S240 Abstracts of the 3rd ITLT Essen 2013 / Digestive and Liver Disease 45S (2013) S233–S260

patients’ performance status, tumor load, and tumor vascularization could beidentified. Nevertheless, even if the current available data on TACE and REin CC are quite encouraging substantial comparative studies are still missingdefining the role of these techniques within the therapeutic concept for CC.

THU-16

Systemic therapies for cholangiocarcinoma: State of the art 2013

A.X. Zhu ∗

Massachusetts General Hospital Cancer Center, Harvard Medical School,Boston, MA

Biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholan-giocarcinomas as well as gallbladder carcinomas, are a genetically diversecollection of cancers. Most patients with BTCwill present with unresectable ormetastatic disease. Although the standard systemic combination chemother-apy approaches are emerging, the prognosis remains poor with a mediansurvival of less than one year. Development of molecularly targeted therapiesin advanced BTC remains challenging. Recent early stage clinical trials withtargeted therapies appear promising, though the relationships between subsetsof patients with positive responses to therapy and tumor genetics remainunexplored. The author will discuss the relevant molecular pathogenesis,recent and ongoing clinical trials with targeted agents, and the key issues inclinical trial design in BTC.

THU-17

Endoscopic treatment options for cholangiocarcinomas

K. Mönkemüller∗ , J. Ramesh, C.M. Wilcox

Basil Hirschowitz Center for Endoscopic Excellence, Division ofGastroenterology, Hepatology, University of Alabama at Birmingham,Alabama, USA

Cholangiocellular carcinomas (CCC) account for approximately 2–3% of allcancer diagnoses with an incidence of about 2.1/100,000. About 60% of casesoccur in patients over the age of 65 years, with a similar distribution betweenwomen and men.CCCs are heterogeneous groups of tumors of the bilary tract. In 1965 GeraldKlatskin described the distinct characteristics of hilar CCC arising at the hep-atic bifurcation. Since then Klatksin tumor has been synonymous with CCC.However, there are several types of CCCs based on their anatomic location,and Klatskin tumors comprise only 10% of CCCs. The most common typeis the peri-hilar variant (pCCC) (50%), followed by the distal type (dCCC)(40%) and intrahepatic (iCCC) (10%). Klatskin tumor is a type of pCCC.Because some CCCs arise from hepatic progenitor cells, some authors preferto call these tumors cholangiocarcinoma (CCA).Therapy for CCC is based on the type, location and size of tumor. Whereassmall dCCC and hCCC can and should be treated using radical surgicalresection, mass tumors located inside the liver or large or metastatic extrahep-atic tumors can only be treated with chemotherapy using a combination ofgemcitabine and cisplatin.If the lesions are causing bilary luminal obstruction with resulting jaundice,endoscopic therapy using stents (plastic or metal) is a definite option. Plasticstents vary in caliber, length, material, and configuration depending on theirdesign and intended application. The preferred plastic stents for biliary de-compression in pCCC and dCCC are “large” diameter (i.e. 10 or 11.5 Fr)polyethylene or Teflon stents. The general rule is to apply the largest possiblestent that can traverse the stricture and, if possible, place several stents. Themajor disadvantage of plastic stents is their high rate of occlusion (about 75%within 90 days of placement). Thus, if the patient is expected to survive longerthan 3 months the use of self-expanding metal stents (SEMS) is indicated.The main advantage of SEMS is their larger diameter (6, 8 and 10 mm) andthus longer patency rate. Most SEMS for malignant biliary strictures are madeof Nitinol, a superelastic nickel-titanium alloy with thermal shape memory,a property of reassuming a predetermined shape through heating. As thesestents are placed through the endoscope fluoroscopy is always needed. Ideally,SEMS should be well visualized during fluoroscopic placement. Thus, the

radiopacity of some metal stents is enhanced by incorporating other metalsinto the body or the ends of the stent. Membrane-covered SEMS offer thepotential advantage of preventing tissue ingrowth. Whereas the use of SEMSis clearly indicated for distal and hilar strictures, the use of double metalstenting into both intrahepatics is less well studied. Nonetheless, achievingdrainage of both intrahepatic ducts is associated with less cholangitis, jaundiceand morbidity.In recent years, intrabilary photodynamic therapy (PDT) delivered throughthe duodenscope has emerged as a good palliative measure in some pCCCand dCCC. Indeed, some data have studies that survival may be improved inpatients undergoing PDT.

Friday, 19 April 2013

FRI-01

The four melanomas

U. Keilholz∗

Charité Comprehensive Cancer Center, Berlin, Germany

Until several years ago, metastatic melanoma has been a disease without atreatment option with proven impact on survival. DTIC was the referencetreatment, based on moderate efficacy and low toxicity. Interleukin-2 andvaccines were immunologic treatment alternatives, and first-line experimen-tal treatment was explicitely accepted. For metastatic mucosal and uvealmelanoma, no reference treatment was defined. During the past three years,the situation has profoundly changed, based on molecular understanding offour different melanoma entities and development of novel therapies. Cuta-neous melanoma has been devided into solar and non-solar melanoma. Solarmelanoma predominantly arises on skin with intermittent UV exposure andfrequently harbors activating braf or nras mutations. Non-solar cutaneousmelanomas develop on skin areas rarely exposed to UV and typically showdisruptive mutations of p53. In addition, a fraction of melanomas arising inareas of the skin with chronic UV exposure and from mucous membranesdisplays activating mutations of ckit, and, lastly, uveal melanomas are charac-terized by activating mutations of GNA11 and GNAQ. These discoveries haveprompted rigorous development of targeted drugs and several compounds haveproven to be highly active in inducing remissions and improving survival.These specifically include agents targeting mutated braf and also mek, andto a lesser extent ckit. Combination treatment studies are under way. Foruveal melanomas, targeted agents still have to be tested. In addition to themolecularly targeted agents, immune checkpoint regulators, such as antibodiesdirected against CTLA4 and PD1/PDL1 have been developed and initiated asolid and efficient new era of immunotherapy of metastatic melanoma. Thesenovel treatment modalities have now to be tested in combinations and insequence in order to further improve quality of life and survival of metastaticmelanoma patients. The indications of liver-directed therapies and all otherlocoregional treatment approaches, which remain effective and important,have to be reconsidered.

FRI-02

Liver metastases from melanoma

R. Adam ∗ ,1, L. Chiche2

1AP-HP Hopital Paul Brousse, and Université Paris-Sud, UMR-S 776,Villejuif, France; 2Hopitaux Universitaires de Bordeaux, Service de ChirurgieDigestive, Maison du Haut Lévèque, Pessac, France

Liver metastases are a frequent mode of recurrence of choroid melanoma(60–90% of cases) and much less frequently of cutaneous melanoma (5–15%of cases). The outcome of metastatic melanoma is poor with median survivalrates of 6–9 months and a 5-year survival inferior to 10%. The clinical presen-tation relies on the discovery of LM in the follow up of a known melanomaor of a multinodular hepatomegaly from an undiagnosed melanoma. Despitethe improvements of imaging, there is frequently an underestimation of thelesions.The role of hepatic surgery is still questioned and the number of reported cases