12:15 – 13:30 Saturday, 15 September 2012

Luncheon Workshop 1: Liver Biopsy: Is It Still Useful?
Chairs: Pierre Bedossa, MD, PhD (France) and Masatoshi Kudo, MD, PhD (Japan)

The place of liver biopsy in management of patients with hepatocellular carcinoma has been considerably reduced overtime. Meanwhile, liver biopsy may still provide valuable information in specific context.

This workshop will focus on the role of liver biopsy in patients with hepatocellular carcinoma along all stages from diagnosis to treatment. The role of biopsy with its advantages and limits as a diagnostic procedure will be presented based on clinical cases presentations. Prognostic factors that may stem from pathological analysis will be also discussed. The role of biopsy in identifying specific tissue biomarkers that may be useful for guiding therapeutic decision will be presented. Discussion will also focus on the need for tissue procurement in the context of clinical trials. Practical problems concerning biobanks will be also considered.

12:15 – 13:30 Saturday, 15 September 2012

Luncheon Workshop 2: Resection vs. Transplant for Non-HCC Malignancies
Chairs: Jacques Belghiti, MD (France) and Vincenzo Mazzaferro, MD (Italy)

The improving results of LT for HCC have led several authors to expand this procedure to other primary and secondary malignant liver tumours. However, both graft shortage and high risk of recurrence with immunosuppression justify a reappraisal of LT in these patients with specific liver malignancies. As a matter of fact, a better knowledge of the natural history and data from large LT series suggest that in many of the cases partial resection should be considered. In these patients indeed, it appears that LT could have a disastrous outcome and that LR is the most efficient treatment providing similar long-term survival. Tumours that may have a disastrous prognosis after LT include cholangiocarcinoma, non-endocrine liver metastasis and even some endocrine liver metastasis. Accordingly, there is a tendency to exclude LT for endocrine metastasis in patients with high grade of proliferative index and to restrict LT for hilar cholangiocarcinoma in patients with primary sclerosing cholangitis. Malignant lesions which should be in priority considered for partial liver resection include fibrolamellar,a variant of HCC and Hemangioendetholioma, a rare vascular tumour. Fibrolamellar, which occurs in young adults with normal underlying parenchyma is associated in almost one third of the cases with positive lymph nodes and has a high risk of peritoneal and pulmonary metastasis. Hemangioendetholioma often displays a low grade of malignancy and although, often multifocal and sometimes associated with pulmonary metastasis, the majority of patients experience long-term survival including spontaneous regression. Altogether, a more conservative approach, including debulking resection should be favored in these situations. The risk of malignant transformation of liver cell adenoma has led many authors to consider LT for patients with multiple and unresectable adenoma. However, the risk of malignant trasnformation is quite exclusively observed in women with large (≥ 5cm) liver cell adenoma of specific genotype. Since partial resection of malignant adenoma represents an efficient treatment with a low risk of recurrence due to the absence of both vascular and lymph nodes invasion, LT in patients with multiple adenoma is not justified.

12:15 – 13:30 Saturday, 15 September 2012

Luncheon Workshop 3: Linking Signaling Pathways and Novel Therapies in HCC
Chairs: Jean-François Dufour, MD (Switzerland) and Augusto Villanueva, MD (Spain)

The introduction of sorafenib in HCC management has profoundly changed the landscape of translational research in the field. It is accepted that beyond its pure scientific interest, a better understanding of the molecular pathogenesis of HCC can improve its clinical management. As a result, different studies have tried to develop a molecular classification of HCC based on whole-genome gene expression analysis. Preliminary data indicate the presence of at least two homogeneous groups of patients in terms of gene expression, characterised by either activation of WNT-ßcatenin or pathways related to cell cycle and proliferation. Also, a genomic signature enriched in IL-6, EGF and NF-Kappaß signaling generated from non-tumoral adjacent cirrhotic tissue was able to identify genomic signals related to aggressive biological behavior (‘field effect’). In addition, activation of other pathways has been reported in human HCC (e.g. RAS/MAPK, IGF/mTOR, MET, TGF-ß, Notch, etc…).

Interestingly, aberrant cascade activation correlates with the molecular classification. Presumably, the integration of all this molecular information with sequencing data will provide a comprehensive landscape of the molecular alterations that govern HCC development and progression. Ultimately, the discovery of oncogenic addiction loops will enable the deployment of personalised medicine approaches for the clinical management of HCC.

12:15 – 13:30 Saturday, 15 September 2012

Luncheon Workshop 4: Management of Cholangiocarcinoma
Chairs: Myron Schwartz, MD (USA) and Gregory Gores, MD (USA)

Cholangiocarcinoma (CCA) represents a diverse group of epithelial tumours arising along the biliary tract. Dependent upon their site of origin these cancers display different biological behavior and require site-specific treatment options. The classification of CCA into intrahepatic, perihilar, and distal subgroups serves to standardise the registration, treatment, and study of this highly lethal malignancy. Recent information highlights cirrhosis and viral Hepatitis B and C as predisposing conditions for developing intrahepatic CCA. Increased awareness of this relationship is critical in management of liver mass lesions. Emerging treatment options for intrahepatic CCA include locoregional therapies and a standardised chemotherapy regimen of gemcitabine plus cisplatin.

The diagnosis of perihilar CCA is challenging and is aided by an advanced cytologic technique of fluorescence in situ hybridisation for polysomy. A better understanding of biliary stent management and the role for liver transplantation is critical in management of perihilar CCA. Distal CCAs need to be distinguished from pancreatic cancer as their outcomes following surgical management differ. In this review we focus on these contemporary advances in the classification, diagnosis and staging of CCA as well as a critical appraisal of the available treatment options.

12:15 – 13:30 Saturday, 15 September 2012

Luncheon Workshop 5: Experimental Models in Liver Cancer
Chairs: Lars Zender, MD (Germany) and Peter Schirmacher, MD (Germany)

Research using human bioprobes especially outside clinical trials is limited to correlative analyses Thus, mechanistic progress in basic and translational liver cancer research is tightly linked to the availability of adequate model systems. Furthermore measures have to exist, how findings in model systems can be related to the complex human individuum. If this is given model systems are indispensable tools to find new tumorigenic mechanisms and factors, to test new therapeutic principles and therapy resistance mechanisms as well as novel diagnostic measures. Especially for liver cancer a large number of different cell culture and mouse models exist (genetic, induced, implant, orthotopic/heterotopic etc.) and recently even high throughput and improved imaging technologies have been introduced for mouse liver cancer models. This has dramatically increased the relevance of animal models also in the preclinical phase of drug development. Nevertheless, it is important to emphasise, that each model system has its advantages, limitations and thus applicability, which are important to be known and reflected.

This workshop will discuss

  1. State of currently available animal and cell culture models, their advantages and limitations, with specific emphasis on recent developments
  2. Modalities how to rationally screen and evaluate animal model systems of HCC
  3. Modalities how to relate findings in model systems to the human situation, especially mouse human comparison