Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.     

The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?

BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). METHODS: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. RESULTS: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.     

Is the treatment outcome of hepatocellular carcinoma inferior in elderly patients?

In view of the increasing life expectancy in different parts of the world, a larger proportion of elderly patients with hepatocellular carcinoma(HCC) requiring oncological treatment is expected. The clinicopathological characteristics of HCC in elderly patients and in younger patients are different. Elderly patients, in general, also have more comorbidities. Evaluation of the efficacy of different HCC treatment options in elderly patients is necessary to optimize treatment outcomes for them. Treatment modalities for HCC include hepatectomy, liver transplantation, radiofrequency ablation, transarterial chemoembolization, and molecular-targeted therapy with sorafenib. In this review, current evidence on the risks and outcomes of the different HCC treatments for elderly patients are discussed. According to data in the literature, elderly patients and younger patients benefited similarly from HCC treatments. More clinical data are needed for the determination of selecting criteria on elderly HCC patients to maximize their chance of getting the most appropriate and effective treatments. As such,further studies evaluating the outcomes of different HCC treatment modalities in elderly patients are warranted.     

Demystifying statistics: How to choose a statistical test?

The young researcher today is confronted with a choice of hundreds of statistical tests, both while reading research works or while planning own research. The principles guiding the choice of statistical tests are simple and this article, aimed at the young researcher, aims to demystify the same.     

Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.     

What is the best treatment?

The treatment of hepatitis C is expensive, difficult and arduous from the patient's perspective. It is similarly difficult for the clinician to decide who and when to treat. If hepatitis C is viewed from the liver's perspective we need only treat those patients who will develop the complications of chronic liver disease within their lifetimes. If we take a more holistic approach, then we have to consider the implications of being a carrier of a potentially transmissible blood borne virus on the patient themselves, their relationships, their families and their sense of wellbeing. There is now evidence of the large impact HCV has on quality of life and we have to consider extra hepatic manifestations of hepatitis C infection, possibly including the syndrome of 'brain fog' recently described. An additional factor that has to be considered in the decision to treat is whether patients perceive hepatitis C as a significant problem for themselves. For some patients, who have chaotic live styles, it is extremely difficult to get them to access healthcare. To then undergo the rigors and tribulations of hepatitis C therapy that is posing no current problem is unlikely to succeed. However, failure to engage these patients with therapy will lead to a significant proportion of them presenting with serious complications of chronic liver disease, with its attendant mortality, morbidity and cost. Underlying all these considerations is the tension between the costs of therapy and the benefits of therapy. Good arguments can be made in terms of cost-effectiveness for treating patients with a high likelihood of progressing to chronic liver disease and its complications. These arguments become much less persuasive when all patients are concerned.