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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  [103 journals]
  • 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
  • Imaging Modalities for Assessment of Treatment Response to Nonsurgical
           Hepatocellular Carcinoma Therapy: Contrast-Enhanced US, CT, and MRI
    • Abstract: Tumor response and time to progression have been considered pivotal for surrogate assessment of treatment efficacy for patients with hepatocellular carcinoma (HCC). Recent advancements in imaging modalities such as contrast-enhanced ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are playing an important role in assessing the therapeutic effects of HCC treatments. According to some HCC clinical guidelines, post-therapeutic evaluation of HCC patients is based exclusively on contrast-enhanced dynamic imaging criteria. The recommended techniques are contrast-enhanced CT or contrast-enhanced MRI. Contrast-enhanced US is employed more in the positive diagnosis of HCC than in post-therapeutic monitoring. Although contrast enhancement is an important finding on imaging, enhancement does not necessarily depict the same phenomenon across modalities. We need to become well acquainted with the characteristics of each modality, including not only contrast-enhanced CT and MRI but also contrast-enhanced US. Many nonsurgical treatment options are now available for unresectable HCC, and accurate assessment of tumor response is essential to achieve favorable outcomes. For the assessment of successful radiofrequency ablation (RFA), the achievement of a sufficient ablation margin as well the absence of tumor vascular enhancement is essential. To evaluate the response to transcatheter arterial chemoembolization (TACE), enhanced tumor shrinkage is relied on as a measure of antitumor activity. Here, we give an overview of the current status of imaging assessment of HCC response to nonsurgical treatments including RFA and TACE.
      Liver Cancer 2015;4:106-114
  • Apple News
    • Abstract:
      Liver Cancer 2015;4:137
  • Apple News
    • Abstract:
      Liver Cancer 2015;4:84
  • Consensus Development from the 5th Asia-Pacific Primary Liver Cancer
           Expert Meeting (APPLE 2014)
    • Abstract: A key mission of the Asia-Pacific Primary Liver Cancer Expert (APPLE) Association is to ensure a coherent view for management of hepatocellular carcinoma (HCC) and to advance new treatment for this difficult disease. At the 5th APPLE meeting, held in July 2014 in Taipei, Taiwan, an APPLE consensus development program was established to facilitate discussion among experts in the Asia-Pacific region on pertinent issues for HCC management, including (1) surgery for intermediate/advanced-stage disease, (2) prevention of HCC recurrence after curative treatment, (3) optimizing imaging diagnosis, (4) radiotherapy: current practice and future clinical trials, and (5) the role of cytotoxic chemotherapy. A pre-congress questionnaire was undertaken with the consensus development committee members to help understand the current practice patterns for HCC in the Asia-Pacific region and to identify issues relating to optimal patient care and further clinical trials for which consensus needs to be developed. In this report, the results of the questionnaire are presented, and the pertinent issues identified by each consensus group for further discussion and consensus development are summarized.
      Liver Cancer 2015;4:96-105
  • 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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