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Journal Cover   Liver Cancer
   Full-text available via subscription Subscription journal
   ISSN (Print) 2235-1795 - ISSN (Online) 1664-5553
   Published by Karger Homepage  [104 journals]
  • Recent Advances in Tumor Ablation for Hepatocellular Carcinoma
    • Abstract: Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.
      Liver Cancer 2015;4:176-187
  • Surgical and Locoregional Therapy of HCC: TACE
    • Abstract: Transcatheter arterial chemoembolization (TACE) is performed worldwide for patients with intermediate-stage hepatocellular carcinoma (HCC). TACE has produced survival advantages in two randomized controlled trials and a meta-analysis, and is currently the mainstay of treatment for this stage of HCC. However, there are currently no global guidelines regarding the dose, choice or combination of cytotoxic agents for TACE; therefore, it is difficult to compare data from different TACE studies. In Japan, most of the TACE procedures have been based on iodized oil as conventional TACE, utilizing the microembolic and drug-carrying characteristic of iodized oil. Superselective TACE with lipiodol is the primary TACE procedure that has reported satisfactory levels of local control associated with a lower risk of complications. Conversely, TACE performed using drug-eluting beads has been widely used in western countries, and this has shown similar tumor response and median survival compared to conventional TACE. Moreover, the combination of TACE and molecular targeted agents is now ongoing to evaluate the synergistic effect. In this review, the indication, technical issues, and complications of TACE are reviewed.
      Liver Cancer 2015;4:165-175
  • The 6th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2015),
           Evidence and Consensus on HCC Management. Osaka, Japan, July 3-5, 2015:
    • Abstract:
      Liver Cancer 2015;4:1-257
  • Locoregional Therapy for Hepatocellular Carcinoma
    • Abstract:
      Liver Cancer 2015;4:163-164
  • Potential Role of Phosphorylation as a Regulator of
           Aspartyl-(asparaginyl)-β-hydroxylase: Relevance to Infiltrative
           Spread of Human Hepatocellular Carcinoma
    • Abstract: Abundant expression of aspartyl-(asparaginyl)-β-hydroxylase (AAH) correlates with infiltrative growth of hepatocellular carcinoma (HCC). Herein, we examine the role of phosphorylation in relation to AAH's protein expression, hydroxylase activity, promotion of cell motility, and activation of Notch signaling in human Huh7 hepatoma cells. Predicted glycogen synthase kinase-3β (GSK-3β) , protein kinase A (PKA), protein kinase C (PKC), and casein kinase 2 (CK2) phosphorylation sites encoded by human AAH cDNA were ablated by S/T#x2192;A site-directed mutagenesis using N-Myc-tagged constructs in which gene expression was controlled by a cytomegalovirus promoter. Functional consequences were assessed in transiently transfected Huh7 cells. Cells transfected with wildtype AAH had significantly increased AAH expression, catalytic activity, HES-1 expression, and directional motility relative to controls. Single phosphorylation site mutations in the C-terminus largely abrogated these effects and further inhibited catalytic activity relative to that in cells transfected with empty vector, whereas the effects of single point mutations within the N-terminus were more varied. In contrast, AAH cDNAs carrying multiple phosphorylation site mutations exhibited wildtype levels of AAH catalytic activity suggesting that the effects of AAH phosphorylation are complex and non-uniform. AAH expression and function can be modulated by direct phosphorylation of the protein. These findings suggest additional strategies for inhibiting infiltrative growth of HCC.
      Liver Cancer 2015;4:139-153
  • Was Hypervascular Hepatocellular Carcinoma Visible on Previous Gadoxetic
           Acid-Enhanced Magnetic Resonance Images'
    • Abstract: Background: During the follow-up of patients with chronic liver disease, hypervascular hepatocellular carcinomas (HCCs) can develop either from pre-existing high-risk nodules or by de novo hepatocarcinogenesis. The purpose of this study was to evaluate, by retrospective analysis, the detectability and signal intensity on previous hepatocyte-phase gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) of hypervascular HCC initially detected on current EOB-MRIs. Methods: We examined 50 initially detected hypervascular HCCs that showed typical enhancement features on EOB-MRI in 39 patients whose previous EOB-MRI images obtained 6-19 months earlier were available. The detectability of each hypervascular HCC on the hepatocyte phase images of previous EOB-MRIs was assessed. The imaging features on hepatocyte-phase images of previous EOB-MRIs at the locations where hypervascular HCCs were found on the current EOB-MRI images were classified as detectable or undetectable. The signal intensities of detectable nodules (defined as group A) on hepatocyte-phase images of previous EOB-MRIs were classified as hypo-, iso-, or hyperintensity. Nodules undetectable on the hepatocyte-phase images of previous EOB-MRIs were assigned to group B. Results: Twenty-two (22/50, 44%) hypervascular HCCs were detectable on the earlier hepatocyte phase images (group A). In contrast, 28 (28/50, 56%) hypervascular HCCs were not detectable on the hepatocyte phase of earlier EOB-MRI images (group B). Conclusion: When the previous EOB-MRI images were used as the reference, more than half (28/50, 56%) of hypervascular HCCs initially appearing on the current EOB-MRI images were found not to have developed from nodules detectable on the previous MRIs through the traditionally accepted process of multistep carcinogenesis. Instead, they seemed to have developed via an “imaging-occult” process of carcinogenesis in patients with chronic liver diseases.
      Liver Cancer 2015;4:154-162
  • Phase I Trial of Sorafenib Following Liver Transplantation in Patients
           with High-Risk Hepatocellular Carcinoma
    • Abstract: Liver transplantation offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who fall within established criteria. For those outside such criteria, or with high-risk pathologic features in the explant, HCC recurrence rates are higher. We conducted a multicenter phase I trial of sorafenib in liver transplantation patients with high-risk HCC. Subjects had HCC outside the Milan criteria (pre- or post-transplant), poorly differentiated tumors, or vascular invasion. We used a standard 3+3 phase I design with a planned duration of treatment of 24 weeks. Correlative studies included the number of circulating endothelial cells (CECs), plasma biomarkers, and tumor expression of p-Erk, p-Akt, and c-Met in tissue micro-arrays. We enrolled 14 patients with a median age of 63 years. Of these, 93% were men and 71% had underlying hepatitis C virus (HCV) and 21% had HBV. The maximum tolerated dose of sorafenib was 200 mg BID. Grade 3-4 toxicities seen in >10% of subjects included leukopenia (21%), elevated gamma-glutamyl transferase (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, one patient died and four recurred. The mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean soluble vascular endothelial growth factor receptor-2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression to correlate with increased risk of recurrence. Post-transplant sorafenib was found to be feasible and tolerable at 200 mg PO BID. The effect of post-transplant sorafenib on recurrence-free survival is potentially promising but needs further validation in a larger study.
      Liver Cancer 2015;4:115-125
  • Apple News
    • Abstract:
      Liver Cancer 2015;4:137
  • Apple News
    • Abstract:
      Liver Cancer 2015;4:84
  • Tumor Markers for Hepatocellular Carcinoma: Simple and Significant
           Predictors of Outcome in Patients with HCC
    • Abstract: Background: The effectiveness of tumor markers in evaluating outcomes of patients with hepatocellular carcinoma (HCC) remains to be clarified. Summary: The usefulness of the HCC tumor markers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), and des-gamma-carboxy prothrombin (DCP) was reviewed. Elevations in these tumor markers at the time of HCC diagnosis correlate with disease progression as assessed by both imaging studies and pathologic examinations. The combination of these three tumor markers results in good predictive ability for patient survival after diagnosis. In addition, combination at the time of HCC diagnosis of these three tumor markers (as a measure of tumor progression) and serum albumin and bilirubin levels (as indicators of remnant liver function) can be used for HCC staging and further predicts prognosis in patients with HCC. Key Message: The prognosis of patients with HCC can be well discriminated based solely on serum markers. Staging of HCC with serum markers is objective; if stored serum samples are available, HCC stages can be standardized across different countries and time periods.
      Liver Cancer 2015;4:126-136
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