. However, the oncologic outcome for transplant vs. resection for iCCA has not been well described.
Methods: From a database of over 2000 liver transplants, we identified 10 patients who had undergone incidental transplant for iCCA. Additionally we identified 74 patients who had undergone resection. The transplant patients were matched 1:3 for patients undergoing resection based on explant pathology.. Statistical analysis was using SAS software.
Results: Average age was 62+/-11years. Lymph node invasion was present in 57% of entire cohort and lymphovascular invasion in 68%. Moderate to poor differentiation was present in 93% of the cohort. Of the resection patients 81% had a recurrence vs. 43% of transplanted patients. In the resection group liver was the first site of recurrence in 43% of patients. No differences were noted in overall survival in transplant vs. resected patients {403(1110+/-1359)days vs 529(841+/-748)days; p=0.8}. Recurrence free survival is depicted below
[Recurrence free survival - transplant vs. resection]

Conclusions: These data show that even in an oncologically high risk cohort, with 57% lymph node invasion, patients with intrahepatic cholangiocarcinoma undergoing transplant have a lower recurrence rate and suggestion of a longer recurrence free survival than resected patients. Therefore, we conclude that transplant for intrahepatic cholangiocarcinoma may be beneficial.
PL02-61 Solid Benign Liver Lesions: Accuracy of Clinical Diagnosis Using Conventional Radiological Techniques at Time of Liver Resection
Sau Mak, United Kingdom

S. Mak, M. Kawka, T.M.H. Gall, S.Y. Qiu, L.R. Jiao
HPB Surgical Unit, Department of Surgery & Cancer, Imperial College London, United Kingdom

Introduction: Solid benign liver lesions (SBLLs) are diverse in pathophysiology, prevalence and clinical manifestations.This study aims to evaluate the diagnostic accuracy of conventional radiological imaging for Solid Benign Liver Lesions (SBLLs) compared with malignant and cystic lesions of the liver at time of liver resection.
Methods: All resections of focal liver lesions between July 2014 and July 2019 at our institution were screened and included if histopathological specimen was available. Preoperative radiological diagnoses were compared with postoperative histological diagnoses. Critical success index (CSI), sensitivity and specificity were used as measures of diagnostic accuracy. Misdiagnosis of solid benign, cystic, and malignant liver lesions was compared using logistic regression to estimate odds ratios with 95%CI. Multivariate logistic regression was used to calculate odds ratios for SBLL misdiagnosis, by pre-operative Ultrasound, CT, MRI, and Fine-needle biopsy.
Results: 466 resections in 402 patients were included for analysis, SBLL (n=37), Cystic (n=43), and Malignant (n=322). SBLLs have a significantly lower CSI at 59% (Sensitivity 76%, Specificity 98%) compared to Malignant at 87% (Sensitivity 100%, Specificity 71%), and Cystic lesions at 98% (Sensitivity 98%, Specificity 100%) (p< 0.01). Haemangioma (n=13), FNH (n=10), and Adenoma (n=9) accounted for 86% of SBLL resections. On Multivariate analysis, pre-operative US, CT, MRI and FNB were not found to significantly correlate to misdiagnoses (p=0.78, 0.26, 0.98 & 0.53 respectively).
Conclusion: Low diagnostic accuracy of SBLLs remains a challenge in the clinical management of liver lesions. Diagnostic inaccuracy of SBLLs did not appear to be correlated with choice of pre-operative investigation modality.
PL02-62 The Aberrant Long Non-Coding RNA NEAT1 Affected Nrf2/HO-1 in the Regulation of Hepatocellular Carcinoma
Qian Zhu, China

Q. Zhu, Y. Yuan
Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, China

Aim: NEAT1 (nuclear-enriched abundant transcript 1) is the lncRNA that upregulated and functions as a promoter in hepatocellular carcinoma. This study aims to investigate the role of NEAT1 interacted with nuclear factor erythroid-derived 2-related factor2 (Nrf2)/ heme oxygenase (HO-1) signaling pathway in HCC.
Methods: The lncRNA expression profiling of in HCC tissues were identified by expression microarray analysis and quantitative real-time PCR. The effects of either Nrf2 or NEAT1 knockdown on the proliferation, invasion, apoptosis and oxidative stress-related enzymes were evaluated using a Milliplex Human Oxidative Stress Magnetic Bead Panel. Xenograft tumor assay was carried out to confirm the role of Nrf2 and NEAT1 in HCC cells in vivo.
Results: Nrf2 and lncRNA NEAT1 were upregulated and positive-correlated in HCC tissues and cell lines. Moreover, we found that under hypoxia/reoxygenation conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in HCC cells was significantly lower than that before treatment(P< 0.01). The expression lncRNA NEAT1 and factors involved in Nrf2/HO-1 were significantly different after H/R treatment compared with pre-treatment which indicating the important relation of Nrf2/HO-1 signaling pathway in oxidative stress. Knockdown of Nrf2 led to the inhibition of cell proliferation and invasion and promotion of cell apoptosis, accompanying with down-regulation of Ki67, Keap-1 and HO-1 and up-regulation of the ROS levels. These observations were confirmed in xenograft mouse models wherein the knockout cells proliferate at a slower rate than the wild-type cells.
Conclusions: lncRNA NEAT1 promotes HCC tumorigenesis by affecting oxidative stress and further regulating Nrf2/HO-1 signaling pathway.
PL02-63 Right Hepatectomy in Hepatocellular Carcinoma in a Third Level Hospital México
Pablo Villegas, Mexico

P. Villegas, S. Pimentel, Y. Nacud
Digestive and Endocrine Surgery, IMSS UMAE 25, Mexico

Introduction: Primary liver cancer accounts for 4% of all cancers worldwide. Of all those 90% corresponds to CHC. The majority in developing countries. In Mexico it was shown that the incidence doubled in 25 years (1965-1990). More recently, 2000-2006, with a national increase of 14% in mortality. Surgical resection is the treatment of choice at early stage.
Case presentation: Male of 62 years, with 2 months with unintended weight loss, asthenia, occasional pain in right hypochondrium.
CT: solid liver injury compatible with CHC. Laboratories: AFP 230.49 ng/ml.
The patient is scheduled for elective surgery, right hepatectomy, complete lesion resection, without accidents or incidents. Discharged on the 9th day.
Pathological report: hepatocellular carcinoma, moderately differentiated, focality solitary size 8x8 cm, negative surgical edges.
Adequate post-surgical follow-up without requiring adjuvant management. Control CT scan without activity. Control AFP 1.58 ng/ml.
Discussion: Approaches to surgical curative management according to the BCLC; liver resection, liver transplantation and local ablation. Liver resection is the treatment of choice in individuals with healthy liver and an alternative in individuals with cirrhosis under strict criteria. In the presence of cirrhosis and under Milan criteria liver transplantation is the treatment of choice, the great disadvantage is the availability. In case of contraindication for transplantation and surgery, the alternative includes locoregional therapies.
Conclusion: Obstacles to effective care include complicated diagnostic evaluation and limited availability. However, through the already established staging and the scrutiny criteria, and access to specialized multidisciplinary care, curative surgical management can be achieved, as in this case
PL02-64 Regulation of Hepatocellular Carcinoma Progression by a Long Noncoding RNA
Qian Zhu, China

Q. Zhu, J. Zhou
Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital of Southeast University, China

Purpose: Long noncoding RNAs (lncRNAs) are emerging RNA species with critical physiological and pathological functions, while their roles in human hepatocellular carcinoma (HCC) remain poorly understood.
Experimental Design: Microarray analysis identified a new lncRNA HClnc1 associates with HCC progression. Antisense RNA-coupled mass spectrometry was then used to identify interacting proteins of HClnc1. The molecular mechanisms of HClnc1 were demonstrated by in vitro experiments using Chromatin Isolation by RNA Purification (ChIRP), RNA pull-down, RNA immunoprecipitation and luciferase analyses, and the in vivo functions of HClnc1 were confirmed by a xenotransplanted HCC tumour model.
Results: HClnc1 was dramatically increased in higher tumour-node-metastasis staged patients and inversely correlated with survival rates. HClnc1 knockdown compromised proliferation and migration in HCC cells. HClnc1 interacts with pyruvate kinase M2 (PKM2) and protects it from degradation to facilitate STAT3 transcriptional activity and aerobic glycolysis. HClnc1 knockdown blunted HCC tumour growth and metastasis in vivo.
Conclusions: HClnc1 promotes HCC tumourigenesis by stabilizing PKM2 and therefore facilitates the Warburg effect. Targeting HClnc1 and its pathway sheds lights on HCC treatment.
PL02-65 Local Ablative and Liver Directed Chemotherapy Can Be Curative for Hepatocellular Carcinoma
Chuanhao Gui, Singapore

C. Gui1, S. Baey1, R.T. D’cruz2, V.G. Shelat1
1Tan Tock Seng Hospital, Singapore, 2National University Hospital, Singapore

Introduction: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer death worldwide. Latest evidence suggests that local ablative techniques, when used in combination with liver directed chemotherapy may provide outcomes comparable to SR. Our study aims to assess the oncologic outcomes and safety profile of such combination therapies (CT) in order to determine if these therapies can potentially be introduced as a curative alternative for HCC.
Methods: A systematic review was conducted for literature published before April 2019. Outcomes measured were disease-free survival(DFS), overall survival(OS) and major complications. DFS was further divided into local tumour progression(LTP), intrahepatic distant recurrence(IDR) and distant metastasis(DM).
Results: Eight retrospective studies and one randomized controlled trial were included. There is no significant difference in 1-year, 3-year and 5-year OS and 1-year DFS between CT and SR. SR had superior 3-year DFS (OR 0.78, 95%CI 0.62-0.98, p=0.03) and 5-year DFS (OR 0.74, 95%CI 0.58-0.95, p=0.02) compared to CT. When analysing only the propensity matched data, the difference in 3-year DFS and 5-year DFS was no longer significant. CT had a higher LTP rate (OR 2.48, 95%CI 1.05-5.86, p=0.04) compared to SR but IDR and DM rates were not significant. CT had lower major complication rate (RR 0.39, 95%CI 0.24-0.62, p< 0.0001), and shorter hospital stay than SR.
Conclusion: CT offer comparable oncologic outcomes in patients with HCC as compared to SR with added benefit of lower morbidity. CT should be introduced as an alternative to SR as they can be potentially curative for HCC.
PL02-67 Bleeding with in a Huge Angiomyolypoma of Liver Presenting as an Acute Abdomen
Reiye Esayas Mengesha, Ethiopia

R.E. Mengesha, Mengesha, Reiye Esayas
Surgery, Mekelle University, Mekelle, Ethiopia

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. It is even rare to present as an acute abdomen. It is usually misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. Most tumors are small and asymptomatic but few of them can be large in which case there is a possibility of hemorrhage into the tumor. Here, we report a case of 19-year-old girl who presented with an acute abdominal pain and 8 cm mass was found on the right lobe of liver with bleeding with in the tumor. With this impression right lobectomy of the liver was done. Grossely there was a clot of blood within the tumor and microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. The final diagnosis was hepatic angiomyolipoma with hemorrhage with in the tumor.
PL02-68 Synchronous Double Primary: A Case Report on Sigmoid Adenocarcinoma with Intrahepatic Cholangiocarcinoma
Rajshree ., India

R. .
Liver Transplant and HPB Surgery, Apollo Hospital, Hyderabad, India

Objective: In this case report, we describe our experience with the patient who was diagnosed incidentally with synchronous double primary.
Method: 28 year old male presented with obstructive jaundice.Patient underwent ERCP and stenting following which he underwent PET CT which showed metabolically active lesion in segment IV /V of liver along the right sided bile duct and CHD with significant narrowing .Metabolically active lesion in proximal sigmoid.
Colonoscopy showed ulceroproliferative growth in sigmoid colon and biopsy showed F/S/O Tubulo- villous adenoma with high grade dysplasia with a focus of intramucosal carcinoma.
Patient underwent simultaneous resection: Right Trisegmentectomy with Sigmoidectomy.
Results: Final biopsy showed Hilar tumor staging: Adenocarcinoma T1b,N0
Sigmoid staging: Well differentiated Adenocarcinoma T1 ,N0
IHC Studies on Liver /CK 7 : Negative/CH19:Positive/CK20 :Negative /Focal positive CK8/18:Postive/Napsin :Negative /CDX2:Negative
IHC Sigmoid mass CH7:Patchy positive /CK20 positive /CDX2:Positive
IHC profile of hilar mass was different from colonic tumor suggestive of Double primary.
Conclusion: Incidence of multiple primary tumor are rare and incidence ranges from 2-17%.
PubMed search revealed only one case report by Jing-qiang Guo at el, showing the rarity of this case.
PL02-69 Long-term Outcomes after Laparoscopic Hepatectomy for Hepatocellular Carcinoma
Daniel Kilburn, Australia

D. Kilburn1,2, D. Cavallucci1, U. Leung1, M. Siriwardhane1, R. Bryant1, S. Yeung2, T. O'Rourke2, N. O'Rourke1
1Royal Brisbane Hospital, Australia, 2Princess Alexandra Hospital, Australia

Aim: Laparoscopic liver resection for hepatocellular carcinoma (HCC) is a common and effective approach for treating this disease. There are few published series that report outcomes with long-term follow-up. This study summarises our experience to date and presents our long-term survival outcomes.
Methods: A retrospective analysis of consecutive patients undergoing laparoscopic liver resection for HCC in 2 tertiary academic hepatobiliary units in Brisbane, Australia, between 1999 and 2015 was performed. Operative characteristics, perioperative morbidity, and pathological data were described. Patients with and without cirrhosis were analysed and compared.
Results: Fifty-two patients underwent resection of 79 HCCs. Sixty-five percent of patients had cirrhosis. Fourteen percent of patients underwent a major hepatectomy. Conversion to an open procedure occurred in 9%. There was one 90-day mortality due to liver failure (1.9%), and 7 patients (13%) experienced a complication. R0 resection was achieved in 92%. Median follow-up was 7.7 years. Overall survival at 1, 3, and 5 years was 88%, 81%, and 73%, respectively. Median survival was 9.8 years.
Conclusion: Laparoscopic liver resection for HCC, including cirrhotic patients, is technically challenging. It can be performed with acceptable morbidity and acceptable long-term survival outcomes.
PL02-70 Influence of Neoadjuvant Transarterial Chemoembolization for BCLC Stage A/B Hepatocellular Carcinoma beyond Milan Criteria
Chengxiang Guo, China

C. Guo1,2, X. Bai1,2
1Zhejiang University, School of Medicine, the First Affiliated Hospital, China, 2Zhejiang Provincial Key Laboratory of Pancreatic Disease, China

Objective: The role of transarterial chemoembolization(TACE) plus sequential curative resection for hepatocellular carcinoma (HCC) beyond Milan criteria is still debated. The aim of our study was to investigate the survival benefits of neoadjuvant TACE in patients with HCC beyond Milan criteria.
Patients and methods: A total of 262 patients with a diagnosis of HCC classified as BCLC stage A but beyond Milan criteria (solitary HCC beyond 5 cm without macrovascular invasion) and stage B between 2015 and 2018 were evaluated. The factors associated with clinical outcomes were retrospectively analyzed. The Kaplan-Meier method was used to calculate survival, and groups were compared with the log rank test.
Results: 76 of 262 patients received neoadjuvant TACE, and had comparable progression-free survival (PFS) and overall survival (OS) as those received primary resection (P >0.05). Among them, patients reached tumor downstaging induced by TACE (35.6%) or total necrosis histopathologically (22.4%) had better PFS and OS than those of no significant response to TACE (19.1 vs 7.73 months, P < 0.001; 32.0 vs 21.8, P < 0.001). Factors associated with unsuccessful downstaging included baseline pretreatment AFP ≥1,000 ng/mL (HR: 0.178, 95% CI: 0.050-0.627, P =0.007) and multiple lesions (HR: 0.175, 95% CI: 0.032-0.939, P =0.042).
Conclusion: Neoadjuvant TACE did not provide a significant benefit compared with curative therapy alone in patients carrying HCC beyond Milan criteria. However, as for those who may not indicate for curative therapy, downstaging or total necrosis of the tumor resulted from TACE was associated with favorable survival.
PL02-71 Multifocal Primary Hepatic Neuroendocrine Tumour: Recognition and Management
Izhar-Ul Haque, Australia

I.-U. Haque1, A. Das2
1HepatoPancreaticoBiliary Surgery, Bankstown Hospital, Australia, 2HepatoPancreaticoBiliary Surgery, Liverpool Hospital, Australia

Introduction: Most Neuroendocrine tumours in the liver are secondary. However, Primary NeuroEndocrine Tumour of the Liver is also possible. Its rare and is usually not considered a possible diagnosis for a multifocal Liver lesion.
Method: This is a retrospective review of a Large multifocal tumour of the Right lobe that underwent Extended Right hemihepatectomy.
Results: A 66 yo female presented with vague abdominal discomfort and bloating. CT abdomen revealed a large multifocal solid/cystic lesion in the Right lobe of the liver, concerning for Cholangiocarcinoma. She unfortunately developed PE preop for which she was put on anticoagulation. She underwent Extended Right Hemihepatectomy from which she made an uneventful recovery. Histology showed three main lesions characterized by trabeculae and cells that stain positively for Synaptophysin, Ki67 3%, and overall Grade 2, consistent with Primary Hepatic NeuroEndocrine tumour. Her Dotatate scan was negative with normal Serum Chromogranin A.
Primary Hepatic NeuroEndocrine tumour is a rare tumour with cells possibly originating from ectopic pancreatic and/or adrenal tissue in the liver or from scattered neuroendocrine cells in the intrahepatic biliary epithelium or differentiation of a stem cell. They can be multifocal or unifocal and can grow to a large size before being noticed.
Conclusions: Primary Hepatic NeuroEndocrine tumours usually are slow-growing, have solid/cystic component on CT and lack of NET elsewhere to confirm the diagnosis. Grade including Ki 67% and Mitotic rate can predict prognosis. Hepatic NET should be considered as a differential diagnosis for newly-diagnosed primary hepatic lesion. Enbloc resection is the key.
PL02-73 Mucinous Cholangiocarcinoma with Hemobilia: A Case Report
Jae-Woon Choi, Korea, Republic of

J.-W. Choi, D.H. Ryu, H. Choi
Chungbuk National University College of Medicine, Korea, Republic of

Pure mucinous cholangiocarcinoma is a very rare variant of intrahepatic
cholangiocarcinoma. An 83-year-old female was presented to our hospital with an
epigastric pain. She had no liver disease. Contrast-enhanced abdominal computed
tomography showed a dilatation of left hepatic duct containing both irregularly
nodular enhancing components and hematomas. Endoscopic retrograde
cholangiogram revealed a hemobilia of common bile duct. We initially diagnosed as
an intraductal papillary neoplasm of the bile duct with hemobilia. Both left
hemihepatectomy including middle hepatic vein and caudate resection was
performed. Pathologic examination reported mucinous adenocarcinoma with directly
invades into hepatic parenchyma and beyond the wall of bile duct. She was
discharged without complication on postoperative day 9 and had no recurrence for 6
months. Herein, we described a rare case of mucinous cholangiocarcinoma with
PL02-74 Mucinous Cystic Neoplasm of the Liver (MCN-L) Presenting as Hilar Intraluminal Mass with Episodic Biliary Obstruction
Nairuthya Shivathirthan, India

N. Shivathirthan, S.M. Waseem
Dept of Surgical Gastroenterology, Apollo BGS Hospital, India

Introduction: Mucinous cystic neoplasm of the liver (MCN-L) is an extremely rare cyst-forming epithelial benign tumor but potentially malignant. We present a rare case of Mucinous cystic neoplasm of the liver (MCN-L) presenting as Hilar Intraluminal Mass with Episodic Biliary Obstruction.
Method: A 20-year-old woman came with complains of episodic jaundice. Laboratory tests revealed T-bil: 12.1 mg/mL. Tumor marker levels were normal (CA 19-9: 5.5 U/mL; CEA ^0.5 ng/mL). Contrast abdominal CT revealed a 61 9 39 mm multilocular cystic lesion with internal septal formation in the left hepatic lobe (S4). ERCP demonstrated no excretion of mucin from the papilla of Vater. Cholangiography revealed a filling defect in the upper bile duct, and the lower tip of the defect area was oval-shaped. The patient was therefore diagnosed with non-malignant MCN-L and an extended left hepatectomy with right hepaticojejunostomy were performed. Patient tolerated the surgery well.
Results: Examination of the resected specimen confirmed that the tumor originating from S4 of the liver with polypoidal extension into the left hepatic duct and common bile duct. Microscopic findings indicated a diagnosis of Mucinous cystic neoplasm with low grade dysplasia.
Conclusion: The diagnosis of MCN-L requires a high degree of suspicion. Histopatho-logical examination establishes definitive diagnosis. Intrahepatic MCN-L can present with episodic jaundice due to its characteristic intraductal growth pattern and intraluminal mass formation. They are best treated radically as they have a definite potential to transform into malignant tumors in nearly 10%.
PL02-75 Liver Resection for Patients with Hepatocellular Carcinoma and Child B Liver Function: A Single-center Experience
Wanguang Zhang, China

W. Zhang, Y. Pei, X. Chen
Hepatic Surgical Center, Tongji Hospital of Huazhong University of Science and Technology, China

Objectives: Liver resection is the first-line treatment option for patients with hepatocellular carcinoma (HCC). Whether patient with HCC and Child B liver function can performed liver resection is still controversial.
Methods: From January 2012 to June 2018, Child B patients with HCC who underwent liver resection were enrolled in this study. Perioperative complications and risk factors for long-term survival were analyzed.
Results: During the study period, 186 Child B patients perform liver resection. Of these, 140 patients (75.3%) were presented with cirrhosis, 154 (82.8%) with ascites, 98 (52.7%) with portal hypertension, and the median tumor size was 7.2 cm. Forty-one patients performed laparoscopic liver resection, and 40 patients received additional splenectomy. Most patients (77.4%) only underwent minor resection and non-anatomical hepatectomy. The minor and major surgical complication was 31.2% and 24.7%, respectively. The 1-, 3-, and 5-year disease-free and overall survival were 49.8% and 69.5%, 33.8% and 47.5%, 24.5% and 30.4%, respectively. The laparoscopic procedure achieved similar long-term survival but better perioperative outcomes. Among those with portal hypertension, patients received additional splenectomy achieved better oncological outcomes. Multivariate analysis showed that portal hypertension (HR 1.490, 95% CI 0.979-2.269, P=0.043), tumor size >5 cm (HR 1.928, 95% CI 1.276-2.914, P=0.002), macrovascular invasion (HR 1.746, 95% CI 1.116-2.733, P=0.015).
Conclusions: Liver resection achieved long-term survival in some selective patients with HCC and Child B liver function, especially for those with small tumor size, and without portal hypertension and macrovascular invasion. A laparoscopic procedure could decrease surgical complications and splenectomy could prolong long-term survival.
PL02-76 Main Portal Vein Thrombosis Post TACE: A Case Report

Q.Z. Lee, I. Chik, F. Fahmy, A. Azman, Z. Zuhdi
Surgery, National University of Malaysia, Malaysia

Introduction: Transarterial Chemoembolization (TACE) is one of the palliative treatments offered in patients staged Barcelona Clinic Liver Cancer (BCLC) B. TACE can lead to many complications, like decompensation of liver, liver abscess, liver rupture, femoral artery pseudoaneurysm and gallbladder pathology.
Methods: We report a case a 58-year old gentleman, which developed extensive portal vein thrombosis immediately post TACE and its management.
Results: In this case report, we discuss the presenting signs and symptoms of developing extensive portal vein thrombosis post TACE, along with other complications that may arise from TACE. A review of the literature of this condition and the discussion of possible management is included.
Conclusion: Development of extensive portal vein thrombosis post TACE is a rare complication, which can lead to severe morbidity and mortality. Although rare, it has to be considered as one of the possible complications of this procedure.
PL02-79 Preoperative Serum Axl/Gas6 Allow Stratification of Oncological Outcome in Patients Undergoing Liver Resection for Hepatocellular Carcinoma
Patrick Starlinger, United States

S. Gabbassova1, D. Pereyra1, G. Ortmayr1, C. Köditz1, B. Rumpf1, J. Santol1, T. Grünberger2, W. Mikulits3, P. Starlinger1,4
1Department of Surgery, Medical University of Vienna, General Hospital Vienna, Austria, 2Department of Surgery, Kaiser Franz Josef Hospital, Austria, 3Institute for Cancer Research, Medical University of Vienna, Austria, 4HPB Surgery, Mayo Clinic, United States

Introduction: Liver resection is routinely performed in patients suffering from primary liver malignancies. Still, this group of neoplastic entities is known to have an unfavourable prognosis. Thus, preoperative risk assessment is vital for clinical decision making. Recently, Axl and its ligand Gas6 were found to be associated to unfavourable tumor characteristics in hepatocellular carcinoma (HCC). Further, a negative correlation with overall survival (OS) and disease-free survival (DFS) were observed, which suggests its potential use as a prognostic marker in HCC patients.
Method: Serum was collected in 27 patients prior to liver resection for HCC. Levels of Axl/Gas6 were measured via ELISA and evaluated as markers for OS and DFS.
Results: Indeed, Axl and Gas6 were elevated in patients with an OS of less than one year and showed a high predictive potential for death within this period as assessed via receiver operating characteristics (p=0.033,AUC=0.809, respectively). Using the Youden index, optimal cut-offs were identified at 45.00 ng/mL for Axl and at 50.00 ng/mL for Gas6. Interestingly, patients above the cut-off for Axl showed significantly reduced OS in Kaplan-Meier analysis (p=0.045), and a tendency towards earlier tumor recurrence (p=0.067). Similarly, patients with increased Gas6 levels tended to display reduced OS (p=0.072), while there was no association to DFS.
Conclusion: The present data underlines a potential benefit of incorporation of Axl/Gas6 in clinical routine. Especially combination with other biological markers could further increase validity. Accordingly, clinical decision making and treatment evaluation could be adapted in concordance with these markers.
PL02-80 Role of Transient Elastography in Determining the Surgical Strategy in Patients with Resectable Hepatocellular Carcinoma
Muthukumarassamy Rajakannu, India

M. Rajakannu, D. Cherqui, A. Sa Cunha, D. Castaing, R. Adam, E. Vibert
Centre Hépato-Biliaire, AH-HP Hôpital Paul Brousse, France

Background: Recurrence is common in patients with chronic liver disease undergoing liver resection (LR) for hepatocellular carcinoma (HCC). The aim was to evaluate if transient elastography (TE) would help in choosing the ideal treatment strategy (resection or transplantation) in these patients.
Methods: Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured preoperatively by TE using FibroScan® in patients planned for LR. Predictive factors of overall survival (OS), recurrence-free survival (RFS), early recurrence (ER) were analyzed.
Results: One hundred and five patients with HCC planned LR were prospectively included in the study. One- and 2-year OS in patients after LR were 88% and 80.9%. One- and 2-year RFS were 59.5% and 39.5%. Median follow-up after LR was 16.3 months. Poor prognostic factors for OS were AFP≥100ng/mL [hazard ratio (HR):6.03, 95% confidence interval (CI):2.13-17.09], LS≥30kPa [HR:3.46, CI:1.15-10.42], open LR [HR:5.31, CI:1.13-25.04], and severe post-operative complications [HR:3.48, CI:1.24-9.79]. Independent predictors of poor RFS were size>50mm [HR:2.22, CI:1.12-4.44], AFP≥100ng/mL [HR:2.42, CI:1.17-4.99], CAP< 240dB/m [HR:2.49, CI:1.21-5.16], Pringle maneuver≥75min [HR:5.29, CI:1.95-14.37], and intra-operative RBC transfusion [HR:4.67, CI:1.39-71]. In subgroup patients with advanced fibrosis (F3/F4) and eligible for liver transplantation (LT), LS≥30kPa [HR:5.33, CI:1.27-184.84], and CAP < 240dB/m [HR:9.46, CI:0.98-91.52] were predictors of ER.
Conclusion: LS and CAP help predict the oncological outcomes after LR and would be good pre-operative prognostic biomarkers of survival and recurrence. Patients with LS≥30kPa and CAP < 240dB/m should preferentially be listed for primary LT and LR would be a bridge to LT.
PL02-82 Multiple Disciplinary Team (MDT) Treatment Could Help Convert Unresectable HCC of Late Stage to Resectable
Xuedong Wang, China

X. Wang, G. Li, Q. Lu, J. Dong
Hepato-Pancreato-Biliary Center, Beijing Tsinghua Chang Gung Hospital, China

Introduction: We report a case of late-stage HCC who was successfully converted from unresectable to resectable with the help of MDT treatment.
Methods: A 60-year-old male patient was admitted for HCC with portal vein tumor thrombus (PVTT) (stage C of BCLC). The liver tumor (with a diameter of 15cm) was located in the right lobe with PVTT at the main trunk of portal vein and was judged to be unresectable for insufficient liver volume of the left lobe. After MDT discussion, the comprehensive treatment was performed to downstage the tumor, including Lenvatinib (12mg/d), checkpoint inhibitor (Sintilimab Injection, 200mg q3w) and radiotherapy(GTV, 3.0Gyⅹ10 times) .
Results: The liver tumor was controlled well and PVTT regressed to the right portal vein. The liver volume of left lobe increased rapidly from 415.7ml to 661.5ml, which is sufficient for right hemi-hepatectomy. The right hemi-hepatectomy was successfully performed and the patient recovered well. The pathological result showed that the majority of liver tumor was necrotic with little middle-low differentiated HCC in the central part of tumor and PVTT. A significant immunological change was found in tumor tissues. The patient continues to take half-dose of Lenvatinib and checkpoint inhibitor after discharger and has survived for 3 months after surgery with no recurrence.
Conclusion: MDT treatment could help downstage the late-stage HCC, convert unresectable HCC to resectable, as well as improve the prognosis of late-stage HCC.