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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]
  • The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014), A
           Bridge to a Consensus on HCC Management, Taipei, Taiwan, July 11-13, 2014:
    • Abstract:
      Liver Cancer 2014;3:285-397
  • 4th International Kyoto Liver Cancer Symposium: Emerging Strategies to
           HCC. Kyoto, Japan, June 7-8, 2014: Abstracts
    • Abstract:
      Liver Cancer 2014;3:133-281
  • Title Page / Table of Contents
    • Abstract:
      Liver Cancer 2014;3:65-67
  • Recent Advances in Bioinformatics Reveal the Molecular Heterogeneity of
           Hepatocellular Carcinoma
    • Abstract:
      Liver Cancer 2014;3:68-70
  • Drug Therapy for Advanced-Stage Liver Cancer
    • Abstract: Liver cancer was traditionally treated by surgery or interventional ablative treatments, or, if these options were not feasible, by best supportive care. Since 2008, systemic therapy with the multikinase inhibitor sorafenib has become available worldwide and has become the standard of care for unresectable/non-ablatable or advanced-stage hepatocellular carcinoma (HCC). Sorafenib is able to improve the median overall survival by approximately 3 months. Despite this significant advance in the non-surgical/non-interventional management of liver cancer, this improvement in overall survival is only a first step toward more potent, more targeted, and better tolerated oral antitumor treatments. Since the introduction of sorafenib into clinical practice, several attempts have been made to develop even more effective first-line treatments as well as an effective second-line treatment for HCC. None of these endeavors has been successful so far. The development of drug treatments for HCC has been particularly hampered by the unfortunate push to establish the diagnosis of liver cancer by non-invasive imaging alone, without requiring a liver biopsy for histologic confirmation: this precluded the very necessary search for informative biomarkers and the search for molecular targets for drug development in HCC. This important drawback is being increasingly recognized and corrected. Despite several obstacles remaining to be overcome, it seems reasonable to assume that using a rational, data-driven approach, we will be able to develop better drug treatments for liver cancer in the coming years. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:125-131
  • How to Define Transarterial Chemoembolization Failure or Refractoriness: A
           European Perspective
    • Abstract: In Europe, trans-arterial chemoembolization (TACE) is usually given to patients with Barcelona Clinic Liver Cancer (BCLC) "intermediate stage" hepatocellular carcinoma (HCC), and is associated with a modest improvement in median overall survival. In the two positive randomized trials that have been reported, TACE was stopped in cases of severe toxicity, worsening of liver cirrhosis or performance status and tumor progression, including local progression, extrahepatic spread and portal vein thrombosis. The necessity to stop TACE leads to the concept of untreatable progression, which is characterized by massive liver involvement, extrahepatic spread, vascular invasion, impaired liver function or performance status. More recently, the assessment for re-treatment with TACE (ART) score has been developed to determine which patients will not benefit from a second or a third TACE therapy. Herein, we propose an algorithm that summarizes our experience with TACE. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:119-124
  • Living Donor Liver Transplantation for Patients with Hepatocellular
    • Abstract: Background: Liver transplantation has become an established treatment for cirrhotic patients with hepatocellular carcinoma (HCC), and the Milan criteria are now widely accepted and applied as an indication for deceased donor liver transplantation (DDLT) in Western countries. In contrast, however, due to the severe organ shortage, living donor liver transplantation (LDLT) is mainstream in Japan and in other Asian countries. Summary: Unlike DDLT, LDLT is not limited by the restrictions imposed by the nationwide allocation system, and the indication for LDLT in patients with HCC often depends on institutional or case-by-case considerations, balancing the burden on the donor, the operative risk, and the overall survival benefit for the recipient. Accumulating data from a nationwide survey as well as individual center experience indicate that extending the Milan criteria is warranted. Key Messages: While the promotion of DDLT should be intensified in Japan and other Asian countries, LDLT will continue to be a mainstay for the treatment of HCC in cirrhotic patients. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:108-118
  • Diagnosis of Pathologically Early HCC with EOB-MRI: Experiences and
           Current Consensus
    • Abstract: Objective: After much debate, the International Consensus Group for Hepatocellular Neoplasia (ICGHN) has recently arrived at a conclusion regarding the pathological criteria for early hepatocellular carcinoma (HCC). They have stated that stromal invasion should be recognized as the most important pathological finding for precisely diagnosing and differentiating early HCC from dysplastic nodules (DN). Methods: We conducted a review of the imaging findings from multi-imaging modalities of early HCC cases diagnosed according to the pathological criteria of the ICGHN. The multi-imaging modalities included gadoxetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI), abbreviated as EOB-MRI, contrast-enhanced CT (CE-CT), CT during arterioportography (CTAP), and CT during hepatic arteriography (CTHA). It has been shown that EOB-MRI is the only imaging modality that has sufficient resolution for the detection and classification of early HCC. Results: The most significant imaging feature for diagnosing early HCC was hypointensity on hepatobiliary-phase (HP) images of EOB-MRI; all of the cases of early HCC that were detected on HP images of EOB-MRI showed hypointensity, while all of the images of DN showed isointensity or hyperintensity compared with the liver parenchyma. The results of the diagnostic performance analysis showed that EOB-MRI had excellent sensitivity (97%) for detecting early HCC and outstanding specificity (100%) for distinguishing early HCC from DN. Conclusions: Considering the results from imaging-pathologic correlations and follow-up studies indicating that many early-stage hepatocellular nodules showing hypointensity on HP images of EOB-MRI tend to develop hypervascularization during a relatively short follow-up period, it is beginning to be accepted that such nodules may be treated as early HCC. However, hepatologists and radiologists should also recognize that some cases of early HCC may show isointensity or hyperintensity on HP images of EOB-MRI, making it impossible to differentiate early HCC from DN, although the low prevalence of such nodules may be unlikely to affect the generally accepted follow-up protocols for cirrhotic patients. Our results and other recent reports have indicated that signal-intensity patterns on HP images of EOB-MRI for DN and early HCC directly correlate with the degree of expression of the organic anion transporting polypeptide (OATP) 1B3 in the nodules. Thus, the diagnostic performance of pathological analyses for early HCC cases may be dramatically improved, nearly up to that of EOB-MRI, by incorporating an OATP1B3 staining method. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:97-107
  • Hypervascular Benign and Malignant Liver Tumors That Require
           Differentiation from Hepatocellular Carcinoma: Key Points of Imaging
    • Abstract: Most liver tumors are benign and hypervascular, and it is important to avoid unnecessary interventions for benign lesions. This review describes the typical and atypical imaging features of common hypervascular benign liver tumors and outlines a general approach to distinguishing between benign and malignant hepatic lesions. There are many types of benign liver tumors that need to be differentiated from hepatocellular carcinoma (HCC). Therefore, it is very important to know the imaging characteristics of benign tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging is helpful in diagnosing hypervascular pseudotumors, focal nodular hyperplasia, and nodular lesions associated with alcohol-induced hepatitis. There are also some hypervascular malignant tumors, such as cholangiocarcinoma, cholangiolocellular carcinoma, mixed type tumors, and metastatic liver tumors, which also required differentiation from HCC. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:85-96
  • Molecular Biology of Liver Cancer Stem Cells
    • Abstract: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased resistance to radiation and chemotherapy. They are considered as the factors responsible for the cases of tumor relapse. Hepatic progenitor cells (HPCs) could form the basis of some hepatocellular carcinomas (HCC) and cholangiocarcinomas. Liver CSCs have been reported in multiple subtypes of HCC and are considered as the master regulators of HCC initiation, tumor metastasis, and progression. HPCs activators such as epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin, transforming growth factor-beta (TGF-β), Notch and Hedgehog signaling systems expedite tumorigenesis or conversely, serve as a powerful cancer-prevention tool. Recent work has also identified Sal-like protein 4 (SALL4) and some epigenetic regulations as important molecules, while several therapeutic drugs that directly control HPCs have been tested both in vivo and in vitro. However, liver CSCs clearly have a complex pathogenesis, with the potential for considerable crosstalk and redundancy in signaling pathways. Hence, the targeting of single molecules or pathways may have limited benefit for treatment. In addition to the direct control of liver CSCs, many other factors are needed for CSC maintenance including angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance. Here, we provide a brief review of molecular signaling in liver CSCs and present insights into new therapeutic strategies for their targeting. © 2014 S. Karger AG, Basel
      Liver Cancer 2014;3:71-84
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