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      Cancer and liver cirrhosis: implications on prognosis and management

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          Abstract

          Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies.

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          Most cited references 263

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          Global cancer statistics, 2012.

          Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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            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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              The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.

              The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor-node-metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms.
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                Author and article information

                Affiliations
                [1 ]Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna, Austria
                [2 ]Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Harvard Medical School & Massachusetts General Hospital , Boston, USA
                [3 ]Department of Gastroenterology & Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee , Klagenfurt, Austria
                [4 ]Austrian Society of Gastroenterology & Hepatology, Working Group GI-Oncology
                Author notes
                [Correspondence to ] Dr Wolfgang Sieghart; wolfgang.sieghart@ 123456meduniwien.ac.at

                MP, MP-R, and WS Liver Cancer (HCC)-Study Group Vienna.

                Journal
                ESMO Open
                ESMO Open
                esmoopen
                esmoopen
                ESMO Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-7029
                2016
                17 March 2016
                : 1
                : 2
                esmoopen-2016-000042
                10.1136/esmoopen-2016-000042
                5070280
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                Product
                Funding
                Funded by: National Institutes of Health, http://dx.doi.org/10.13039/100000002;
                Award ID: R01 DK103879
                Funded by: National Cancer Institute, http://dx.doi.org/10.13039/100000054;
                Award ID: P01 CA080124
                Funded by: Austrian Science Fund, http://dx.doi.org/10.13039/501100002428;
                Award ID: J 3747-B28
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                Review
                1506

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