MS 4 – Hepatocellular carcinoma
B. Sangro, A. Benito, J.I. Bilbao, F. Pardo | Friday, March 8, 08:30 – 10:00 / Room F1
A-075 Chairman’s introduction
A variety of options are available for the treatment of hepatocellular carcinoma (HCC) from liver transplantation or resection to percutaneous ablation by chemical or physical procedures, intraarterial injection of embolizing particles that may also serve as carriers of chemotherapeutic agents or radiation-emitting isotopes, or systemic delivery of molecularly targeted agents. Although large scale studies have identified groups of patients that may certainly benefit from some of these therapeutic tools, many areas of uncertainty still exist. Only by the coordinated action of HPB Oncology multidisciplinary teams may patients with HCC receive the best possible treatment.
A-076 Abdominal radiology
Worldwide accepted staging procedures for hepatocellular carcinoma include dynamic CT or MRI, both based on typical tumoural behaviour after contrast in arterial (hypervascular) and in portal-venous phases (“washout” appearance). However, some tumours may show ambiguous features that precludes staging. Recent advances such as perfusion for CT or diffusion and liver-speciﬁc contrast agents for MRI have demonstrated a potential role to solve disagreements in diagnosis, staging, or distinguishing the grade of malignancy. Imaging tumoural response after non-surgical treatments (ablation, chemoembolization, radioembolization or sorafenib), based on tumoural viability as estimated by the degree of hypervascularization in the arterial phase (modified-RECIST) seems to be more appropriate than conventional systems (WHO/RECIST). However, uncommon radiological patterns can be seen after sorafenib (gradual decrease in tumor hypervascularity before shrinkage) or after radioembolization (heterogenous patchy hypervascular areas and/or fibrosis) leading to misinterpretation or late recognized responses if only morphologic changes are considered. Ethanol injection and RFA have been the two most employed local ablative techniques for the local control of HCC. However, other procedures could offer potential benefits. The use of microwave ablation is growing recently due to some presumed advantages such as larger ablations, shorter duration, less susceptibility to heat sink effect, or no requirement of grounding pads. Irrevesible electroporation is also a new non-chemical, non-thermal technique (still under clinical investigation) that is based in the application of multiple direct pulses that result in an irreversible disruption of the cell membrane leading to cellular death.
A-077 Interventional radiology
The rationale to perform endovascular procedures for the treatment of patients with Hepatocellular Carcinoma (HCC) is based on the anatomical fact that liver neovascular networks are nourished exclusively by arteries. Thus, HCC may be selectively treated by delivering therapeutic agents through the afferent arteries. Ischaemia, provoked by the selective endovascular deployment of particles, may induce tumoral necrosis with high local control. The drawback is that ischaemia will also actively induce neoangiogenesis which may facilitate tumoural recurrence. Targeting of tumoural vessels is higher if smaller particles (or fluids like Lipiodol) are used and, for this reason, they could be loaded with anticancer agents. It has been widely reported the high local control rates obtained with the mixed effect given by ischaemia (macroembolization) and the delivery of drugs (chemoembolization, drug-eluted-embolization). Since macroembolization will provoke ischaemia in the embolized volume the procedure must be performed, as selective as possible trying to avoid any damage to the surrounding, usually cirrhotic, liver parenchyma. If not achievable the treatment should not be performed in patients with liver insufficiency or in the presence of thrombosis of the main portal branches. Endovascular treatments may, even, pursue the superselective deployment of an anticancer agent (drug, radionucleide, antibodies) avoiding any ischaemic effect (microembolization). Taking into account these considerations, their indications are increasing in patients with HCC. Several reports demonstrated its usefulness as a palliative method improving both local control and patients´ survival. But also tumours can be downstaged and then patients can receive curative treatments (surgery or ablation).
The goals of hepatocarcinoma (HCC) surgery are to achieve an R0 resection, to protect the liver remnant parenchyma and to prevent morbidity and mortality. Multiple factors have been associated with morbidity and mortality as remnant liver volume, age, comorbidities (cardiovascular disease, diabetes, renal function), liver functions tests, transfusion or the degree of portal hypertension. The requirements for safe resection are a sufficient remnant liver parenchyma and an adequate liver function. Contraindications for resection would be given by tumour size, preoperative staging and the degree of portal hypertension. Tumour size and location determines the type of surgery needed to perform oncological resection. Recent studies have shown that it is feasible to perform a major hepatectomy even in cirrhotic livers without increasing the risk considerably. Preoperative portal vein embolisation is a good strategy to increase the future liver remnant and reduce the morbi-mortality even in cirrhotic patients. Liver transplantation is the best option for patients with HCC and poor liver function. In 1996, Mazzaferro published excellent long term results of HCC transplantation when patients had a single nodule less than 5 cm in diameter or up to three nodules, none larger than 3 cm. These “Milan criteria” were adopted by most transplant teams in the world and confirmed by numerous series. Other groups also published good results with broader criteria (UCSF, Kyoto, Pamplona). Locoregional treatments such as TACE or SIRT are very useful for assessing the biological behaviour of HCC and also for achieve down staging, allowing the rescue of initially inoperable patients.
The scientific basis supporting the current treatment paradigm of hepatocellular carcinoma (HCC) is relatively week due to the scarcity of large-scale randomized clinical trials. Several staging systems have been developed and most of them take into account not-only tumour burden but also liver function, since the frequently underlying cirrhosis may determine prognosis as much as tumour growth does. In Europe, the Barcelona Clinic Liver Cancer (BCLC) system has been endorsed by EASL and EORTC. Generally speaking, patients with small tumours are ablated surgically (resection or liver transplantation depending on the presence of cirrhosis) or percutaneously (radiofrequency or ethanol injection). Intraarterial procedures (bland embolization, chemoembolization or radioembolization) are used for larger or multiple tumorus not extended beyond the liver, while systemic therapy is used for patients with extrahepatic disease or a contraindication to transarterial therapy (mainly because of portal vein thrombosis). However, guidelines issued by different scientific societies worldwide diverge in the definition of patients that benefit the most from each treatment. Sorafenib (an oral agent with antiangiogenic properties) has been shown to prolong the survival of patients with unresectable, advanced disease and preserved liver function. After this proof of concept, a great number of clinical trials exploring agents with different molecular targets have been launched but so far none of this trial has yielded positive results. Sorafenib has failed to show any advantage in survival when given in combination with chemoembolization and its role as an adjuvant therapy after resection or ablation is is currently being studied.