- Email: [email protected]
Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
POSTER PRESENTATIONS THU-072 Pancreatic insufficiency related to hepatocellular carcinoma treatment: early detection and treatment improves therapeutic adherence A. Diaz-Gonzalez1, A. Darnell2, J. Rimola3, E. Belmonte3, B. Loreto4, L. Neus1, A. Forner1, G. Iserte1, C. Ayuso3, F. Feu5, J. Bruix1, M. Reig1. 1 Liver Unit, Hospital clínic of Barcelona. IDIBAPS. CIBERehd; 2Radiology, Hospital Clínic of Barcelona. IDIBAPS. CIBERehd; 3Radiology, Hospital Clínic of Barcelona. IDIBAPS. CIBERehd; 4Liver Unit, IDIBAPS. CIBERehd; 5 Gastroenterology, Hospital clínic of Barcelona, Barcelona, Spain E-mail: [email protected] Background and Aims: The most frequent sorafenib-related adverse events are dermatologic reaction, diarrhea and hypophosphatemia but weight-loss appears in about 9% of patients. The physiopathological mechanism of them is unknown but hypophosphatemia, diarrhea and weight-loss may be secondary to malabsorption (MA). Aim: To describe MA incidence in hepatocellular carcinoma patients treated with sorafenib treatment. Methods: From 2014 to 2016, we prospectively evaluate MA (upper endoscopy, colonoscopy, enteral-CT, fecal elastase, xylose, celiac disease tests, stool culture and C. Difficile toxine detection, serological and urinary parameters for the diagnosis of hyperparathyroidism and Vitamin D deficiency) in all patients who developed chronic diarrhea (diminution of stool consistency lasting at least 4 weeks) or presented at least 10% of total body weight lost without concurrent radiological progression. Results: 190 patients were treated during the study, 21 of them (11%) were included in this analysis (85.7% male, Child-Pugh-A 81.5%, 47.6% BCLC-C). The most frequent etiology was HCV (52.4%), followed by alcohol (23.8%). The median treatment duration, time on sorafenib when MA studies were carried on and overall survival were 12.7, 5.9 and 30.1 months, respectively. Eleven out of 21 patients had at least one sorafenib dose modification for diarrhea or weight-loss. 10/21 patients were diagnosed of hyperparathyroidism secondary to vitamin D deficiency (HSVD) and 8/21 patients (38.1%) were diagnosed of exocrine pancreatic insufficiency using fecal elastase. Only four patients presented concomitantly pancreatic insufficiency and HPTS. In 5 patients with pancreatic insufficiency, pancreatin supplementation was administered (2 patients re-started sorafenib and are on treatment without MA recurrence; 2 recovered from MA after discontinuation of sorafenib and were included in second line trials and the last-one discontinued sorafenib because of severe pancreatic insufficiency and deceased three months after sorafenib suspension). Conclusions: Around 10% of patients receiving Sorafenib have diarrhea or weigh lost with a possible malabsorption syndrome that may be related to a variable degree of exocrine pancreatic insufficiency. Early detection and treatment will contribute to a better tolerance and treatment adherence, fact that goes along with maintaining treatment antitumor effect and improving quality of life of these patients. THU-073 Mipsagargin, a PSMA-directed prodrug, provides clinical benefit in patients with advanced sorafenib-refractory hepatocellular carcinoma D. Mahalingam1, J. Peguero2, P. Cen3, V. Allgood4, R. Shazer4, L. Campos5. 1Oncology, University of Texas Health Science Center San Antonio, San Antonio; 2Oncology, Oncology Consultants Research; 3 University of Texas Health Science Center Houston, Houston; 4Inspyr Therapeutics, Westlake Village, California; 5Oncology Consultants Research, Houston, United States E-mail: [email protected] Background and Aims: HCC is a highly-vascularized tumor and tumor angiogenesis is essential to its growth. HCC tumors are sensitive to therapies targeting the tumor vasculature. PSMA is expressed on the tumor vasculature of HCC. Mipsagargin (M) is a
derivative of the SERCA pump inhibitor thapsigargin linked to a masking peptide targeting PSMA. Cytotoxic activity is directed to PSMA-expressing cells by PSMA-mediated cleavage of the masking peptide. PSMA-activated, thapsigargin-based pro-drug M disrupts blood flow in HCC tumors and provide clinical benefit in patients with advanced, sorafenib-refractory HCC. Methods: A multicenter, single-arm Phase II study of M was conducted in patients with advanced sorafenib-refractory HCC. M was administered intravenously on Days 1, 2 and 3 of a 28-day cycle until disease progression or unacceptable toxicity. The primary objective was to evaluate TTP. Secondary objectives were tumor response rate, PFS and OS. Consenting patients underwent evaluation of HCC tumor blood flow via dynamic contrast enhanced MRI before treatment and after treatment in Cycle 2. Blood flow metrics were descriptively represented by quantitation of Ktrans and evidence of decreased arterial phase hyper-enhancement. Results: 25 patients were enrolled to the study; 19 patients completed at least two cycles of treatment and underwent posttreatment objective disease assessment, thereby comprising the efficacy evaluable (EE) population. RECIST defined objective responses were not observed in this study. However, among the 19 evaluable for response, 8 (42%) patients experienced some degree of tumor volume reduction and 12 (63%) patients had SD. Median TTP in the EE population was 4.5 months and median PFS was 4.3 months. With a range of 74–421 days, median OS was 6.8 months. Blood flow metrics were assessed in 11 lesions from 5 patients. All lesions demonstrated a reduction in Ktrans, with an average 52% reduction (range 13–90%). Conclusions: Despite the advanced stage of disease of the enrolled patient population, 63% of EE patients experienced disease stabilization. The median TTP of 4.5 months was statistically significantly greater ( p < 0.001) than the historic median TTP of 2.1 months. Blood flow in HCC lesions and in metastatic sites was reduced by approximately half within 2 cycles of M exposure. Taken together, the observation of disease stabilization, decreased tumor blood flow and prolonged TTP demonstrate that M may have clinical activity in patients with advanced, refractory HCC. THU-074 Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma A. Arbelaiz1,2,3, M. Azkargorta4,5, Á. Santos-Laso1,2,6, M.J. Perugorria1,3,5,7, O. Erice1,2,3, E. Gonzalez8, A. Lapitz2,3,6, L. Izquierdo1,3, P. Olaizola1,2,3, P.Y. Lee1,3, A. Arregi1,2,3, R. Jimenez-Aguero1,2,3, A. Lacasta1,3, C. Ibarra9, A. Sánchez-Campos9, J.P. Jimeno10, M. Krawczyk11,12, F. Lammert11, M. Marzioni13, R. Macias5,14, J.J. Marín5,14, T. Patel15, G. Gores16, I. Martinez17, F. Elortza5,18, J.M. Falcón-Pérez5,7,8, L. Bujanda2,3,5,19, J.M. Banales2,3,5,7,19. 1Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute; 2University of the Basque Country (UPV/EHU); 3Donostia University Hospital, San Sebastian; 4Proteomics Platform, CIC bioGUNE, Derio; 5National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid; 6Department of Liver and Gastrointestinal Diseases, Donostia University Hospital, San Sebastian; 7IKERBASQUE, Basque Foundation for Science, Bilbao; 8Metabolomics Unit, CIC bioGUNE, Derio; 9 Universitary Hospital of Cruces, Bilbao; 10“Complejo Hospitalario de Navarra”, Pamplona, Spain; 11Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; 12 Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Varsaw, Poland; 13Department of Gastroenterology, “Università Politecnica delle Marche”, Ancona, Italy; 14Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain; 15Department of Cancer Biology, Mayo Clinic Jacksonville, Florida; 16Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States; 17OWL Metabolomics; 18Proteomics Platform, Carlos III National Institute of
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POSTER PRESENTATIONS Health, Derio; 19Division of Gastroenterology and Hepatology, Biodonostia Health Research Institute, San Sebastian, Spain E-mail: [email protected] Background and Aims: Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions such as primary sclerosing cholangitis (PSC) are risk factors. Accurate non-invasive biomarkers for CCA or PSC are not available. In the last years, extracellular vesicles (EV) have emerged as an important tool in the search of biomarkers for different disorders as well as pathogenic players involved in disease development and progression. In this study, we investigate the potential role of serum EV as carriers of protein biomarkers for PSC and CCA, as well as oncogenic proteins that might be involved in tumor growth and dissemination. Methods: Serum EV were isolated from CCA (n = 13) or PSC (n = 9) patients and healthy individuals (n = 10) using well-established ultracentrifugation/filtration methods. In addition, EV were isolated from the culture medium of normal human cholangiocytes (NHC), SV-40 immortalized human cholangiocytes (H69) and two CCA human cell lines (i.e. EGI1 and TFK1). The characterization of EV was performed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and immunoblot. The proteome of EV was determined by mass spectrometry-based proteomics. Results: Using NTA, serum EV concentrations were found higher in CCA and PSC than in controls. Round morphology (by TEM), size (∼165 nm diameter by NTA) and markers (CD9, CD63 and CD81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed 128, 121 and 43 proteins differentially expressed in CCA vs. control, PSC vs. control, and CCA vs. PSC groups, respectively. These proteins showed high diagnostic values [maximum of 92.3% sensitivity (SEN), 90.0% specificity (SPE) and an area under the ROC curves (AUC) of 0.983 for CCA vs. control, 100% SEN, 90.0% SPE and AUC of 0.967 for PSC vs. control, and 83.3% SEN, 88.9% SPE and AUC of 0.898 for CCA vs. PSC]. The proteomic analysis of EV isolated from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by NHC. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release of EV containing some similar human oncogenic proteins into the serum. Conclusions: Novel proteomic signatures found in serum EV of CCA and PSC patients show potential usefulness as diagnostic and prognostic tools. CCA-derived EV contain increased concentration of oncogenic proteins that might participate in tumor progression. THU-075 Albumin-Bilirubin grade based novel risk prediction model for patients with hepatocellular carcinoma undergoing chemoembolization D.H. Sinn1, B.G. Song1, W. Kang1, G.-Y. Gwak1, Y.-H. Paik1, J.H. Lee1, K.C. Koh1, S.W. Paik1, M.S. Choi1. 1Samsung Medical Center, Seoul, South Korea E-mail: [email protected] Background and Aims: Recently, albumin-bilirubin (ALBI) grade was suggested as a better surrogate for liver function than Child Pugh (CP) class as a predictor of survival for patients with hepatocellular carcinoma (HCC). We developed and validated a novel risk prediction model integrating ALBI grade for patients with HCC undergoing transcatheter arterial chemoembolization (TACE). Methods: A retrospective cohort of HCC patients who received TACE as the first-line therapy between January 2007 and December 2012 at Samsung Medical Center, Seoul, Korea [age: 62.7 ± 10.6, men = 757 (79.6%), median 3.1 years of follow-up (range: 0.1–8.8 years)] were analyzed. Study population was randomly assigned into training (n = 476) and validation (n = 475) sets. From a multivariate Cox-regression model for overall survival, five objective variables (ALBI grade, BCLC stage, Response after the first TACE session, Alpha-fetoprotein, Sex; the ABRAS model) were developed and scored to generate a 8-point S208
risk prediction model. The prognostic performance was assessed in the validation set. Results: ALBI grade could stratify patient overall survival within the same CP class. The time-dependent area under receiver-operating characteristics curves (AUROCs) for overall survival at 1-, 3- and 5years were 0.776, 0.734 and 0.746 in the training set, and were 0.783, 0.708 and 0.715 in the validation set, respectively. According to the risk score, patients were stratified into three groups; low (score 0–2), intermediate (score 3–4) and high risk (score 5–8). The overall survival was significantly different without overlap between three groups (the 3-years survival rate: 71%, 36%, and 5% in the training set, and 69%, 41% and 6%, in the validation set, respectively, p < 0.001). Second TACE in high risk group was not associated with better overall survival. Conclusions: ABRAS model was useful in estimating prognosis for patients who underwent TACE, and can be useful to guide further treatment strategy after first TACE. THU-076 CEUS LI-RADS are effective in predicting the risk hepatocellular carcinoma of liver nodules E. Terzi1, L. De Bonis2, S. Leoni1, F. Benevento1, A. Granito1, F. Tovoli1, P. Pini1, L. Bolondi1, F. Piscaglia1. 1Department of Digestive Disease and Internal Medicine; 2Digestive Disease and Internal Medicine, Sant’Orsola-Malpighi Hospital, Bologna, Italy E-mail: [email protected] Background and Aims: The recently released scheme of American College of Radiology (ACR) – Liver Imaging Reporting and Data System (LI-RADS) for CEUS is an algorithm that, on the basis of CEUS patterns categorizes patients in different classes of risk of having an HCC (HepatoCellular Carcinoma), and accounts for the characteristics differentiating HCC from CC (CholangioCarcinoma), based on timing and intensity of contrast changes. The aim of the study was to validate the proposed classes of CEUS LIRADS to stratify patients with different risk of HCC focusing on LR-3 (intermediate probability for HCC), 4 (high probability HCC) and 5 (definitely HCC) and LR-M ( probable malignancy not specific for HCC), to test the rate of HCC in each class, in order to support decision making. Methods: We retrospectively evaluated the CEUS pattern of 146 patients with a total of 350 liver nodules (2005–2015) for all of whom the diagnostic reference standard had been performed with a time interval of <12 weeks from CEUS. Wash-out was defined by the lesion becoming hypo-echoic (loss of contrast uptake) compared to the surrounding parenchyma in portal-venous phase and classified “early” if starting before 60 seconds and “marked” when the lesion became echofree. A definitive diagnosis of each nodule was made according to noninvasive criteria reported by AASLD guidelines (with CT and/or MRI) in the instance of HCC or with histological confirmation when CT or MRI were not conclusive for HCC. Patients with inconclusive CT/ MRI findings and unsuitable for biopsy or with inconclusive histology pattern were excluded from the present analysis. Results: A total 350 consecutive solid nodules were investigated. CC were 2.2%. The risk of having HCC increases from LR-3 to LR-5 (Table 1). In particular, 45/75 LR-3 nodules (60%) were HCC, 90/102 (88%) LR-4 nodules were HCC and 150/152 LR-5 (99%) were either HCC (n = 149) or mixed HCC-CC (n = 1) ( p < 0.001). LR-M were 15 nodules (4.3%) of which 6 were HCC, 2 mixed HCC-CC, 7 pure CC. One case was LR-1 (hemangioma). Conclusions: CEUS LI-RADS classes are effective in predicting the risk of HCC in patients with liver nodules, with the LR-5 class definitely diagnostic for HCC at practically no risk of misdiagnosis for CC. The present algorithm may be useful for restoring CEUS for the diagnosis of HCC and for guiding the diagnostic approach of “atypical” nodules, all of which remain at relatively significant risk of HCC (>50% if LR-3 or LR-4).
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derivative of the SERCA pump inhibitor thapsigargin linked to a masking peptide targeting PSMA. Cytotoxic activity is directed to PSMA-expressing cells by PSMA-mediated cleavage of the masking peptide. PSMA-activated, thapsigargin-based pro-drug M disrupts blood flow in HCC tumors and provide clinical benefit in patients with advanced, sorafenib-refractory HCC. Methods: A multicenter, single-arm Phase II study of M was conducted in patients with advanced sorafenib-refractory HCC. M was administered intravenously on Days 1, 2 and 3 of a 28-day cycle until disease progression or unacceptable toxicity. The primary objective was to evaluate TTP. Secondary objectives were tumor response rate, PFS and OS. Consenting patients underwent evaluation of HCC tumor blood flow via dynamic contrast enhanced MRI before treatment and after treatment in Cycle 2. Blood flow metrics were descriptively represented by quantitation of Ktrans and evidence of decreased arterial phase hyper-enhancement. Results: 25 patients were enrolled to the study; 19 patients completed at least two cycles of treatment and underwent posttreatment objective disease assessment, thereby comprising the efficacy evaluable (EE) population. RECIST defined objective responses were not observed in this study. However, among the 19 evaluable for response, 8 (42%) patients experienced some degree of tumor volume reduction and 12 (63%) patients had SD. Median TTP in the EE population was 4.5 months and median PFS was 4.3 months. With a range of 74–421 days, median OS was 6.8 months. Blood flow metrics were assessed in 11 lesions from 5 patients. All lesions demonstrated a reduction in Ktrans, with an average 52% reduction (range 13–90%). Conclusions: Despite the advanced stage of disease of the enrolled patient population, 63% of EE patients experienced disease stabilization. The median TTP of 4.5 months was statistically significantly greater ( p < 0.001) than the historic median TTP of 2.1 months. Blood flow in HCC lesions and in metastatic sites was reduced by approximately half within 2 cycles of M exposure. Taken together, the observation of disease stabilization, decreased tumor blood flow and prolonged TTP demonstrate that M may have clinical activity in patients with advanced, refractory HCC. THU-074 Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma A. Arbelaiz1,2,3, M. Azkargorta4,5, Á. Santos-Laso1,2,6, M.J. Perugorria1,3,5,7, O. Erice1,2,3, E. Gonzalez8, A. Lapitz2,3,6, L. Izquierdo1,3, P. Olaizola1,2,3, P.Y. Lee1,3, A. Arregi1,2,3, R. Jimenez-Aguero1,2,3, A. Lacasta1,3, C. Ibarra9, A. Sánchez-Campos9, J.P. Jimeno10, M. Krawczyk11,12, F. Lammert11, M. Marzioni13, R. Macias5,14, J.J. Marín5,14, T. Patel15, G. Gores16, I. Martinez17, F. Elortza5,18, J.M. Falcón-Pérez5,7,8, L. Bujanda2,3,5,19, J.M. Banales2,3,5,7,19. 1Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute; 2University of the Basque Country (UPV/EHU); 3Donostia University Hospital, San Sebastian; 4Proteomics Platform, CIC bioGUNE, Derio; 5National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid; 6Department of Liver and Gastrointestinal Diseases, Donostia University Hospital, San Sebastian; 7IKERBASQUE, Basque Foundation for Science, Bilbao; 8Metabolomics Unit, CIC bioGUNE, Derio; 9 Universitary Hospital of Cruces, Bilbao; 10“Complejo Hospitalario de Navarra”, Pamplona, Spain; 11Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; 12 Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Varsaw, Poland; 13Department of Gastroenterology, “Università Politecnica delle Marche”, Ancona, Italy; 14Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain; 15Department of Cancer Biology, Mayo Clinic Jacksonville, Florida; 16Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States; 17OWL Metabolomics; 18Proteomics Platform, Carlos III National Institute of
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POSTER PRESENTATIONS Health, Derio; 19Division of Gastroenterology and Hepatology, Biodonostia Health Research Institute, San Sebastian, Spain E-mail: [email protected] Background and Aims: Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions such as primary sclerosing cholangitis (PSC) are risk factors. Accurate non-invasive biomarkers for CCA or PSC are not available. In the last years, extracellular vesicles (EV) have emerged as an important tool in the search of biomarkers for different disorders as well as pathogenic players involved in disease development and progression. In this study, we investigate the potential role of serum EV as carriers of protein biomarkers for PSC and CCA, as well as oncogenic proteins that might be involved in tumor growth and dissemination. Methods: Serum EV were isolated from CCA (n = 13) or PSC (n = 9) patients and healthy individuals (n = 10) using well-established ultracentrifugation/filtration methods. In addition, EV were isolated from the culture medium of normal human cholangiocytes (NHC), SV-40 immortalized human cholangiocytes (H69) and two CCA human cell lines (i.e. EGI1 and TFK1). The characterization of EV was performed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and immunoblot. The proteome of EV was determined by mass spectrometry-based proteomics. Results: Using NTA, serum EV concentrations were found higher in CCA and PSC than in controls. Round morphology (by TEM), size (∼165 nm diameter by NTA) and markers (CD9, CD63 and CD81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed 128, 121 and 43 proteins differentially expressed in CCA vs. control, PSC vs. control, and CCA vs. PSC groups, respectively. These proteins showed high diagnostic values [maximum of 92.3% sensitivity (SEN), 90.0% specificity (SPE) and an area under the ROC curves (AUC) of 0.983 for CCA vs. control, 100% SEN, 90.0% SPE and AUC of 0.967 for PSC vs. control, and 83.3% SEN, 88.9% SPE and AUC of 0.898 for CCA vs. PSC]. The proteomic analysis of EV isolated from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by NHC. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release of EV containing some similar human oncogenic proteins into the serum. Conclusions: Novel proteomic signatures found in serum EV of CCA and PSC patients show potential usefulness as diagnostic and prognostic tools. CCA-derived EV contain increased concentration of oncogenic proteins that might participate in tumor progression. THU-075 Albumin-Bilirubin grade based novel risk prediction model for patients with hepatocellular carcinoma undergoing chemoembolization D.H. Sinn1, B.G. Song1, W. Kang1, G.-Y. Gwak1, Y.-H. Paik1, J.H. Lee1, K.C. Koh1, S.W. Paik1, M.S. Choi1. 1Samsung Medical Center, Seoul, South Korea E-mail: [email protected] Background and Aims: Recently, albumin-bilirubin (ALBI) grade was suggested as a better surrogate for liver function than Child Pugh (CP) class as a predictor of survival for patients with hepatocellular carcinoma (HCC). We developed and validated a novel risk prediction model integrating ALBI grade for patients with HCC undergoing transcatheter arterial chemoembolization (TACE). Methods: A retrospective cohort of HCC patients who received TACE as the first-line therapy between January 2007 and December 2012 at Samsung Medical Center, Seoul, Korea [age: 62.7 ± 10.6, men = 757 (79.6%), median 3.1 years of follow-up (range: 0.1–8.8 years)] were analyzed. Study population was randomly assigned into training (n = 476) and validation (n = 475) sets. From a multivariate Cox-regression model for overall survival, five objective variables (ALBI grade, BCLC stage, Response after the first TACE session, Alpha-fetoprotein, Sex; the ABRAS model) were developed and scored to generate a 8-point S208
risk prediction model. The prognostic performance was assessed in the validation set. Results: ALBI grade could stratify patient overall survival within the same CP class. The time-dependent area under receiver-operating characteristics curves (AUROCs) for overall survival at 1-, 3- and 5years were 0.776, 0.734 and 0.746 in the training set, and were 0.783, 0.708 and 0.715 in the validation set, respectively. According to the risk score, patients were stratified into three groups; low (score 0–2), intermediate (score 3–4) and high risk (score 5–8). The overall survival was significantly different without overlap between three groups (the 3-years survival rate: 71%, 36%, and 5% in the training set, and 69%, 41% and 6%, in the validation set, respectively, p < 0.001). Second TACE in high risk group was not associated with better overall survival. Conclusions: ABRAS model was useful in estimating prognosis for patients who underwent TACE, and can be useful to guide further treatment strategy after first TACE. THU-076 CEUS LI-RADS are effective in predicting the risk hepatocellular carcinoma of liver nodules E. Terzi1, L. De Bonis2, S. Leoni1, F. Benevento1, A. Granito1, F. Tovoli1, P. Pini1, L. Bolondi1, F. Piscaglia1. 1Department of Digestive Disease and Internal Medicine; 2Digestive Disease and Internal Medicine, Sant’Orsola-Malpighi Hospital, Bologna, Italy E-mail: [email protected] Background and Aims: The recently released scheme of American College of Radiology (ACR) – Liver Imaging Reporting and Data System (LI-RADS) for CEUS is an algorithm that, on the basis of CEUS patterns categorizes patients in different classes of risk of having an HCC (HepatoCellular Carcinoma), and accounts for the characteristics differentiating HCC from CC (CholangioCarcinoma), based on timing and intensity of contrast changes. The aim of the study was to validate the proposed classes of CEUS LIRADS to stratify patients with different risk of HCC focusing on LR-3 (intermediate probability for HCC), 4 (high probability HCC) and 5 (definitely HCC) and LR-M ( probable malignancy not specific for HCC), to test the rate of HCC in each class, in order to support decision making. Methods: We retrospectively evaluated the CEUS pattern of 146 patients with a total of 350 liver nodules (2005–2015) for all of whom the diagnostic reference standard had been performed with a time interval of <12 weeks from CEUS. Wash-out was defined by the lesion becoming hypo-echoic (loss of contrast uptake) compared to the surrounding parenchyma in portal-venous phase and classified “early” if starting before 60 seconds and “marked” when the lesion became echofree. A definitive diagnosis of each nodule was made according to noninvasive criteria reported by AASLD guidelines (with CT and/or MRI) in the instance of HCC or with histological confirmation when CT or MRI were not conclusive for HCC. Patients with inconclusive CT/ MRI findings and unsuitable for biopsy or with inconclusive histology pattern were excluded from the present analysis. Results: A total 350 consecutive solid nodules were investigated. CC were 2.2%. The risk of having HCC increases from LR-3 to LR-5 (Table 1). In particular, 45/75 LR-3 nodules (60%) were HCC, 90/102 (88%) LR-4 nodules were HCC and 150/152 LR-5 (99%) were either HCC (n = 149) or mixed HCC-CC (n = 1) ( p < 0.001). LR-M were 15 nodules (4.3%) of which 6 were HCC, 2 mixed HCC-CC, 7 pure CC. One case was LR-1 (hemangioma). Conclusions: CEUS LI-RADS classes are effective in predicting the risk of HCC in patients with liver nodules, with the LR-5 class definitely diagnostic for HCC at practically no risk of misdiagnosis for CC. The present algorithm may be useful for restoring CEUS for the diagnosis of HCC and for guiding the diagnostic approach of “atypical” nodules, all of which remain at relatively significant risk of HCC (>50% if LR-3 or LR-4).
Journal of Hepatology 2017 vol. 66 | S95–S332