Monofocal hepatocellular carcinoma: How much does size matter?

BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.

Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization.

BACKGROUND: MicroRNAs (miRNAs) have been proposed as biomarkers in hepatocellular carcinoma (HCC). We aim at evaluating miR-21 and miR-122 in HCC patients treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) as prognostic biomarkers and investigating their correlation with hypoxia inducible factor-1α (HIF-1α) serum levels. METHODS: In this retrospective study, 12 healthy subjects, 28 cirrhotics, and 54 HCC patients (tested before and four weeks after DEB-TACE) were included. Whole blood miR-21 and miR-122 levels were measured by quantitative real time (qRT)-PCR, while serum HIF-1α was assessed by an enzyme-linked immunosorbent assay (ELISA) test. RESULTS: The highest level of miR-21 was found in cirrhotics, while HCC patients had the highest level of miR-122 (which was even higher in "viral" HCC, p = 0.006). miR-21 ratio (after/before DEB-TACE) and miR-122 below their respective cut-offs identified patients with longer progression-free survival (p = 0.0002 and p = 0.02, respectively). The combined assessment of alpha-fetoprotein and miR-21 ratio, both independent prognostic predictors, identified early progressors among patients with complete or partial radiological response. miR-21 levels positively correlated with HIF-1α before (p = 0.045) and after DEB-TACE (p = 0.035). CONCLUSIONS: miR-21 ratio and miR-122 are useful prognostic markers after DEB-TACE. miR-21 correlates with HIF-1α and probably has a role in modulating angiogenesis in HCC.

SCCA-IgM in hepatocellular carcinoma patients treated with transarterial chemoembolization: gender-related differences.

Aim: Squamous cell carcinoma antigen immune complexed with immunoglobulin M (SCCA-IgM) is a useful but not completely satisfactory biomarker of hepatocellular carcinoma (HCC). Considering its gender-specific behavior in preclinical models, we investigated gender-related differences of SCCA-IgM as a prognostic marker in HCC. Patients & methods: Two hundred and eight prospectively recruited patients treated with transarterial chemoembolization in a single tertiary care hospital were retrospectively evaluated. Correlations between SCCA-IgM levels, clinical characteristics and survival were assessed according to gender. Results: When the disease was advanced, SCCA-IgM was higher in males and lower in females. Levels below 130 AU/ml predicted a significantly longer survival in males (p = 0.007) and a shorter survival in females (p = 0.01). Conclusion: In predicting the prognosis of HCC patients, the interpretation of SCCA-IgM should consider gender as a relevant variable.

Capecitabine in advanced hepatocellular carcinoma: A multicenter experience.

BACKGROUND: Recent data suggest a potential activity and a good tolerability of capecitabine in advanced hepatocellular carcinoma (HCC). AIMS: To evaluate capecitabine activity and safety in a wide cohort of advanced HCC patients. METHODS: Retrospective analysis of 143 capecitabine-treated patients (January 2010 to December 2017) in three centers of the Veneto Oncology Network. RESULTS: Capecitabine was administered in second and third line, but also in first line instead of sorafenib in Child-Pugh B patients (70%), compromised clinical conditions (14%) or contraindications to antiangiogenetics (16%). Median overall survival (OS) and time to progression (TTP) were 6.9 and 2.8 months, respectively. There were no differences in OS and TTP between the 32 patients treated with non-metronomic scheme (2000 mg/day for 14 days) and the 111 patients treated with metronomic scheme (1000 mg/day) after correction for prognostic factors at baseline with a propensity score analysis. Capecitabine was more active in patients intolerant to sorafenib than in those progressing during treatment (p = 0.024). At least one adverse event (mainly hematological) was experienced by 73% of patients but discontinuation was necessary only in 11 (8%). CONCLUSIONS: Capecitabine can be considered an active and safe option in advanced HCC, especially for patients unfit for other treatments.

When and how should we perform a biopsy for HCC in patients with liver cirrhosis in 2018? A review.

The role of liver biopsy in the diagnosis of hepatocellular carcinoma (HCC) has changed over time. The diagnostic algorithm for this tumor is nowadays mainly based on radiological imaging, relegating histology to controversial cases, in which imaging techniques cannot establish a clear-cut diagnosis. This most commonly happens in small lesions, where biopsies frequently become mandatory, or in larger hypovascularized lesions. In this case however, the histological examination may not be reliable enough to grade the lesion, as different cell clones, deriving from sequential mutations, can originate heterogeneous cell populations. The risk of complications of liver biopsy, such as tumor seeding and intra-abdominal bleeding, needs to be reconsidered in light of new scientific evidence and of the technical improvements that have been introduced. Furthermore, increasing knowledge of the immunohistochemical and molecular characteristics of hepatocellular carcinoma opens a new scenario in which biopsy may play a decisive role in defining prognosis, and even treatment, by identifying the patient populations who could most benefit from target-driven hepatocellular carcinoma treatments, and therefore improving the success rate of experimental therapies. All the above reasons suggest that, overall, the role of liver biopsy in the management of HCC needs a reappraisal.