08:00 – 11:00 Friday, 4 September

Basic workshop: Current Frontier in Genomic and Epigenetic Research on Liver Cancer
Chairpersons: Snorri Thorgeirsson, MD, PhD (USA) and Peter Schirmacher, MD (Germany)

  1. Chromosomal Instability (CIN) analyses in HCC
    Speaker: Thomas T. Longerich, MD (Germany)
  2. Mutational Analyses of Cancer: Application of genomic/deep Sequencing
    Speaker:  Derek Y. Chiang, MD (USA)
  3. Epigenetic Analyses in HCC
    Speaker: Yae Kanai, MD (Japan)
  4. Translational Bioinformatics
    Speaker: Marc Zapatka, PhD (Germany)
  5. Mouse-Human Comparison
    Speaker: Lars L. Zender, MD (Germany)
  6. Options for Transnational Genomics/Epigenomics Networking
    Speakers: Snorri Thorgeirsson, MD, PhD (USA) and Peter Schirmacher, MD (Germany)

09:00 – 11:00 Friday, 4 September

Clinical workshop: Diagnosis and curative treatments of HCC
Chairpersons: Vincenzo Mazzaferro, MD (Italy) and Jorge Marrero, MD (USA)

Background:
The incidence of hepatocellular carcinoma (HCC) is rising.  This rise is projected to continue over the next decades mostly due to the Hepatitis C epidemic. The increasingly widespread practice of surveillance for HCC using ultrasound has led to the identification early and very early stage HCC.  In addition, since the publication of the AASLD HCC guidelines, advances in both imaging and treatment of early stage tumors have enhanced our ability to diagnoses and treat small HCC.  However, the existence and approach of these early lesions is not well known among any of the clinical, pathology or radiology communities.  In addition there is little unanimity about treatment.  This symposium will aim to increase awareness of these early lesions and provide the most up to date state of diagnosis and treatment of very early stage HCC.

Learning Objectives:

  1. Participants will be able to review the existing literature on the diagnosis of early stage HCC
  2. Participants will be able to recognize the radiological and pathological characteristics of early HCC.
  3. Participants will understand the necessity of early treatment of these lesions. And what treatments might be offered.

Program Outline:

  1. Open issues on diagnosis
    Speaker: Morris Sherman, MD (Canada)
  2. Head to head comparison of classification systems
    Speaker: Jorge Marrero, MD (USA)
  3. Update on interventional approaches
    Speaker: Riccardo Lencioni, MD (Italy)
  4. The role of surgical strategies
    Speaker: Vincenzo Mazzaferro, MD (Italy)

07:30 – 08:30 Saturday, 5 September

New trends in Interventional Oncology for Liver Tumors
Chairpersons: Riccardo Lencioni, MD (Italy) and Riad Salem, MD (USA)

Background:
The attendees will be exposed to the latest updates on state-of-the-art treatment for HCC with locoregional therapies.

Learning Objectives:

  1. to learn about results from the PRECISION V study comparing conventional with drug-eluting bead TACE for HCC
  2. to learn about the comprehensive safety, toxicity and survival analysis from a 285 patient study with Y90 microspheres for HCC
  3. to learn about the newest thermal and non-thermal ablative techniques for treating HCC

Program Outline:

  1. Conventional TACE vs Drug-Eluting Bead in HCC
    Speaker: Johannes Lammer, MD (Austria)
  2. Radioembolization with Y90 for HCC: final analysis of single center 285 patient study
    Speaker: Riad Salem, MD (USA)
  3. New thermal and non-thermal techniques for liver tumor ablation
    Speaker: Riccardo Lencioni, MD (Italy)

07:30 – 08:30 Saturday, 5 September

Guidelines for research and management of HCC     
Chairpersons: Morris Sherman, MD (Canada) and Andrew X. Zhu, MD, PhD (USA)

Background:
This workshop will discuss the complexictiy of HCC staging, the prognosis, and the standard as well as evolving strategies for the management of different stages of HCC.  

Learning Objectives:

  1. Learn to recognize the importance of aggressive management of small lesions detected by ultrasound screening
  2. Learn to recognize the earliest radiological and histological changes of HCC
  3. Learn what standard treatments are available for different stages of disease
  4. Learn the indication and management of toxicity of sorafenib in advanced disease

Program Outline:

  1. Early HCC: The consequences of HCC screening
    Speaker: Morris Sherman, MD (Canada)
  2. Management of unresectable and advanced HCC
    Speaker: Andrew X. Zhu, MD, PhD (USA)

07:30 – 08:30 Saturday, 5 September

Liver Transplantation for Rare Tumors in Adult Recipients
Chairpersons: Pierre-Alain Clavien, MD (Switzerland) and Vincenzo Mazzaferro, MD (Italy)

Background:
Whether liver transplantation should be offered to patients with tumors (primary or metastatic) others than HCC is still strongly debated. Unique and successful experiences have been proposed in the field of rare tumors such as vascular benign and malignant tumors and liver metastases from neuroendocrine tumors, balancing the actual transplant benefit with the constant evolution of other approaches and target therapies, natural history of disease and modulation of immunosuppression

Learning Objectives:

  1. Participants will be able to review the existing literature on the indication of liver transplantation for neuroendocrine metastatic liver tumors and other non-HCC primary tumors
  2. Participants will be able to identify the correct indications for liver transplantation for rare tumors within a rationale allocation of different patients categories

Program Outline:

  1. Transplantation for Metastatic Neuroendocrine Tumors
    Speaker: Vincenzo Mazzaferro, MD (Italy)
  2. Liver Transplantation for Primary Non-HCC Tumors
    Speaker: Pierre-Alain Clavien, MD (Switzerland)

07:30 – 08:30 Saturday, 5 September

Apoptotic and interleukin pathways in HCC
Chairpersons: Lewis Roberts, PhD (USA) and Jesus Prieto, MD (Spain)

Background:
Regardless of its etiology HCC usually develops on a background of chronic inflammation and hepatocellular injury. Hepatocellular death is accompanied by the activation of resident liver macrophages (Kupffer cells), and the recruitment of inflammatory cells, which produce a number of cytoprotective cytokines and growth factors. This is generally viewed as a defensive and regenerative response of the liver, aimed at the restoration of the lost hepatic parenchyma. However, accumulating evidence suggests that a sustained regenerative response also contributes to carcinogenesis by promoting the survival and proliferation of initiated cells harboring oncogenic mutations. In line with this idea, recent investigations have also demonstrated that prevention of liver injury may reduce the risk of HCC development. Interestingly, upon malignant transformation, the survival and proliferation of neoplastic hepatocytes depend to a great extent on many of the growth factors and intracellular pathways activated during inflammation and injury.
The purpose of this workshop is to discuss the latest developments on the mechanisms connecting inflammation, liver injury and HCC development. In addition we will also discuss the key cytokines and growth factors able to regulate hepatocellular survival and proliferation and the mechanisms that regulate their signaling pathways. The potential of these molecules and pathways as therapeutic targets/tools for HCC treatment and/or prevention will be addressed.

Learning Objectives:

  1. Identify the most relevant cytokines and growth factors triggered during liver injury and regeneration, and their contribution to neoplastic transformation.
  2. Gain further insight on the interaction between extracellular signals and intracellular pathways in regulation of HCC cell growth and survival.
  3. Understand the potential application of hepatoprotective strategies for the prevention of HCC development.

Program Outline:

  1. Inflammation, IGF system and HCC
    Speaker: Jesus Prieto, MD (Spain)
  2. EGFR ligands and tumor cell survival
    Speaker: Matias A. Avila, PhD (Spain)
  3. Extracellular matrix, growth factors and tumor progression
    Speaker: Lewis Roberts, PhD (USA)

07:30 – 08:30 Sunday, 6 September

Novel concepts in pre-neoplastic lesions
Chairpersons: Masamichi Kojiro, MD (Japan) and Tania Roskams, MD (Belgium)

Background:
Liver carcinogenesis is a multistep process involving clonal expansion of a single cell into the initial, microscopically small preneoplastic lesions: small cell dysplastic foci (smaller then 1mm). Some of these lesions will grow into dysplastic nodules (larger then 1mm), which are classified into low grade and high grade dysplastic nodules. The next step into early cancer is now well established and diagnostic criteria for the different preneoplastic lesions are internationally accepted and recently published.

Learning Objectives:
Describe the histopathological characteristics of the different preneoplastic lesions.
Understand new developments in the molecular pathogenetic pathways of preneoplastic/early neoplastic lesions and know their clinical significance.

Program Outline:

  1. Short introduction by chairs
  2. Histopathological and underlying molecular aspects of preneoplastic liver lesions
    Speaker: Massimo Roncalli, MD, PhD(Italy)
  3. Clinical and radiological aspects of preneoplastic liver lesions
    Speaker: Masatoshi Kudo, MD, PhD (Japan)

07:30 – 08:30 Sunday, 6 September

Etiology and pathway activation in HCC                     
Chairpersons: Curtis Harris, MD (USA) and Massimo Levrero, MD (Italy)

Background:
The major cause of HCC is hepatitis viruses. Inflammation, free radials and environmental chemicals, e.g. aflatoxin B1, are contributing factors and conditions and mechanisms that increase the risk of HCC. Epigenetic changes and somatic mutations have been identified in the molecular pathogenetics of HCC. Animal models have been developed to investigate the tumor suppressor mechanisms including senescence that are negated in liver carcinogenesis. MicroRNAs have been recently shown to be a significant epigenetic mechanism, involved in liver carcinogenesis.

Learning Objectives:

  1. Describe the etiology of HCC.
  2. Understand the interactive molecular pathways involved in liver carcinogenesis
  3. Compare animal models of HCC with the molecular pathogenesis of human HCC

Program Outline:

  1. Short introduction
    Speaker: Curtis Harris, MD (USA)
  2. Oncogenic and Tumor Suppressor Mechanisms in HCC
    Speaker: Massimo Levrero, MD (Italy)
  3. Identifying Inflammatory and Tumor Suppressor Mechanisms in an Animal Model of HCC
    Speaker: Scott Lowe, PhD (USA)

07:30 – 08:30 Sunday, 6 September

Future of chemotherapy in liver cancer
Chairpersons: Eric Raymond, MD (France) and Tim Meyer, MD (UK)

Background:
Single agent and combination chemotherapies are acknowledged to induce limited tumor responses and provide modest overall benefits in patients with primary liver tumors, including hepatocellular carcinoma. Chemotherapy inhibits DNA synthesis and replication, inducing cellular stress that may eventually be overcome by the activation of growth factors such as TGF-α/EGFR, HGF/MET, VEGF/VEGFR, IGF/IGFR, and downstream serine/threonine kinases such as Raf/MAPK and PI3k/AKT/mTOR. As the third leading cause of cancer death worldwide, hepatocellular cancer has been the focus of intense preclinical and clinical research to develop more effective therapy, and targeting theses known molecular pathways has been moderately successful. But in addition to the development of novel agents there is a need to optimize the use of chemotherapy in liver cancer by overcoming drug resistance and applying genomic technology to define patient sub-populations that will benefit from therapy. In addition, improvements in local drug delivery may be achieved using either TACE (with/without chemotherapy-loaded micro-beads) or by means of targeted drug delivery with liposomes, biopolymer-linked chemotherapy and nanoparticles. Recent advances in targeted therapy also suggest that overcoming resistance to chemotherapy may be achieved by inactivation of kinase dependent signalling pathways providing a strong rational for combining targeted therapy with classical anticancer agents. In this workshop we provide an update of current chemotherapeutic approaches using novel chemotherapy and set the basis of future clinical trials using chemotherapy-based combinations, focusing on hepatocellular carcinoma.

Learning Objectives:

  1. review the current evidence base for chemotherapy in the treatment of patients with hepatocellular carcinomas
  2. understand main mechanisms of action and resistance to cytotoxic agents
  3. update current knowledge on methods improving intratumoral drug delivery
  4. update on the rational for combining targeted therapies with cytotoxic agents
  5. how genomic technology can be applied to the selection of patients for chemotherapy
  6. identify current trials using chemotherapy in patients with hepatocellular carcinoma

Program Outline:

  1. Background introduction – what is the evidence base for chemotherapy in HCC
    Speaker: Tim Meyer, MD (UK)
  2. Update on novel approaches using cytotoxic agents in hepatocellular carcinoma: combinations with novel agents and targeted delivery
    Speaker: Ghassan Abou-Alfa, MD (USA)  
  3. Overcoming drug resistance and the application of genomics in treating HCC.
    Speaker: Olivier Rosmorduc, MD, PhD (France)
  4. Review of ongoing and planned trials – Priorities for clinical research
    Speaker: Eric Raymond, MD (France)
  5. Closing remarks
    Speaker: Eric Raymond, MD (France) and Tim Meyer, MD (UK)