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Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics

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      Abstract

      Hepatocellular carcinoma (HCC) is a common malignancy in developing countries and its incidence is on the rise in the developing world. The epidemiology of this cancer is unique since its risk factors, including hepatitis C and B, have been clearly established. The current trends in the shifting incidence of HCC in different regions of the world can be explained partly by the changing prevalence of hepatitis. Early detection offers the only hope for curative treatment for patients with HCC, hence effective screening strategies for high-risk patients is of utmost importance. Liver transplantation and surgical resection remains the cornerstone of curative treatment. But major advances in locoregional therapies and molecular-targeted therapies for the treatment of advanced HCC have occurred recently. In this review, current trends in the worldwide epidemiology, surveillance, diagnosis, standard treatments, and the emerging therapies for HCC are discussed.

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      Most cited references 167

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      The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
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        Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed. Copyright © 2010 UICC.
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          Sorafenib in advanced hepatocellular carcinoma.

          No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.) 2008 Massachusetts Medical Society
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            Author and article information

            Affiliations
            Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA
            Author notes
            Correspondence: Roniel Cabrera, Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, PO Box 100277, Gainesville, FL 32610, USA, Email rcabrera@ 123456uf.edu
            Journal
            Hepat Med
            Hepat Med
            Hepatic Medicine: Evidence and Research
            Hepatic Medicine : Evidence and Research
            Dove Medical Press
            1179-1535
            2012
            08 May 2012
            : 4
            : 19-37
            24367230
            3846594
            10.2147/HMER.S16316
            hmer-4-019
            © 2012 Dhanasekaran et al, publisher and licensee Dove Medical Press Ltd

            This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

            Categories
            Review

            tace, liver cancer, sorafenib, hepatitis c

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