Special ArticleClinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference
Section snippets
Incidence and risk factors
The incidence in developing countries is two to three times higher than in developed countries. In Eastern Asia and Middle Africa the Age-Adjusted Incidence Rate (AAIR) ranges from 20 to 28 cases per 105 in men, while this is less than five per 105 in Northern Europe, Australia and America [1]. However, a steady increase has been observed in North America [2], but figures are still lower than in Southern Europe where the AAIR is around ten per 105 in men [1]. The calculation of the risk
Surveillance
Surveillance for HCC meets some but not all of the standard criteria for assessing the feasibility of instituting a cost-effective surveillance program for any disease [32]. HCC occurs sufficiently frequently in some at-risk populations and it induces significant morbidity and mortality. In the Western world, the population at risk readily accepts the need for screening, and physicians generally do believe that surveillance is necessary. However, the surveillance tests are imperfect, and recall
Surveillance tools
The available data on tumor growth suggest that the time from an undetectable lesion to 2 cm is about 4–12 months [35], [36], [37], [38]. Thus, with an aim of detecting tumors below 3 cm in diameter, the suggested interval for surveillance in patients with cirrhosis has been set at 6 months. Patients with a particularly high risk do not warrant a more intense surveillance schedule since a higher risk does not mean faster tumor growth. The surveillance tools are AFP concentration and
Recall procedures and diagnostic confirmation
There are no studies to define unequivocally the best recall policy, but based on the available clinical data the following scheme is advised (Fig. 1). The detection of a hypo- or hyperechoic nodule during follow-up US should raise the suspicion of HCC. However, pathological studies have shown that half of the nodules less than 1 cm in size do not correspond to HCC [41]. In addition, even if such a nodule corresponded to a true HCC, it is almost impossible to correctly diagnose it as such with
Assessment of disease extension
The indication to have accurate staging depends on the clinical need. In patients diagnosed at an advanced stage of disease with no therapeutic options, the results of diagnostic US provide enough information and no other techniques are necessary. In those individuals in whom a treatment decision has to be taken, tumor staging should be based on US and spiral CT. The use of lipiodol CT is not recommended because of its limited accuracy [50], [51]. CT should be done with latest generation
Prognostic assessment
The ideal system to estimate the prognosis of patients diagnosed with HCC should be as simple as possible to use, and yet include all important descriptive information associated with survival. Since the goal is to improve the prognosis by using a therapeutic intervention and because the possible interventions depend on the stage of the disease, both the stage and the various types of intervention should ideally be built into the prognostic system. The prognostic models in their present state
Definitions within clinical studies
Clinical investigations aiming to provide the most accurate and useful information should include a detailed and comprehensive report of the descriptive variables of all patients included. The variables to be recorded and described in outcome research should include those parameters that have been identified as significant predictors in previous investigations (Table 2). The data should be collected and reported in a standardized way to allow assessment of the comparability between groups of
Assessment of treatment response
The local response to treatment is relevant for the investigation of new therapeutic options. The evaluation of surgery is not subject to controversy, but the assessment of loco-regional treatment (i.e. percutaneous and transarterial procedures) requires a careful assessment of the treated HCC by imaging techniques. Spiral CT at least 4 weeks after the treatment is currently accepted as the standard imaging modality for this purpose [64]. Non-enhanced tumoral areas reflect tissue necrosis after
Definitions of response
Local response to treatment is usually defined following the World Health Organisation (WHO) criteria [65] as follows: complete response (CR): complete disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; partial response (PR): >50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart; stable disease (ST): does not qualify for CR/PR or progressive disease; progressive
Treatment
There are no data to propose a universal treatment algorithm to be implemented worldwide. If diagnosed at an early stage, patients should be considered for any of the available options that may provide a high rate of CR. If these are not feasible, patients should be included in prospective investigations, preferably RCTs aiming to identify therapies that ultimately may lead to a survival improvement. Each group, center or country must establish the best treatment approach for patients with HCC
Prevention of HCC
Vaccination against HBV has decreased the incidence of HCC in areas with high prevalence of this viral agent [121]. Other strategies for primary prevention of HCC (i.e. Oltipraz [122]) are being tested but no solid data are yet available. Antiviral treatment for chronic hepatitis decreases the proportion of patients developing cirrhosis [123] and this should reduce the long-term incidence of this neoplasm [124]. When cirrhosis is already established, there is no evidence supporting a preventive
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